Studies in pharmacokinetics and tolerance of substances temporarily retained in the liver by microsphere embolization. Earlier investigation has shown that a temporary arrest of arterial blood flow can be achieved by embolization with degradable microspheres. This study was made to investigate the change in pharmacokinetics, and drug tolerance which takes place when a substance is retained in the liver by a microsphere embolization. 14C-labelled inulin and 5-fluorouracil were studied. The administration of these substances with microspheres led to a delay in their systemic distribution. Furthermore there was an increased tolerance to 5-fluoro-uracil, probably due to a prolonged first pass effect when the substance was temporarily retained in the liver by a microsphere embolization.


Massive pulmonary hemorrhage: surgical approach as choice of treatment. Massive pulmonary hemorrhage is still a life-threatening problem with high mortality. The surgical versus medical approach to this condition was compared in 146 patients who were treated over a ten-year period. Our evidence shows that early operation is the only choice of treatment.


The effect of hemodilution with albumin or Ringer's lactate on water balance and blood use in open-heart surgery. To determine the effect of intraoperative albumin administration on blood use, water balance, and postoperative clinical course, we studied two groups of adult cardiac surgical patients. Group I (30 patients) received 25 gm of albumin during withdrawal of 2 units of blood prior to cardiopulmonary bypass (CPB) and 50 gm of albumin in the oxygenator prime. Group II (32 patients) received no albumin prior to the end of CPB. No difference in clinical course could be identified, nor was there a significant difference in blood use. Group I patients had lower hematocrit values intraoperatively from the time of blood withdrawal until the conclusion of operation. Coronary artery bypass operations were associated with greater positive water balance than were heat valve operations. Forty-three percent of the patients having coronary artery bypass grafting had a positive water balance greater than 5 liters, whereas 50% of those undergoing valve procedures had a balance less than 3 liters. We conclude that the principal effect of withholding albumin under these circumstances is to increase net positive water balance. The greater positive water balance does not appear to be detrimental.


Similarity of clinical and laboratory results obtained with microporous teflon membrane oxygenator and bubble-film hybrid oxygenator. For 80 elective clinical cardiopulmonary bypasses we alternately used either a commercial microporous Teflon membrane oxygenator or a commercial hybrid bubble-film oxygenator. Setup time was a little longer with the membrane unit (20 minutes), but priming volume (2,250 ml) was the same. No problems were encountered with the hybrid oxygenator. However, despite our monitoring of additional variables, including shim and inlet pressure and recirculation flow, gas exchange abnormalities were encountered in 5 patients on whom the membrane oxygenator was used; in 4 of these cases the abnormalities were encountered prior to our recognition of the potential for occasional internal shunting with this device. There were no hospital deaths. When the two groups, matched except for oxygenator selection, were compared, there were no significant differences clinically or hematologically. For cardiopulmonary bypass of 2 hours or less, both oxygenators studied are definite improvements over previous silicone membrane and high-gas-flow bubble oxygenators. However, lower cost and reduced complexity favor the hybrid oxygenator.


Atrial septal defect: acute left heart failure after surgical closure. Sixteen of 766 patients operated on for isolated arterial septal defect developed severe acute left heart failure that necessitated partial reopening of the defect; 6 died. The prognosis depended mainly on prompt surgical intervention. The most frequent pathological and anatomical finding was marked hypoplasia of the left ventricle. Pulmonary hypertension appeared to be of minor importance. Hemodynamic data published by others support the hypothesis that this complication is often the result of markedly impaired left ventricular compliance associated with left ventricular hypoplasia.


Sinus venosus atrial septal defect: early and late results following closure in 109 patients. The clinical course of 109 patients who underwent closure of a sinus venosus atrial septal defect is reviewed, with emphasis on the incidence, type, and severity of arrhythmias before and after operation. There were no operative deaths and only 1 late death. No instances of obstruction of the superior vena cava were detected clinically. One patient had a probable hemorrhagic pulmonary infarction that cleared; another may have a persistent left-to-right shunt. Excellent results were achieved in 72% of the patients, good results in 5%, and poor results in 3%. The type of arrhythmia, both before and after operation, varied with the age of the patient: younger patients had bradyarrhythmias, and older patients had tachyarrhythmias. Ten patients experienced persistent new arrhythmias postoperatively, but none were disabled, required a pacemaker, or died. The arrhythmias in all severely symptomatic patients were supraventricular tachycardias that had occurred before operation. Although functional classification after operation was clearly related to age at the time of the procedure (with younger patients having the best functional results), 19 of 21 patients over age 40 were noticeably improved after surgical closure of the sinus venosus atrial septal defect.


Tetralogy of Fallot with subpulmonary ventricular septal defect. Among a total of 608 patients with tetralogy of Fallot, 35 with tetralogy and subpulmonary ventricular septal defect (VSD) have undergone intracardiac repair at the Children's Hospital, Buenos Aires. The crista supraventricular was absent in 62.9% of these patients; it was hypoplastic in 37.1%. Only 3 patients (8.6%) were severely cyanotic and required operation in infancy. The main and left and right pulmonary arteries were relatively large in all but 1 patient. Nevertheless, patch-graft enlargement across the pulmonary valve ring was necessary in 20 (57.1%). We believe that closure of the subpulmonary VSD increase the apparent severity of the pulmonary stenosis and necessitates patch-graft enlargement in patients in whom the appearance of the right ventricular outflow tract before repair would not have suggested its need.


Repair of aortic coarctation in the first year of life. Twenty-five infants under 1 year of age (mean, 10.3 weeks and 4.0 kg) underwent coarctation repair. Eight had ventricular septal defect (VSD), 3 had transposition of the great arteries with VSD, and 5 had severe tubular hypoplasia. One infant required mitral valve replacement, and 1 required repair of total anomalous pulmonary venous return. Fifteen had repair by primary anastomosis. Seven underwent Dacron or subclavian aortoplasty; the advantages and technique of angioplasty are reviewed. Three patients required bypass grafts. Seventeen patients survived operation. All 5 patients who had severe tubular hypoplasia died postoperatively. The mortality for repair of coarctation with VSD by simultaneous pulmonary artery banding was high; for coarctation with VSD we currently recommend repair without banding, followed by VSD closure if indicated. Three infants have been treated successfully in this manner, with early VSD closure in 1 and regression of the VSD during follow-up in 2. The 17 survivors have been followed for a mean of 41 months with 3 late deaths. Of the 17 survivors, all of whom had a primary anastomosis, 3 have residual gradients. Of the 11 survivors who had preoperative hypertension, 6 are still hypertensive; 3 of these have a gradient between the upper and lower extremities. It is striking that 3 have persistent hypertension despite repair under the age of 1 year.


Epicardial atrial pacing.

Epicardial atrial pacing. A modification of the technique for placing a permanent epicardial electrode to the atrium is described. It results in long-term atrial pacing and low sensing thresholds. The method requires meticulous surgical technique but is reliable, safe, and free from serious or long-term complications.


Cecal necrosis after open-heart operation. Two patients with isolated transmural ischemic necrosis of the cecum after cardiopulmonary bypass are discussed. Superimposed upon the multiple cardiovascular abnormalities in these patients, cardiopulmonary bypass adds another risk factor for nonocclusive intestinal infarction. In patients undergoing open-heart procedures, postoperative nonspecific abdominal complaints should be evaluated with a high degree of suspicion for this lethal complication. An intensive diagnostic effort is indicated, including contrast and angiographic radiological studies. Consideration of early abdominal exploration is indicated.


Esophagopleural fistula following pulmonary resection. The development of esophagopleural fistula following pulmonary resection is an uncommon but serious complication. The fistula may appear either soon after operation, due to direct trauma to the esophagus or to its blood supply during extensive dissection, or later, in association with the development of a bronchopleural fistula and empyema following the pulmonary resection. Treatment of these fistulas is usually complicated, and the recovery period is prolonged. Control of infection, hyperalimentation, obliteration of the empyema space, and closure of the fistula with a muscle or pleural flap are recommended methods of management. The pathogenesis, treatment, results, and prevention of this complication are discussed.


Pancreatic cancer treated with carmustine, fluorouracil, and spironolactone: a randomized study. A prospective randomized trial between two drug regimens in 38 patients with advanced pancreatic carcinoma was performed. The two-drug regimen consisted of carmustine and fluorouracil. The survival rate and response to these two drugs was compared to a three-drug regimen consisting of these same two drugs plus spironolactone. Objective partial responses were rare in both groups, being 3/18 in the two-drug group and 2/20 in the three-drug group. Life table analysis in previously untreated patients from time of treatment shows longer survival for the three-drug group, but this difference was not statistically significant.


Nerve conduction velocity in hypertensive patients. Due to conflicting reports in the literature regarding nerve conduction velocities (NCVs) in hypertensives, peroneal and sural NCVs and facial nerve conduction latencies were studied in 30 hypertensives and in 30 controls. An improved technique of NCV measurement was used. Twenty-one of the hypertensives were retested after five weeks, and five of them were tested for motor and sensory NCVs of the median nerve during a short period of partial occlusion of blood flow in the arm. No changes were found that could be related to blood pressure, duration of hypertension, eyeground changes, or partial restriction of blood flow.


On reporting cases of acute nontransmural myocardial infarction. ST-segment elevation in the electrocardiogram with development of Q waves in the presence of enzyme changes and chest pain have been thought to be adequate for the unequivocal diagnosis of transmural myocardial infarction. Unlikely, detection of nontransmural myocardial infarction (NMTI) is often difficult. A variety of ECG alterations, enzymatic criteria, and chest pain patterns have been used in the diagnosis of this type of infarct. Since ECG criteria used in the diagnosis of NMTI are not specific for this entity, enzymes, isoenzymes, and myocardial imaging should be used for differentiation of NMTI from other ischemic syndromes. Characterization of the entity of NMTI will improve by acquiring information on chest pain patterns, serial enzyme and isoenzyme changes , sequential ECG alterations, myocardial imaging profiles, and autopsy data from patients with myocardial necrosis and atypical ECG pictures.


Aspirin, hyperventilation, and cerebellar infarction in sickle cell disease. Aspirin ingestion was followed by hyperventilation, cerebellar signs, and fatal brain stem dysfunction in a patient with sickle cell disease. Autopsy showed a swollen, recently infarcted cerebellum with tonsillar herniation compressing the medulla. We propose that hypocapnea from aspirin-induced hyperventilation caused carotid artery constriction and focal cerebral hypoxia, resulting in cerebellar sickling nad infarction. Hypocapnea should be treated promptly to prevent brain damage in patients with sickle cell disease.


Survival in patients with intraventricular conduction defects. All 42,000 electrocardiograms taken at the University of Oregon Health Sciences Center from 1969 through 1971 were reviewed; 325 patients (0.77%) had left bundle-branch block (LBBB) or right bundle-branch block (RBBB) with axis deviation (AD). In December 1974, 90% were contacted or found to be dead. The five-year survival rate (actuarial technique) (mean +/- SE) was 45.5 +/- 2.9%. It was significantly worse than that of age- and sex-matched "controls." In most patients the cause of death could not be determined. Survival of 164 LBBB patients (40.7 +/- 4.1%) at five years was not significantly worse than that of 161 RBBB and AD patients (49.5 +/- 4.2%). Those with syncope did no worse in terms of survival than did those without. The five-year survival in coronary artery disease patients was 33.7 +/- 4.4%, in those with primary conduction system disease (20% of patients), it was 50.6 +/- 6.6%. It will be necessary to know the causes of death and of syncope in conduction disease patients before it can be determined whether or not pacemakers can prevent either.


Does intervention by a nurse improve medication compliance? A random sample of patients taking two or more drugs, at least one of which was digoxin or methyldopa, was drawn from a medical clinic population. After giving informed consent, the patients were randomized into control and experimental groups. The experimental group was seen by a specially prepared nurse interventionist who attempted to improve medication compliance. The levels of the drugs in the blood were taken as indicators of medication compliance. Our results document that patients exposed to nurse intervention were more compliant than the general clinic population, but were not more compliant than a nonintervention control group. Problems encountered in the collection and interpretation of compliance study data were identified and discussed.


Hemostatic effects of uniform, low-dose subcutaneous heparin in surgical patients. Two hours before surgery and every 12 hours thereafter 5,000 units of heparin sodium was administered subcutaneously to 100 general surgical patients. Hemostasis was evaluated by a template bleeding time and an activated partial thromboplastin time (PTT). The latter was sensitive to 0.05 units/ml of heparin and gave a straight-line response up to 0.2 units/ml. In the great majority of patients, only a modest elevation of the PTT occurred two and four hours after heparin therapy. However, in 10% to 15% the PTT was prolonged two times or more and in a similar number, PTT after surgery was shorter than baseline values despite heparin. No correlation between PTT prolongation and weight, ponderal index, age, or sex was found. Significant bleeding occurrred in three patients, two from the group of hyperresponders to heparin. Recent aspirin ingestion was implicated in one patient and our evidence indicates that low-dose heparin potentiates aspirin-induced prolongation of bleeding time in certain individuals. Local hematoma formation and discomfort from the injections was not a problem.


Typical and atypical ('silent') subacute thyroiditis in a wife and husband. Typical subacute thyroiditis was diagnosed in a woman. Three weeks later, signs and symptoms of hyperthyroidism developed in her husband. Although the right lobe of his thyroid gland was slightly enlarged, pain and tenderness were absent throughout the course of his illness. The free thyroxine equivalent (FTE) value and the sedimentation rate were elevated; the low uptake of radioactive iodine by the thyroid gland was consistent with "silent" subacute thyroiditis. We postulate that a common etiolgoy, probably viral, was operative in both cases. Nine additional cases of hyperthyroidism with low levels of thyroidal uptake of radioactive iodine are described. The thyroid glands of these patients were normal or slightly enlarged. Antithyroglobulin antibody levels determined in seven patients were not substantially elevated. The clinical course of these patients was characteristic of "silent" subacute thyroiditis. Although the origin of the syndrome remains unclear, the disease is self-limited and therapy, if any, is supportive.


Treatment of alcoholic acidosis: the role of dextrose and phosphorus. We have made serial metabolic observations in 18 acute episodes of alcoholic ketoacidosis in ten patients. Data from patients treated with only saline initially were compared to data from patients who received modest amounts of intravenous dextrose (7.0 to 7.5 gm/hr). More rapid improvement in the acidotic state was seen in the latter group (P less than .001). The quicker decline in absolute levels and ratio of beta-hydroxybutyrate to acetoacetate when glucose was given suggests that this treatment induced mitochondrial oxidation of the reduced form of nicotinamide adenine dinucleotide (NADH). Since phosphorus is a critical cofactor necessary for NADH oxidation and the glucose-induced correction of the acidosis was associated with a rapid decline in serum phosphorus from an initial mean of 6.79 +/- .82 mg/100 ml SEM to 0.96 +/- 0.12 mg/100 ml in 24 hours, we propose that glucose enhanced the mitochondrial capacity to oxidize NADH by increasing hepatocyte phosphorus. This effect combined with decline in free fatty acid levels results in reversal of acidosis. Our data suggest that glucose provides the safest, most effective treatment for this disorder; addition of either insulin or bicarbonate is usually unnecessary.


A university medical center occupational health service: shoes for the cobbler's children. A university medical teaching center can provide adequate health care for its employees by using the medical manpower and facilities it already possesses. Certain elements are of prime importance in the success of the development of such a service: (1) organization--concise knowledge of objectives, cost, and benefits, with emphasis on employee satisfaction; (2) staff--selection of interested, imaginative medical personnel and use of expanded role nurses as full-time health providers requiring a minimum of direct medical supervision; (3) collaboration--participation by both medical and nursing professions, educators as well as clinicians, in the formulation and direction of the service.


HLA in maturity-onset type of hyperglycemia in the young. HLA haplotypes in a kindred with a maturity-onset type of hyperglycemia in the young (MOHY) were studied. All diabetics had mild hyperglycemia of early onset, and the inheritance pattern suggested an autosomal dominant trait. Eight of 11 subjects with hyperglycemia shared haplotype A3, Bw15. When only this haplotype was considered, there appeared to be a significant association with hyperglycemia chi2 = 6.36). However, since both haplotypes in the proband could be associated with hyperglycemia (both proband's parents had hyperglycemia), the data for both haplotypes were combined, and analysis for an association between both haplotypes and hyperglycemia was not significant (chi2 = 2.53). Linkage between a diabetes gene causing MOHY and the HLA, evaluated by lod score analysis, was suggested, but the values were not significant.


Iron-containing plasma cells.

Iron-containing plasma cells. Iron in plasma cells has been described in patients with diseases characterized by iron overload. We observed iron-containing plasma cells in 21 anemic alcoholic patients admitted to the hospital for treatment of complications of alcoholism. The presence of iron-containing plasma cells is suggestive of alcoholism and its complications, and diseases associated with iron overload or inability of RBCs to utilize iron. The mechanism of entry of iron into plasma cells is unknown.


Psychiatric manpower for state mental hospitals. A continuing dilemma. A shortage of psychiatrists continues to exist in state mental hospitals (SMHs), and Public Law 94-484 is likely to aggravate this problem. A telephone survey was done of 50 state departments of mental health to collect data about (1) the number and kinds of SMHs in each state;(2) the percentage of psychiatrists in SMHs who are foreign medical graduates; and (3) strategies for attractiing psychiatrists to SMHs. States with SMH residency training programs employed significantly more psychiatrists and paid significantly lower salaries than did states without these programs. Nine states reported no or few problems obtaining psychiatric staff. These nine states employed more psychiatrists and had a smaller proportion of foreign medical graduates than the remaining 41; salaries were similar. Sets of strategies for obtaining psychiatrists were identified for all 50 states. The strategies of competitive salaries, university affillation, and incorporating the SMH into an interdependent network of quality mental health care delivery systems are examined in detail.


Teaching behavioral sciences to medical students. Education or training? Accepted paradigms in medical behavioral science education are development, conflict and defense, and disease. Teaching under these paradigms blurs distinctions between preclinical and clinical education, and between education and training--most commonly by including an introduction to clinical psychiatry in preclinical courses. Such approaches may provide students with technical skills at the expense of their developing conceptual bases for continuing self-education. We developed a first-year behavioral sciences course using the paradigm of symbolic function and language. This paradigm can organize knowledge that underlies clinical skills involved in talking with patients and establishing an effective physician-patient relationship. Believing that fostering knowledge should be the primary goal of preclinical education, we emphasized primary sources and classics. Our goal was to encourage analysis and synthesis rather than memorization; evaluating such higher taxonomic levels of education is extraordinarily difficult.


Biorhythms and highway crashes. Are they related? Biorhythm, a theory that purports to identify periods of increased individual susceptibility to accident or misfortune on the basis of recurring biological cycles, is currently enjoying world-wide popularity. In view of the implications of such a theory for both public health and safety, the present study was undertaken as an empirical test of its validity. Using data from 205 carefully investigated highway crashes (135 fatal; 70 nonfatal) in which the drivers were clearly at fault, the authors computed specific points in drivers' biorhythm cycles at which the accidents occurred. The observed frequencies of accidents occurring during so-called critical and minus periods were then compared with the frequencies to be expected on a chance basis alone. The results provided no evidence for a relationship between purported biorhythm cycles and accident likelihood.


The effects of hyperbaric and normobaric oxygen on cognitive impairment in the elderly. Eighty-two elderly subjects with significant cognitive impairment were randomly assigned to treatment with either hyperbaric oxygen, hyperbaric air, normobaric oxygen, or normobaric air. Treatment consisted of two 90-minute sessions a day for 15 consecutive days. Subjects were evaluated on measures of memory and intellectual capacity, as well as on psychiatric symptom rating scales. Results immediately after treatment and at one, two, three, and eight weeks following treatment did not show enhanced cognitive functioning or significantly greater symptom reduction in experimental subjects who received either normobaric or hyperbaric oxygen as compared to controls who received hyperbaric or normobaric air. There was also no evidence of differential treatment effects as a function of initial severity of illness, sex, response to a CO2 loading test, or presumed evidence of cerebrovascular disease.


Are there social class differences in patients' treatment conceptions? Traditionally, lower-class individuals who have sought psychiatric help have been hampered in their efforts by classrelated inequities in the delivery of psychiatric services. A common explanation for this phenomenon has been that the treatment conceptions of lower-class individuals are "inappropriate." This report presents theoretical and research evidence challenging this notion. A review of the literature from 1954 through 1974 yielded no good evidence that lower-class patients need, expect, or want treatments incongruent with those of upper-middle-class therapists. An experimental study of the requests for help made by 278 walk-in clinic patients confirmed this observation. Patient requests, as measured by an 84-item, self-rated questionnaire, were largely independent of social class. It was concluded that social class differences in treatment disposition and outcome cannot be attributed to social class differences in patients' treatment conceptions. The possibility that methodological and sociological factors can account for the discrepancies between the findings of this study and past studies is discussed. Strategies for minimizing treatment biases against lower-class patients and for maximizing treatment effectiveness with higher-class patients are also suggested.


Prognosis in schizophrenia. Prognostic predictors and outcome. Eighty-eight of 92 first-admission schizophrenics from 1963, an incidence by first admission cohort, were followed up in 1974 and 1975. Epidemiologically the sample was more comparable to lower European rates and expectancy rather than to higher American figures. Prior to follow-up, factors said to predict outcome were scored. This prognostic information was complete for 79 cases. Outcome was measured on a variety of criteria. The patients fell into a "poor prognosis" group based on the prognostic indicators, which were of little value in predicting prognosis within this group. However, patients who received extensive service during the follow-up period had poorer outcomes. Outcome was better than in most earlier studies of schizophrenia, but similar to that in some other recent studies of first-admission patients; also, the use of phenothiazines, short-term hospitalization, and community services may play a part. The failure of prognostic indicators to predict more than about 25% of the outcome variance for this group of "poor prognosis" patients supports the viewpoint that "good" and "poor" prognosis schizophrenia are two different entities.


Therapist characteristics and the outcome of treatment in schizophrenia. The broad task of identifying and characterizing specific components of personality and behaviours of therapists that may be differentially helpful in the treatment of schizophrenia still remains to be addressed. This report presents data systematically collected in the course of a controlled study of the outcome of five different treatment methods in schizophrenia. Therapists seem to play a significant role in determining the outcome of the treatment of schizophrenia by drugs and by psychotherapy plus drugs. The salient therapist behaviors that seem to make a difference in outcome are yet to be identified and studied. The A-B dimension as customarily defined seems of little value for this task. The findings show a distinct need to identify cognitive and affective personality characteristics of the therapist relevant to eliciting patient cooperation, and the degree of knowledge and sophistication in the use of particular methods of treatment necessary for good results.


Sex differences in psychiatric evaluation and treatment. An empirical review. This article reviews the research evidence concerning sex-related differences in psychiatric/psychological assessment and treatment. The effects of both sex of patient and sex of judge are considered. The article also raises methodological criticisms of the existing research, and draws some tentative conclusions.


Dopamine excretion and vulnerability to drug-induced Parkinsonism. Schizophrenic patients. Before and during a standardized course of trifluoperazine therapy, 18 schizophrenic patients underwent repeated examinations for extrapyramidal motor signs, clinical psychopathology, and urinary excretion of free and conjugated forms of dopamine and its metabolites. Patients excreting more free dopamine and metabolites, or showing less complete conjugation, before drug treatment, were much less likely than others to develop parkinsonian akinesia and rigidity during drug treatment. Neither catatonic rigidity nor akinesia before treatment was predictive of a parkinsonian response to trifluoperazine, but pretreatment tremor may have been. The severity of schizophrenic psychopathology was unrelated to dopamine excretion. This study of schizophrenic patients, and our previous research in Parkinson's disease, suggest that urinary dopamine excretion may reflect dopaminergic function of the extrapyramidal motor system in both conditions.


Sensory nerve conduction velocity in children using cerebral evoked potentials. Sensory nerve conduction velocity was measured in 16 healthy volunteers from 3 to 16 years of age by using evoked cortical potentials. Using the latencies to the peaks of the 2nd and 3rd components (N1 and P2) of the average evoked response, conduction velocities for the wrist-to-elbow segment of the median nerve were found to have a range of 58 to 74 meters/second (m/s). Mean values using N1 and P2 were not significantly different. Conduction velocities in the same children obtained by stimulation of the median nerve at the elbow and wrist while recording the digital nerve action potential from the index finger had a range of 58 to 70 m/s. Mean values determined using cortical and digital potentials were not significantly different. In individual subjects, values obtained with the two techniques differed by 0 to 9 m/s using the N1 peak and 0 to 11 m/s using the P2 peak of the of the cortical potential. Reliable conduction velocity measurements for sensory nerves can be obtained in children using evoked cortical potentials with relatively simple methods. This technique has been successful when conventional methods did not detect peripheral sensory responses.


Urinary output and incidence of acute urinary tract infection in patients with indwelling bladder catheters. This study was designed to test the hypothesis that high urinary output in patients with an indwelling bladder catheter tends to protect the patients from acute urinary tract infection. Thirty-five cases of acute spinal cord injury were analyzed for average daily urine volume and frequency of acute urinary infection (defined as oral temperature above 101 F and requiring treatment for the infection). The study period encompassed the time from entry into the Rehabilitation Unit until a definitive effort was made to remove the catheter, a mean of 59 days. Twenty-six patients developed acute urinary infections while nine did not. Mean 24-hour urine output in the two groups was 2530 cc and 2540 cc, respectively. The only difference which could be found was a significant decrease in urinary output in the symptomatic group during the seven days preceding onset of acute infection.


Sensory conduction in the musculocutaneous nerve. This report describes an antidromic technique for studying conduction in the sensory branch of the musculocutaneous nerve, the lateral cutaneous nerve of the forearm. Surface stimulation was done at the elbow where the nerve becomes superficial, and surface recordings were made 12 cm distally over the course of the nerve. Sixty nerves in 30 normal persons were examined. The mean latency to onset of the action potential was 1.8 +/- 0.1 msec with a mean conduction velocity of 65 +/- 3.6 meters/sec. Mean amplitude of the action potential was 24 +/- 7.2 muv.


Residual latency: new applications of an old technique. Median and ulnar nerve conduction velocity was studied using residual latency techniques in a control population and in a population with neuropathy. Midpalmar stimulation sites were used to determine the residual latency of the distal short segment. The residual latency index (RLI) was the short segment residual latency divided by the residual latency for the entire terminal nerve segment. While it was 0.61 in the control population, it increased to 0.69 in the patients with ulnar neuropathy distal to the wrist and decreased to 0.36 in patients with neuropathy of the median nerve at the carpal tunnel. In five cases of median neuropathy at the carpal tunnel, muscle biopsy specimens revealed evidence consistent with neuropathic processes. The RLI is an accurate and relevant method of evaluating the sensory and motor conduction of very small nerve segments.


Electromyographic effect on serum creatine phosphokinase in normal individuals. Seven normal healthy individuals were investigated to determine the effect of needle electromyography (EMG) on serum creatine phosphokinase (CPK) levels. No changes were noted as the result of EMG. Exercise resulted in increased serum CPK activity and persons with large muscle mass showed higher initial CPK levels.


Sexual adjustment of spinal cord injured veterans living in the community. Data were gathered from interviews conducted by the investigators with 145 spinal cord injured outpatients from the Veterans Administration Hospital, Bronx, NY. The index of Sexual Adjustment was developed based on factors such as adaptation to sexual limitations, partner satisfaction, sexual self-concept, and regularity of sexual contact. The index was correlated with 21 variables permitting a description of significant factors which are related to successful rehabilitation. Higher scores on the index were significantly and positively associated with better physical function, higher level of income, the roles of worker and community participant, higher morale, injury at an earlier age, younger current age, positive attitudes of self-acceptance and independence. Abstinence from sexual relations as a form of adjustment is also considered. Results of this study support the hypothesis that sexual adjustment is related to psychologic, social and physical factors that are relevant for successful rehabilitation. These findings suggest that sexuality is an integral part of the disabled person's personality and behavior and that adjustment to disability includes a sexual dimension.


Metastatic disease of the paraspinal muscles: electromyographic and histopathologic correlation in early detection. Electromyographic examination may demonstrate severe segmental compromise of the posterior primary ramus and relative sparing of the anterior ramus as the earliest objective evidences of spinal and paraspinal metastases. Antecedent studies, including roentgenographic, radioisotopic and neurologic investigations, are often initially normal, failing to reveal the underlying cause of the progressive back pain. The present report demonstrates metastatic spread both through the paravertebral venous plexus and by direct extension in contiguous muscle. In this special instance, segmental 4+ fibrillations in the paraspinal muscles are electrophysiologic manifestations of a local, active process of denervation rather than a remote effect of the malignant disease, as has been suggested by others.


Intermittent catheterization to obtain catheter-free bladder function in spinal cord injury. The intermittent bladder catheterization technique has been proposed as an effective way of eliminating the need for an inlying. Foley catheter in patients with neurovesical dysfunction following spinal cord injury. In the study reported here, a group of 41 male patients with spinal cord injuries achieved a catheter-free state with this method. Of these 41 patients, 19 have been followed for 1 year. Data obtained from the 19 patients are presented here for comparison with data from other recent studies. In the present study, the patients' fluid intake was restricted to 2,000 cc daily. A detrusor reflex was triggered by lower abdominal percussion followed by a Credé maneuver. A 6-hour catheterization schedule was used unless autonomic dysreflexia required more frequent catheterizations. Ascorbic acid, methenamine mandelate and nitrofurantoin were routinely administered, and specific antibiotics were also given following trial off-catheter, depending on the results of urine cultures and sensitivity studies. All patients achieved a catheter-free state in an average time of 17.1 days; no late failures have occurred. Two patients developed vesicoureteral reflux, but no evidence of hydronephrosis was observed. At 1 year only 16% of the patients were found to have infected urine, as compared to 100% at initiation of the trial off-catheter.


Intermittent catheterization failure and an approach to bladder rehabilitation in spinal cord injury patients. Forty-six patients with spinal injury with dysfunctional neurogenic bladder were analyzed. Fourteen patients on prolonged intermittent catheterization from 12 weeks to more than 1 year did not develop a balanced bladder, 14 patients had indwelling catheters after intermittent catheterization failed elsewhere and 18 patients on external condom drainage presented with difficult voiding and repeated infections. There were 16 quadriplegics (1 incomplete), 21 paraplegics, and 9 incomplete cauda equina lesions. Urologic and urodynamic evaluation revealed detrusor-sphincter dyssynergia in 15 patients, vesicoureteral reflux in 10, and areflexic bladders in 11. Five patients over the age of 55 years showed slight enlargement of the prostrate. Some degree of bladder neck fibrosis was suspected in 26. More than one urologic pathology was encountered in the same patient. Transurethral sphincterotomy was carried out in 38 patients and only one transurethral resection of the prostrate (TURP) in an incomplete quadriplegic patient. In seven patients with no obvious urodynamic abnormality, a balanced bladder was achieved with intermittent catheterization; however, one of these patients needed a transurethral sphincterotomy on subsequent admission. A balanced bladder was achieved in all patients except the one with incomplete quadriplegia. Significant improvement in vesicoureteral reflux and relief from autonomic dysreflexic symptoms were recorded in all patients.


Hereditary neonatal hyperparathyroidism. Neonatal hyperparathyroidism usually presents as a "failure to thrive" syndrome. It may be transmitted as an autosomal dominant trait and may involve more than one offspring. We report on two brothers with neonatal primary hyperparathyroidism. One underwent a total parathyroidectomy and has lived for 14 years. Hyperparathyroidism was found in their father, suggesting autosomal dominant inheritance. The disease is fatal unless recognized early and treated. The characteristic pathological change is chief cell hyperplasia of the parathyroid glands. Near-total parathyroidectomy is the minimal operation required to control the hypercalcemia. Permanent hypoparathyroidism may be the sequel of appropriate surgical management. Treatment of the totally parathyroidectomized infant, however, is possible and can result in normal growth and development.


Testing the lipid hypothesis. Clinical trials. It is generally accepted that we still lack a conclusive answer, to whether lowering of the lipid level will prevent the development or reverse the progression of coronary atherosclerosis. Multiple risk factor intervention trials now have the merit of addressing themselves to probable and practical needs for intervening on several of the major risk factors to obtain the maximum impact on populations at risk.


Effect of vagal stimulation on the concentration of gastrin in serum and antral mucosa in dogs. The concentration of gastrin in serum and antral mucosa was studied in anesthetized dogs after electrical stimulation of the antral branch vagus nerve. Vagal stimulation caused immediate and sustained release of gastrin into the circulation. After stimulation for one hour, the gastrin concentration of antral mucosa increased significantly. This suggests that vagal release of gastrin triggers its rapid synthesis.


Reactive hyperemia vs treadmill exercise testing in arterial disease. We compared the ankle pressure response during reactive hyperemia to the response to treadmill exercise in 28 limbs of 14 normal individuals and 26 legs of 15 patients with arterial occlusive disease. The mean percent maximum drop in ankle blood pressure during reactive hyperemia in normal limbs, 17% +/- 11% (+/- 1 SD) was significantly less than that of legs with arterial disease, 54% +/- 15% (P less than .001). Abnormal values were recorded in all but three diseased limbs. There was good correlation between the ankle pressure responses to reactive hyperemia and treadmill exercise (r = 0.71, P less than .001). This study suggests that measurement of ankle pressure during reactive hyperemia may be a useful substitute for treadmill testing to determine the functional capacity of the circulation during stress in patients with arterial occlusive disease. Reactive hyperemia testing requires less time and equipment and may be performed in patients who might be at risk or unable to carry out treadmill exercise.


The effect of size, histologic elements, and water content on the visualization of cerebral infarcts. We correlated the radiologic and pathologic examination of 13 human brains, analyzing the size, different histologic elements, and water content in 40 ischemic and hemorrhagic infarcts. Acute infarcts appear in the computerized cranial tomographic (CT) image as low density areas due to high content of fluid, however, a histological-chemical correlation is not concomitant. The addition of blood in hemorrhagic infarcts may result in a normal CT image. Subacute infarcts appear as low density areas, with lower attenuation values due to the presence of large amounts of lipids. Subacute lesions with prominent mineral deposits may be negative on CT scan. Chronic infarcts also appear as low density areas due to cavitation and residual fats. Attenuation values are slightly higher than those of subacute infarcts, possibly due to gliosis. Infarcts smaller than 2 cm in diameter are usually not visualized.


Development of cerebrovascular architecture and its relationship to periventricular leukomalacia. Using microangiography combined with benzidine stains, we studied the development of vessels in the meninges, cortex, and white matter in 30 neonates, 16 infants and children, and eight neonates with periventricular leukomalacia. The vessels of the deep white matter, especially the ventriculofugal arteries, are useful as an index of cerebrovascular maturity. The lesions of primary leukomalacia utilizing the combined radiographic-histological techniques are localized to the ends of ventriculofugal arteries or between medullary arteries. The infants with leukomalacia have either poorly developed vessels or severe clinical complications producing ischemia or both.


Febrile seizures and later intellectual performance. The relationship of febrile seizures to later intellectual and academic performance was examined in a sibling-control study. Amont 431 sibling pairs tested at the age of 7 years, the mean full scale IQ on the Vechsler Intelligence Scales for Children was not different for children who had febrile seizures as compared with siblings who were seizure-free. Neither recurrent seizures nor those lasting 30 minutes or longer were associated with IQ deficit. Poor academic achievement, defined as Wide Range Achievement Test performance more than one grade level below school placement in children with IQs of 90 or above, was equally frequent in index cases and control patients. Febrile seizures were not associated with a decrement in IQ or early academic performance, as judged by comparison of affected children with their siblings.


Binding of iodine 125 alpha-bungarotoxin to the thymus of mice. alpha-Bungarotoxin is known to bind with nicotinic acetylcholine receptors of skeletal muscle. Binding of iodine 125-labeled alpha bungarotoxin to the murine thymus, muscle, and liver was estimated. The toxin was bound to the muscle. The thymus was also capable of binding a considerable amount of the toxin, and the binding was obviously blocked by tubocurarine chloride. Binding to the liver, an organ containing no nicotinic acetylcholine receptor, was very slight. These results may indicate the presence of nicotinic acetylcholine receptors in the thymus, which could have implications in the pathogenesis of myasthenia gravis. Degenerating myoid cells and their receptors may represent autoantigens that induce an immunological cross-reaction with the receptors of skeletal muscles, giving rise to myasthenia gravis.


Cervical myelopathy due to ossification of the posterior longitudinal ligament: a clinicopathologic study. A clinicopathologic study was done of a Japanese patient with symptomatic ossification of the posterior longitudinal ligament in the cervical spine. Post-mortem specimen showed characteristic distribution of degenerations at C5-6 segments similar to chronic cervical spondylosis or disk protrusion. The degenerative changes were confined to the ventral two thirds of the posterior and lateral columns. In addition to demyelination, loss of axons, and neuronal cell death, thickening of venular wall and fine capillary neovascularization strongly suggested chronic circulatory insufficiency. Spinal immobilization produced by the ossified ligament may have contributed to the long clinical course, lasting for 30 years. Review of literature showed that the myelopathy can be distinguished clinically and radiographically from that produced by cervical spondylosis.


The clinical significance of spontaneous pulsations of the retinal vein. A search for spontaneous retinal venous pulsations was carried out in 218 subjects. Spontaneous venous pulsations were present in 87.6% of 146 unselected subjects 20 to 90 years of age and absent in 100% of 33 patients with raised intracranial pressure without papilledema and ten patients with papilledema. Lumbar puncture in nine patients with raised intracranial pressure established the upper level at which spontaneous pulsations disappear as 190 mm H2O, and no pressure above 180 mm H2O was found in 29 patients with venous pulsations present prior to lumbar puncture. There was no correlation between the presence or absence of venous pulsations and blood pressure. Some normal subjects with absent pulsations showed definite pulsations on subsequent examinations. These findings confirm that the presence of spontaneous venous pulsations is a reliable indicator of an intracranial pressure below 180 to 190 mm H2O, while the absence of pulsations may be found with normal intracranial pressure and is therefore not a reliable guide to raised intracranial pressure.


Psychological factors in the face-hand test. Young children's failure to report double-simultaneous stimulations of the side of the face and the contralateral hand has been attributed to cerebral deficiencies. When tested under optimal psychological conditions, 3- to 6-year-old children correctly report simultaneous stimulations of the face and contralateral hand. Performance on the face-hand test, which has been used as an index of cerebral functioning, is influenced in a significant way by the child's ease in the testing situation and understanding of the task.


Acute encephalopathy, streptococcal infection, and cryoglobulinemia. A 9-year-old girl had an acute encephalopathic illness characterized by disordered consciousness, seizures, and multiple cortical deficits. The acute illness was associated with serologic evidence of an antecedent streptococcal infection and the presence of a mixed cryoglobulin with specific antistreptococcal antibody activity. Although the patient had no other evidence of a systemic or central nervous system vasculitis, computerized tomography demonstrated changes compatible with a vasculitic process. Treatment with corticosteroids was associated with resolution of the cryoglobulinemia and complete clinical recovery.


Changes in the symptoms of neglect induced by changing task strategy. Six patients with left side unilateral neglect from lesions of the right cerebral hemisphere were tested with verbal and visuospatial crossing-out tasks. The symptoms of neglect were less severe with the visuospatial than with verbal tasks. We hypothesize that changes in the symptoms of neglect were produced because the tasks altered hemispheric arousal.


The effect of pharmacologic acetylcholine receptor on fibrillation and myotonia in rat skeletal muscle. Myotonic discharges in rats given 20, 25-diazacholesterol hydrochloride and fibrillation discharges in denervated rat muscle both were silenced by procaine hydrochloride, tetrodotoxin or ischemia, or potassium chloride (after initial activation). They both were activated by succinylcholine, but only the fibrillations were silenced by alpha-bungarotoxin or atropine sulfate. It is hypothesized that fibrillations and diazacholesterol-induced myotonia are mediated through mechanisms involving ionic channels, that both can be produced by activation of the junctional/nonjunctional acetylcholine receptors (or some mechanism coupled to the receptors), but that an unfettered alpha-bungarotoxin-binding portion of the acetylcholine-receptor molecule and an unblocked atropine-binding site are obligatory only for production of fibrillations.


Central auditory testing with peripheral hearing loss. Seventy subjects with sensorineural hearing losses participated in this study. The goal of the study was to examine the effect of peripheral hearing loss on auditory tasks that are used to assess dysfunction within the central auditory pathways. Each subject received a central auditory processing (CAP) test battery that consisted of: (1) a dichotic sentence listening task; (2) a monosyllabic filtered word task; (3) a spondaic word binaural fusion task; and (4) a rapidly alternating speech task. All of these tasks were affected by certain degrees/configurations of sensorineural hearing loss, with the monosyllabic filtered word task being the most seriously affected. From the results of this study, it was concluded that while the CAP test battery can be administered to certain persons with sensorineural hearing losses, all results must be interpreted with caution and in view of the basic audiological assessment.


Nasal tip projection changes related to cheeks and lip. Nasal profiles are altered in almost every rhinoplasty operation. Often neglected in diagnosis and surgery are alterations in profiles of the cheeks and upper lip that should be made at the same time. We show aesthetic effects produced by alterations in these structures and describe how we measure and record the adjustment. A few examples of results are presented to indicate the techniques used and the importance of including changes in profiles of the cheeks and upper lip in cosmetic rhinoplastic diagnosis and treatment.


Histologic findings in the temporal bone in trisomy D (D/D translocation). The temporal bones of an infant in whom the diagnosis of unblaanced trisomy D (D/D translocation) had been made by chromosomal analysis during life were studied histologically. Most of the findings resembled those that have been described by others in trisomy D (13-15) syndrome. A previously unreported abnoramlity was substrial edema displacing the stria vascularis. The importance of this finding remains to be defined by further study.


The frontal lift.

The frontal lift. Indications and advantages of the frontal lift are seen in comparison to the limitations of the conventional browplasty. The anatomy is reviewed, including the planes of dissection, nerves, vessels, muscles, and bony landmarks. Temporal and frontal ptosis, as well as glabellar and frontal creases are treated through this approach. The surgical procedure includes site of incision, extent and plane of dissection, and treatment of frontalis, procerus, and corrugator muscles. Some variations of technique have been performed. These include the V-Y shaped closure technique in the temple area and retaining separate anatomic compartments when combined with meloplasty.


Influence of alcohol on the acoustic reflex and temporary threshold shift. Blood alcohol levels between 0.09% and 0.15% were found to reduce the protective action of the acoustic reflex in five human subjects with normal hearing. Specifically, acoustic reflex thresholds were raised, reflex magnitude decreased, and temporary threshold shift increased under alcohol conditions. Stimuli consisted of a narrowband noise (500 to 1,000 Hz) and a 500-Hz pure tone. Measurements were made at blood alcohol concentrations from 0.05% to 0.15%. Temporary threshold shift at 1,000 Hz was determined three minutes after a ten minute exposure of narrowband noise at -5, +5, and +20 dB relative to the subject's prealcohol acoustic reflex threshold.


Tympanometry as a predictor of middle ear effusion. Tympanometry is often used as a major component of medical referral criteria in both diagnostic audiometry and hearing screening programs. This use is based on an assumption that a relationship exists between the tympanogram type and the presence of middle ear effusion. The present investigation examined this relationship in 142 ears immediately prior to myringotomy. The results suggest that prediction of middle ear effusion on the basis of tympanometric data alone is difficult at best. The only exception is in the case of a flat tympanometric curve (type B), when a 90% occurrence of notable effusion was found. The clinical implications of these data are discussed.


Aspergillosis of the sphenoid sinus.

Aspergillosis of the sphenoid sinus. Three of the four previously described patients with isolated aspergilosis of the sphenois sinus died, owing to intracranial extension of the infection. The case reports of two patients with sphenoid aspergillosis are presented in which surgical exteriorization and aeration of the involved sinus was curative.


Effect of the menstrual cycle on voice quality. The question addressed was whether most young women with no vocal training exhibit premenstrual hoarseness. Spectral (acoustical) analyses of the sustained productions of three vowels produced by 20 undergraduates at and at premenstruation were rated for degree of hoarseness. Statistical analysis of the data indicated that the typical subject was no more hoarse of premenstruation than at ovulation. To determine whether this finding represented a genuine characteristic of women's voices or a type II statistical error, a systematic replication was undertaken with another sample of 27 undergraduates. The finding replicated that of the original investigation, suggesting that premenstrual hoarseness is a rarely occurring condition among young women with no vocal training. The apparent differential effect of the menstrual cycle on trained as opposed to untrained voices deserves systematic investigation.


[Finding of anaerobic bacteria in blood cultures]. Out of the blood cultures sent to the Bacteriology Laboratory of Hospital del Niño DIF, during the period of one year, in 1.4% of samples, isolation of anaerobic bacteria was obtained. Isolation was more frequent in infants under one year of age, but specially in newborns. The species most frequently found were Propionibacterium acnes, Bacteroides melaninogenicus and Clostridium subterminale. The presence of this finding in blood cultures of infants is noted, but there is no purpose to establish a clinical relationship with the finding of this group of bacteria.


[Clinicopathologic study in children of a diabetic mother. Review of 16 cases]. 16 cases of infants of diabetic mothers were analyzed; 10 of them were live-born and died shortly afterwards; the other 6 were born dead. Among the live-born there was a high frequency of respiratory illnesses, neonatal jaundice and hemorrhagic tendency more often in lungs and C.N.S. At the necropsy, together with the findings atributtable to the mentioned illnesses there was also hyperplasia of the pancreatic islands in 100%, a high tendency to the visceral gigantism, specially in the liver, heart and lesser in the brain. And 20% had congenital malformations, chiefly in the C.N.S. genitourinary and lymphohematopoietic system. The descriptions are accompanied by a brief review of the literature.


[Concentric centering of the normal hip and concentric reduction of the dislocated hip. Radiological study on their determination and clinical application]. A radiological method to determine the ideal, geometrical, center of the acetabulum and femoral head is described by the author; the proceedings for these localizations and the interrelationship between them, are also described. These factors were taken from a series of simple radiography and arthograms, which is called; "Concentrical Centring" in normal hips, as well as other seires of dislocated hips, which were radiographed in anteroopsterior view, and in frog position, as well as in histological sections. The necessity to look for the concentrical reduction of the dislocated hips is also emphasized, as a basic point for the good development of the acetabulum, which is achieved, at the time of treatment, if the location is made of the point of the femoral head with that of the acetabulum (Concentrical Reduction). This method will permit to evaluate this interrelationship easily in a numerical scale figure and with a minimum of error. This is a useful resource previous to the arthrography in those hips which have been just recently reduced; and latter, in their follow-up.


[Complications of chickenpox].

[Complications of chickenpox]. A patient with typical varicella (chickenpox) developed several complications: nephrotic syndrome following glomerulonephritis, trombocytopenic purpura, gastrointestinal bleeding, disseminated intravascular coagulation, encephalitis and bronchopneumonia. The course was satisfactory having been given antibiotics, heparin and peritoneal dialysis. Recovery was 100%.


[Diphenoxylate poisoning].

[Diphenoxylate poisoning]. During the year 1976, 18 patients intoxicated with lomotil were admitted to the Emergency Service of the Centro Medico La Raza, I.M.S.S. with ages fluctuating between 4 months and 3 years; the average age was 22 mos. 88.8% of intoxications were accidental. Initial manifestations of atropinism and diphenoxylate showed the same proportion and 22% showed mixed symptoms. There were no deaths. All patients were given stomach washings and it was seen that the earlier the washing was given, the lesser the symptoms showed. The specific treatment given was with naloxone chloride (Narcanti) at a dose of 10 micrograms, per kilo and per dose intravenously and was repeated as often as necessary. Response was spectacular with improvement within 15 seconds. No patient showed side-effects to the application of the antagonist. Lomotil intoxication rated up to 15% of the total sum of intoxications admitted.


Some aspects of the cardiovascular pharmacology of UK 14,275 in patients with coronary artery disease. 1. A phosphodiesterase inhibitor, UK 14,275 (Pfizer) was administered intravenously to six patients with suspected coronary artery disease under-going diagnostic cardiac catheterisation to assess its inotropic activity. 2. Intracardiac haemodynamic measurements included pulmonary and systemic arterial pressure. Left ventricular end diastolic pressure and left ventricular dP/dtmax were also measured, in addition to cardiac output using the indocyanine green dye technique. 3. UK 14,275 resulted in a significant increase in LV dP/dtmax and cardiac output. 4. No chronotropic action was observed using this agent. 5. This agent may have potential therapeutic value in the management of cardiovascular failure associated with low cardiac output.


[Intestinal obstruction ducts ascarides in childhood]. Intestinal ascariasis is the first among the most frequent parasitosis in Acapulco, Gro. Studying one of its most frequent complications, such as intestinal obstruction or subobstruction, it was found to occupy the 5th place as cause of admission to this service. The number of admissions was 1461 pediatric patients in a year, out of which there were 85 cases with total or partial obstruction due to ascarides. Routine studies were made including plain and barium X-ray plates. With the treatment instituted and adequate management there was no mortality. Only 8 cases required surgery. Stress is placed on X-ray studies to confirm the diagnosis.


The role of the clinical pharmacologist in district general hospitals. Since its inception, the Clinical Pharmacology Section of the British Pharmacological Society has been discussing the wider role and responsibility of the clinical pharmacologist beyond the university department, in the district general hospital. The following policy statement is the product of these discussions, and is published in this international journal because, although the organization of the health service and its hospitals is peculiar to the United Kingdom, the concept of a clinical pharmacology service in general hospitals has far-reaching implications. The Editorial Board hopes that its publication will lead to recognition of the part that a general physician with a special interest in clinical pharmacology can play in patient care.


[Psoas abscess in children. Report of 6 cases]. Six children with abscess of the psoas muscle are presented. Previous trauma pain, claudication and antalgic position of a lower limb, fever, abdominal tenderness and leukocytosis were prominet features. Four patients improved and two died. Treatment included surgical drainage and antibiotics. Differential diagnosis and possible pathogenesis are discussed.


A controlled release papaverine tablet (Papacontin): a study in normal volunteers. 1. A controlled release tablet containing 300 mg of papaverine hydrochloride was compared with a capsule containing the same dose. 2. The in vitro release pattern showed a steady dissolution of the tablet, with release of the papaverine over 10 h, whereas the capsule release time was 40 min. 3. Plasma levels in volunteers who were given the tablet showed a rapid rise to therapeutic levels (150-300 ng/ml) within 1 h, and maintenance of these levels for 10-12 h, with no accumulation on repeated 12 hourly dosage. Administration of the capsule produced early peaking and a subsequent rapid fall in plasma levels.


[Chronic peptic ulcer among students and adolescents]. The clinical records of 13 school-age children and of 22 adolescents with chronic peptic ulcer were reviewed. There was a predominance of the male sex and duodenal localization showed greater frequency than the gastric. The duration of symptoms previous to the diagnosis was greater in adolescents and repeated X-ray studies were required in school-agers to confirm the presence of an ulcer niche. The common symptoms were abdominal pain and vomiting. However, in 43% of the patients, abdominal pain was not typical of ulcer; therefore, all school-age children and adolescents with recurrent abdominal pain should be submitted to careful investigation. Anxiety and depression were found in 92.3% of the cases. Special ulcer diets and antiacids were given to all patients, but 8 cases showed no improvement. Psychiatric treatment and administration of psychodrugs may be useful. Diazepam was given to 50% of the patients who recovered and to one who did not recover.


[Acid-base balance in the newborn infant. II. 3 technics of sample collection and the difference between amniotomy]. The study included 32 healthy newborns to evaluate the acid-base balance between two groups of newborns whose mothers underwent early or late amniotomy. The results were compared to the first study finding important differences, unquestionable due to  amniotomy and age. Significant difference was found only in PO2 between arterial blood and arterialized capillary showing difference in pH, PCO2 and CO2 between the two capillaries. With the criterion pointed out in this work, the usefulness of late amniotomy and the stabilization of acid-base balance is established in newborns under 4 hours of age. Arterial blood is still being proposed to obtain an "ideal" acid-base balance and the arterialized capillary as a practical and useful method.


Monitoring digoxin therapy: III. How useful are the nomograms? 1. A previously described set of guidelines for digoxin therapy has been evaluated in twenty-four patients. 2. Six different published methods (nomograms and equations) for predicting digoxin requirements have been studied to determine their clinical usefulness in the context of the twenty-four patients. 3. The limitations of the nomograms and equations are discussed.


The inotropic effects of UK 14,275, a phosphodiesterase inhibitor, in man. 1. UK 14,275 (Pfizer) an inotropic agent with cardiac phosphodiesterase inhibitory activity, was administered to ten healthy male volunteers. 2. The inotropic activity was assessed by non-invasive measurement of systolic time intervals (STI). 3. The compound had significant inotropic activity in the doses administered, as judged by the shortening of pre-ejection period (PEP), without any significant chronotropic activity. 4. The inotropic effect was abolished when measurements were repeated following beta-adrenoceptor blockade with oral propranolol. 5. The inotropic activity was compared to that of intravenous isoprenaline.


Drug metabolism in epileptics: in vivo and in vitro correlations. 1. The effect of inducing drug therapy on the relationship between in vitro (cytochrome P-450 content) and in vivo (antipyrine kinetics) was investigated by comparing eleven consecutively treated epileptics with two groups of controls, eleven subjects with normal liver histology and eleven disease matched non-epileptics, all underwent diagnostice liver biopsy. 2. The epileptics had significantly higher cytochrom P-450 level in biopsies and they also metabolized antipyrine faster than the controls. 3. Decrease in antipyrine half-life in epileptics was related with alterations in liver histology, whereas the level of cytochrome P-450 was not. 4. There was a linear relationship between these two indices of enzyme induction when regressed on logarithmic data.


Evaluation of the anticholinergic actions of glycopyrronium bromide. 1. Glycopyrronium was evaluated by intramuscular, intravenous and oral routes in six adult volunteers for its efficacy as an antisialogogue as also for its action on other aspects of cholinergic activity. 2. It was found to be an effective antisialogogue of long duration of action by all three routes. When given orally the effects were delayed in onset and persisted for too long. Intramuscular and intravenous routes were useful. The intramuscular absorption of the drug is rapid and consistent. 3. Sweat gland activity was affected in a similar fashion but less consistently and other parameters were mostly unaffected. 4. Glycopyrronium 0.2 mg intramuscularly was found to be the optimal dose. Larger doses produced subjective discomfort out of proportion to a further reduction in salivary secretion. 5. Intravenous administration causes no changes in cardiovascular stability.


Contribution of individual differences in gastric emptying to variability in plasma propranolol concentrations. 1 No correlation was found between the rate of gastric emptying and peak plasma propranolol concentrations in six hypertensive patients after single oral doses of 80 mg. 2 In four normal subjects given oral propranolol the peak plasma concentration was highest when a simultaneous injection of metoclopramide and lowest when propantheline was given. The mean time to peak was 1.5 h after metoclopramide, 2.8 h after normal saline and 4.5 h after propantheline. 3 Gastric emptying has some influence on the time of peak plasma propranolol concentrations but individual variation in its bioavailability is determined mainly by first-pass metabolism in the liver.


The effect of tubocurarine and suxamethonium on directly and indirectly elicited contractions of skeletal muscle in unanaesthetized man using single and train of four impulses. 1 Contractions of adductor pollicis in unanaesthetized man were elicited by direct and indirect stimulation. Single twitch responses as well as those by a train of four impulses at 2 Hz for 2 s were elicited for indirect stimulation. 2 After a suitable control period, tubocurarine (0.05 mg/kg) or suxamethonium (0.08 mg/kg) was administered intravenously. 3 A stepwise diminution in the train of four impulses was noticed after tubocurarine. Indirectly elicited contractions due to single stimulus and direct muscle stimulation remained unaltered. 4 Partial blockade of transient duration occured after suxamethonium for single as well as train of four stimuli. Directly elicited contractions remained unchanged. The intensity of blockade depended on the rate of injection of suxamethonium. 5 Indirectly elicited contractions by train of four impulses is a reliable and sensitive method for testing neuromuscular blocking drugs in unanaesthetized man.


A comparison of some physiological and psychological effects of Motival (fluphenazine and nortriptyline) and diazepam in normal subjects. 1 The effects in normal subjects of a single oral dose of Motival (one tablet, containing fluphenazine 0.5 mg and nortriptyline 10 mg) on the contingent negative variation (CNV), reaction time, heart rate, blood pressure and self-rating scales for alertness, anxiety, tension, detachment and depression were compared with those of diazepam (5 mg and 7.5 mg) and placebo or propranolol (60 mg). 2 After diazepam (5 mg: twelve subjects and 7.5 mg: seven subjects) there was a significant decrease in CNV magnitude while after Motival (twelve subjects) there was no significant alteration in CNV magnitude compared to placebo. 3 After diazepam (7.5 mg: seven subjects) there was also a fall in subjective ratings for alertness and tension; this fall was significantly greater than the changes after Motival which did not reduce subjective ratings for alterness or tension below "average" levels. Anxiety ratings did not differ significantly between the two drugs. Changes after propranolol were intermediate in all scales. 4 It is concluded that under these conditions diazepam caused central nervous system depression while Motival did not.


Effect of aluminium hydroxide and glycopyrrhonium on the absorption of ethambutol and alcohol in man. 1 The effect of aluminium hydroxide and/or of glycopyrrhonium on the absorption of a single oral 50 mg/kg dose of ethambutol (EMB) was investigated on thirteen tuberculous in-patients and on two groups of healthy volunteers with six subjects each. The EMB concentrations in serum and 10+h urine were measured by colorimetry. 2 In order to assess gastric emptying the healthy volunteers ingested ethanol, either 0.5 g/kg in 10% solution or 0.8 g/kg in 20% solution, simultaneously with the drug, and breath alcohol levels were measured repetitively. 3 Aluminium hydroxide significantly lowered the serum EMB levels of the patients during the first 4 h after the EMB intake. No consistent effect was found in the first student experiment, whereas in the second experiment aluminium hydroxide and glycopyrrhonium, alone or in combination, clearly retarded the EMB absorption. 4 Repeated breath alcohol analysis proved unsuitable to indicate the time course of gastric emptying in these circumstances.


The effect of vitamin supplementation upon antipyrine metabolism in the elderly. 1 Antipyrine plasma half-life and clearance rates were studied in 19 elderly patients shortly after admission to a geriatric ward and again 2 weeks after a course of dietary supplementation with Vitamins A, B complex, C and D. 2 Antipyrine half-life fell and clearance increased in the nine who had sub-clinical evidence of ascorbic acid deficiency. No correlation was found with other indices of nutritional status. 3 Vitamin supplementation in elderly people with no demonstrable deficiencies did not alter the metabolism of antipyrine.


Effect of route of administration of 5-fluorouracil on its concentration in blood and lymph. The concentration of 5-fluorouracil (FU) in thoracic-duct lymph, portal-vein blood and peripheral arterial blood of beagle dogs was greater after administration into the submucosa of the stomach than after the bolus i.v. injection. The concentration of FU in thoracic-duct lymph, portal-vein blood and arterial blood was least following administration into the lumen of the stomach. The total FU recovered over 6 h from thoracic-duct lymph was compared following the three routes of administration and was found to be greatest following injection into the submucosa of stomach.


Space-time clustering of Burkitt's lymphoma in the West Nile district of Uganda: 1961-1975. Epidemiological data relating to all 202 patients diagnosed with Burkitt's Lymphoma (BL) in the West Nile District of Uganda in the period 1961 to 1975 have been reviewed and analysed. Statistically significant evidence of space-time clustering of cases, first reported for the period 1961-65, was also present during 1972-73, but not during other periods. The patients involved in such clusters were found to be older than other patients (P less than 0.001). The average annual incidence of BL in the District was 2.45 x 10(-5) and overall there was no change in the incidence during the study period. However, there were statistically significant changes in incidence in different counties, which could not be explained as case-ascertainment artifacts. One sib pair of patients with BL was found and the series also included 7 instances of BL in two cousins. It is suggested that study of variation in the intensity and type of malarial infestation in different areas at different times may help explain the epidemiological findings and suggest what, if any, aspects of this infection are critical for inducing BL.


Immunoadherence and complement in cancer-bearing mice. Shortly after grafting of Ehrlich ascites carcinoma cells, the serum of tumour-bearing mice loses the capacity to mediate immunoadherence phenomena, because of a sharp decrease in the concentration of C3b and C3d, while the cellular receptors for such factors are unaffected by tumour growth. It is suggested that complement is consumed through the alternative pathway which is activated during the inflammatory responses accompanying tumour growth.


High incidence of spontaneous transplantable tumours in BDX rats. Untreated male and female BDX rats were observed over a period of 30 months for spontaneous tumours of a size suitable for transplantation. At the age of 13-30 months 60/97 animals developed tumours, 53 of which were considered as malignant, and 7 as benign tumours. The spectrum of malignant tumours included sarcomas of connective tissue and bone, skin carcinomas, tumours of the lung, the gastrointestinal tract, the genito-urinary tract, the mammary glands, the testis, the adrenal glands and also sarcomas of the neural system and malignancies of the lymphoreticular system. Out of 41 tumours implanted s.c., 34 of them could be passaged further. The primary latent period varied between 1 and 12 months.


Influence of carbon tetrachloride on induction of tumours of the liver and kidneys in mice by netrosamines. Mice were given a single dose of nitrosolimethylamine, nitrosoliethylamine or nitrosomethylethylamine and the yield of tumours and related lesions in the livers determined 12 months later. A hepatonecrotic dose of CCl4 24 or 48 h before the nitrosamines, increased the yields of hepatocellular tumours and proliferative foci in the livers, whereas when given 60 h before the nitrosamines there was no significant effect.


Influence of lodgement site on the proliferation of metastases of Walker 256 carcinoma in the rat. The growth of s.c. Walker 256 carcinoma was found to be independent of secondary growths induced by i.v. injection. Tumour cells injected i.v. lodged mainly in the lungs, with small clusters of cells in the lymph nodes. The rate of cellular proliferation of these secondary growths of Walker carcinoma was significantly higher than that observed in the s.c. tumour. In addition, host lung tissue was found to inhibit the development of metastases, and it is postulated that the host tissue may produce a diffusible inhibitor and that differences in the effectiveness of these humoral factors may account, in part, for locational differences in tumour growth patterns.


Life span, leukaemia and amyloid incidences of untreated and polycation-treated AKR mice. AKR mice, which have a short mean survival time and usually die with leukaemia, were studied from one month of age for correlation between these two parameters. For untreated animals we found the same mean survival time whether or not leukaemia occurred. By treating sucklings with the polycations diethylaminoethyl-dextran or hexadimethrine bromide the leukaemia incidence was significantly reduced. However, the mean survival time was unchanged, and remained the same in leukaemic and non-leukaemic animals. It is therefore suggested that the early death of AKR mice results from an ageing process and does not require leukaemia for implementation. Our prophylactic polycation treatment was furthermore found to induce spleen amyloid in some but not all of the mice that remained non-leukaemic.


Influence of secondary inoculum of tumour cells on growth of primary tumour. The effect of successive inocula of tumour cells given to rats at intervals of 1 to 10 days was examined. If W256 cells were injected on both occasions, the second inoculum failed to grow if given into the footpad as early as 1 day, or intravenously as soon as 4 days, after the first administration. However, although a second inoculum failed to grow, it produced significant augmentation of the growth of the primary implant if given during its latent or growth phases. If the second inoculum contained cells from a fibrosarcoma unrelated to W256, its growth was effectively curtailed if the initial inoculum had preceded it by 24 h or more. However, secondary inocula of fibrosarcoma cells did not augment the growth of the primary W256 tumour.


Effect of toxic thioureas on resistance of rats to growth in the lungs of intravenously and intratracheally seeded tumour cells. Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.


The B-vitamin group and the activity of hepatic microsomal mixed-function oxidases of the growing Wistar rat. 1. Male Wistar rats were given isoenergetic, semi-synthetic diets deficient in thiamin, riboflavin, pyridoxine or all the B-vitamins. 2. In rats given these deficient diets the 'sleeping time' induced with pentobarbital (PB) and the 'paralysis time' with zoxazolamine (Zz) were prolonged. 3. The tolerance effect against both drugs was nearly independent of the levels of B-vitamins in the diets. 4. In preparations from vitamin-B deficient animals the activities of the following hepatic microsomal enzymes were reduced: the aliphatic hydroxylase of PB, the aromatic hydroxylases of aniline (EC 1.14.14.1) and of Zz, the N-demethylase of aminopyrine, the UDP glucuronyltransferase (EC 2.4.1.17) of p-nitrophenol. The reactions most influenced were those of 'type-1' substrates, particularly those involving the hydroxylases. 5. The effects observed were caused mainly by deficiency of riboflavin and to a lesser extent of thiamin or pyridoxine.


Protein utilization in rats receiving a low-protein diet with various limiting amino acids. 1. A study was made of protein utilization in rats given a variety of low-protein diets containing (g/kg) egg albumin 18, casein 49, gluten 50, or mixtures of either maize protein and gelatine 58, or casein and gelatin 37, each with supplemental methionine. The diets were limiting in leucine, tryptophan or lysine, or in both tryptophan and the sulphur-containing amino acids. 2. Values obtained for net protein utilization (NPU) at these low levels of nitrogen intake were markedly higher than the amino acid score calculated for the different test proteins, except with casein for which the two values were similar. The NPU values agreed more closely with chemical score values based on the content of S-amino acids or isoleucine in the dietary protein.


Leucocyte ascorbic acid and pregnancy.

Leucocyte ascorbic acid and pregnancy. 1. Leucocyte ascorbic acid concentrations have been measured in 1147 females during early pregnancy and in smaller numbers of women before conception, throughout pregnancy and at 6 months post partum. 2. The leucocyte concentration in the 1st trimester was found to be affected by season, social class and smoking. Selecting individuals by extremes of social class, season and smoking produced two small populations with almost separate ascorbic acid distributions and mean concentrations of 21.7 and 45.1 microgram/10(8) leucocytes. 3. Early pregnancy had little effect on leucocyte ascorbic acid concentrations but values decreased in the second trimester. However, this was associated with a leucocytosis so that the total leucocyte ascorbic acid content of blood was unchanged. 4. Low ascorbic acid concentrations during the 1st trimester were not associated with subsequent spontaneous abortions, still-births or neonatal deaths, but there was an increased frequency of low values in women who gave birth to infants smaller than 3250 g. 5. The adequacy of ascorbic acid reserves in early pregnancy is discussed.


Serum cholesterol, triglycerides and heart disease of nomadic and sedentary tribesmen consuming isoenergetic diets of high and low fat content. 1. The effects were examined of two approximately isoenergetic diets differing widely in saturated fat content on the levels of serum cholesterol and triglycerides of nomads and non-nomads in eastern Niger. Each person was also examined for clinical and electrocardiographic evidence of heart disease. 2. No significant differences could be found between serum cholesterol and triglyceride levels of 297 Anagamba nomad men consuming 73% energy as fat and 303 Kanouri sedentary men consuming 9% energy as fat. 3. Rheumatic heart disease was common in nomads and four possible cases of ischaemic heart disease were found in sedentary men only.


The effects of dietary nitrogen level on the collagen of rat skin. 1. Male rats of approximately 120 g body-weight were maintained on a commercial stock diet containing 204 g crude protein (nitrogen x 6.25)/kg, a hydroxyproline-free high-protein (HP) diet containing 200 g casein/kg as the only protein source, or a low-protein (LP) diet containing 40 g casein/kg. After 6 weeks on these diets half of each group was transferred to a non-protein (NP) diet and the experiment was continued for a further 6 weeks. Animals from each group were killed at 4 d, 3 weeks and 6 weeks after the transfer to the NP diet. 2. Throughout the experiment the urinary excretion of N, hydroxyproline and creatinine, and the content and solubility of the skin collagen were determined. 3. When compared with a control group killed at the beginning of the experiment the rats maintained on the LP diet showed an increase of 25% in total N content of the skin but collagen content increased by 100%. Rats transferred from the HP to the NP diet lost both N and collagen from the skin, but those transferred from the LP to the NP diet lost N but increased the collagen content by 42%. 4. Protein deprivation brought about marked changes in the solubility of the skin collagen, suggesting an increase in the rate of maturation of skin collagen.


Efficiency of use of nitrogen from dried microbial cells after a period of N deprivation in growing pigs. 1. Semi-synthetic diets, with dried microbial cells (Pruteen) as the nitrogen source, were used to measure N retention in 50 kg pigs which had been given only sufficient N (5.3 g/d) to maintain N equilibrium for the previous 12 d. Control pigs were given 33.2 gN/d. 2. Metabolic faecal N losses were 1.62 g/d (1.2 g/kg dry matter eaten) and endogenous urinary losses were 3.90 g/d. 3. Realimentation of N-deprived pigs was achieved with diets providing 20.0, 33.2 and 67.4 g N/d and daily rates for N retention were 11.2, 17.8 and 25.9 respectively; the corresponding value for control pigs was 15.0 g. 'Catch-up' protein growth was demonstrated in pigs given both 33.2 and 67.4 g N/d. In the former instance, this was associated with an increase in the efficiency of utilization of dietary N. 4. The biological value of the protein in Pruteen was 0.85, and it appeared that under conditions of increased demand for N the pig could utilize some of the nucleic acid-N fraction of this protein source.


The nutritional and metabolic impact of gamma-linolenic acid (18:3omega6) on cats deprived of animal lipid. 1. The syndrome induced by depriving cats of animal lipid is partially cured by feeding 18:3omega6. This is associated with an increase in levels of 20:3omega6, but not 20:4omega6, in plasma phospholipids. 2. It is concluded that the cat lacks delta5 desaturase activity and has a dietary requirement for 18:3omega6 and possible 20:4omega6.


Influence of overfeeding on growth, obesity and intestinal tract in young chicks of light and heavy breeds. 1. Heavy-breed (HB) chicks differed from light-breed (LB) ones in their propensity to be overfed. Whereas in the LB chicks the amount by which they could be overfed reached 70% more than the food consumed daily by the ad lib.-fed chicks, in the HB chicks the maximal excess was only 13%. 2. Overfeeding caused a slight but statistically significant increase in the linear growth rate (shank length) of the LB chicks, with an opposite effect in the HB chicks. 3. Overfeeding increased the weight of the crop, proventriculus, small intestine, pancreas, liver and adipose tissue but had no such effect on the heart, cerebrum or cerebellum. 4. Overfeeding had no effect on the specific activities of the pancreatic digestive enzymes, liver xanthine dehydrogenase, or tryptophan oxygenase (EC 1.13.1.12). The increase in the total activities was due entirely to organ hypertrophy. 5. Obesity induced in young chicks had no residual effects on the adult LB chicks, but reduced the linear growth of the adult HB chicks. 6. An explanation for the difference between breeds in response to overfeeding at an early age is discussed.


Effect of leucine at different levels of pyridoxine on hepatic quinolinate phosphoribosyl transferase (EC 2.4.2.19) and leucine aminotransferase (EC 2.6.1.6) in rats. 1. Effects of incorporating 30 g leucine/kg into diets on quinolinate phosphoribosyl transferase (QPRT; EC 2.4.2.19) activity and leucine aminotransferase (EC 2.6.1.6) activity were studied in groups of rats receiving 5, 30 and 60 micrograms of pyridoxine/10 g diet. 2. The results indicated that 30 g leucine/kg diet significantly reduced the QPRT activity when the diets provided 5 micrograms pyridoxine/10 g and that the effect was only marginal when the diet included 30 micrograms pyridoxine/10 g. The inhibitory effect was completely absent when the diet provided higher amounts of pyridoxine (60 microgram/10 g). 3. These results suggest that additional amounts of pyridoxine are necessary to counteract the effects of excess of leucine in the diet. 4. Leucine aminotransferase activity was increased in rats given diets containing higher amounts of pyridoxine; supplementary leucine also increased the enzyme activity.


Quantitative aspects of the transformations of sulphur in sheep. 1. [35S]sulphate was used to obtain quantitative estimates of the transfer of sulphur between the blood, rumen and postruminal tract of four sheep given brome grass (Bromus inermis) pellets or lucerne (Medicago sativa) pellets at the rate of 33 or 66 g/h. Sodium sulphate (0-4 g S/d) was infused into the rumen or abomasum of sheep given brome grass during four periods of 19 d and was not infused into the sheep during a subsequent period in which lucerne was given. The flow of sulphide, sulphate, microbial S and non-microbial organic S from the abomasum was estimated using 103Ru and 51Cr. 2. The concentration of inorganic sulphate in serum was increased to maximum values of 35-46 mg S/l by infusion of sulphate into the rumen or abomasum. The rate of irreversible loss of serum sulphate and rumen sulphide was positively related to the amount of sulphate infused. 3. Reabsorption of sulphate by the kidney reached a maximum of 0.69-1.1 mmol sulphate/l glomerular filtrate. 4. The transfer of sulphate from blood to the rumen was related to the concentration of inorganic sulphate in serum, attaining maximum values of 133 (+/- 13) mg S/d for sheep given brome grass plus sulphate, and 127-159 mg S/d for sheep given lucerne. 5. Bacteria derived 0.52-0.67 of organic S from rumen sulphide in sheep given brome grass, and approximately 0.45 of bacterial organic S was derived from sulphide for sheep given lucerne. Protozoa derived approximately 0.90 of organic S from bacteria. 6. It was estimated that endogenous organic S contributed 300-340 mg S/d to the rumen, and that 0.24-0.45 of S digested in the rumen was derived from endogenous sources.


The influence of the gut microflora and of dietary fibre on epithelial cell migration in the chick intestine. 1. The renewal of the intestinal mucosal epithelium has been investigated in germ-free and conventional chicks given a practical chick diet and a low- and high-fibre diet, using tritiated thymidine to label the nuclei of mucosal cells undergoing division. 2. Villus height, crypt depth and number of mitoses in the crypt were generally, although not always significantly, greater for conventional chicks than for germ-free chicks at all sites investigated in the intestine, and all became progressively lower from the upper intestine to the lower intestine. 3. There was a linear relationship between the height of the radioactively labelled mucosal cells on the villus and the period after injection, and the rates of epithelial cell migration were higher for conventional than for germ-free chicks, the relative differences being greater in the lower intestine than the upper intestine. 4. The inclusion of wheat bran as a source of dietary fibre had no effect on the rate of epithelial renewal, either in germ-free or conventional birds.


Inhibition of lipase adsorption at interfaces. Role of bile salt micelles and colipase. The effects of bile salts and colipase on the adsorption of lipase at an interface were studied by hydrophobic affinity chromatography on phenyl- and octyl-Sepharose. In the absence of bile salts, lipase or colipase binds separately to the gel. This is unchanged in the presence of adsorbed bile salts, when one bile salt molecule is associated per hydrophobic ligand. The same data are obtained in the presence of monomeric bile salt solutions. In contrast, lipase adsorption is totally prevented in a micellar bile salt solution. These results favor the idea that the formation of a lipase-bile salt complex in solution is responsible for the lack of interfacial lipase adsorption.


In vitro metabolism of 4-chlorobiphenyl by control and induced rat liver microsomes. The in vitro metabolism, mechanism of metabolism, and macromolecular binding of a monochlorobiphenyl component of commercial polychlorinated biphenyls (PCB) have been investigated. 4-Chlorobiphenyl was metabolized by rat liver microsomes in the presence of NADPH to yield a major metabolite, 4'-chloro-4-biphenylol, and a number of minor metabolites. The metabolism of deuterium-labeled 4-chlorobiphenyl proceeded with the NIH shift of the isotope and no observed isotope effect thus indicating the intermediacy of an arene oxide. Noninduced rat liver microsomes mediated the covalent binding between the 4-chlorobiphenyl and 4'-chloro-4-biphenylol substrates and endogenous microsomal protein. Prior in vivo administration of a commericial PCB preparation, Aroclor 1248 (Monsanto Chemical Co., containing 48 percent by weight of chlorine), resulted in an induced microsomal preparation which significantly increased the substrate-protein binding. The effect of various inhibitors on protein binding was investigated. Aroclor 1248 induced microsomes mediated binding of 4-chlorobiphenyl to endogenous and exogenous nucleic acids, indicating a possible mechanism for the previously reported mutagenic action of this chlorobiphenyl. The spectral properties of Aroclor 1248 induced cytochrome P-450 were investigated and compared with the pentobarbital-induced cytochrome fraction.


Conversion of oxyhemoglobin to methemoglobin by organic and inorganic reductants. Human oxyhemoglobin is converted to methemoglobin by a wide array of organic and inorganic reductants. Depending upon the concentration and nature of the reductant, varying amounts of deoxyhemoglobin are produced. The general overall sequence is: FeO2 leads to (1) FeIII leads to (2) FeII. The intermediacy of methemoglobin can be demonstrated by direct spectral observation and by cyanide trapping. For organic reductants, the second-order rate constants for (1) vary from greater than 300 (phenylhydroxylamine) to 1.4 X 10(-4) M-1 s-1 (malononitrile). Generally the rates parallel the ease of hydrogen abstraction by iron-bound oxygen from the substrate, and simply hydrocarbons are reactive. Rates for these processes have been ascertained with recrystallized protein, lysed cells, and intact human erythrocytes. At room temperature oxyhemoglobin quantitatively converts benzaldehyde to benzoic acid and hydroquinone to benzoquinone. Rates for inorganic species (process 1) range from greater than 7 X 10(3) (chromous ion) to 0.015 M-1 s-1 (ferrocyanide). Ferrous ion rapidly deoxygenates oxyhemoglobin by direct attack on the oxy complex but methemoglobin is not an intermediate with this reagent. Taken together the results support the theoretical prediction that reductants should oxidize oxyhemoglobin, and they demonstrate at least some degree of radical character to the oxy complex.


Oxidation-reduction reactions of hemoglobin A, hemoglobin M Iwate, and hemoglobin M Hyde Park. The kinetics and equilibrium of the redox reactions of hemoglobin A, hemoglobin M Iwate, and hemoglobin M Hyde Park using the iron (II) and iron (III) complexes of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetate (CDTA4-) as the reducing and oxidizing agents have been studied. With respect to the equilibrium it was found that hemoglobin M Iwate (where the beta chains were reduced) was more readily reduced than hemoglobin M Hyde Park (where the alpha chains are reduced). This difference was shown to be a result of a difference in the rate constant for reduction but not oxidation. The observed rate contants for the reduction of all three hemoglobins were shown to decrease with increasing pH. This was attributed to a decrease in the [T]/[R] ratio. The observed rate contants for the oxidation reaction were shown to increase with increasing pH. Accompanying this increase was a change in the kinetic profile for hemoglobin A from pseudo first order to one in which the rate increased as the extent of reaction increased. Inositol hexaphosphate had no effect on the rate of oxidation of deoxyhemoglobin A. This was a result of binding of FeCDTA2- or HCDTA3- to the protein. However, in the presence of inositol hexaphosphate, the reduction of methemoglobin A exhibited biphasic kinetics. This result was interpreted in terms of the production of a small amount of a conformation which was more readily reduced.


Magnetic resonance studies of the binding site interactions between 19F-labeled nitrophenyl haptens and specific mouse myeloma immunoglobulin MOPC-315. The interactions between MOPC-315, a mouse myeloma protein with specificity for nitrophenyl haptens, and 19F-substituted haptens have been investigated using nuclear magnetic resonance (NMR) spectroscopy. The haptens studied are mono- or dinitrophenyl derivatives of gamma-aminobutyric acid, lysine, or glycine which have trifuoromethyl groups attached to the phenyl rings. Upon binding to immunoglobulin, the 19F nucleus experiences a downfield shift whose magnitude depends on the position of the trifluoromethyl group on the phenyl ring but is independent of other structural changes in the hapten such as the number of nitro groups attached to the phenyl ring. Further, the chemical shift of bound hapten is not influenced by the amount of the constant region attached to the binding site; we accordingly conclude that the presence of the distal, constant regions of the immunoglobulin molecule does not influence binding site interactions.