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Hemorrhoids. A practical approach to an aggravating problem. Although hemorrhoids are considered a minor medical problem, they may cause considerable discomfort and anxiety. Fortunately, treatment is often simple and surgery is rarely necessary. In this practical article, Dr Cocchiara describes internal and external hemorrhoids, a classification system, and treatment choices based on the degree of involvement.

Unusual haemostasis for an unusual tumour. Catastrophic bleeding from a tactile neurofibroma affecting the thoracic vertebrae. Case report. The symptomatology of a typical acute descending thoracic aorta dissection was imitated by profuse haemorrhage caused by a benign tumour composed almost exclusively of Wagner-Meissner like tactile corpuscles and fatty tissue. The tumour caused extensive destruction of the bodies of the fifth and sixth thoracic vertebrae at the level of the vertebro-costal articulation. Emergency cross clamping of the descending aorta and haemostasis of the bleeding from osteal defects by tamponade with bone polymethyl methacrylate appeared the only way to control the life threatening haemorrhage. It seems that an intrathoracic tactile neurofibroma with a similar case history has not been reported till now.

Clinical trials. Access and reimbursement. Clinical trials continue to play an extremely important role in clinical oncology, but of the nearly 1 million cancer patients diagnosed in the United States each year, only 2.5% (25,000) participate in such trials. Access to clinical trials has been enhanced by the adoption by the NCI of a promotional campaign that involves seminars, dissemination of information to national and local news media, and assisting in making information about clinical trials available to patients and physicians. Factors that hinder accrual of patients to clinical trials include: (1) physicians' concern about losing contact with patients, (2) physicians who feel that "experimental therapy" is not as good as "standard therapy," and (3) the time it takes to discuss and implement clinical trials. Reimbursement for clinical trials has also become a major concern. Who should pay for clinical research? Many insurance companies have been reluctant to pay for "experimental therapy" but will pay for "standard therapy." If this trend continues, the whole concept and organization of clinical trials, i.e., Phase I, II, and III trials, will be greatly hindered. Solutions must be found, and third party payers need to realize that an investment in clinical trials today will decrease the long term costs of state-of-the-art care.

Inpatient theophylline toxicity: preventable factors. OBJECTIVE: To identify preventable factors contributing to inpatient theophylline toxicity. DESIGN: Case series. SETTING: Tertiary care public hospital. PATIENTS: Forty consecutive adult inpatients (mean age, 56.5 years) with theophylline levels greater than 140 mumol/L (25.0 mg/L). MEASUREMENTS AND MAIN RESULTS: A retrospective chart audit was done. Toxicity was produced in 27 of 40 patients by inpatient or emergency department theophylline administration. Management errors found included delay (greater than 10 hours) in taking action from time toxic blood levels were drawn (20 patients), inappropriately high dosing of patients with congestive heart failure (17 patients), failure to recognize obvious symptoms (16 patients), recurrent toxicity (11 patients), additional emergency department treatment of already toxic patients (7 patients), overlap of intravenous and oral therapy (6 patients), patient discharged with no physician awareness of toxicity or dosage change (5 patients). CONCLUSIONS: A set of recurring management errors was identified as contributing to inpatient theophylline toxicity. Effective preventive mechanisms could have prevented most toxicity and associated morbidity. Theophylline's overall risk-benefit ratio in the inpatient setting may be less than that measured in well-controlled studies of the drug's efficacy because of these management errors.

Effects of repeated temporary clipping of the middle cerebral artery on pial arterial diameter, regional cerebral blood flow, and brain structure in cats. Temporary clipping of the major arterial trunk is an important maneuver to control excessive unexpected bleeding in neurosurgical operations; however, repeated temporary clipping can give rise to severe neurological deficits after surgery. The present study was performed to confirm and explain these clinical findings. Initially, a single 20-minute or 1-hour occlusion of the middle cerebral artery was performed in each of 5 cats. Pial arterial diameter was determined by video imaging, regional cerebral blood flow was measured by autoradiography, and cerebral edema and infarction were observed. In the 20-minute occlusion group, no abnormal changes were found 5 hours after recirculation. In the 1-hour occlusion group, pial arteries were dilated by 45%, and regional cerebral blood flow increased to more than twice the resting cortical values. The extent of cerebral edema was 41.2 +/- 7.5% (SE) and infarction was 34.5 +/- 9.5% (SE) of the hemisphere. In the second experiment, three 20-minute occlusions of the middle cerebral artery in a 1-hour interval were performed in 20 cats. In 10 of them, thiopental (40 mg/kg) was used to protect the brain. In the group without barbiturate treatment, pial arteries were dilated by 40% at the end of experiment, regional cerebral blood flow decreased to about 70% compared with single 20-minute occlusion, cerebral edema was 19.5 +/- 8.1% (SE), and infarction was 8.1 +/- 3.7% (SE) of the hemisphere. In the treated group, these were only trivial changes. The effect of repeated clipping may cumulatively cause brain damage, and barbiturates should be used whenever repeated clipping is necessary.

Effect of emitted power on waveform intensity in transcranial Doppler This study assesses the problem of transcranial Doppler recording failure and seeks to determine the extent to which this can be ameliorated by increased emitted power. We hypothesized that waveform intensity is directly related to the rate and quality of successful recording and may be compared quantitatively among groups of patients. Among a large group of patients recorded at 800 mW/cm2 emitted power, intensity was strongest in white men, weakest in black women, and intermediate in black men and white women. It declined with age in women of either race, but not in men of either race. Analysis of the effect of emitted power on intensity predicted that significant numbers of waveforms recorded at 800 mW/cm2 could not be recorded at the current clinical standards of 100 mW/cm2, the difference being most pronounced in elderly black women. Temporal bone window thickness measured in a series of adult cadaver skulls was least in white men, greatest in black women, and intermediate in black men and white women. The findings of this study support the hypothesis that temporal bone window thickness is an important determinant of recording difficulty and suggest that increased emitted power can significantly increase successful recording, particularly in black and elderly patients. Increased power alone, however, cannot completely solve the recording problem within safe limits.

Propranolol and the morning increase in sudden cardiac death: (the beta-blocker heart attack trial experience). To provide insight into the protective effect of propranolol on mortality after myocardial infarction observed in the beta-Blocker Heart Attack Trial, the time of occurrence of sudden cardiac death was examined in this population. Between 5 A.M. and 11 A.M., 25 of the 56 total deaths (38%) occurred in the placebo patients compared with 11 of 45 (24%) in the propranolol patients. Excluding this period, there were nearly equal numbers of sudden cardiac deaths in the propranolol and placebo groups. This retrospective analysis suggests that beta blockade is protective during the morning hours when a surge of sympathetic activity may increase the risk of sudden cardiac death.

Migraine and vertebrobasilar ischemia. I studied 9 patients with migraine and posterior circulation ischemia. Inclusion criteria were (1) brainstem or cerebellar infarcts or transient ischemic attacks, (2) satisfactory vertebrobasilar angiograms, and (3) migraine. Excluded were patients with only occipital lobe ischemia, known arteriosclerosis, or other nonmigrainous vascular disease. Two women and 7 men, ages 6 to 58 years (mean, 34.7), had transient attacks only (2), single strokes (4), single stroke followed by attacks (1), or multiple strokes (2). Five had antecedent classic, 2 common migraine, and classic migraine began only after the initial ischemic event in the other two. The 7 stroke patients all had CT- or MRI-documented brainstem (4) or cerebellar (6) infarcts. Angiography was normal (3) or demonstrated basilar artery (BA) narrowing (2) or occlusion (4), or branch occlusion (1). In 3 patients the initially occluded BA later reopened. At follow-up (average 4.3 years, range 1 to 9 years), 5 were normal and 4 had important clinical deficits. I conclude that (1) "basilar migraine" is not always benign; it affects both sexes and a wide age range; (2) the pattern of headaches, attacks, and strokes varies; (3) migraine may appear only after ischemia; (4) some patients have BA occlusion or diffuse narrowing; and (5) BA occlusion can be temporary.

CR leads in cardiac emergencies. A preliminary study. The purpose of this study was to find a set of simplified electrocardiographic (ECG) leads that would be useful in cardiac emergencies. In 27 ambulatory cardiac patients and in 15 patients admitted to the hospital, we found that ECG records obtained with six bipolar CR leads were, in most respects, similar to records obtained previously in the same patients with six V leads. Records obtained with two abdominal-upper extremity leads, tested as possible alternatives to limb leads 2 and 3, were quite similar to records obtained with leads 2 and 3 in patients with an inferior wall infarction. Records obtained with leads CR7, CR8, and CR9 in a patient with a posterior wall infarction revealed a QS pattern that was not seen in the conventional 12-lead hospital record. In patients with anterolateral and inferior myocardial infarctions and in patients with unstable angina, the diagnostic patterns recorded with 11 bipolar leads described in this report were identical to patterns recorded with 12-lead ECGs. Although a larger number of observations, including patients with arrhythmias, would be required to reach a definitive conclusion, our results provide preliminary evidence that cardiac potentials may be adequately analyzed by using only two electrodes, using CR and abdominal leads, in succession. The technique described in this report, in which the reference electrode is attached to the right arm, and the exploring electrode is moved successively over nine preselected chest sites and over the umbilicus, can be completed in less than 3 minutes in a given patient, and provides records that are comparable to those obtained with the conventional 12-lead system.

Partial cytochrome b deficiency and generalized dystonia. An 18-year-old female had clinical features of idiopathic torsion dystonia with bilateral hypodense putaminal lesions on computed tomography. Mitochondrial encephalomyopathy was suspected because of persistent lactic acidemia and myopathy. Studies of oxidative metabolism on isolated skeletal muscle mitochondria revealed partial cytochrome b deficiency indicating a defect in the cytochrome b- c1 complex. This finding represents a unique, multisystem syndrome of progressive dystonia, putaminal degeneration, myopathy, and mitochondrial cytochrome b deficiency. Mitochondrial metabolic disorders may be a cause of torsion dystonia when other known associated factors are absent.

Nursing home patients transferred by ambulance to a VA emergency department. Nursing home residents are frequently transferred to hospital emergency departments. Delayed transfer may lead to poor outcomes. However, inappropriate transfer of the frail elderly may cause social and financial problems. We prospectively evaluated 221 consecutive ambulance transfers from community nursing homes to a VA emergency department. The objectives of the study were to describe the process and outcomes of transferred patients and to determine if alternative interventions were feasible. The results indicate that the problems of nearly half the study group could have been treated at the nursing home by a visiting physician with minimal medical equipment. Those admitted to the hospital (52%) were seriously ill, had prolonged lengths of stay (23.6 days), and had a high mortality rate (11%). Complex issues of physician reimbursement, proprietary nursing home budgeting, and day-to-day expediency appear to be involved in decisions to transport patients by ambulance to VA emergency departments.

Surgery for thoracoabdominal aortic aneurysms. From July 1985 to July 1989, Loma Linda University Medical Center evaluated 46 thoracoabdominal aortic aneurysms (TAAAs). Forty patients were taken to surgery--18 (45%) were operated on an emergency basis for reasons including rupture (12 patients, 30%), dissection (5 patients, 12.5%), and severe pain (1 patient). The overall mortality for all operated patients was five (12.5%-17% for emergency surgery versus 9% for elective surgery). Nonfatal complications occurred in 40 per cent of patients (16). The overall incidence of paraplegia was 10 per cent (4/40), emergency patients 17 per cent (3/18) versus elective patients 4.5 per cent (1/22). Careful preoperative evaluation, standardization of operative technique, and good postoperative management have improved the outlook for these patients who otherwise would progress to eventual rupture and death. Because mortality and morbidity are substantially reduced in elective patients, we recommend that all patients with TAAAs be evaluated for surgery as soon as diagnosis is made.

Exacerbation of acute platelet thrombus formation in stenosed dog coronary arteries with smoke from a non-tobacco-burning cigarette. The tobacco industry proposes to release a "new" cigarette with a burning charcoal tip, which heats the tobacco as air is drawn through it and into the lungs of the smoker. It is claimed to be safer because the tobacco does not burn. Using our established canine model of coronary artery stenosis with moderate intimal damage, we compared this new cigarette (0.4 mg nicotine) with a regular cigarette by ventilating dogs (n = 10) with room air and then either new or regular smoke (two cigarettes over about 10 minutes). In our dog model, periodic acute platelet thrombus formation followed by embolization produced cyclical flow reductions in coronary blood flow where the rate of flow decline was proportional to the degree of in vivo platelet-vessel wall interaction. The rate of flow decline increased from -4.81 +/- 1.29 ml/min2 to -9.60 +/- 2.29 ml/min2 after ventilation with the new-type smoke (p less than 0.01). Similarly, the rate of flow decline increased from -5.43 +/- 1.28 ml/min2 to -9.28 +/- 2.31 ml/min2 after ventilation with regular cigarette smoke (p less than 0.01). Despite the lack of a clear causal link between cigarette smoking and the acute manifestations of cardiovascular disease, the data presented here indicate that the new cigarette is just as potent as regular cigarettes at increasing in vivo platelet activity and exacerbating acute platelet thrombus formation in the dog. We conclude that the new proposed non-tobacco-burning cigarette has deleterious effects similar to those of conventional cigarettes, and thus does not eliminate smoking as a risk factor in cardiovascular disease in human beings.

Toxic shock syndrome associated with use of latex nasal packing. We treated a previously healthy young man who developed toxic shock syndrome 2 days after elective septoplasty with nonabsorbent latex packing. This case emphasizes that non-menstrual wound-associated toxic shock syndrome can occur after surgery that does not involve absorbent splinting or packing and should be considered in patients who present within a few days after surgery with fever, sunburnlike rash, hypotension, and multisystem complaints and laboratory abnormalities.

Selective intestinal decontamination increases serum and ascitic fluid C3 levels in cirrhosis. Selective intestinal decontamination for 7 days with norfloxacin was performed in 14 cirrhotic patients with ascites and low ascitic fluid total protein. Variations in serum and ascitic fluid of C3 and C4 and ascitic fluid total protein after therapy were compared with those of a control group of 14 untreated patients with similar characteristics. After oral norfloxacin administration, we saw a significant increase of C3 in serum (p less than 0.05) and ascitic fluid (p = 0.01). A significant increase was also observed in ascitic fluid total protein (p less than 0.05) but not in serum and ascitic fluid C4. There were no changes in serum C3, ascitic fluid C3, ascitic fluid C4 or in ascitic fluid total protein in group 2. These data demonstrate that selective intestinal decontamination increases serum and ascitic fluid C3 levels and, therefore, might be useful in preventing spontaneous infections in cirrhotic patients at high risk of infection.

Massive hemorrhage from an arterioureteral fistula associated with chronic renal transplant failure. A case of arterioureteral fistula from the graft artery stump of a failed transplant and the native ureter is reported. This case illustrates one of the possible complications of graft anastomosis. The etiological factors involved in the formation of the aneurysm and eventually the fistula are discussed.

The effects of methoxamine and epinephrine on survival and regional distribution of cardiac output in dogs with prolonged ventricular fibrillation This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival.

Restenosis after percutaneous transluminal coronary angioplasty: pathologic observations in 20 patients Histopathologic examination was performed in 20 patients undergoing antemortem coronary angioplasty. Thirty-four lesions were dilated and the interval between coronary angioplasty and death ranged from several hours to 4 years. Intimal proliferation of smooth muscle cells, as a major cause of restenosis, was observed in 83% to 100% of 28 lesions examined 11 days to 2 years after coronary angioplasty. In 20 lesions examined within 6 months, proliferating smooth muscle cells were predominantly of the synthetic type and there was abundant extracellular matrix substance chiefly composed of proteoglycans. In eight lesions examined between 6 months and 2 years, contractile type smooth muscle cells were dominant and extracellular matrix was composed chiefly of collagen. In three lesions examined after 2 years, evidence of antemortem coronary angioplasty was hardly identifiable and these lesions were almost indistinguishable from conventional atherosclerotic plaque. These temporal changes in histologic pattern provide a pathologic background for clinical reports that restenosis is predominantly found within 6 months after coronary angioplasty. Morphometric analysis revealed that the extent of intimal proliferation was significantly greater in lesions with evidence of medial or adventitial tears than in lesions with no or only intimal tears.

Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques. In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway.

Hemodynamic and electrophysiologic evaluation of patients with hypertrophic cardiomyopathy surviving cardiac arrest. Hemodynamic and electrophysiologic studies were performed in 30 survivors of sudden cardiac arrest with hypertrophic cardiomyopathy (HC) to determine responsible factors. Electrophysiologic abnormalities alone were present in 27 patients (90%): sinus node dysfunction in 14 (47%), delayed atrio-ventricular nodal conduction in 1 (3%), abnormal His-Purkinje conduction in 7 (23%), an inducible atrial tachycardia in 7 (23%), and inducible sustained ventricular arrhythmia in 21 (70%). Sustained ventricular arrhythmia was polymorphic ventricular tachycardia (VT) in 18 patients (86%), monomorphic VT in 2 patients (7%) and ventricular fibrillation in 1 patient (3%). In 1 patient the arrhythmia recorded during an episode of cardiac arrest and induced at electrophysiologic study was polymorphic VT. VT was induced with less than or equal to 2 extra-stimuli in only 1 patient (3%) but with less than or equal to 3 extra-stimuli in 20 patients (97%). Potential causes of sudden cardiac arrest were found in all patients and were multiple in 13 patients (43%). These were (1) ventricular electrical instability in 21 patients (70%), (2) severe left ventricular outflow tract obstruction in 8 patients (27%), (3) bradycardia in 5 patients (17%), (4) myocardial ischemia associated with hypotension in 5 patients (17%), and (5) atrial tachycardia resulting in hypotension in 4 patients (13%). Of the 21 patients with inducible sustained ventricular arrhythmia, 17 received an implantable defibrillator device and 4 were treated with antiarrhythmic drugs. Seven patients underwent left ventricular septal myectomy.

Developmental dysmnesia in a poor reader. A 22-yr-old subject with moderate developmental dyslexia experienced poor memory from an early age. In spite of normal intelligence he had great difficulty in learning historical and geographical names, mathematical formulae, poems and songs, and verbal series such as the letters of the alphabet and the months of the year. His recognition of familiar faces was also faulty at times. A battery of memory tests confirmed a moderate deficit of verbal as well as visual memory, whereas spatial memory was preserved. Other cognitive functions were intact, except for a mild reading disability. No evidence of brain pathology was provided by his history, neurological examination and CT scanning.

Human central nervous system primitive neuroectodermal tumor expressing nerve growth factor receptors: CHP707m. A primitive neuroectodermal tumor (PNET) presented as a cerebral hemispheric mass in a 33-year-old man. Bone marrow metastases were discovered 11 months later. A cell line (CHP707m) was derived from these metastases. In culture, the cells showed features of neuronal differentiation, forming short neurites and synthesizing low-molecular-weight neurofilament protein. Northern blotting showed the tumor cells express nerve growth factor (NGF) receptor messenger RNA, and fluorescence-activated cell-sorting demonstrated NGF receptors on the cell surface. Western blotting showed CHP707m NGF receptors are truncated. The receptors are functional; they bind iodine 125-labeled mouse NGF with an affinity of 1.6 x 10(-9) M, and short-term treatment with NGF induces expression by the tumor cells of the proto-oncogene, c-fos. Although CHP707m is the first central nervous system PNET cell line proven to express NGF receptors, immunohistological survey of tissue sections prepared from human central nervous system PNETs showed that 13 of 35 contained NGF receptor-positive tumor cells. Thus, more than one-third of such tumors might be responsive to the effects of NGF.

Cardiovascular effects of nicardipine. Nicardipine, a new 1-4 dihydropyridine calcium antagonist, has chemical properties that allow oral and stable intravenous preparations. It is the first intravenous dihydropyridine calcium antagonist available in the United States. Among its drug class it has a unique chemical structure that affords properties useful in the treatment of acute cardiovascular conditions, such as myocardial ischemia, congestive heart failure, hypertension, cerebrovascular disease, and other related disorders. In patients with coronary artery disease, intravenous nicardipine has been found to reduce myocardial oxygen demand by reducing afterload and increasing myocardial oxygen supply through coronary vasodilatation. It enhances left ventricular performance and augments coronary blood flow beyond that required by increased myocardial oxygen consumption. Nicardipine may also offer protection from ischemic injury to the heart and central nervous system. Alone and in combination with other antihypertensive agents, nicardipine has been shown to be effective in the treatment of mild to moderate hypertension. It is safe for use in patients with certain types of conduction disturbances because it does not greatly affect sinoatrial and atrioventricular conduction. Additional advantages for nicardipine's use in the management of acute cardiovascular disorders are its rapid onset and short duration of action.

Effects of head trauma from motor vehicle accidents on Parkinson's disease. During 1 year we monitored changes in clinical disability scores in 10 patients with Parkinson's disease (PD) who sustained head trauma from motor vehicle accidents. Disability significantly increased immediately after trauma, but returned to baseline levels in subsequent weeks. These patients' signs deteriorated over the subsequent year, but this decline was equivalent to that of a matched control group with PD who did not have a motor vehicle accident or trauma. Based on these data, we conclude that trauma or stress caused by motor vehicle accidents can transiently exacerbate parkinsonian dysfunction without causing persistent increased disability or an alteration in disease course.

Gastrointestinal disease and oral contraception. Oral contraceptive steroids play a major role in modern family planning. With the present tendency to decrease the doses of both estrogens and progestogens, any factor that reduces the bioavailability of the lower-dose preparations may have an impact on contraceptive protection. Although ethinyl estradiol, the most commonly used oral estrogen, is liable to an enterohepatic circulation as unchanged drug, the commonly used progestogens are not. At present, no convincing evidence exists in the human subject that disruption of the enterohepatic circulation by antibiotics or antacids does reduce contraceptive efficacy of the pill. Oral contraceptive steroids are mainly absorbed from the small bowel, and contraceptive efficacy depends on its absorptive capacity. Enhanced passage of gastrointestinal contents or impaired absorption may thus contribute to contraceptive failures in patients who have chronic inflammatory disease, diarrhea, ileostomy, or jejunoileal bypass.

Does use of gastroepiploic artery graft increase surgical risk? Seventy patients in whom the gastroepiploic artery was used for coronary artery bypass grafting were compared with 70 patients in whom the gastroepiploic artery was not used. Mean age was 56.8 years in the group in which this artery was used and 61.8 years in the group in which it was not (p less than 0.001). All other preoperative characteristics including number of women, extent of coronary artery disease, previous myocardial infarction, unstable angina, and preoperative left ventricular function were not significantly different between the two groups. An internal mammary artery graft was concomitantly used in 68 patients (97%) of the group with a gastroepiploic artery graft and in 61 patients (87%) without such a graft. The mean number of distal anastomoses was 3.3 and 3.4, aortic crossclamp time was 65.3 +/- 19.9 minutes and 54.0 +/- 20.1 minutes, and cardiopulmonary bypass time was 114.8 +/- 23.6 minutes and 112.9 +/- 25.0 minutes, respectively, in the groups with and without a gastroepiploic artery graft. Only aortic crossclamp time was significantly (p less than 0.05) longer in the group with a gastroepiploic artery graft. There were two (2.9%) early deaths and two (2.9%) new Q-wave infarctions in both groups. Intraaortic balloon pumping was required in five patients (7.1%) in the group with a gastroepiploic artery graft and in three patients (4.3%) without this graft. Postoperative complications were similar and rare in both groups. Intraoperative endoscopic laser Doppler study demonstrated no significant change of gastric mucosal blood flow before and after division of the gastroepiploic artery. We concluded that there is no additional risk in the use of the gastroepiploic artery for coronary bypass grafting, and a favorable outcome can be expected.

Latent sensitisation to respiratory syncytial virus during acute bronchiolitis and lung function after recovery. To determine whether latent sensitivity to respiratory syncytial virus antigen(s) occurs after infection, 27 infants with acute bronchiolitis were studied and compared with 15 hospital controls. Blood was collected for whole blood challenge, and histamine release was measured by a high performance liquid chromatography technique with fluorometric detection. There was a significantly greater histamine release to respiratory syncytial virus antigen(s) in those with bronchiolitis than in controls, expressed either in amount (median 154 nmol/l compared with 104 nmol/l) or percentage release (median 20% compared with 3%). There was a significant difference between index and control groups in terms of individual histamine responses. These findings strongly suggest that infants develop latent sensitivity to respiratory syncytial virus antigen(s) during the course of acute bronchiolitis. Serial lung function tests were performed in 15 infants. All infants had abnormalities of lung function at some stage, but the small numbers of subjects precluded comparison between 'sensitised' and 'non-sensitised' infants. Further study is indicated to define the relation of latent sensitisation and subsequent bronchial hyper-responsiveness after respiratory syncytial virus infection in infants.

A retrospective study of spontaneous remission and long-term outcome in patients with infantile spasms. The spontaneous remission rate and long-term outcome in 44 patients with infantile spasms not treated with hormonal drugs were studied. The cumulative spontaneous remission rate during the first 12 months after onset of infantile spasms, as determined by retrospective analysis, was as follows: 1 month, 2%; 2 months, 2%; 3 months, 5%; 4 months, 7%; 5 months, 9%; 6 months, 11%; 7 months, 11%; 8 months, 14%; 9 months, 16%; 10 months, 18%; 11 months, 25%; 12 months, 25%. The average age at follow-up was 80 months. Nine percent of patients had normal development or only mild impairment. The remainder showed various degrees of retardation. These data should be useful in the design and interpretation of therapeutic drug trials in patients with infantile spasms.

Hypertension during pregnancy in insulin-dependent diabetic women. Insulin-dependent diabetic patients are at increased risk for hypertensive disorders of pregnancy. This study was designed to study prospectively the rate of pregnancy-induced hypertension (PIH) in 175 insulin-dependent diabetic pregnancies (88 White classes B-C, 87 classes D-RT). Pregnancy-induced hypertension was defined as two or more occurrences after 20 weeks' gestation of a mean arterial pressure (MAP) of 105 mmHg or greater or an increase of 20 mmHg or greater from the baseline MAP. The rate of PIH in the diabetic population was 15.4% and was significantly associated with nulliparity, poor glycemic control in the first and second trimesters, and advanced White class. Neonatal outcome was not significantly altered in the presence of PIH. We speculate that improved glycemic control throughout pregnancy might reduce the rate of this complication in diabetic patients.

High- versus standard-dose megestrol acetate in women with advanced breast cancer: a phase III trial of the Piedmont Oncology Association. One hundred seventy-two patients with advanced breast cancer were randomized to receive oral standard-dose megestrol acetate (MA), 160 mg/d or high-dose MA, 800 mg/d. All but two patients had one prior trial of tamoxifen therapy for either metastatic disease (74%) or as adjuvant treatment (26%). Pretreatment characteristics were similar for both arms. High-dose MA resulted in a superior complete plus partial response rate (27% v 10%, P = .005), time to treatment failure (median, 8.0 v 3.2 months, P = .019), and survival (median, 22.4 v 16.5 months, P = .04) when compared with standard-dose therapy. These differences remained significant after adjustment for other covariates. Thirty-four patients were given high-dose MA after failure of standard-dose MA treatment, and none responded. Weight gain was the most distressing side effect, with 13% of standard-dose and 43% of high-dose patients gaining more than 20 lbs. Four major cardiovascular events occurred in patients receiving high-dose treatment and one in patients given standard doses. Other toxicity was modest. High-dose MA may represent a significant improvement in secondary endocrine therapy for advanced breast cancer patients refractory to initial endocrine treatment, but its use on a regular basis should be reserved until these results are confirmed by other clinical trials.

Fungal pulmonary infections after bone marrow transplantation: evaluation with radiography and CT. The authors reviewed 55 pairs of chest radiographs and computed tomographic (CT) studies obtained in 33 febrile bone marrow transplant (BMT) recipients. The images were read separately, without knowledge of the clinical diagnosis. Twenty-one episodes of fungal infection were documented. One chest radiograph showed a pneumonia-like opacity, and 17 showed nodular opacities, five with cavitation. In 20 of 21 episodes, CT showed nodules with cavitation (n = 7), halo (n = 4), hazy margin (n = 5), air bronchogram (n = 2), cluster of fluffy nodules (n = 1), or sharp margin (n = 1). In none of the nine bacteremic episodes, however, were there opacities on chest radiographs or CT studies. CT studies demonstrating complicated nodules in febrile BMT patients strongly suggest a fungal infection, whereas negative CT studies suggest bacteremia or non-filamentous fungal infection of nonpulmonary origin. CT appears to add useful information to radiographic analysis during the assessment of febrile episodes in BMT patients, especially when invasive diagnostic procedures pose a high risk.

Expression of aminopeptidase N (CD13) in mesenchymal tumors. For a long time, CD13 molecules have been considered to be restricted to myeloid cells and related neoplasms. Meanwhile, however, expression of CD13 has also been detected in some hepatocellular, gallbladder, renal, and lung carcinomas, and even in some fibrosarcomas and malignant melanomas. In this study, expression of CD13 antigen was immunohistochemically examined in non-neoplastic mesenchymal cells, along with 33 benign and 83 malignant mesenchymal tumors (MET) using CD13 monoclonal antibodies (MAb) My7, U71, WM-15, and MoU48. In non-neoplastic mesenchymal cells, expression of CD13 was restricted to perivascular fibrocytes/blasts, tissue histiocytes, osteoclasts, and to the perineurium of peripheral nerve trunks. Under neoplastic conditions, CD13 was detectable in some tumors of smooth muscle, fibrous, fibrohistiocytic, synovial, osteogenic, and peripheral nerve sheath origin, and even in some tumors of adipose tissue. Tumors of striated muscle origin, of autonomic ganglia, and of cartilage-forming tissues were CD13-negative throughout. Thus in most but not all tumors studied the pattern of expression of CD13 mirrors the situation found in their cells of origin. These findings enrich the data on expression of leukocyte differentiation antigens in extra-hematopoietic tissues. Expression of CD13, which meanwhile is known to be identical to aminopeptidase N, an important peptide-cleaving enzyme, in only some MET might reflect a special functional state of these neoplasms.

Epidemiologic perspectives on life-style modification and health promotion in cancer research. The clinical, patient-oriented focus of medicine and psychology is contrasted with the epidemiologic (public health) approach in assessing the role of life-style factors and health promotion in cancer research. The unifying host-agent-environment epidemiologic paradigm is applied to contemporary cancer prevention issues, principally smoking cessation and dietary modification, to demonstrate differences in inferences, prevention strategies, and research opportunities. An integration of population-based approaches with the dynamics of patient behavior and risks for cancer is especially salient when considering the role of psychosocial stress and personal and social resources. The social epidemiologic perspective, the study of the psychosocial determinants of physical health status, offers one approach for resolving the outlined differences in perspectives and is particularly relevant for understanding the etiology of life-style behaviors and how they might be altered.

Anorectal function in incontinent patients with cerebrospinal disease. Anorectal manometry and the electrical activity of the external anal sphincter were measured in 20 patients with well-defined, incomplete spinal lesions who were referred because of fecal incontinence and in 30 normal subjects. Six patients had a high spinal lesion, 11 had a low spinal lesion, and 3 had mixed high and low spinal lesions. Patients with high spinal lesions had normal basal pressures but abnormally low squeeze pressures and impaired rectal sensation. Unlike normal subjects, there was no relationship between the depth of sphincter relaxation and the distention volumes. The external sphincter responses to rectal distention and increases in intraabdominal pressure were enhanced, and leakage of perfusion fluid was uncommon. Patients with low spinal lesions had abnormally low basal and squeeze pressures, blunted rectal sensation, and showed impaired external anal sphincter responses to rectal distention or increases in intraabdominal pressures. Most of these patients leaked the infused fluid during these maneuvers. Sphincter function in patients with mixed lesions was more severely impaired than in patients with low and high spinal lesions. Patients with mixed lesions showed abnormally low basal and squeeze pressures, impaired rectal sensation, and no external anal sphincter responses to either rectal distention or increases in intraabdominal pressure. Leakage occurred during these maneuvers in all patients with mixed lesions.

Rupture of a giant carotid aneurysm after extracranial-to-intracranial bypass surgery. We report a case of a fatal rupture of a previously unruptured giant aneurysm of the bifurcation of the internal carotid artery (ICA), which occurred after an extracranial-intracranial (EC-IC) bypass and the partial occlusion of the ICA. Interim angiography showed retrograde filling of the proximal middle cerebral artery to the aneurysm. There have been four previously reported cases of giant aneurysms rupturing after treatment with an EC-IC bypass and carotid ligation, and it appears likely that a change in pressure/flow dynamics produced by the bypass may have been the cause. The technique of carotid ligation with an EC-IC bypass is used frequently to treat unclippable intracranial aneurysms, and the resulting hemodynamic changes need to be considered carefully to prevent this type of complication. To minimize hemodynamic stress on the aneurysm, we suggest that 1) the bypass caliber should be as small as possible consistent with sufficient cerebral blood flow after ICA occlusion, and 2) complete ICA occlusion should be performed as soon as possible after the bypass.

Disorders of esophageal motility. Patients with esophageal motility disorders usually have dysphagia and many also have chest pain similar to angina. The diagnosis is suggested by the clinical presentation, and supporting evidence is often provided by contrast roentgenography. Esophageal manometry is usually necessary to confirm the diagnosis. Conservative therapy using pharmacologic agents is often useful as an initial trial, although many patients who continue to be symptomatic ultimately require surgical intervention.

Influence of the menstrual cycle on systemic diseases. Physiological changes associated with the menstrual cycle influence the clinical course of some diseases such as bronchial asthma, allergies, anaphylaxis, epilepsy, migraine, dermatoses, and porphyria. Hormonal manipulation can be beneficial in some patients.

Prognostic significance of valvular regurgitation in patients with infective endocarditis. PURPOSE: Doppler ultrasound is a sensitive modality for detecting and quantitating valvular regurgitation in patients with infective endocarditis. Because valvular regurgitation leads to heart failure, we evaluated the prognostic significance of Doppler-detected valvular regurgitation in patients with endocarditis who had not yet developed clinical heart failure. PATIENTS AND METHODS: We reviewed the medical records of 65 patients with a clinical diagnosis of infective endocarditis from May 1985 to March 1990. A total of 49 patients were included in the study: 33 patients with native valve endocarditis and 16 patients with prosthetic valve endocarditis. The initial Doppler echocardiogram was examined in these patients to determine the presence and degree of valvular regurgitation. RESULTS: Significant (moderate to severe) valvular regurgitation was detected in 23 (47%) patients. The presence or absence of significant valvular regurgitation did not predict the development of congestive heart failure, the need for surgery, or death (p = NS). The development of congestive heart failure was significantly associated with the need for surgery (p less than 0.0001) and death (p less than 0.05). CONCLUSION: We conclude that the detection of significant valvular regurgitation in patients with infective endocarditis who have not yet developed heart failure is not predictive of future complications nor does the absence of significant valvular regurgitation identify a group of patients with a more favorable prognosis. In our series, patients who developed congestive heart failure had a significantly higher incidence of surgery and death. Therefore, decisions regarding clinical management in patients with infective endocarditis should not be made solely on the presence or absence of echocardiographically detected valvular regurgitation.

Bile acids in human plasma interfere with cholecystokinin bioassay using dispersed pancreatic acini. A bioassay using dispersed pancreatic acini was used to measure fasting plasma cholecystokinin (CCK) concentrations in 105 patients with various kinds of gastrointestinal diseases, 17 patients with diabetes mellitus, and 6 healthy volunteers. High plasma CCK bioactivities were observed in patients with obstructive jaundice, choledocolithiasis, and primary biliary cirrhosis. Twenty-three samples with high CCK bioactivities were assayed by the same bioassay after the addition of a specific CCK antagonist and by a CCK radioimmunoassay in order to determine whether the high CCK-like bioactivity was due to circulating CCK or other factors. High CCK bioactivities were partially inhibited by the specific CCK antagonist, CR-1409, but the activities were not totally abolished. The residual bioactivities (not inhibited by CR-1409) correlated with plasma bile acid concentrations. The inhibitable CCK bioactivities correlated with plasma CCK levels obtained by radioimmunoassay. Although the bioassay using dispersed pancreatic acini has several advantages for measuring plasma CCK, this method overestimates CCK bioactivities in patients with high plasma bile acid concentrations.

Imaging bone tumors in the 1990s. Progress in bone tumor management has occurred as a result of cooperation among surgeons, oncologists, pathologists, and radiologists. During the 1990s radiologists will contribute to care of patients with bone tumors in major ways. Tumor detection and preliminary diagnosis will be accomplished by radiography. Tumor local extent will be assessed by magnetic resonance imaging (MRI) and to a lesser degree by computed tomography (CT). Distant spread of malignancy will be documented by radionuclide scintigraphy (skeleton) and by CT (lungs). The combined estimate of local extent and distant spread will assure adequate staging before definitive management decisions. Preoperative closed percutaneous biopsy for histologic diagnosis will be accomplished on an outpatient basis under fluoroscopic or CT guidance. Arteriography will be employed for delivery of local chemotherapy. Some combination of arteriography, MRI, and MR spectroscopy will be used to evaluate tumor response. After limb-salvage surgery, MRI will sequentially assess the tumor bed; bone scintigraphy and CT will detect skeletal and pulmonary metastases. The radiologist's role will undergo continuous redefinition.

Malignant left-sided large bowel obstruction managed by subtotal/total colectomy. Of 60 patients presenting with acute obstructing carcinoma of the left colon, 49 underwent immediate resection either by radical subtotal/total colectomy (31 patients, group I) or by radical segmental resection (18 patients, group II) of whom three had immediate anastomosis after on-table bowel irrigation and 15 had a planned staged procedure. The operative mortality rate was 3 per cent in group I and 11 per cent in group II (not a statistically significant difference). However, substantial differences were found for major morbidity (6 versus 44 per cent in groups I and II respectively; P less than 0.01) and mean length of hospital stay (17 days in group I versus 35 days in group II; P less than 0.05). All three patients who had on-table lavage developed anastomotic leaks which necessitated a second operation to form a stoma. Six patients (19 per cent) in group I required antidiarrhoeal medication in the immediate postoperative period. However, subsequent improvement in stool frequency was noted in all patients. It is concluded that subtotal/total colectomy is an acceptable means of managing patients with obstructing carcinoma of the left colon in that it is associated with a low morbidity and mortality rate and good functional results.

Endoscopic appearance and significance of functional lymphangiectasia of the duodenal mucosa. Intestinal lymphangiectasia is found in a wide variety of pathologic conditions. Functional lymphangiectasia has not been well characterized. We report 20 patients followed for 9 to 55 months (mean 30 months) after incidental detection at endoscopy of lymphangiectasia. Our study indicates that functional lymphangiectasia is not pathologic and does not warrant repeat endoscopy in the absence of other clinical indications.

Angiosarcoma of the uterus: a case report. We are reporting a case of angiosarcoma of the uterus in which the diagnosis was confirmed ultrastructurally by demonstration of Weibel-Palade bodies in the tumor cells. Only 10 cases of this entity have been previously documented in the literature.

Primary neoplasms of the hollow organs of the gastrointestinal tract. Staging and follow-up. The number of imaging modalities available to stage and follow-up patients with primary neoplasms of the gastrointestinal (GI) tract continues to increase. Magnetic resonance imaging (MRI), computed tomography (CT), and ultrasonography are useful techniques for both staging and follow-up. For staging, CT is most frequently used for the detection of liver metastases and is increasingly used as a substitute for the chest radiograph in the detection of lung metastases. CT is still the imaging test of choice for the preoperative staging of esophageal carcinoma. CT is less helpful in staging the patient with gastric carcinoma or colorectal carcinoma. The current usefulness of MRI in the staging of GI tract malignancies is limited by the lack of an adequate oral intraluminal contrast agent and degradation of images due to motion. Sonography, especially the new technique of endoscopic ultrasound, is promising for the detection of local invasion from GI tract malignancies. CT is used in the follow-up of patients with tumors of the GI tract to detect liver, adrenal, and nodal metastases as well as local recurrence because of the ability of CT to detect extraluminal masses. CT of the pelvis has been recommended as a routine follow-up procedure in patients who have undergone abdominal-peroneal resection. Both CT and MRI can be used to detect local recurrence, but suffer from the inability to differentiate scar from recurrent tumor. The initial hope that MRI would be capable of differentiating postoperative scar tissue from recurrent tumor has not been realized. Therefore, with positive CT or MRI findings, occasionally a percutaneous biopsy will be required to confirm local recurrence.

The role of lasers in hemorrhoidectomy. Eighty-eight patients who received treatment for hemorrhoids were randomized into two groups. Group A received the Nd-YAG laser phototherapy for internal hemorrhoid combined with the CO2 laser for external hemorrhoid. Group B was treated with closed Ferguson hemorrhoidectomy. The need of narcotic injections for pain relief was 11 percent in group A vs. 56 percent in group B (P less than 0.001). The incidence of postoperative urinary retention was 7 percent in group A, vs. 39 percent in group B (P less than 0.05). No enema was required postoperatively in group A, vs. 9 percent in group B; 84 percent of the patients in group A were discharged on the second postoperative day, vs. 83 percent of the patients in group B discharged on the fifth postoperative day. The cost was 20 percent less in the former group. The overall complications in both groups were insignificant in difference, except prolonged wound healing in group A was noted. One year follow-up showed satisfactory results. Laser treatment is considered one of the alternatives to conventional treatment, but the surgeon needs to be aware of laser hazards.

Chylous ascites should suggest constrictive pericarditis even in a patient with cirrhosis. Chylous ascites, a milky, high triglyceride fluid is usually found in patients with lymphatic obstruction from malignancy. We describe a patient with cirrhosis who developed constrictive pericarditis and chylous ascites. Long-standing portal hypertension compounded by elevated central venous pressure provided several pathophysiologic contributions to the formation of the chylous ascites. Chylous ascites even in a cirrhotic requires prompt assessment for conditions leading to elevated central venous pressure.

Loop ileostomy after ileal pouch-anal anastomosis--is it necessary? Construction of a loop ileostomy is usually advised in patients having an ileal pouch-anal anastomosis to minimize the complication of chronic pelvic sepsis. Formation and closure of a loop ileostomy was associated with a 41 percent and 30 percent complication rate, respectively, in a prospective series of 34 patients. This morbidity must now be assessed in relation to the benefits of avoiding temporary fecal diversion in restorative proctocolectomy.

Morphological observations late (greater than 30 days) after clinically successful coronary balloon angioplasty. This report describes clinical, morphological, and histological findings late (1.6-24.1 months [average, 8.2 months]) after clinically successful coronary balloon angioplasty in 20 necropsied patients with coronary angioplasty restenosis. Clinical evidence of restenosis occurred in 14 (70%) of patients, including six patients with sudden coronary death. Of the 20 patients, 14 (70%) had cardiac causes of death and six (30%) had noncardiac causes of death. Two major subgroups of histological findings were observed: 1) intimal proliferation (60%) and 2) atherosclerotic plaques only. Of the eight sites with atherosclerotic plaques only, six were eccentric lesions and two were concentric lesions. No morphological evidence of previous angioplasty injury (cracks, breaks, or tears) was observed in the eight patients with atherosclerotic plaques only. Proposed mechanisms for the development of intimal proliferation involve the reaction of smooth muscle cells and platelets, whereas elastic recoil of overstretched eccentric or concentric atherosclerotic lesions represents the most likely explanation for the findings in the latter subgroup. On the basis of these morphological findings at angioplasty restenosis sites, specific treatment strategies for coronary artery balloon angioplasty restenosis are proposed.

Amiloride blocks the onset of ACTH-induced hypertension in the sheep. This study investigated the ability of two diuretics, amiloride and frusemide, to prevent the development of ACTH induced hypertension in conscious sheep. Infusion of amiloride (20 mg/day) or frusemide (50 mg/day) for three days into normotensive sheep did not have any significant effects on blood pressure. Amiloride blocked ACTH-induced hypertension and the sodium retention and hypokalemia which is usually associated with ACTH administration. Frusemide failed to completely block the hypertension and potassium loss, however it blocked the transient initial urinary sodium retention associated with ACTH-induced hypertension. As frusemide failed to completely block the hypertension it is unlikely that the amiloride effect is due primarily to effects on urinary Na excretion. It is possible that amiloride is exerting its antihypertensive effects by blocking sodium channels.

Cervical spine stabilization. A three-dimensional, biomechanical evaluation of rotational stability, strength, and failure mechanisms. The three-dimensional rotational biomechanical properties of several different types of posterior stabilizing procedures are reported. A severe ligamentous and bony injury was simulated with three vertebral body human cervical spine segments. Good stabilization was noted for all of the repairs in flexion loading. Without polymethylmethacrylate supplementation, none of the repairs was stable in extension. All of the repairs provided reasonable stabilization for lateral bending except for the posterior wiring without methacrylate, and all but the posterior wiring and facet fusion provided reasonable stabilization against axial rotation loading. The supplementation of all of these repairs with polymethylmethacrylate added considerably to the stability of all the constraints. These findings may be useful in clinical decision-making for determining the kind of repairs and postoperative brace protection to use.

Pain experiences of intensive care unit patients. The purpose of this study was to describe various dimensions of the pain experiences of intensive care unit (ICU) patients. A purposive, primarily surgical sample of 24 ICU patients from two hospitals was interviewed after transfer from ICU. All but one patient remembered their ICU stay. Although this and six other patients had no recall of pain, 63% of the sample rated their pain as being moderate to severe in intensity. In a subgroup of nine patients having cardiac surgery, mean morphine sulfate administration during the first three postoperative days was 14 mg/day. This group of patients reported a lack of total pain relief from analgesics. Patients also described various sources of their pain, difficulties they had in communicating their pain, and nonpharmacologic methods that helped relieve their pain. Results of this study clearly indicate that not only pain but its communication and treatment were significant problems for a substantial portion of this ICU sample. Further descriptive and experimental research of pain characteristics and treatment practices for ICU patients is urgently needed. Improvements in nursing practice that result from such research may make a substantial difference in the comfort and well-being of critically ill patients.

Human dose-response relationship for decompression and endogenous bubble formation. The dose-response relationship for decompression magnitude and venous gas emboli (VGE) formation in humans was examined. Pressure exposures of 138, 150, and 164 kPa (12, 16, and 20.5 ft of seawater gauge pressure) were conducted in an underwater habitat for 48 h. The 111 human male volunteer subjects then ascended directly to the surface in less than 5 min and were monitored for VGE with a continuous-wave Doppler ultrasound device over the precordium or the subclavian veins at regular intervals for a 24-h period. No signs or symptoms consistent with decompression sickness occurred. However, a large incidence of VGE detection was noted. These data were combined with those from our previously reported experiments at higher pressures, and the data were fit to a Hill dose-response equation with nonlinear least-squares or maximum likelihood routines. Highly significant fits of precordial VGE incidences were obtained with the Hill equation (saturation depth pressure at which there is a 50% probability of detectable VGE [D(VGE)50] = 150 +/- 1.2 kPa). Subclavian monitoring increased the sensitivity of VGE detection and resulted in a leftward shift [D(VGE)50 = 135 +/- 2 kPa] of the best-fit curve. We conclude that the reduction in pressure necessary to produce bubbles in humans is much less than was previously thought; 50% of humans can be expected to generate endogenous bubbles after decompression from a steady-state pressure exposure of only 135 kPa (11 ft of seawater). This may have significant implications for decompression schedule formulation and for altitude exposures that are currently considered benign. These results also imply that endogenous bubbles arise from preexisting gas collections.

Beta-lactam resistance mechanisms of methicillin-resistant Staphylococcus aureus. In vitro and in vivo activity of amoxicillin and penicillin G alone or combined with a penicillinase inhibitor (clavulanate) were tested against five isogenic pairs of methicillin-resistant Staphylococcus aureus (MRSA) producing or not producing penicillinase. Loss of the penicillinase plasmid caused an eight times or greater reduction in the MICs of amoxicillin and penicillin G (from greater than or equal to 64 to 8 micrograms/ml), but not of the penicillinase-resistant drugs methicillin and cloxacillin (greater than or equal to 64 micrograms/ml). This difference in antibacterial effectiveness correlated with a more than 10 times greater penicillin-binding protein 2a affinity of amoxicillin and penicillin G than of methicillin and a greater than or equal to 90% successful amoxicillin treatment of experimental endocarditis due to penicillinase-negative MRSA compared with cloxacillin, which was totally ineffective (P less than .001). Amoxicillin was also effective against penicillinase-producing parent MRSA, provided it was combined with clavulanate. Penicillinase-sensitive beta-lactam antibiotics plus penicillinase inhibitors might offer a rational alternative treatment for MRSA infections.

Occlusion of umbilical artery in acardiac, acephalic twin. In the acardiac, acephalic twin malformation the normal co-twin is put at risk because of the extra cardiac work-load. Surgical procedures may be hazardous to the mother. We describe a novel approach--the insertion of a helical metal coil to induce thrombosis in the umbilical artery of the acardiac twin--which immediately interrupted flow. The co-twin was delivered at 39 weeks and his neonatal course has been normal.

Evidence of a local immune activation in cystic brain tumors. The fluid of cystic brain tumors was characterized with regard to the protein content. In most malignant tumors, the concentrations of immunoglobulins G and M (IgG and IgM) were higher relative to other proteins in the cyst fluid than in the serum of the same patient. A markedly elevated ratio of monomeric to pentameric IgM was detected in the cyst fluid of two patients with glioblastomas. The results indicate a local immunoglobulin synthesis in malignant cystic brain tumors. It is hypothesized that higher-than-expected concentrations of IgG and IgM in cyst fluid as compared to plasma are a sign of an ongoing immune response triggered by the tumor.

Gallstone pancreatitis. Gallstone pancreatitis is caused by transient obstruction of the ampulla of Vater by a migrating gallstone. Intraglandular activation of pancreatic enzymes occurs (by an unclear mechanism), and their entry into the circulation causes most of the local and systemic events of pancreatitis. The diagnosis is based on history and physical examination, an elevation of serum amylase above 1000 IU/L, and ultrasound and CT scans. Endoscopic retrograde cholangiopancreatography can be used in less certain cases to confirm the presence of common bile duct stones. Because of the absence of an agent that can abort progression of the disease, therapy should consist of adequate resuscitation, nutritional support, and careful monitoring to detect early complications. In patients with mild pancreatitis, surgery usually can be performed within 48 or 72 hours of admission or as soon as symptoms and amylase levels return to normal. For patients with severe disease, endoscopic sphincterotomy is emerging as the therapeutic modality of choice. Elective treatment of the associated biliary disease should be performed during the same hospitalization after the acute phase of the disease has subsided.

Simultaneous operative repair of multilevel lower extremity occlusive disease. Sixty-two patients (39 men (63%), 23 women (27%), mean age 68 years) with multilevel lower extremity arterial occlusive disease underwent simultaneous inflow and outflow operative arterial repair consisting of aortofemoral bypass in 22 (35%), axillofemoral bypass in 17 (28%), femorofemoral bypass in 15 (24%), iliac endarterectomy in 7 (11%), and unilateral aortoiliac bypass in 1 (2%), combined with 69 outflow procedures (unilateral in 55 patients, 89%), including above-knee femoropopliteal in 12 (17%), below-knee femoropopliteal in 35 (51%), femoroinfrapopliteal in 20 (29%), popliteal tibial in 1 (1%), and femoropedal bypass in 1 (1%). Multiple criteria were used to identify patients with multilevel disease likely to benefit from multilevel procedures. The operations were performed by two operating teams in a median time of 240 minutes. Prosthetic grafts were used for eight (13%) distal bypasses, the remainder were autogenous vein. There was one operative death (1.8%). The mortality rate, morbidity rate, and operative time were not significantly different from a group of patients who underwent concurrent, isolated inflow operations (aortofemoral, axillobifemoral, femorofemoral bypass or iliac endarterectomy). Mean follow-up was 14.9 months (range, 0 to 120). The life-table primary patency for the inflow procedures was 92.6% at 24 months, the outflow was 94.9% at 24 months. Cumulative limb salvage was 90.9% at 48-month follow-up. All patients with claudication were relieved of their symptoms. We conclude that complete correction of multilevel disease can be accomplished with operative time, morbidity rate, and patency equal to that of single level repair. Multilevel procedures provide complete relief of symptoms in a higher percentage of patients than has been reported after single level repair.

Clinical analyses and short-term prognoses of neonates with subependymal cysts. Twenty-one neonates with subependymal cysts detected by neurosonography soon after birth were prospectively examined. The clinical and cranial sonographic findings were evaluated with respect to short-term prognosis. The prognosis was poor in 6 patients with congenital viral infection (4 with cytomegalovirus infection and 2 with rubella infection). Five patients also had neurodevelopmental abnormalities (2 with neonatal epileptic seizures, 2 with chromosomal abnormalities, and 1 with lissencephaly). The remaining 10 patients had normal psychomotor development. The incidence of congenital viral infection was statistically correlated with a poor neurodevelopmental outcome. A correlation did not exist between the short-term prognosis and each of the other clinical factors or cranial sonographic findings. Our evidence suggests that further investigation of possible subependymal cyst etiologies is required during a careful, long-term follow-up period.

Bilateral impairment of somesthetically mediated object recognition in humans Thirty adult patients (six in each of five groups--neurologically normal, lacunar infarct-related hemiparesis, unilateral thalamic lacunar infarction, right cortical infarction with mild left hemineglect, and extensive right cortical infarction with severe left hemineglect) were asked to perform various tasks that encompassed basic and intermediate somatosensory functions and tactile and visual object recognition. Patients with thalamic and cortical infarctions had severe impairment of contralateral hand-mediated somatosensory functions in all three categories of somesthetic tasks, although patients with cortical infarction were more impaired on the object recognition task than were patients with thalamic infarction. Patients with extensive damage to the right hemisphere and severe left hemineglect also had impairment of somesthetically mediated object recognition in the ipsilateral hand despite normal basic and intermediate somatosensory function and visually mediated object recognition analogous to unilateral tactile agnosia. All other groups had normal ipsilateral tactile object recognition.

Primary malignant peritoneal mesothelioma. A report of seven cases and a review of the literature. Mesothelioma of the peritoneum is a rare malignant neoplasm easily mistaken by both surgeon and pathologist for one of the more common neoplasms of the abdomen. Review of our records from metropolitan-area hospitals for the past 15 years identified seven patients with primary peritoneal mesotheliomas. Their diagnosis, management, and survival is analyzed. We report a case of an extended survivor (7 years) and one of a long-term survivor (15 years), as well as what we believe to be the only case in the literature presenting with a coexistent malignant neoplasm. Prevention of this commonly fatal neoplasm is linked to avoiding occupational exposure to asbestos; long-term survival for a few patients may be achieved with correct identification of the neoplasm and aggressive management. This report includes a review of the literature.

Natural history and prognostic factors for chronic hepatitis type B. One hundred and five hepatitis B surface antigen (HBsAg) positive patients presenting with chronic persistent hepatitis (n = 46) or chronic active hepatitis without cirrhosis (n = 59) were followed longitudinally for one to 16 years (mean 5.5 years) and underwent follow up biopsy. During a mean histological follow up of 3.7 years, active cirrhosis developed in 21 (20%) patients one to 13 years after entry to the study with a calculated annual incidence of 5.9%. The probability of evolution to cirrhosis was significantly higher in patients with chronic active hepatitis and bridging hepatic necrosis than in those with moderate chronic active hepatitis or chronic persistent hepatitis (p less than 0.0001). Cox multiple regression analysis showed that the following three variables independently implied poor prognosis: older age, presence of bridging hepatic necrosis, and persistence of hepatitis B virus DNA in serum (p less than 0.0001). These findings indicate that patients with severe chronic active hepatitis and persistent hepatitis B virus replication are at very high risk of rapid progression to cirrhosis.

Cutaneous manifestations in patients with essential thrombocythemia. In a retrospective study of 268 patients with essential thrombocythemia, related cutaneous manifestations were found in 58 (22%). In 27 cases (10%) the related skin lesions were present at the time of the primary diagnosis of essential thrombocythemia. Hematomas, ecchymoses, petechiae, or purpura occurred in 24 (41%) of the 58 patients. Fifteen patients (26%) had erythromelalgia, in 11 of whom it was the initial complaint. Livedo reticularis, recurrent superficial thrombophlebitis, ischemic complications with gangrene, leg ulcers, or ulcers on the toes were other manifestations. Urticaria occurred in two patients, and Raynaud's phenomenon and necrotizing vasculitis were each observed in one patient. Platelet function may be abnormal, and this was found in 13 of 19 patients studied, 9 of whom had spontaneous platelet aggregation. Knowledge of the cutaneous manifestations in essential thrombocythemia may lead to its earlier detection. Prompt diagnosis of essential thrombocythemia is important because treatment may prevent severe hemorrhagic or thrombotic events.

Potential role of the tissue renin-angiotensin system in the pathophysiology of congestive heart failure. The circulating renin-angiotensin system (RAS) plays an important role in the maintenance of cardiovascular homeostasis. It has recently been demonstrated that endogenous RAS exist in target tissues that are important in cardiovascular regulation. This article reviews the multiple effects of angiotensin II in target tissues, the evidence for the presence of functional tissue RAS and the data that suggest a role for these tissue RAS in the pathophysiology of heart failure. Activation of circulating neurohormones is predictive of worsened survival in heart failure; however, cardiac and renal tissue RAS activities are also increased in the compensated stage of heart failure, when plasma renin-angiotensin activity is normal. It is hypothesized that the plasma RAS maintains circulatory homeostasis during acute cardiac decompensation, while changes in tissue RAS contribute to homeostatic responses during chronic sustained cardiac impairment. This concept of different functions of circulating and tissue RAS in the pathophysiology of heart failure may have important pharmacologic implications.

Stage IV neuroblastoma in infants. Long-term survival. Before the advent of multiagent chemotherapy, the prognosis for patients with Stage IV neuroblastoma of all ages was dismal. More recently, marked improvement in infants with Stage IV neuroblastoma has been reported. Twenty-four infants with Stage IV neuroblastoma have been treated at the Dana-Farber Cancer Institute/The Children's Hospital, and the Joint Center For Radiation Therapy, Boston, Massachusetts, between 1970 and 1988. Twenty-three of these patients were treated with multiagent chemotherapy and one with a single drug. In the initial report, ten of 11 patients were alive without evidence of disease after intensive therapy. In this report the authors update their initial series of patients and include 13 additional patients who subsequently presented to our institutions with Stage IV neuroblastoma younger than 1 year of age. The 5-year actuarial event-free survival for the 24 patients is 75%. No patient without bone metastases died from neuroblastoma, and 12 of 16 patients with bone metastases remained disease free. These results confirm that infants with Stage IV neuroblastoma have a very good prognosis when treated with intensive multiagent chemotherapy.

Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. Ninety-eight pediatric patients were treated with three separate protocols (Treatment and investigation of Osteosarcoma [TIOS] I, II, and III) and 47 developed recurrent disease (metastases and/or local recurrence). Actuarial overall disease-free survival (hereafter designated survival) was 43%. Over 90% of the patients were treated initially with preoperative intraarterial cisplatin (CDP). Postoperative chemotherapeutic regimens comprised high-dose methotrexate with leucovorin rescue (MTX-CF), Adriamycin [( ADR] doxorubicin; Adria Laboratories, Columbus, OH), and cyclophosphamide. Primary definitive treatment comprised amputation or limb salvage (TIOS I and TIOS III). Patients treated with preoperative CDP and surgery (TIOS I and III) had a 62% survival. Patients in TIOS II refused surgical extirpation; they were treated exclusively with chemotherapy and had a 23% survival. Survival in patients treated with amputation was 55% and limb salvage 58%. Prognostic factors considered significant in relation to development of pulmonary metastases comprised tumor burden (P = .04) and the percentage of tumor necrosis induced by preoperative chemotherapy (P = .01). Histopathologic subtype was marginally significant: chondroblastic was more favorable as opposed to osteoblastic (P = .05). These findings are compared with results and prognostic factors published in the literature.

Embolism during caesarean section. We investigated the occurrence of gas embolism during Caesarean section using a Doppler ultrasound probe and found that it occurs between uterine incision and delivery. Embolism is less common during general anaesthesia than has been reported during regional anaesthesia. Both ruptured membranes and a protracted uterine incision to delivery interval predispose to embolism.

Oxygen-exacerbated bleomycin pulmonary toxicity Bleomycin is an antineoplastic agent with potential for producing pulmonary toxicity, attributed in part to its free radical-promoting ability. Clinical and research experiences have suggested that the risk of bleomycin-induced pulmonary injury is increased with the administration of oxygen. We report a case in which the intraoperative administration of oxygen in the setting of previous bleomycin therapy contributed to postoperative ventilatory failure. Our patient recovered with corticosteroid therapy. Physician awareness of a potential interaction between oxygen and bleomycin may help reduce the morbidity and mortality related to bleomycin therapy.

Plasma homocyst(e)ine levels in men with premature coronary artery disease. Plasma homocyst(e)ine (that is, the sum of free and bound homocysteine and its oxidized forms, homocystine and homocysteine-cysteine mixed disulfide) levels were determined in 170 men (mean age +/- SD 50 +/- 7 years) with premature coronary artery disease diagnosed at coronary angiography and in 255 control subjects clinically free of coronary artery disease (mean age 49 +/- 6 years). Patients with coronary artery disease had a higher homocyst(e)ine level than control subjects (13.66 +/- 6.44 versus 10.93 +/- 4.92 nmol/ml, p less than 0.001). High density lipoprotein (HDL) cholesterol levels were lower (32 +/- 10 versus 46 +/- 13 mg/dl, p less than 0.001) and triglycerides levels were higher (193 +/- 103 versus 136 +/- 106 mg/dl, p less than 0.001) in the coronary disease group. Plasma total cholesterol and low density lipoprotein (LDL) cholesterol levels were not significantly different between patients with coronary disease and control subjects. The presence of hypertension, smoking or diabetes mellitus did not significantly alter homocyst(e)ine levels in the patient or the control group. Patients who were not taking a beta-adrenergic blocking drug (n = 70) had a nonsignificantly higher homocyst(e)ine level than did patients taking this class of drugs (n = 100) (14.67 +/- 8.92 versus 12.95 +/- 3.77 nmol/ml, p = 0.087). By design, none of the control subjects were taking a beta-blocker. No significant correlations were observed between homocyst(e)ine and age, serum cholesterol, LDL cholesterol, HDL cholesterol or triglyceride levels. It is concluded that an elevated plasma homocyst(e)ine level is an independent risk factor for the development of premature coronary atherosclerosis in men.

Integrated magnetic resonance imaging and phosphorus spectroscopy of soft tissue tumors. Eighteen patients with soft tissue masses underwent integrated magnetic resonance imaging (MRI) and phosphorus spectroscopy (31P-MRS) to evaluate benign and malignant tumor morphology and metabolism. Spectra from soft tissue tumors had a significantly higher proportion of phosphate in the low-energy portion of the 31P spectrum (P less than 0.001) with a concomitant decrease in phosphocreatine (P less than 0.01) compared with 31P spectra from normal muscle. Malignant tumors had a mean pH of 7.35 +/- 0.13 which was greater than that of muscle tissue with a mean pH of 7.08 +/- 0.07 (P less than 0.001). All tumors had greater relative levels of phosphomonoesters, inorganic phosphate, and phosphodiesters compared with those in muscle tissue but considerable variability among tumors was noted due to tumor size, extent of tumor necrosis, and muscle contamination. Integrated MRI/MRS studies are necessary to provide exact localization of the tumor and a more correct interpretation of the 31P-MRS data.

Muscle rehabilitation in impaired elderly nursing home residents. Based on observations of changes in muscle function associated with aging, and the exacerbation of these changes with frailty, a program of muscle strengthening has been developed to correct specific defects in muscles. This pilot study was undertaken on 18 functionally impaired nursing home residents (age range 60 to 90 years) with markedly deteriorated muscle function (50%) secondary to age, disuse, and multiple chronic illnesses. Fourteen of the subjects completed the six-week program without adverse effects. In 75% of the patients, there was improved muscle function, with endurance, strength, and speed increasing 35%, 15%, and 10%, respectively. After the program, many subjects increased their spontaneous activity and decreased their dependency. The improvements were still evident four months after rehabilitation. These results suggest that it may be possible, through a carefully supervised, short-term program of muscle rehabilitation, for nursing home residents to achieve an enhanced level of physical functioning.

Motility changes in primary achalasia following pneumatic dilatation. The changes in esophageal motility after pneumatic dilatation were evaluated prospectively in 51 patients with achalasia. The patients were evaluated for a median of 14 months. Pneumatic dilatation led to a clinical improvement in 41 patients. On manometric evaluation, a significant decrease in lower esophageal sphincter pressure was observed (28.4 +/- 14.9 mmHg vs. 13.5 +/- 7.2 mmHg; p = 0.001); the resting pressure of the esophageal body dropped from 4.8 +/- 4.2 mmHg above gastric baseline to 0.1 +/- 3.9 mmHg below gastric baseline. After therapy, peristaltic activity was present in 10/51 (20%) patients; in 1 case, complete relaxation of the lower esophageal sphincter was recorded. Treatment-induced motility changes could not be predicted by clinical history or the lower esophageal sphincter pressure before or after therapy. However, the resting pressure of the esophageal body before and after therapy was significantly lower in these patients in whom peristalsis recurred after therapy than in patients with an unchanged motility pattern. The reappearance of peristaltic activity after pneumatic dilatation was unrelated to lower esophageal sphincter pressure. In conclusion, motility disturbances of the esophageal body in patients with achalasia do not simply reflect the functional obstruction of the lower esophageal sphincter. These findings support the hypothesis that achalasia is not a distinct motility disturbance but should be regarded as part of a broad spectrum of different interrelated esophageal motility disorders.

Clinical outcome of emergency repeat coronary artery bypass surgery. To determine the clinical outcome of patients requiring emergency repeat coronary artery bypass graft (CABG) procedures, we reviewed 23 such procedures performed for ongoing myocardial ischemia refractory to medical management. The operative mortality was 17%. On follow-up, an average of 24.9 months after emergency reoperation, 14 of the 19 survivors (74%) had recurrent angina. As compared to a randomly selected group of 25 patients who underwent elective repeat CABG procedures during the same time period, the incidence of late cardiac events was significantly higher (79% in the emergency group, 30% in the elective surgery group) and fewer patients had received internal mammary artery (IMA) grafts (9% vs 52%). Emergency repeat CABG operations have considerable operative mortality and poor postoperative functional results with the majority of survivors developing recurrent ischemic syndromes within a short period of time.

Antivenom therapy in Russell's viper bite. Bleeding and renal failure are the two main manifestations responsible for the high morbidity and mortality in untreated Russell's viper bite victims. This study was an effort to find prognostic factors and a practical therapeutic approach for the care of such patients. Early detection of abnormalities in the clot quality test and/or evidence of systemic bleeding followed by immediate correction of the clotting defects using specific antivenom can reduce morbidity in Russell's viper envenomation.

Phenotypic variability in glutaric aciduria type I: Report of fourteen cases in five Canadian Indian kindreds. We describe 14 patients with glutaric aciduria type 1 in five Canadian Indian kindreds living in Manitoba and northwest Ontario. The patients had marked clinical variability of the disease, even within families. Eight followed the typical clinical course of normal early growth and development until the onset of neurologic abnormalities, often precipitated by infection, between 6 weeks and 7 1/2 months of age. Five patients had early developmental delay; one was thought to be normal until 8 years of age. Three patients died, seven are severely mentally and physically handicapped, and four have only mild mental retardation or incoordination. Six patients had macrocephaly in the neonatal period. Computed tomography was done for 12 patients, and findings were abnormal in 11. Glutaric acid and 3-hydroxyglutaric acid were detected in increased amounts in the urine of all patients, but the concentrations were much lower than those in most other reported patients. Glutaryl coenzyme A dehydrogenase activity in skin fibroblasts, interleukin-2-dependent lymphocytes, or both, ranged from 0% to 13% of control values. There was no correlation between clinical severity and urine glutaric acid concentration or level of residual enzyme activity. We recommend that organic acid analysis of the urine be done in patients with unexplained cerebral palsy-like disorders, especially if the computed tomographic scan is abnormal. If there is suspicion of glutaric aciduria, glutaryl-coenzyme A dehydrogenase should be measured in fibroblasts or lymphocytes even if glutaric acid is not increased in the urine.

Giant hemangioma of the liver with pain, fever, and abnormal liver tests. Report of two cases. In conclusion, we report the cases of two patients with large hemangiomas of the liver, abdominal pain, increased ESR and fibrinogen, increased serum alkaline phosphatase and gamma-glutamyltransferase activity, and normal white blood cell counts. Clinical and biochemical abnormalities disappeared after surgical resection. Increased ESR and fibrinogen are probably related to thrombosis within the tumor. This mode of presentation may suggest a diagnosis of hepatocellular carcinoma.

Coronary collateral recruitment: functional significance and relation to rate of vessel closure. Studies in animals and humans have demonstrated the anatomic presence and functional significance of coronary collaterals. The extent of collateralization varies among species and among individuals. Collateral vessels are usually adequate for preserving resting regional and global ventricular function in the face of coronary obstruction. During stress, however, collateral supply may be inadequate. Collateral development is a time-dependent process during both the initial occlusion and following transient reflow and reclosure. Therefore when a previously collateralized coronary occlusion is recanalized and then recloses, the extent of the resulting collateral recruitment will depend, at least in part, upon the period of reflow between the two occlusions. The longer the reflow period, the less enhanced will be the collateralization. This is illustrated in the cases presented and has also been demonstrated in animal studies. The exact mechanisms for this recurrent collateral recruitment need further study.

Heffalumps, jagulars, and cheshire cats. A commentary on cytokeratins and soft tissue sarcomas. Historically, antibodies to cytokeratin intermediate filaments have been models of target specificity. In most diagnostic settings, the utility of these antibodies was unquestioned; reactivity for cytokeratin was dogmatically equated with epithelial differentiation. Recently, however, the diagnostic importance of these antibodies has been challenged, prompted by the demonstration of cytokeratin reactivity in a variety of "nonepithelial" neoplasms. In this review, the evolving literature on this topic is explored, and the practical implications of these findings are discussed.

Abnormal differentiation of human papillomavirus-induced laryngeal papillomas. We studied the proliferation and differentiation of human laryngeal papillomas, which are benign tumors induced by human papillomaviruses. Immunofluorescent stains of tissues for a number of differentiation-specific proteins showed abnormal differentiation. Papilloma tissue fragments in vitro showed a slightly decreased fraction of proliferating cells that incorporated tritiated thymidine and a markedly reduced incorporation of tritiated uridine when compared with normal tissue. We propose that papillomavirus infection results in normal basal cell proliferation but abnormal terminal differentiation and that this abnormality significantly contributes to the hyperplasia of the papillomas.

Epithelial cyst of the fourth ventricle. Case report. A case of epithelial cyst in the fourth ventricle of a 4-year-old child is described. A single epithelial layer with a clear basement membrane lining the cyst wall was observed. There were no prominent histological findings to suggest a pathogenesis for this cyst based on immunohistochemical or ultrastructural studies; however, the cyst fluid contained significant amounts of carcinoembryonic antigen. It is considered that the epithelial layer lining the cyst wall was possibly of endodermal origin.

Multimodality preoperative treatment for advanced stage IV (MO) cancer of the head and neck. Sixty-three patients with advanced unresectable squamous cell carcinoma of the head and neck were treated with a combination of chemotherapy, radiation, and surgery. We observed a 75% response to neoadjuvant chemotherapy. The 5-year survival rate for all 63 patients was 20%, and only 3 patients were alive at 8 years. The 5-year survival rate for patients who completed the treatment plan and received chemotherapy, radiation, and surgery was 43% compared with 20% for those who had chemotherapy and radiation but refused surgery. Development of a second primary cancer was the cause of death in 62% of the patients who survived more than 24 months.

The effect of ambulation on recovery from postoperative ileus. To determine whether ambulation hastens recovery from ileus following laparotomy, 34 patients were studied, 10 of whom followed an ambulatory regimen beginning on postoperative day 1 (group A). The other 24 patients (group C) did not become ambulatory until postoperative day 4. All patients underwent placement of seromuscular bipolar recording electrodes on the Roux limb, if present, stomach, jejunum, and colon at laparotomy. Group A was recorded before and after ambulation so comparisons could be made to determine if ambulation had an acute effect on myoelectric activity. Group A preambulation and group C recordings were compared to judge whether there was an over-all effect of ambulation on myoelectric recovery. No effect on slow wave frequency or percentage of slow waves with associated spike potentials was noted acutely or overall in the stomach, colon, or jejunum in continuity with the duodenal pacemaker. Transient increases in phase II spike activity in patients having a Roux limb and their jejunum distal to the enteroenterostomy were noted on postoperative days 1 to 2, but these differences resolved by postoperative days 3 or 4. The data suggest that ambulation as a means to help resolve postoperative ileus and its accompanying cramps and bloating may be more perceived than real.

Chronic rupture of the Achilles tendon: a new technique of repair. A new operative technique is described for the treatment of patients who have a rupture of the Achilles tendon. The large gap between the proximal and distal stumps of the Achilles tendon in seven patients was bridged by use of the tendon of the flexor digitorum longus as the graft. At the most recent follow-up examination (average follow-up, thirty-nine months; range, two to six years), the result was excellent or good in six patients and fair in one. Postoperatively, two patients needed an adjuvant procedure: one, a local rotation flap and the other, a split-thickness skin graft. Both patients had excellent restoration of function. The patient who had a fair result had a persistent limp and residual discomfort. There were no re-ruptures.

Prospective observations of 100 high-risk neonates by high-field (1.5 Tesla) magnetic resonance imaging of the central nervous system: I. Intraventricular and extracerebral lesions. The results of observations of the first 100 neonates at the University of Texas Health Science Center (Houston) who received magnetic resonance imaging of the central nervous system by means of a high-field image (1.5 T) are reported. All were assessed prospectively to be at risk neurodevelopmental delay. This first report specifically addresses the appearance of primarily hemorrhagic intracranial lesions, including intraventricular hemorrhage (n = 28), and extracerebral lesions, which include 3 cases of venous sinus thrombosis (n = 20). The signal intensities of hemorrhage underwent a characteristic evolution with time with only minor variations in the study group. Magnetic resonance imaging detected direct evidence of hemorrhage for up to 2 months, but hemosiderin was detected as a late indicator of hemorrhage for up to 9 months. Magnetic resonance imaging was equal in benefit to head ultrasonography and computed tomography for the diagnosis of intraventricular hemorrhage, but magnetic resonance imaging was also able to approximate the time of onset of hemorrhage. Magnetic resonance imaging was superior for the evaluation of extracerebral hemorrhage; ultrasonography failed to detect any of these lesions and computed tomography detected only 3 of 7. Short-term neurological abnormality was assessed, but the ability of magnetic resonance imaging to predict long-term neurodevelopmental delay is unknown and is the subject of an ongoing project.

Results of treating ductal carcinoma in situ of the breast with conservative surgery and radiation therapy. To determine the frequency, pattern, and time course of tumor recurrence in the breast, the outcome of 38 women with ductal carcinoma in situ (DCIS) treated with conservative surgery and radiation therapy between 1976 and 1985 was studied. Surgery typically consisted of local excision without evaluation of the microscopic margins of resection. The median radiation dose to the tumor site was 6400 cGy. With a median follow-up time of 81 months, eight patients (21%) have experienced a recurrence in the breast. The time course to recurrence was protracted in some cases, with failures occurring at 17, 27, 43, 63, 71, 83, 92, and 104 months. The 5-year and 8-year actuarial rates of tumor recurrence in the breast were 8% and 27%, respectively. Seven patients had a recurrence at or near the primary tumor site, four with invasive carcinoma, and one had an invasive recurrence at a site elsewhere in the breast. No clinical or pathologic factor was significantly associated with an increased risk of recurrence, but the number of patients in the study population was small. The authors reached the following conclusions for patients with DCIS treated with conservative surgery and radiation therapy without careful mammographic and pathologic evaluation: (1) recurrence in the breast may be seen in at least one fifth of the patients; (2) recurrence typically occurs at or near the primary site; and (3) recurrence can occur long after treatment. Careful mammographic and pathologic assessment may be useful in reducing the local recurrence rate and should be considered essential if patients are considered for conservative surgery and radiation therapy.

Validation of a surveillance case definition of carpal tunnel syndrome The National Institute for Occupational Safety and Health (NIOSH) has proposed a surveillance case definition for work-related carpal tunnel syndrome (CTS). The case definition requires the presence of median nerve symptoms; one or more occupational risk factors; and objective evidence of CTS including one of three physical examination findings or nerve conduction tests diagnostic of CTS. We evaluated the performance of the NIOSH case definition, restricting our analysis to cases in which physical examination findings served as the objective criterion. Nerve conduction studies were used as the gold standard. Seventy-eight workers were studied; 38 percent had CTS. The NIOSH case definition had sensitivity of 0.67 (95% CI = 0.57, 0.77), specificity of 0.58 (95% CI = 0.47, 0.69), and positive and negative predictive values of 0.50 (95% CI = 0.39, 0.61) and 0.74 (95% CI = 0.64, 0.84), respectively. Overall 38 percent of subjects were classified incorrectly. In a sample with a prevalence of 15 percent, as might be encountered in high risk workplaces, the positive predictive value would be 0.22. In conclusion, when physical examination findings serve as the objective criterion the performance of the case definition is modest reflecting the limited diagnostic value of its component tests and indicating that effective screening for CTS awaits improved diagnostic techniques.

Evidence of an antiplatelet aggregation action of doxazosin in patients with hypertension: an ex vivo study. Eighteen patients with a mean age of 54.7 years were included in the study. All patients had a diagnosis of mild or moderate essential hypertension (sitting diastolic blood pressure of 96 to 114 mm Hg). The study design was single blind and in two phases: phase I, placebo (4 weeks), and phase II, the active treatment (8 weeks) with increasing doses, if needed, of doxazosin every 2 weeks (1, 2, 4, and 8 mg/day). Results show that doxazosin has an antihypertensive effect that is dose dependent. Systolic, diastolic, and mean blood pressures were decreased significantly, and no effect on heart rate was observed. Doxazosin significantly inhibited the platelet aggregation induced by epinephrine, adenosine diphosphate, and collagen in a dose-dependent manner. In addition, treatment with doxazosin lowered total serum cholesterol and triglyceride levels, without changing other standard biochemical parameters. This indicates that doxazosin could offer a distinct therapeutic advantage in the modulation of atherogenic and thromboembolic factors associated with coronary heart disease.

Fulminant hepatitis after lisinopril administration. A case of fulminant hepatitis in a patient taking lisinopril for 5 weeks for arterial hypertension is reported. Jaundice, fever, myalgia, and marked increase in serum aminotransferase activities occurred after 2 weeks of treatment. Continuation of lisinopril administration for 3 weeks after the onset of jaundice was associated with the development of grade III encephalopathy and a marked decrease in prothrombin and proaccelerin levels. This case strongly suggests that lisinopril may induce acute hepatitis and that continuation of the treatment after the onset of jaundice can lead to life-threatening hepatic failure.

Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: a randomized, placebo-controlled, crossover trial. Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 +/- 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 +/- 2.3 versus 7.3 +/- 2.7 min) nor peak oxygen consumption (18.7 +/- 3.7 versus 18.4 +/- 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = -0.64, p less than 0.05). At maximal treadmill effort, heart rate (138 +/- 16 versus 141 +/- 21 beats/min), oxygen pulse (10.3 +/- 2.1 versus 9.9 +/- 2.2 ml/beat), ventilation (40.3 +/- 10.6 versus 42.0 +/- 10.8 liters/min) and ventilatory equivalent (29.4 +/- 4.8 versus 31.5 +/- 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 +/- 23.1 versus 153.2 +/- 25.3 mm Hg, p less than 0.05).

Cardiac involvement in AIDS. Cardiac involvement in AIDS may occur at any stage of HIV disease and may manifest as congestive cardiomyopathy, potentially lethal arrhythmia, or pericardial effusion and tamponade. The heart may be affected by nearly all of the opportunistic infections and many of the malignancies associated with the syndrome. Although often clinically unobtrusive, cardiac lesions may be important in the pathogenesis of significant clinical symptoms and play an often unrecognized role in the prognosis and natural history of AIDS.

The abdominal trauma index--a critical reassessment and validation. The Abdominal Trauma Index (ATI) was devised to quantify the risk of complications following abdominal trauma. With scores greater than 25, the risk of postoperative complications became exponential. The purpose of the present study was to determine if: 1) the organ risk factors previously assigned were more statistically valid; and 2) the addition of physiologic variables would enhance the prediction of postinjury intra-abdominal sepsis. Fifteen abdominal organ systems and 17 physiologic variables in 300 consecutive patients were analyzed to determine ability to predict intraabdominal sepsis. There were no significant differences in predictive ability between the old and new organ risk factors. The addition of physiologic factors did not enhance the prediction of intra-abdominal sepsis. This clinical study demonstrates that: 1) the risk of intra-abdominal sepsis increases with increasing ATI score; 2) the previous (1979-initial) organ risk grading concept is statistically valid; 3) six of the 15 organ systems warrant a change in their relative rank order (1989-revision); 4) the addition of demographic, physiologic, and immunologic variables did not significantly improve the prediction of intra-abdominal sepsis.

Carbamazepine dose requirements during stiripentol therapy: influence of cytochrome P-450 inhibition by stiripentol. The inhibitory effect of stiripentol (STP) on disposition of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZE) was quantitated to establish CBZ dosage reduction guidelines for future clinical add-on efficacy trials of STP. In seven epileptic patients, STP (1,500-3,000 mg/day for 2 weeks) inhibited CBZ clearance by 50 +/- 16% (p = 0.001) and reduced the CBZE/CBZ plasma ratio by 45 +/- 14% (p = 0.0005). The inhibitory effect was gradually manifested over a period of 7-10 days after initiation of STP therapy. In contrast to inhibition of CBZE formation, STP had no effect (p greater than 0.05) on elimination clearance or half-life (t1/2) of CBZE in six healthy volunteers. STP most likely exerts inhibitory effects through inhibition of cytochrome P-450. This hypothesis was confirmed in the present study by the finding that a therapeutic concentration of STP (7 micrograms/mL) inhibited 10,11-epoxidation of CBZ in human liver microsomes by 40-50%. On the basis of results from this study, we propose that (a) CBZ dosage should be reduced in steps over a period of 7-10 days after initiation of STP, and (b) a CBZ dosage of 4.3 to 8.7 mg/kg/day will maintain therapeutic CBZ plasma levels of 5-10 micrograms/mL.

Diffusion and binding of monoclonal antibody TNT-1 in multicellular tumor spheroids. Tumor spheroids of HT-29 human colon adenocarcinoma and A375 melanoma were established to investigate the uptake and clearance kinetics of TNT-1, a monoclonal antibody that targets necrotic cells of tumors. Our data reveal that there was rapid uptake of TNT-1 and its F(ab')2 fragment in both spheroid models, whereas an antibody of irrelevant specificity, Lym-1, and its F(ab')2 fragment bound poorly to the spheroids. Unlike previously reported monoclonal antibodies to tumor cell-surface antigens, TNT-1 showed 1) a linear uptake that increased over time without saturation in tumor spheroids and 2) an unexpected uptake by a subpopulation of cells in the viable outer rim of the spheroids. These preclinical studies provide important information concerning the therapeutic potential of TNT monoclonal antibodies for the treatment of cancer and micrometastases.

Extracranial repair of cerebrospinal fluid fistulas: technique and results in 37 patients. Although neurosurgeons have traditionally preferred intracranial repair for the management of cerebrospinal fluid (CSF) fistulas, this approach is associated with the complications of a craniotomy, anosmia, and a high incidence of recurrent fistulas. Extracranial repair, on the other hand, produces no central nervous system morbidity, preserves olfaction, and is associated with a low incidence of recurrence. Although there have been several reports of extracranial repair of CSF fistulas by otorhinolaryngologists, this approach has received scant mention in the neurosurgical literature. We report here our experience with 37 patients with CSF rhinorrhea or otorrhea who underwent extracranial repair. The etiology of the fistula was postoperative in 22, traumatic in 6, and spontaneous in 9. The fistulas were repaired using one of four techniques: external ethmoid-sphenoid in 18 patients, transmastoid in 9, transseptosphenoid in 7, and osteoplastic frontal sinusotomy in 3. In 32 of the 37 patients (86%) the fistulas were successfully repaired with the initial procedure. Of the 5 patients requiring a second operation, the fistula was successfully closed in 4 for an overall success rate of 97%. Complications were few and consisted of a transient facial paresis in a patient undergoing transmastoid repair and one death from meningitis. The authors conclude that because of low morbidity and mortality and a high success rate in closing fistulas, extracranial repair is the preferred technique for the operative management of CSF rhinorrhea and otorrhea.

Acute limb ischaemia: the place of intravenous streptokinase. Intravenous streptokinase infusions (100,000 units/h) have been used to treat 48 patients, with 50 episodes of acute limb ischaemia who were unlikely to benefit from a surgical approach. These included 17 acute thromboses, 14 late or distal emboli and 19 bypass graft occlusions. Overall, 17 (34 per cent) instances had complete lysis with reappearance of distal pulses and a further 28 per cent had clinical improvement without change in pulse status. Final outcome after 30 days was limb salvage in 60 per cent, amputation in 24 per cent and death in 16 per cent, but this was achieved after eight patients without lysis had vascular reconstructive surgery. Serious complications were infrequent, but included a fatal stroke, a haematemesis and two episodes of distal embolization. The outcome was not related to the duration of ischaemia or the site of occlusion. Lysis was more frequent with emboli (50 per cent) and graft occlusions (47 per cent) than arterial thromboses (6 per cent). Limb salvage was more likely in patients with no neurological deficit in the limb (70 per cent) than if a deficit was present (37 per cent). In conclusion, intravenous streptokinase produced a moderate benefit with low morbidity and has a role in acute limb ischaemia if surgery is inappropriate and intra-arterial lysis unavailable. In particular, selected patients with emboli or graft occlusions without a neurological deficit may be most suitable.

Anomalous origin of the left coronary artery from the pulmonary artery. Surgical alternatives depending of the age of the patient. Four cases of anomalous origin of the left coronary artery from the pulmonary artery, three of which were operated upon in our Centre, are presented. An aortocoronary bypass with reversed autologous saphenous vein was carried out in both of the children; and in the adult, the anomalous ostium was closed from the interior of the pulmonary artery. After 84, 72, and 4 months of evolution, respectively, they were found to be asymptomatic, the mitral insufficiency had disappeared and the venous graft remained patent. In this paper, the clinical form of presentation, diagnostic possibilities and surgical treatment are analysed.

Calcium entry blockade and adrenergic vascular reactivity in hypertensives: differences between nicardipine and diltiazem. The interference of nicardipine and diltiazem infused into the brachial artery at systemically ineffective rates, with the forearm vascular response to graded exogenous norepinephrine, was evaluated in hypertensive patients. Nicardipine (1 and 3 micrograms/dl forearm tissue/min in both absence and presence of propranolol) increased forearm blood flow (venous plethysmography) and antagonized dose dependently the vasoconstrictor effect of norepinephrine, suggesting that functional alpha-antagonism may participate in the vasodilating and possibly the antihypertensive effect of the drug. On the contrary, no antagonism but rather potentiation of the responses to norepinephrine occurred after diltiazem (0.5 and 1 microgram/dl forearm tissue/min). Because intra-arterial propranolol abolished that potentiating action of the drug, whereas the local vasodilation to isoproterenol was clearly reduced, diltiazem probably interfered with beta-adrenergic receptor-mediated vasorelaxing mechanisms in human forearm arterioles. The data further stress the heterogeneity of calcium entry blockers in humans.

Endotoxin requirements for alveolar macrophage stimulation. Acute pulmonary failure or ARDS in severely injured patients continues to be a significant problem. The most important clinical risk factor identified is sepsis syndrome. Sepsis syndrome is the clinical correlate of a malignant systemic inflammatory process and is directed in large part by the tissue-fixed macrophage (M phi), such as the alveolar M phi. The M phi is capable of producing most of the central inflammatory mediators responsible for the pathophysiology seen during sepsis and organ injury. Two major mediators are procoagulant activity (PCA), leading to diffuse microvascular thrombosis, and tumor necrosis factor (TNF), causing much of the physiologic derangement of sepsis. Endotoxins (LPS) derived from Gram-negative bacterial cell walls are the primary inflammatory stimulus for the tissue-fixed M phi production of inflammatory mediators. It is not completely known how LPS interacts with its various cellular targets, but it is hoped that knowledge of the molecular interactions involved in stimulation of the M phi by endotoxin will lead to therapies to modulate the response and prevent deleterious processes such as ARDS. In the present studies, LPS from E. coli 0111:B4 was shown in a dose response to stimulate large levels of both PCA and TNF in alveolar M phi. LPS from Bacteroides fragilis and Lipid X (the monosaccharide precursor of endotoxin) were unable to cause stimulation of the M phi in vitro. However, both moieties, B. fragilis LPS and Lipid X, were able to effectively and specifically compete with E. coli LPS and block M phi stimulation.

Prospective study of estrogen replacement therapy and risk of breast cancer in postmenopausal women [published erratum appears in JAMA 1991 Apr 10;265(14):1828] We prospectively examined the use of estrogen replacement therapy in relation to breast cancer incidence in a cohort of women 30 to 55 years of age in 1976. During 367 187 person-years of follow-up among postmenopausal women, 722 incident cases of breast cancer were documented. Overall, past users of replacement estrogen were not at increased risk (relative risk, 0.98; 95% confidence interval, 0.81 to 1.18), including even those with more than 10 years since last [corrected] use (relative risk after adjustment for established risk factors, 0.70; 95% confidence interval, 0.45 to 1.10). However, the risk of breast cancer was significantly elevated among current users (relative risk, 1.36; 95% confidence interval, 1.11 to 1.67). Among current users, a stronger relationship was observed with increasing age but not with increasing duration of use. These data suggest that long-term past use of estrogen replacement therapy is not related to risk of breast cancer but that current use may modestly increase risk.

Cerebellar syndrome caused by isoniazid. Treatment of tuberculosis in a hemodialysis patient with isoniazid, rifampin, and pyrazinamide resulted in the development of acute cerebellar dysfunction. This resolved rapidly following the discontinuation of isoniazid and pyrazinamide, reinstitution of isoniazid at a lower dose, and addition of pyridoxine. We discuss why we believe this syndrome was caused by isoniazid. Patients with renal failure who undergo antituberculous therapy with isoniazid should receive supplemental pyridoxine to reduce the likelihood of isoniazid-related neurotoxicity.

The interspinous method of posterior atlantoaxial arthrodesis. Thirty-six patients underwent C1-2 posterior wiring and fusion procedures over a 5-year period for unstable C-2 fractures (eight cases), unstable atlas-axis combination fractures (six cases), rheumatoid C1-2 instability (14 cases), os odontoideum (four cases), traumatic C1-2 ligamentous instability (three cases), or instability secondary to a C-2 tumor (one case). In each case, the atlantoaxial arthrodesis utilized sublaminar wire at C-1 and incorporated an iliac-crest strut-graft positioned between the posterior arches of C-1 and C-2, held in place by securing wire around the base of the spinous process of the axis. Follow-up examination was performed in all patients after a mean postoperative duration of 33.7 months. The technical aspects and clinical merits of this fusion procedure, which led to a 97% union rate (one nonunion) and minimal morbidity and mortality rates, are presented.