Sociobiological theories of kin selection and reciprocal altruism and their relevance for psychiatry. The revelance of sociobiology to psychiatry is examined through a consideration of the theories of kin selection and reciprocal altruism. Predictions developed from these theories are compared with currently available mental-health statistics. The theory of kin selection is used to predict a positive correlation between mental health and the existence of an active kin-support system. Similarly, the theory of reciprocal altruism is used to predict a positive correlation between mental health and the existence of an active friend-support system. The findings tend to support both sets of predictions in that individuals with access to kin-support and/or friend-support systems are less likely to be hospitalized with psychiatric disorders than are individuals without access to such systems. Sociobiology may be useful to psychiatry in that in some cases it provides: a) a new focus on the adaptive functions of human behavior which may serve to aid the psychiatrist in evaluating individual problems; b) functional predictions which may help to identify segments of the population which are more at risk for psychiatric disorders than others, thereby providing guidelines for preventive psychiatry; and c) direction for research into unexplored aspects of human social relationships and their relevance to psychiatric disorders.


The overlapping territories of psychiatry and ethology. There have been numerous attempts since 1965 to stimulate more utilization of ethological methods and concepts in psychiatry. This literature is reviewed and an attempt is made to identify the factors which have inhibited an enhancement of this interaction to date. Most of the previous articles on this subject have appeared in edited collections, rather than in more widely circulated psychiatric or medical journals. Some of the articles focus on ethological theory, others on ethological research findings, and several on clinical analogies between animal and human situations. Regarding the specific way in which to integrate ethological thought into psychiatry, most frequently a phylogenetic approach is emphasized, however a few authors stress methodological considerations. In this paper, it is argued that artifactual differences have been the primary impediment to more interaction between these two rather similar fields. Scientific language difficulties, educational differences, and personal factors are described in this regard. Also, the real differences in approach and methodology, relative interest in normal vs. abnormal behavior, the degree of willingness to accept a phylogenetic approach, and the breadth of behavior being studied by the two fields are described. Examples of current areas of applicability of ethology to psychiatry are given: the attachment systems, early infantile autism, methodology, social psychiatry, and psychiatric education. Of these, the area where the most utilized is that of the occurred and in which the findings of ethology have been the most utilized is that of the attachment systems. Clinically applicable studies based upon the premise that attachment systems exist as understood ethologically are reviewed. These include study of extra physical contact between mothers and infants at birth, the prediction of child abuse and neglect utilizing observations from the immediate postpartum period, the treatment of failure to thrive by teaching attachment behavior, and developmental differences at 1 year correlated with differences in maternal responsiveness at 3 months. The usefulness of a biological approach to behavior is discussed, particularly in terms of utilizing operational criteria and from the point of view of differentiating etiological, phenomenological, and treatment models. A curriculum stressing the writings of Tinbergen, Lorenz, Bowlby, and Hailman is presented for possible use in psychiatric training programs interested in teaching an ethological approach to psychiatry. A briefer curriculum is also suggested from the psychiatric literature for use by ethologists. The epistemology and methodology of ethology possible will be of more use to psychiatry than the content. It is the opinion of the authors that the difficulties which have inhibited significant cooperation between psychiatry and ethology in the past are mostly artifactual, that such cooperation could be useful to both fields, and that a beginning to such interaction will require mutual familiarity with the literature.


An ethological view of human adolescence. In modern times the essential "normality" of adolescence has been acknowledged. With its pan-cultural and functional perspective, ethology is in a position to elaborate a description of normal human adolescence. Ethologists attempt to elucidate four interrelated aspects of a given behavior: its survival function, evolution, development, and elicitation by internal and external factors. The basic research strategy is two-fold: to identify biologically based, or evolved, behaviors (chiefly by controlling for the effects of experience and seeing if a core of evolved behavior remains); and to discover their functions by isolating the necessary and sufficient ecological conditions for their evolution. Applying this evolutionary analysis to human adolescence, we find that two developments seem to be basic: reproductive maturation and gaining independence from parents. The remainder of the article is an interpretation of various behavioral, morphological, and cultural data in accordance with these two developmental functions. Puberty seems to be timed so as to promote these functions most effectively. Pubertal changes parallel somatic growth and are delayed by poor nutrition, disease, and psychological stress--patterns consistent with functional considerations. The influence of natural selection on the sequencing of pubertal events is also emphasized. The role of pubertal hormones in altering behavior as well as morphology is illustrated. The adolescent gains independence from his parents by means of maturation and sex differentiation. Males become specialized for vigorous exertion, and females for work near the settlement--although considerable overlap in morphological and behavioral tendencies exists between the sexes. Various examples of sex differentiation demonstrates how morphological, behavioral, and cultural factors complement each other. Adolescent initiation rites help channel boys and girls into appropriate adult roles, teach respect for one's culture, and favor the fittest individuals. Hopi rites of passage are described as an example. Reproductive maturation likewise involves adaptive morphological and behavioral changes that are reinforced by cultural mores. Males rely on intimidation more than females, in order to dominate other males and attract females; contrariwise, females employ an endearment strategy more than males do. Many sex differences in human reproductive behavior can be explained with reference to man's parental behavior pattern. These include the male's greater aggressiveness, the preponderance of polygyny over polyandry, and differences in the antecedents of jealousy. Lastly, the need for an ethological understanding of adolescence is underscored as promising to offer a useful perspective on the problems of U.S. youth.


An ethological analysis of manic-depressive disorder. Hospitalized manic-depressive patients were studied using ethological techniques. Within the sample three subgroups were created: a) manic patients whose psychiatric condition improved during the course of hospitalization (N = 3); b) manic patients who showed little or no improvement (N = 3); c) depressed patients (N = 2). Time-sampling procedures were employed to monitor the occurrence of a wide variety of behaviors in various parts of the hospital. Data were analyzed in terms of behavioral diversity, frequency, constancy, and profiles of behavior. Findings included: a) distinctive patterns of behavior characteristics of manic and depressed patients: manics had higher frequencies for most behavioral categories: b) characteristic patterns of behavior for patients who improved as compared to patients who showed no improvement: manic-improved patients showed a marked decrease in diversity as hospitalization progressed. Theoretical and clinical implications are discussed in relation to the kinds of data typically generated from ethological investigations.


Vasovagal syncope in aircrew. Psychosocial aspects. Twenty-four aircrew members with the diagnosis of vasovagal syncope were compared to 26 controls on variables of personality characteristics, psychosocial antecedents to the onset of their conditions, and hyperventilation experience. The syncope group was found to be younger, slightly less adaptable, and to have significantly more negative feelings about their work. The authors argue that syncope in aircrew should be considered from a psychosocial perspective as well as from a medical-neurological perspective.


Multiple group rape: psychosocial considerations. Psychiatric examination of the participants in repeated episodes of rape demonstrated that sexual assault combined with stealing represents symbolically an attack upon the bad mother, such hostile acting out enabling the individual to defend against strong, but ambivalent, wishes to be nurtured. Separation from home in each case was considered a crucial precipitant of such behavior. It is suggested that exhibitionistic-voyeuristic conflict may be an important determinant of whether or not rape is committed in group fashion.


The fear of object loss, responsiveness to subliminal stimuli, and schizophrenic psychopathology. Thirty schizophrenic patients were seen individually for three sessions in a balanced design. In each session, following subliminal stimulation with a neutral stimulus, a baseline assessment of pathology was made. Then, in different sessions, in counterbalanced order, each patient received one of three experimental (or "critical") stimuli: a) a neutral control stimulus; b) a message--CANNIBAL EATS PERSON--intended to activate aggressive ideation; c) a message--I AM LOSING MOMMY--intended to activate fantasies of object loss. Each of these conditions was followed by an initial and later assessment of pathology, and finally by a measure of the patients' sense of differentiation from a mothering figure. In the final session other measures were also obtained, including each patient's conscious association to the critical stimuli when presented supraliminally. The major results were: a) as in previous experiments, the subliminal aggressive message intensified pathology and aggressive ideation--especially for relatively undifferentiated and relatively nondefended patients; b) subliminal stimulation of fantasies of object loss also increased pathology--especially for nondefended patients--and also increased the patients' sense of merging with the mothering object; c) the patients' response to subliminal stimuli--including presumably neutral ones--was a function of the conscious meaning(s) of such stimuli. It was concluded that: a) the threat of object loss (real or fantasied) may be one of the motivations supporting the development of pathology in schizophrenics; b) the activation of fantasies of aggressive destruction can exacerbate schizophrenic pathology--perhaps by activating fantasies of object loss; c) future research with subliminal stimulation should consider carefully the differential responsiveness of subjects to the content of particular messages.


Analysis of patient states and state transitions. Psychiatric diagnoses and formulations have classically focused on the chief complaint of the patient as part of a larger pattern of episodes and reactions. This is a form of state analysis in which the problem states of a person are carefully described and distinguished from other states. The authors suggest methods for deepening such formulations by grounding description of problem states in models of other states and models of state transitions. The resultant method of state analysis can be applied to examination of change processes during treatment as well as to initial diagnostic formulations. As an example of its use and possible extension to quantification, state analysis is applied to description of status and change in a person treated by brief psychotherapy. Because state analysis is based on observable behavior and reportable conscious experiences, it serves as a useful beginning point upon which to anchor more extended inferences about psychodynamics.


Angiomas of the spinal cord: review of the pathogenesis, clinical features, and results of surgery. Twenty-four patients with angiomas of the thoraco-lumbo-sacral region of the spinal cord, which characteristically occur in elderly men and are situated on the dorsum of the cord, were subjected to surgery after diagnosis by selective arteriography. It is suggested that in this variety of angioma the operation produced its effect by eliminating the raised pressure in the venous and capillary vessels within the spinal cord. There was no evidence of an arterial "steal." In all cases, followed up for a mean of five years, progression of neurological symptoms was arrested but, apart from motor disability and pain, any improvement among this already seriously disabled group was small. Diagnosis in the early stages is difficult but the history of mechanical factors exacerbating the symptoms and which occur in the majority of patients should suggest the presence of such a lesion and indicate the need for myelography. Any improvement in results can only come from greater awareness of the condition leading to earlier diagnosis and operation.


Diagnosis and management of tuberculous paraplegia with special reference to tuberculous radiculomyelitis. Paraplegia occurred in eight of 17 patients with central nervous system tuberculosis. In six of these paraplegia was the presenting feature. Paraplegia may complicate tuberculous meningitis, or vertebral tuberculosis, but it may also occur, as in three of our cases, as a primary localised spinal tuberculous radiculomyelitis. These cases are presented in relation to the concept that paraplegia complicating these forms of tuberculosis is caused by radiculomyelitis.


Brain damage complicating septic shock: acute haemorrhagic leucoencephalitis as a complication of the generalised Shwartzman reaction. The neuropathological findings in six patients who developed neurological signs after the onset of "septic shock" caused by Gram-negative septicaemia are described. The changes in the brains were characteristic of acute haemorrhagic leucoencephalitis, and there was evidence, particularly in the kidneys, of disseminated intravascular coagulation with tubular necrosis and, in some, appearances indistinguishable from membrano-proliferative glomerulonephritis. It is agreed that acute haemorrhagic leucoencephalitis is another manifestation of a generalised Shwartzman reaction, and it is suggested that activation of complement is the final common pathway that produces tissue damage in the brain and kidney.


Electrical properties of motor units in Parkinsonism and a possible relationship with bradykinesia. The electrical activity of single motor units was recorded from the first dorsal interosseous muscles of nine patients with Parkinson's disease. Six of these patients had a combination of the following abnormal motor unit properies: (1) a variable delay period of 20 seconds to 3 minutes between the initiation of voluntary effort and the recruitment of the first group of motor units; (2) after recruitment, some of the motor units stopped firing for durations of 10s, 40s, 75s... 3 min.; (3) some of the motor units fired at abnormally low frequencies of 2-3 per second. All these six patients had slowed finger movement, and five of the six were studied while off levodopa for two to seven days. One of these patients, reinvestigated after levodopa therapy had been restarted, demonstrated improvement in motor unit control. The three remaining patients who were studied while on uninterrupted levodopa therapy could make rapid finger movements, could recruit motor units without delay, and could fire recruited motor units continuously at normal frequencies of 6-14 per second. These results suggest that levodopa therapy is effective in Parkinson's disease at least partly because of its ability to correct abnormalities in the recruitment of motor units. Levodopa also corrects the abnormal motor unit firing pattern. The abnormal motor unit properties found in these patients could account for some aspects of bradykinesia.


Uraemic myoclonus: an example of reticular reflex myoclonus? Two patients are described who developed action, reflex myoclonus during acute renal failure. In both cases the myoclonus was abolished after the intravenous administration of clonazepam. We suggest that the characteristic action myoclonus, which occurs in both acute renal failure and postanoxic encephalopathy, is caused by a disturbance of function in the lower brainstem reticular formation.


Regional impairment of cerebral oxidative metabolism in Parkinson's disease. Twenty-two patients affected by idiopathic Parkinsonism were studied using the oxygen-15 inhalation technique. The production of labelled metabolic water was found to be decreased in the parietal cerebral cortex, indicating an impairment in oxidative metabolism. This metabolic defect was localised mainly to the parietal cortex of the affected hemispheres; in non-affected hemispheres of patients presenting with unilateral Parkinsonism, the uptake was normal. In contrast, regional blood flow was not significantly altered. It is possible that this metabolic impairment is caused by chronic deafferentation.


Tactual and auditory vigilance in split-brain man. Two studies are reported of tactual and auditory vigilance performance in patients with a split-brain or partial commissurotomy to examine the attentional behaviour of the right and left hemisphere, and to identify defects in attention which may be related to the division of the cerebral commissures. The performance of the right hemisphere on all tasks of sustained attention so far studied was substantially better than that of the left. Considerable depletion of concentration was observed for the total split-brain group but not in patients with partial commissurotomy. One of the more unusual phenomena of the split-brain condition is that gaps of attention, often lasting many seconds, occur predominantly on the left hemisphere. The switch to a different type of signal on the same hemisphere does not stop them but the switching of signals from one hemisphere to another does. The defect is interpreted as a failure of attention peculiar to the individual hemisphere under test.


Value of EEG in acute confusional states. Electroencephalograms of 95 patients with an acute confusional state, referred over three years, were studied to determine their usefulness. The majority were abnormal, and those from patients with intracranial pathology often showed asymmetry of delta activity and paroxysmal discharges. These, and other features, suggested that the EEG was a helpful investigation.


Beats produced between a rhythmic applied force and the resting tremor of Parkinsonism. Rhythmic forces have been applied to the wrist of patients with Parkinsonism tremor by means of a printed motor. The tremor rate was not altered to that of the applied force. On the contrary, beats were established, the rate of which depended on the difference in rate between the tremor and the applied rhythm. Most of the observations have been for horizontal motion of the hand but similar phenomena have been seen for vertical movements, and for other parts of the body--for example, foot, elbow, finger joint, and head. The observations are regarded as supporting the view that the tremorgenic mechanism is central. There was no electromyographic evidence of servo driving or servo assistance in the genesis of the tremor.


Serial recording of visual and somatosensory evoked potentials in multiple sclerosis. Pattern reversal visual evoked potentials (VEP) and short-latency somatosensory evoked potentials (SEP) were recorded at frequent intevals in 7 patients with multiple sclerosis (MS). A persistent increase in latency of VEP was found to accompany evanescent visual symptoms. SEP, whether normal or abnormal, remained stable in patients without relapse. In 3 patients with active disease the cervical SEP was labile but this could not be related to specific clinical changes. In 51 patients VEP were recorded on two or more occasions at varying intervals. There was a reasonable correlation between alteration in visual acuity and in VEP. The return of abnormal latency to normal values was seen on 9 occasions. In 27 patients in whom SEP were similarly recorded the potentials became more abnormal in the majority of those with relapse involving the spinal cord but SEP did not return to normal with remission. It was concluded that the use of EP for diagnostic purposes in MS depended on persistence of abnormalities during quiescent phases of the disease and that this property was incompatible with the use of these techniques as an effective means of monitoring the course of the disease.


Experimental ischemic myopathy. Effects of aortic ligation and serotonin. Support for the hypothesis that biogenic amines are involved in the production of muscle diseases comes from a report that rat muscle is damaged by combining distal aortic ligation with serotonin injection. Our studies explore the role of serotonin in the production of the myopathic changes in the aortic ligation-serotonin model. Twenty-six young Sprague-Dawley rats were subjected either to aortic ligation alone, aortic  ligation followed by injection of serotonin (40 mg/kg, i.p.), or injection of serotonin alone. Following sacrifice 7--14 days later, 10 micrometer frozen sections of the soleus muscle were stained by trichrome, NADH-TR, and ATPase methods. Focal necrosis and phagocytosis or focal regeneration were seen after aortic ligation with, or without, subsequent serotonin injection. Serotonin alone produced only occasional mild changes in muscle. Therefore, we conclude that the significant damage to muscle in the ligation-serotonin model is provided by the aortic ligation, not the serotonin injection.


Arteriovenous aneurysm of the vein of Galen. A clinical, angiographic CT scan and neuropathological study. An autopsied case of arteriovenous aneurysm of the vein of Galen in a 31/2-month-old female is reported. Arteriovenous aneurysm of the vein of Galen is a rare vascular malformation of the central nervous system consisting of a saccular dilatation of the vein which receives blood shunted through enlarged arteries. These peculiar structural and hemodynamic characteristics differentiate this particular malformation from the other AVMs of the central nervous system. In infants the arteriovenous aneurysm of the vein of Galen is characterized clinically by hydrocephalus and cardiomegaly. In the present paper the clinical features and diagnostic indications are discussed and, in particular, the role of computerized cranial tomography (CT) is emphasized as a rapid and noninvasive procedure for detection of intracranial disorders.


Electromyographic recording and muscle biopsy in lepromatous leprosy. The aim of this study was to detect early muscular changes in lepromatous leprosy using simultaneously electromyography and muscle biopsy. In 13 subjects a single clinically normal muscle innervated by the popliteal nerve was studied. Three were found to be normal. All the others were electromyographically denervated. Histopathologic findings included only 3 cases of fascicular atrophy. In 8 cases inflammatory nodules were observed in the connective tissue of the muscle and acid-fast bacilli were present in Virchow cells in 5. In only one patient were intact acid-fast bacilli found in muscle cells. It was concluded that electromyography was the better method of detecting early denervation, while muscle biopsy was the better examination to detect "lepromatous myositis". In practice these techniques are complementary in the study of muscle data in lepromatous leprosy.


Carnitine palmitoyltransferase II deficiency with normal carnitine palmitoyltransferase I in skeletal muscle and leucocytes. Deficiency of carnitine palmitoyltransferase II (CPT II), was found to be the cause of the syndrome of muscle pain and myoglobinuria following strenuous exercise in an otherwise healthy young man. During fasting, serum creatine kinase remained low and ketogenesis was normal. The clearance of a fat emulsion and the activity of extrahepatic lipoprotein lipase was lowered, while the hepatic lipoprotein lipase was normal. A skeletal muscle biopsy did not show abnormal lipid storage. CPT II was deficient in skeletal muscle and leucocytes, while CPT I activity was normal and exhibited normal kinetic properties. CPT I has a higher affinity for palmitoylcarnitine than CPT II, and is more inhibited at increasing palmitoylcarnitine concentrations. In erythrocytes only CPT I is present.


An intravenous 133xenon clearance technique for measuring cerebral blood flow. An intravenous 133Xe clearance technique for measuring cerebral blood flow (CBF) is described. Results obtained compared well with those using the intracarotid 133Xe technique. The reproducibility of the method was checked by repeating measurements within a few hours in 14 patients, when no significant overall change occurred, and after some days in 23 patients when a mean fall in flow of 8% was observed. CBF was measured in 52 control subjects. The mean fast component flow (Ff) was 68.6 ml/100 g/min (SD 11.3). No difference between the two hemispheres was found. Flow was confirmed to be higher anteriorly in the cerebral hemispheres. A significant inverse correlation was found between CBF and age.


Increased prostaglandin synthesis in childhood diabetes mellitus. Prostaglandins are synthesized from the fatty acids, linoleic and arachidonic acids, and are associated with increased platelet aggregation as has been found in blood from patients with diabetes mellitus. In the present study blood was obtained from 40 children with diabetes and from 20 control children for measurements of fatty acid and PGE1, PGE2, and PGF2alpha levels. The production of PGE2 and PGF2alpha was significantly elevated in blood from the children with diabetes at all times measured. The mean quantitative plasma linoleic acid levels were also higher in the patients. The increased PG synthesis may be related to the vascular problems that occur in patients with diabetes.


Serum concentrations of 24,25(OH)2D in uremic children: a reflection of renal function. The mean serum concentration of 24,25(OH)2D determined by competitive protein-binding radioassay was significantly lower in ten uremic children maintained on hemodialysis (0.82 +/- 0.43[SD] ng/ml) than in ten patients with impaired renal function not requiring hemodialysis (1.30 +/- 0.54 ng/ml, P less than 0.05), or in 12 normal children (2.98 +/- 1.57 ng/ml, P less than 0.01). The serum levels of 250HD were similar in all groups. There were significant (P less than 0.01) positive correlations between the serum concentration of 24,25(OH)2D or the ratio 24,25(OH)2D/25OHD and the creatinine clearance. The serum concentration of 24,25(OH)2D was significantly decreased also in six anephric adults relative to normal adult values. The data indicate that production of 24,25(OH)2D is impaired in subjects with compromised renal function. Inasmuch as the major active metabolite of Vitamin D, i.e., 1,25(OH)2D, is requried for renal synthesis of 24,25(OH)2D measurement of the latter metabolite may provide a convenient method for assessment of renal vitamin D metabolism. The role of this metabolite in the pathogenesis of renal osteodystrophy remains speculative.


An evaluation of methods to monitor infants receiving intravenous lipids. Nephelometric measurement of light-scattering index and visual estimates of turbidity have been advocated to monitor serum Intralipid levels. This study describes a simple modified fluorometric method for accurately measuring lipid particles in serum and examines the reliability of such estimates compared with other chemical measurements. Ten percent IL was diluted with either saline or serum to various concentrations (0 to 250 mg/dl). The LSI showed an excellent correlation with known IL standard solutions in saline or serum (R = 0.99) and with triglyceride concentrations (R= 0.98). One hundred nine blood samples were obtained from 35 patients (28 neonates) receiving IL. An elevated TG, free fatty acid, or cholesterol level could not be reliably predicted from the LSI. The ability of clinical personnel to visually grade the degree of turbidity was evaluated by having them assign a turbidity score of 0 to 4+ to 39 hematocrit tubes which contained clear, hemolyzed, or icteric serum, each of which had IL concentrations varying from 0 to 292 mg/dl. The 15 tubes of identical IL concentration of 99 mg/dl were graded from 0 to 4+ by two of the observers, from 1 to 4+ by three of the observers, and 0 to 3+, 1 to 3+, and 2 or 3+ by one each of the observers. This study shows that (1) in vitro fluorometric LSI correlates well with IL concentrations; (2) in vivo correlations of LSI with FFA, cholesterol, and TG are poor; and (3) personnel are unable to reliably grade turbidity by visual examination of hematocrit tubes. Infants on IL should be monitored by TG and FFA levels.


A therapeutic approach to childhood pelvic rhabdomyosarcoma without pelvic exenteration. A therapeutic approach using chemotherapy rather than radical surgery as the initial modality of treatment was employed in 13 children with pelvic rhabdomyosarcoma. One patient failed to respond to chemotherapy and required anterior pelvic exenteration. Eight patients are alive and free of disease 24 to 96 months after diagnosis. Limited surgery for minimal residual disease was used in two patients. Radiation therapy at lower than conventional doses was used in seven of eight patients. This experience supports a therapeutic approach to childhood pelvic rhabdomyosarcoma with an initial chemotherapy regimen, resulting in the use of surgical procedures less detrimental to pelvic organs without compromising survival.


The hematopoietic effects of prednisone therapy in four infants with osteopetrosis. Sequential hematologic studies were performed in four infants with malignant osteopetrosis who received prednisone. Prednisone therapy resulted in decreased liver and spleen size, decreased numbers of circulating immature blood cells, and increased hemoglobin concentration and platelet counts in all infants. The quantity and quality of hematopoietic tissue in bone marrow biopsies improved during prednisone therapy but showed no significant improvement without therapy. Sequential indium 111 chloride scans in one infant showed increased uptake in long bones and pelvis and decreased uptake in liver and spleen during therapy. We conclude that prednisone therapy of infantile osteopetrosis results in increased bone marrow hematopoiesis and decreased extramedullary hematopoiesis.


Hyperreninemia and secondary hyperaldosteronism in pheochromocytomas. Foremost in the differential diagnosis of hypertension is the identification of surgically correctable lesions. Increased plasma renin activity in a hypertensive patient suggests the presence of a renovascular or renal etiology. We have recently seen two adolescent patients whose hyperreninemia was cuased by a pheochromocytoma. Secondary hyperaldosteronism was an associated finding.


Abnormalities of the complement system in Reye syndrome. Sixteen patients with Reye syndrome had diminished concentration of serum complement proteins and/or hemolytic activity in the earliest blood sample. All 12 studied with hemolytic methods had significantly reduced C1 activity; total hemolytic complement activity was reduced in only three. Low Cl activity was accompanied by equivalent reduction of Cls in 11 of 12 patients; Clq was less than normal in only two of 12. Decreased levels of at least one other classical pathway complement hemolytic activity or protein concentration were found in 13 patients, whereas factor B or the alternate complement pathway was normal or elevated in the ten patients studied. The consistent reduction of Cls protein concentration in Reye syndrome suggests that early metabolic abnormalities regularly affect the production or catabolism of this protein. Although normal serum Clq concentration in the majority of these patients does not support an immune pathogenesis, decreased Clq, C4, and C2 in three patients does suggest that immune mechanisms may be responsible for the serum complement abnormalities in this latter group of patients.


Cell-mediated immunity to varicella-zoster virus infection in subjects with lymphoma or leukemia. Normal subjects and patients with lymphoma or leukemia were tested for the levels of lymphocytes, E-rosette--forming T-cells, serum and vesicle fluid interferon, and specific in vitro proliferative response to varicella-zoster antigen after clinical varicella or herpes zoster illness. The effect of polyinosinic acid/polycytidilic acid on the immune response was also evaluated. The development of VZ specific cell-mediated response in normal subjects was characterized by intense proliferative activity eight to ten days after the onset of illness, with significant decline 70 to 80 days later. The responses in subjects with lymphoma or leukemia were much lower. Few subjects with chickenpox or zoster with lymphoma or leukemia died during the infection. Death was associated with significant depletion of E-rosette--forming T-cells, and grossly deficient specific cellular response to VZ antigen. Treatment with Poly IC frequently induced elevations in serum as well as vesicle fluid interferon levels, and increased the proliferative activity of lymphocytes against VZ antigen.


Epidemiology of subacute sclerosing panencephalitis. The Subacute Sclerosing Panencephalitis Registry has compiled data from 453 instances of SSPE occurring in the United States from 1960 through 1976. The mean annual incidence during this period was 3.5 per 10 million persons under 20 years of age, 2.3 times higher for males than females, and 4.0 times higher for whites than blacks. Although the long-term pattern of incidence is unknown, the incidence of reported SSPE declined dramatically from 1970 to 1976. There are marked geographic variations of SSPE activity within the United States and also a higher incidence for children from farms (9.4 per 10 million persons under 20) compared with children from other rural domiciles (3.7 per 10 million), suburban children (2.9 per 10 million), and inner-city children (1.6 per 10 million). Available epidemiologic evidence suggests that some extrinsic factor, unrelated to measles or measles vaccine, is important in the pathogenesis of the disease.


Transient myocardial ischemia of the newborn infant demonstrated by thallium myocardial imaging. Five term and two premature newborn infants were referred for respiratory distress and congestive heart failure, and were found to have electrocardiographic Q or ST-T abnormalities suggesting ischemia. Echocardiographic and/or hemodynamic assessment excluded anatomic heart disease in six infants. In three infants, moderate or severe hemodynamic impairment within 36 hours of age was suggested by these studies. Myocardial perfusion images in all patients showed very poor myocardial uptake of thallium 201, compatible with global myocardial ischemia. Infants of similar age with myocarditis, or with congenital heart disease and congestive failure, had normal myocardial uptake. Rapid clinical improvement occurred within three to seven days. Two to five months later, all infants were well. Two had persistent electrocardiographic abnormalities but repeat thallium 201 imaging in six demonstrated almost normal myocardial uptake. These data provide further evidence that perinatal respiratory distress may be associated with myocardial dysfunction and congestive heart failure in some infants without anatomic heart disease, and suggest that myocardial dysfunction in these infants is associated with global myocardial ischemia, most of which is transient. The timing and nature of the insult causing the ischemia are unclear.


Arterial oxygen tension during active and quiet sleep in the normal neonate. The effect of sleep state on arterial oxygen tension was determined in ten healthy term infants by means of continuous transcutaneous PO2 monitoring. In all ten infants, PaO2 was significantly lower and more variable during active as compared to quiet sleep. This fall in PaO2 during active sleep was accompanied by asynchronous (or paradoxical) chest wall movement. These findings may be important in our understanding of the higher incidence of apnea during active sleep in both preterm and term infants.


Spontaneous neck flexion and airway obstruction during apneic spells in preterm infants. Forty-three apneic episodes were observed in eight preterm infants, four of whom had a history of spells. Measurements of expiratory airflow and respiratory effort indicated that 36 of 43 spells were mixed, consisting of central apnea preceded or followed by airway obstruction. The episodes occurred more frequently during periods of spontaneous neck flexion. This association can be related to previous studies indicating that neck flexion interferes with neuromuscular regulation of pharyngeal patency and can produce intermittent airway obstruction. Our observations suggest that airway obstruction may be an important factor in the pathogenesis of apnea in certain preterm infants.


Head growth in sick premature infants--a longitudinal study. Serial weekly measurements of somatic growth and head circumference were made for ten weeks on 41 appropriately grown sick preterm infants (gestational age 28 to 32 weeks) with severe neonatal problems. Twenty-seven (66%) required prolonged assisted ventilation. During the period of acute illness, the velocity of growth for the sick infants was below that of the normal fetus, with deviation away from and below the normal fetal growth curve. During recovery, head growth paralleled that of normal fetal growth, and subsequently rapid "catch-up" growth in head circumference occurred. By comparison, six similar infants, whose head circumference followed the intrauterine growth curve, proved to have hydrocephalus. These results suggest that: (1) the brain participates in the growth retardation associated with being sick and premature and that apparently normal head growth under comparable circumstances may be associated with hydrocephalus; (2) in spite of an energy intake ranging from 80 to 120 kcal/kg/day by the end of the second postpartum week, normal growth in the sick low-birth-weight infant does not occur until their acute illness has resolved.


Adolescent secondary amenorrhea: association with hypothalamic hypothyroidism. In adolescent girls, secondary amenorrhea can result from a variety of physiologic and psychologic disturbances. Previous reports associating amenorrhea and primary hypothyroidism have not distinguished between the alternative etiologic roles of thyroxine deficiency and hyperprolactinemia. We have evaluated two girls with secondary amenorrhea who had clinical and chemical evidence of hypothyroidism. Both had low basal T4 values (0.8 and 3.2 microgram/dl), calculated free T4 (0.1 and 0.7 ng/dl), and T3 (51 and 81 ng/dl). Both had undetectable basal TSH with normal TSH response to TRH. Basal FSH and LH values were normal, as was the response to LHRH. Basal prolactin levels were 6 and 14 ng/ml, respectively, and both girls had growth hormone responses of greater than or equal to 15 ng/ml in response to insulin-induced hypoglycemia. Pituitary-adrenal function and reserve were also normal. In neither patient was there any historical, physical, or laboratory features compatible with anorexia nervosa. After treatment with 1-thyroxine, both girls had a resumption in menses. These two adolescent girls thus appear to have isolated hypothalamic hypothyroidism. The associated secondary amenorrhea demonstrates that thyroid deficiency alone, without hyperprolactinemia, can interfere with normal hypothalamic-pituitary-ovarian function.


Adrenal steroids indirectly modulate morphine and beta-endorphin effects. The pharmacological effects of morphine or the postulated physiological opiate, beta-endorphin, were compared in adrenalectomized and sham control animals. Pretreatment of adrenalectomized rats and mice with the synthetic glucocorticoid dexamethasone 2 hr before opiate injections abolished the adrenalectomy-induced sensitization to parenteral opiates. This effect of dexamethasone was completely blocked by cycloheximide, a protein-synthesis inhibitor. After parenteral injection ot tritiated morphine, total tritium counts in the blood and brains of adrenalectomized mice were greater than in sham controls; this effect was also blocked by dexamethasone pretreatment. Administration of SKF 525-A before morphine produced results which suggest that this putative inhibitor of the mixed-function oxidase metabolizing enzyme system also alters opiate potency. Collectively, these studies provide evidence that adrenalectomy causes a decrease in morphine metabolism which enhances the parenteral potency of this opiate through increased bioavailability. Furthermore, the dexamethasone reversal of this effect appears to depend upon its de novo induction of protein components of the opiate-metabolizing system. The possibility that a physiological interplay between endorphins and corticosteroids exists is suggested by the dexamethasone blockade of both the pharmacological effects and the toxicity of intravenous beta-endorphin in adrenalectomized mice.


Morphine persistence in rat brain and serum after single doses. The disposition of morphine in rat brain and serum was determined over 48 hr after subcutaneous doses. Free morphine was measured by a specific assay using 3H-labeling together with high-pressure liquid chromatography separation, with a sensitivity of 1 nM (0.3 ng of morphine per ml). This study revealed the persistence of free morphine in nanomolar concentrations over at least 24 hr after a single analgesic dose. The terminal half-life of morphine elimination was 5 hours. Total radioactivity was retained in the body at much higher concentrations. Similar disposition of [C-1-3H]morphine and [N-14CH3] morphine ruled out any major metabolic alterations at these positions, including N-demethylation. Irreversible binding to insoluble tissue components, which has previously been linked to tolerance, was observed only to the extent of less than 20% of total tissue radioactivity and was not unique to brain tissue. The persistence of morphine and its metabolites may be related to protracted opiate effects such as withdrawal symptoms after addiction.


Inhibition of the enzymatic activity of ligandin by organogermanium, organolead or organotin compounds and the biliary excretion of sulfobromophthalein by the rat. Ligandin binds several classes of compounds, has glutathione-S-transferase activity and is postulated to function in the intracellular transport of substances which bind to it and/or are substrates for its enzymatic activity. The effects of a group of organometals reported to inhibit the enzymatic activity of ligandin on the biliary excretion of sulfobromophthalein have been investigated to determine what role the enzymatic activity of ligandin has with respect to the biliary excretion of the dye. Triethyllead reduced the rate of dye excretion into the bile without affecting blood pressure, blood or liver sulfhydryl compounds or the volume of bile flow. The organometal had no effect on the initial rate of plasma dye clearance. Inhibited biliary sulfobromophthalein excretion by triethylead-treated rats correlated with relative increases in liver and bile unconjugated dye, decreases in liver and bile conjugated dye and reduced glutathione-S-aryltransferase activity in supernatant fractions isolated from the liver. The results clearly demonstrated that the tested organometals can inhibit the enzymatic activity of ligandin in vivo and suggested that, if ligandin has a role in the translocation of the dye from the blood to the liver, the enzymatic activity of the protein may not be involved.


Pharmacokinetics of naloxone and naltrexone in the dog. The serum kinetics of 5 mg/kg of i. v. naloxone or naltrexone were studied in each of two groups of five dogs; serum samples were obtained from 2 min to 2 hr after injection. Serum concentrations were determined by radioimmunoassay. Serum levels of both naloxone and naltrexone fell rapidly; serum half-life during the elimination phase was 71.2 +/- 8.9 min (mean +/- S.E.) for naloxone and 85.1 +/- 9.0 min (mean +/- S.E.) for naltrexone. Although human and dog kinetics are similar for naloxone, naltrexone is long-acting in man, but is quickly dissipated in the dog.


The effect of pregnancy on the biliary excretion of [14C]phenytoin in the rat. The biliary excretion of [14C]phenytoin (DPH) was examined in pregnant and nonpregnant female control rats. After administration of [14C]DPH (1 mg/kg i.v.), the bile concentration (nanomoles per milliliter) and biliary excretion (nanomoles per minute per kilogram) of the glucuronide conjugate of the major primary metabolite of DPH, 5-phenyl-5-p-hydroxyphenyl[4-14C] hydantoin ([14C)]HPPH), was significantly decreased at 15 and 30 min in pregnant rats relative to controls. Bile flow averaged 50 and 70 microliter/min/kg in control and pregnant rats, respectively. The concentration in blood of [14C]HPPH-glucuronide was increased 2 to 6-fold in pregnant rats relative to controls. After administration of [14C]HPPH (10 mg/kg i.v.), the disappearance of [14C]HPPH from the blood, biliary excretion and bile concentration of [14C]HPPH-glucuronide were very similar in control and pregnant rats. The blood concentration of [14C]HPPH-glucuronide was elevated 2 to 6-fold in pregnant rats and the half-life was increased from 43 min in controls to 70 min in pregnant rats. Maximal bile/blood concentration ratios of [14C]HPPH-glucuronide were 630 and 300 in control and pregnant rats, respectively, indicating a decreased ability of the liver to concentrate the glucuronide in the bile in pregnancy.


The relationship of age to the metabolism and protein binding of digoxin in sheep. The relationship of age to the protein binding and metabolism of digoxin was studied in newborn and adult sheep. Protein binding, studied by equilibrium dialysis, varied directly with albumin concentration. The percentage of digoxin bound to protein did not differ with age: 17.2 +/- 1.2% in newborn lambs and 17.6 +/- 1.7% in ewes. The percentage of drug bound did not change significantly over a concentration range of 0.5 to 5 ng/ml. Metabolic studies were performed by thin-layer chromatography on samples of serum, myocardium and urine obtained after animals had been treated for 4 days with [3H]-digoxin. In both newborns and adults, more than 70% of digoxin remained unmetabolized. The mean metabolic composition of all three tissues for newborns and adults, respectively, was: digoxin--80.3%, 77.0%; digoxigenin bisdigitoxoside--9.6%, 12.5%; digoxigenin monodigitoxoside--6.4%, 7.0%; digoxigenin--3.7%, 3.5%. These studies suggest that age-related differences in the effects of digoxin in sheep are not due to variations in drug binding or drug metabolism.


The deleterious effect of Bordetella pertussis vaccine and poly(rI.rC) on the metabolism and disposition of phenytoin. The elimination of phenytoin from blood was significantly decreased in rats pretreated 24 hr previously with Bordetella pertussis vaccine or the synthetic polynucleotide poly(rI.rC.). Phenytoin half-life was increased about 4-fold by both agents. In microsomes prepared from rats pretreated with B. pertussis vaccine or poly(rI.rC) the hydroxylation of phenytoin in vitro was decreased by 36 nad 53%, respectively. The addition of these agents to normal microsomal suspensions had no effect on phenytoin hydroxylation, demonstrating that the decrease in biotransformation was not due to direct enzyme inhibition. The decrease in phenytoin hydroxylation and elimination rate resulted from depressed levels of cytochrome P-450 in the hepatic endoplasmic reticulum of rats treated with B. pertussis vaccine or poly(rI.rC).


Determinants of the renal handling of 2, 4-dichlorophenoxyacetic acid by winter flounder. The factors determining the renal handling of 2,4-dichlorophenoxyacetic acid (2,4-D) were examined in winter flounder, Pseudopleuronectes americanus, using isolated tubules and clearance techniques. In vitro, extensive energy-dependent uptake was seen with tissue/medium ratios of 30-fold at 1 micronM 2,4-D. The velocity of uptake was concentration-dependent with apparent Km and Vmax v,lues of 70 micronM and 3.6 micronmol/g of tubules per hr, respectively. Uptake was inhibited by other organic acids and 2,4-D competitively inhibited p-aminohippurate uptake. 2,4-D did not inhibit organic cation transport by the tubules. In vivo, 2,4-D was actively secreted with clearances of nearly 500 times the glomerular filtration rate at 1 micronM 2,4-D in plasma. At higher plasma concentrations (10-60 micronM) a transport maximum of 0.85 micronmol/g of kidney per hr was observed. Secretion was inhibited by other organic acids. 2,4-D also inhibited p-aminohippurate secretion in vivo. Little metabolism was noted; approximately 10% was excreted as the taurine conjugate. Plasma binding was 70%. Examination of the effects of added proteins on in vitro uptake showed that protein binding could limit 2,4-D transport but that flounder plasma (low in albumin) was far less effective than bovine serum albumin in binding and inhibition of transport. The roles of plasma binding, intracellular binding and metabolism in determining the rate of 2,4-D elimination by the kidney are discussed.


Effect of anesthesia on cardiovascular and renal function in the newborn piglet. The effects of anesthetic agents, nitrous oxide-oxygen, nitrous oxide-oxygen plus ketamine, pentobarbital sodium and halothane, were determined in piglets 6 to 76 hr of age. After observations of cardiovascular and renal function in the unanesthetized state, the drugs were administered and observations were repeated in the anesthetized state. All of the anesthetics caused a decrease in cardiac output and an increase in total peripheral resistance in the newborn piglet. Both nitrous oxide-oxygen plus ketamine and halothane produced a decrease in heart rate while pentobarbital caused an increase and halothane a decrease in systemic blood pressure. Changes in renal function were minimal. Changes in renal blood flow were inconsistent and renal vascular resistance was not modified by any of the drugs. There was little evidence of redistribution of intrarenal blood flow and no significant changes in glomerular filtration rate or sodium excretion. Plasma renin concentration increased after halothane. It was concluded that changes in renal and cardiovascular function due to anesthesia in the newborn were small. Differences between newborn and adult animals may be related to several factors including the state of development of the autonomic nervous system and species differences used in different studies.


Effects of antihypertensive treatment on systolic blood pressure and renin in experimental hypertension in rats. The effects of pretreatment with hydralazine and alpha-methyldopa were assessed in rats made hypertensive by ligation of the left renal artery (LRA). Systolic blood pressure and peripheral renin activity (PRA) were measured 7 and 1 day before LRA and 2, 7 and 28 days after LRA. Systolic blood pressure increased 2 days after LRA in control and alpha-methyldopa-treated rats but not in the hydralazine-treated rats. Peripheral renin activity levels did not correlate with changes in systolic blood pressure. Peripheral renin activity first increased 7 days after LRA but decreased 28 days after LRA despite persistent hypertension in controls and alpha-methyldopa-treated rats. It is concluded that factors other than renin are involved in the initial and maintenance phases of this experimental model. In addition, hydralazine protects the rat with LRA from developing hypertension.


Effects of veratrine on the in situ dog heart: evidence for increased ventricular fibrillation threshold. The present work studied the effect of veratrine on electrical stability of the mammalian ventricles. In a group of anesthetized open-chest dogs we determined the effects of veratrine (0.001-0.3 mg/kg) on the threshold for ventricular fibrillation (VFT), both during sinus rhythm (SR) and during atrial drive (AD) at 166 +/- 7 beats/min. Veratrine (0.3 mg/kg) increased the VFT during SR from control levels of 33 +/- 5 mA to 56 +/- 4 mA (P less than .05) and during AD from 34 +/- 6 to 57 +/- 9 mA (P less than .05). VFTs after infusion of veratrine were higher than in a control group of dogs given the saline diluent in which VFT during SR was 26 +/- 3 mA (P less than .001) and during AD was 24 +/- 3 mA (P less than .005). The increase in VFT during SR was independent of the decrease in heart rate, which fell from 147 +/- 8 to 106 +/- 6 beats/min (P less than .001). It was associated, however, with an increase in the QT interval during SR from control values of 254 +/- 13 to 308 +/- 19 msec (P less than .02) and during AD from 238 +/- 8 to 267 +/- 8 msec (P less than .005). We conclude that small doses of veratrine increase the electrical stability of the ventricles in the normal dog heart.


Cardiovascular and respiratory chemoreflexes from the hindlimb sensory receptors evoked by intra-arterial injection of bradykinin and other chemical agents in the rabbit. Intra-arterial injections of bradykinin into the hindlimb of the rabbit cause two types of cardiovascular reflex effects displayed in succession. The first-type effects appear early and are of inhibitory nature, being represented by systemic hypotension, contralateral hindlimb vasodilation and bradycardia; the second-type effects appear later and are excitatory in nature, consisting of hypertension, hindlimb vasoconstriction and tachycardia and occur closely associated with behavioral manifestations typical of the reaction to pain. Both the depressor and pressor effects are accompanied by hyperventilation. Analogous biphasic reflex responses may be caused by intraarterial injections of potassium ions. On the contrary, hypertonic solutions (NaCl, glucose) usually only produce second-type excitatory responses. No significant cardiocirculatory reflex effects are induced by even high doses of serotonin, nicotine, adenosine, adenosine triphosphate, adrenalin, noradrenalin, angiotensin, vasopressin and oxytocin. General anesthesia greatly inhibits the pressor reflexes and potentiates the depressor responses (to bradykinin and K ions) but does not appear to be a necessary condition for provoking depressor reflexes by chemical stimulation of somatic afferents. Both chemoreflex responses are prevented by sectioning the somatic nerves of the injected limb. Denervation of sinoaortic areas and of cardiopulmonary receptors by bilateral cervical vagotomy or complete removal of the skin from the injected limb does not prevent either type of chemoreflex response. These depressor and pressor chemoreflexes have been ascribed to activation of two functionally distinct types of sensory receptors in the skeletal muscle, differently sensitive to chemical substances and selectively concerned with different patterns of cardiocirculatory reflex response.


Effects of LSD on learning as measured by classical conditioning of the rabbit nictitating membrane response. Acquisition of the classically conditioned, nictitating membrane response was used to assess effects of LSD on learning. Tone and light conditioned stimuli (CS) were presented 800 msec before delivery of the unconditioned stimulus, consisting of a 100 msec electric shock to the skin over the paraorbital region of the head. Extension of the membrane to the CSs in the 800 msec prior to shock onset was recorded as a conditioned response (CR), while extension to shock onset was recorded as an unconditioned response (UCR). LSD (1, 10, 30, 100 or 300 nmol/kg) was injected i.v., 30 min before each daily conditioning session. Dosages of 1 to 100 nmol/kg of LSD produced a dose-dependent enhancement of CR acquisition. Acquisition to a criterion of 10 successive CRs required 184 trials at 30 nmol/kg of LSD as compared to 293 trials with controls. Separate groups of rabbits received explicity unpaired presentations of stimuli (tone alone, light alone and shock alone). The frequency of responding within 800 msec of CS onset or in the 800 msec before shock onset was low (2-3%) and was not affected by any dosage of LSD, indicating that the effects of LSD on acquisition were not due to sensitization, pseudoconditioning or changes in baseline responding. LSD also had no effect on UCR amplitude. Hence, the systematic effects of LSD on acquisition of CRs reflects the action of the drug on learning.


Some measurements of autonomic nervous system influence on production of cerebrospinal fluid in the cat. The effects on cerebrospinal fluid (CSF) production of specific agonists and antagonists for the autonomic nervous system were studied during ventriculocisternal perfusion in cats. Both carbachol and phenylephrine increased the rate of CSF formation 11 microliter/min from control rates of 17 and 11 microliter/min, resepctively; albuterol increased formation 6 microliter/min above the control 16 microliter/min. Atropine or phentolamine administered alone caused slight but significant decreases in CSF production; propranolol had no effect. All three antagonists reduced the changes in fluid formation elicited by their respective agonists. Atropine also blocked the action of phenylephrine. Hemicholinium-3, which reduced the synthesis of acetylcholine, sharply attenuated the increase caused by phenylephrine. These observations were taken to indicate that phenylephrine increased CSF production by stimulating a cholinergic pathway to the choroid plexus. Bilateral electrical stimulation of the cervical sympathetic trunks decreased CSF formation. Agents which increased CSF production caused no significant changes in cerebral or choroid plexus blood flow, possibly indicating that their effect is a direct action on the choroid plexus secretory mechanisms.


The teaching of interpersonal skills in U.S. medical schools. In response to the increasing recognition of the importance of interpersonal skills (IPS) to the physician, there has recently been a rapid growth in the number and variety of medical school teaching programs in IPS. This is a report of a national survey which was part of a study designed to determine the extent and characteristics of IPS-teaching. Most medical schools have specific IPS programs, 80 percent of which are less than five years old. Most teachers in the programs are psychiatrists and psychologists. Most programs teach process (for example, listening, responding), information-gathering, and psychological intervention (for example, demonstrating empathy) skills. Less than one-third teach any specific information-giving/counseling skills. IPS programs are taught mostly in the preclinical years, with a notable lack of formal follow-through into the clinical years. Ninety percent of the programs use videotechnology in teaching or assessing IPS. Only about one-third use any kind of outcome index for evaluation.


The Helping Professions Group: interpersonal dimensions in health sciences education. At Queen's University an extramural interprofessional discussion group, involving students and faculty members from medicine, nursing, theology, education, and law, has been meeting since February 1977. The discussions center on actual persons and problems with implications for a number of professional groups. This format provides an alternative opportunity for learning and may enhance personal growth and the development of interpersonal skills. It seems to meet certain needs which are not fulfilled by the more traditional university programs.


Predicting performance in a child psychiatry program for pediatric residents. As part of an evaluation of a program to train pediatric residents in child psychiatry, measures were made of the following variables predictive of the residents' performance in the program: personality traits, attitude toward psychiatry, willingness to treat psychological problems, preprogram interview performance, length of commitment to pediatrics, and frequency of interaction with teachers in the program. Outcome variables were pediatric residents' course evaluation, frequency of interaction with teachers in the program, and postprogram interview performance. In multiple regression equations the variables predictive of the residents' performance explained up to 72 percent of the variance of the residents' participation in the program, 88 percent of the variance of the postprogram interview, and 61 percent of the variance of the residents' course evaluations.


Using Delphi to achieve congruent objectives and activities in a pediatrics department. This study demonstrated the use of the Delphi technique in conjunction with activity analysis to obtain consensus on and clarity of objectives and activities of full-time members of an academic medical department. The results indicated that the Delphi technique is an effective method not only for obtaining a consensus on objectives but also for elucidating areas where there is no apparent consensus. The results also revealed which activities contributed to the objectives of the department and in which areas there was a divergence of objectives from the actual activities being carried out.


Electrocardiograph course.

Electrocardiograph course. Instruction in electrocardiogram interpretation was provided for students by distributing complete electrocardiograms to them at the beginning of the week, for nine weeks, followed by analysis by an instructor at the end of the week. This problem-solving method required minimal instruction in theory and lecture time. Skills in interpretation were promoted by teaching recognition of specific electrocardiographic patterns and their differential diagnosis rather than electrocardiogram aberrations produced by particular diseases. Reinforcement was provided by the frequent repetition of similar electrocardiograms during the course. This course was evaluated by examining students before and after the course and comparing their results with those of general internists who took the same examination. The students significantly improved their mean score and scored significantly higher than the general internists.


Specialty certification in North America: a comparative analysis of examination results. The pass/fail results of 44 North American medical specialty certification examinations are compared and analyzed. A calculated annual failure rate was used to equate one- and two-part examinations. Failure rates on American boards generally varied between 8 and 61 percent. Foreign medical graduates (FMGs) had failure rates two to three times higher than those of North American graduates in almost all specialties. Failure rates for comparable North American and FMG candidates tended to be higher on Royal College of Physicians and Surgeons of Canada specialty certification examinations than on equivalent American specialty board examinations. The place of specialty certification in the continuum of American graduate medical education is delineated. Questions are raised concerning the standards required for specialty certification.


The interinstitutional development of an international health course. An interinstitutional project to develop a self-instructional course in international health is described. Included is the rationale which supported the creation of the project and the operating procedures used to produce the course materials. The design and results of a field trial which provided the evaluative feedback for revising course materials are also described. The conclusion offers specific practical recommendations for the interinstitutional development of instructional materials and for the utilization of the course materials produced in this project.


Verbal response mode profiles of patients and physicians in medical screening interviews. The medical importance of the patient-physician relationship is widely acknowledged, but research on its effects has been hampered by the lack of a method to quantify its clinically relevant features. In this study a new method of coding verbal interaction was applied to 52 interviews with adults in a general medical screening clinic. "Average interaction profiles" for patients and for physicians in the medical history, physical examination, and conclusion segments of the interviews provided detailed descriptions of the relationship that appear to be accurate and coincide with descriptions derived from clinical experience, textbooks, and other studies. The profiles yield quantitative indexes of such crucial aspects of the relationship as the manner in which patients give a history and physicians trasmit information to patients.


Developing the medical curriculum at King Abdulaziz University. The kingdom of Saudi Arabia has placed a high priority on medical education. King Abdulaziz University is developing a medical curriculum aimed at being responsive to the health needs of the people of the kingdom. In creating the curriculum, planners devoted considerable time and effort to studying health manpower resources and needs, regional developments, demographic patterns, socioeconomic and cultural factors, general education development plans, vital statistics, and existing and projected health facilities. These and many other factors played a role in determining the format and the content of the curriculum, which is intended to produce individuals for leadership roles as medical educators, medical practitioners, and researchers.


Construction and evaluation of a hydromechanical simulation facility for the assessment of mitral valve prostheses. A hydromechanical simulator of the human left heart and systemic circulation system has been built for evaluating the dynamic actions of mitral valve prostheses. The facility includes a transparent and compliant model ventricle pumping into a simulation of the systemic circulation impedance. Transparent materials permit detailed high speed photography of valve action from the left ventricular aspect. This action has been analyzed by digitizing the valve open area and computing the variation of area with time. Additionally, pressures across and flows through the valves have been measured. Comparison has been made between the maximum observed valve open areas and the areas computed using the appropriate pressure and flow measurements substituted in clinically used equations.


A BSc level option in biomedical electronics. 1. The application of electronic instruments in medical diagnosis and therapy is well established. 2. There is a demand for electronic engineers both in industry and in the Health Service at all ranges of educational attainment. 3. It is possible to identify a set of objectives for a first degree course in Biomedical Electronics. An important element of this course should be the provision of practical experience in industry and in hospitals. 4. Such courses are available both in Europe and in the United States. Although the postgraduate course provision was satisfactory in the UK in the early seventies, only one full time undergraduate course was in operation. 5. A sandwich course can be designed in Biomedical Electronics as a major option of an existing BSc course in Electrical and Electronic Engineering. Provision can be made for entering and leaving the option. The option can be arranged to follow the guidelines laid down by the IEE for exemption from its educational requirements. 6. The option described started at the Lanchester Polytechnic in Coventry in September 1977.


Solid state delay unit for a cardiac arrhythmia monitor. A cheap alternative to tape loop delays has been described which is easy to construct. Although the system described here is for an arrhythmia monitoring system, it can be simply adapted to any device requiring a signal delay. Using 1024 shift registers, a delay of 2 1/2 seconds with a 3 dB signal bandwidth well in excess of 100 Hz is obtained; in theory, this delay and bandwidth combination should be obtained using 512 bit shift registers which would considerably reduce the cost. Full details including a circuit diagram are available on request.


A solid state laboratory timer for viscosity measurement. A low cost timer originally for use with the Harkness Viscometer is described. The timer, which may be used as a general purpose laboratory stop watch, is quiet in operation and counts to 99 seconds with 0.01 second resolution.


The pyroelectric vidicon camera as a medical thermograph. The operating principles of a pyroelectric vidicon (PEV) tube as an infra red (IR) image detector tube are explained. Characteristic requirements such as pedestal operation and sensitivity to time varying scenes are outlined. Of the possible read-out modes, the synchronous chopper mode is considered. The PEV camera properties are discussed in terms of measurement errors. The largest such as pedestal variations, noise and thermal blurring can be reduced to an acceptable level by image processing. A future PEV camera system with specifications comparable to, or even better than, those of existing commerical medical IR scanners seems to be possible.


The evaluation of head trauma by computed tomography. A retrospective study of 133 patients with documented head trauma is presented. Computed tomography (C.T.) has replaced cerebral angiography in the evaluation of these patients at our institutions. C.T. provides a rapid noninvasive diagnosis, plus accurate localization of lesions; it also allows for the assessment of multiple lesions. The authors feel that C.T. should be the first neurological mode of investigation after plain skull radiographs. It is important to obtain good quality scans, and intravenous sedation or general anaesthesia may be required.


Experience with a simplified trauma registry: profile of trauma at a university hospital. A simplified computer-based trauma registry system with well-defined limits of data capture is presented. This registry was utilized to describe the profile of trauma at a university hospital. In 1 year there were 882 trauma victims hospitalized, with an overall mortality of 3.3%. The majority of the patients had relatively minor injuries, primarily involving soft tissue and bone. Severe multiple trauma was associated with a significant mortality. Intracranial or intra-abdominal injuries occurred in less than 10% of the patients. Transport accidents, falls, and assaults were the cause of injury in 70%. Key access to specific information about the trauma patient population demonstrated the potential of the registry system. The advantages and limitations of the registry are discussed.


Changes in metabolism and muscle composition associated with total hip replacement. Metabolic changes in 10 patients undergoing total hip replacement were studied. Metabolic expenditure postoperatively remained within 5--10% of preoperative values. Net nitrogen loss for the postoperative period was less than 35 gm for the first 4 postoperative days, well below changes seen in major nonsurgical trauma. Fluid balance was positive in all patients for the first 4 postoperative days. Patients not in negative fluid balance by the fourth postoperative day should be closely monitored for complications. Recognition of delayed fluid excretion is essential in order to avoid the complications of further fluid loading in the postoperative period. Muscle composition reveals predictable changes in extracellular water, sodium, and chloride composition following surgery. Our data showed that metabolic changes following total hip replacement are in the order of major general surgical procedures and well below that observed with major trauma.


The role of NADH-NADPH oxidase activity in the leukocyte function of burned patients. Irreversible sepsis, in spite of advancements in topical therapy and antimicrobial agents, remains the leading cause of death in major thermal injury. A defect in intracellular bactericidal capacity in leukocytes from severely burned patients appears to correspond with increases in bacterial wound colonization and ultimate sepsis. This leukocyte defect has been demonstrated by abnormally low nitroblue tetrazolium reduction (NBT) and oxygen consumption of white cells in patients with major thermal injury. The subcellular mechanisms responsible for decreased bactericidal capacity were therefore investigated. Nicotinamide-adenine dinucleotide (NADH) and nicotinamide-adenine phosphodinucleotide (NADPH) oxidase activity was measured in patients with major burns, controls (normals), and in patients with nonburn stress or infection. NADH and NADPH oxidase levels in leukocytes from burn patients were not significantly different from those of normal nonchallenged controls but were significantly lower than the leukocyte values found in the patients with nonburn infections or stress. This NADH and NADPH defect in the subcellular leukocyte fraction suggests that it may be a significant factor in the reduced bactericidal function of the intact leukocyte in thermally injured patients.


The effect of immediate and delayed cold immersion on burn edema formation and resorption. Massive wound edema after a burn may impair healing and help to convert partial to full-thickness injury. Cold treatment (usually by immersion) has been reported to decrease wound edema and is useful in first-aid treatment of burns. Reliable quantitative data have been lacking and frequently a superficial burn has been studied. Since cold by decreasing peripheral blood flow could actually be harmful to a deep burn, especially if applied late, we measured the effect of cold immediately and 2 minutes postburn on edema formation and resorption in a deep second-degree burn in sheep hindlimbs. We used Dichromatic Absorptiometry, a noninvasive, reliable method for measuring tissue fluid, to quantitate edema. Immediate application of cold by immersion in 15 degrees C saline for 30 minutes reduced the edema of a deep second-degree burn and did not impair resorption rate compared with control limbs, fluid content returning to baseline after 1 week. Cold treatment beginning 2 minutes after the burn did not decrease edema formation and did impair resorption. Fifteen per cent of the edema fluid was still present 1 week postburn, suggesting further injury to the burn wound vasculature with use of cold immersion 2 minutes postburn.


Traumatic pneumocephalus: a hazard of resuscitators. A patient with traumatic pneumocephalus following use of an oxygen-powered resuscitator with a face mask is presented. Pressures of 50 cm H2O delivered by the device apparently were sufficient to force air into the cranium through a fracture communicating with the nasal cavity. The authors feel that manual-powered resuscitators should be used on patients suspected of skull fracture.


Rotational displacement of the distal tibial epiphysis without fibular fracture. Rotational displacement of the distal tibial epiphysis, a rare injury, is reported in a 14-year-old girl. A high clinical index of suspicion and roentgenograms of the entire leg, including knee and ankle, are necessary for diagnosis. Long-term followup is indicated to determine if epiphyseal closure will eventuate as it did in our patient.


Traumatic hematocele of the gallbladder with hemobilia. An unusual case of traumatic hemobilia in which blood reached the bile duct through transhepatic penetration of the gallbladder is reported. The salient features of this variant of traumatic hemobilia are described: antecedent subcapsular liver injury; variant time interval to GI hemorrhage and episodic hemorrhage; and necrosis or hematoma at the bleeding site.


Longitudinal fractures of the sacrum: case report. A longitudinal fracture of the sacrum without an associated neurologic deficit is described. It was treated by bedrest successfully. The case is compared to the usual transverse or oblique sacral fracture: we feel that because the sacral nerve roots were pushed to either side of the fracture there were no neurologic problems in the case presented.


Peripheral embolization following blunt thoracic trauma. The case of a 41-year-old man with an embolus in the left popliteal artery following multiple injuries suffered in an auto accident is presented. Following popliteal embolectomy, a rupture of the descending thoracic aorta was demonstrated and repaired. The need for aortography in patients with severe blunt chest trauma who develop hypertension is emphasized.


Arthrography as a method of diagnosing tear of the ulnar collateral ligament of the metacarpophalangeal joint of the thumb ("gamekeeper's thumb"). Arthrography of the metacarpo-phalangeal (MP) joint of the thumb was performed on 47 thumbs. The normal arthrographic appearance shows a closed joint space, whereas leakage of contrast material indicates tear of the joint capsule with or without an associated tear of a stabilizing ligament. Arthrographic demonstration of the heads of the adductor pollicis muscle was found to be specific for tear of the ulnar collateral ligament (UCL) of the MP joint, a tear which is commonly responsible for its instability. Arthrography is suggested as a safe and accurate diagnostic examination for the early detection of tears of the UCL of the MP joint.


Rupture of the left atrium from blunt trauma. Severe cardiac injury may occur in multiple-trauma patients and the associated injuries may obscure a significant and potentially fatal cardiac wound. In the patient presented, a left auricular appendage tear was found after he suddenly became hypotensive intraoperatively. After its repair he has recovered and returned to his previous employment.


Displaced transverse fracture of the sacrum with nerve root injury: report of a case with successful operative management. A displaced transverse fracture of the sacrum occurred in a young woman along with lumbar transverse process fractures, displacement suggesting instability in flexion, and nerve root injury, all features common to this injury. Open decompression, reduction, and Harrington rod fixation were successful for this patient, but the method is not recommended for all sacral fractures.


Esophago-bronchial fistula 8 years after blunt trauma. A case of an esophago-bronchial fistula 8 years post-blunt trauma is described. Prompt diagnosis and early surgical treatment are indicated to prevent irreversible lung damage or extrathoracic complications.


Coronary angiography after traumatic myocardial contusion. A patient with myocardial trauma following blunt chest injury is presented who returned 4 months later with persistent cardiac symptoms. Left ventriculography showed asynergy of the mid-diaphragmatic surface of the left ventricle while coronary angiography showed normal coronary arteries. The value of cardiac catheterization and coronary angiography in patients in whom symptoms persist after traumatic myocardial contusion and in patients in whom additional coronary artery or other cardiac disease is suspected is emphasized.


Traumatic bitemporal hemianopsia: case report. Bitemporal hemianopsia due to trauma to the optic chiasm is uncommon following head injury. In the patient described, a hemianopic field defect was seen 12 days after frontal basilar skull fracture. We feel the cause is intrachiasmatic contusion, edema, and hemorrhage. Serial ophthalmologic examinations and possibly use of steroids are recommended.


Bilateral scapular fractures from accidental electric shock. This report presents a patient with bilateral scapular fractures resulting from an accidental electric shock (440 volt, 60 cps current). This appears to be a previously unreported injury. A postulated mechanism of injury is discussed.


An analysis of the components of the pulmonary shunt equation: significance of the alveolar-arterial oxygen gradient, arterio-venous oxygen content difference, and mixed venous oxygen pressure. Pulmonary shunt calculated by the Berggren method is commonly used as an indicator of pulmonary function. Although there is usually a good correlation between the shunt and the A-aDO2, other physiologic parameters involved in the shunt equation may significantly alter pulmonary function. The purpose of this study is to show the contribution of the PVO2 and a--v diff to the shunt equation. Data from eight selected patients with A--aDo2 values ranging from 300 to 395 torr and calculated shunts ranging from 6 to 35% were selected for this purpose. In patients with significant changes in PVO2 and a--v diff, the A--aDO2 is more reliable as an indicator of pulmonary function than is the calculated shunt.


White blood cell consumption in the microcirculation after a major burn. The mesenteric microvasculature was observed before and after a distant full-thickness cutaneous burn in rats. Diameters, flow velocities, and white blood cell sticking and emigration were measured. Between 30 and 360 minutes postburn 13 to 16 WBC's were found to stick to the venular walls which had an area of 1.57 x 10(4) microns(2). Therefore, the number of WBC's emigrating from the vascular compartment during the 6-hour observation period could be as many as 0.51 X 10(9)/kg. Based on known values for total stores of WBC's, the data suggest that granulocyte sticking and emigration could account for a consumption of granulocytes that on an acute basis could deplete the body stores, which could explain the apparent decrease in total body granulocytes seen clinically following major thermal trauma.


Severity indices and their implications for emergency medical services research and evaluation. The present paper explores the rationale for the development of severity indices and the role such indices can play in various research and evaluation situations. Concrete examples from Emergency Medical Services research and evaluation settings are used to illustrate the potential shortcomings of designs that fail to incorporate measures of severity. A short critical review of existing indices is presented, and the ways that the indices can be refined and improved, and better used to evaluate emergency care, are summarized.


The treatment of pulmonary edema in the absence of renal function. A role for sorbitol and furosemide. In doses sufficient to induce a rapid osmotic loss of fluid from the bowel, sorbitol can provide an alternate method of removing fluid in patients who lack renal function. Two patients with acute pulmonary edema and oliguric renal failure were treated with a combined therapy of sorbitol and furosemide. Their clinical, hemodynamic, and metabolic responses were strikingly similar to those achieved with furosemide therapy alone in patients with normal renal function.


Psychiatric symptoms in disliked medical patients. Twenty-two patients seen in a clinic for systemic lupus erythematosus were tested for organicity, depression, anxiety, and hostility. Four of the clinic's physicians ranked these patients from most liked to least liked. In three of the four physicians, dislike was significantly correlated with the patient's degree of organicity. Ten of the patients were ranked among the three most disliked patients by one or more of the ranking physicians. This group of most disliked patients contained all patients with signs of organic brain damage and all suicidal patients. Dislike of a patient by the physician may be a clue to serious psychiatric impairment.


The epidemiology of sudden infant death in upstate New York. The epidemiology of sudden infant death among infants born during 1974 to mothers residing in upstate New York was studied. Death-certificate characteristics for 190 infants with sudden infant death syndrome (SIDS) are compared with those for 434 infants dying of other causes in the same age range. The overall incidence of SIDS was 1.43 per 1,000 live births. No relationship was found between SIDS rate and population density. The SIDS deaths peaked in January, with an overall seasonal pattern compatible with that of viral respiratory infections. The SIDS infants were more likely to die during sleeping hours than infants dying suddenly of other causes. Their age at death distribution is significantly different from that of other infant deaths. Progress in understanding sudden death in infancy is still hampered by the lack of positive diagnostic criteria.


Serum lithium levels and long-term diuretic use. In normal volunteers whose conditions were stablized with lithium carbonate, there were no significant changes in serum lithium levels during a two-week period while they received 40 mg/day of furosemide. During another two-week period, a 50 mg/day dosage of hydrochlorothiazide did cause a significant rise in serum lithium levels. These observations suggest that a substantial amount of lithium and a loop diuretic may not require modification of the lithium dosage.


Exposure to lead in firing ranges.

Exposure to lead in firing ranges. Members of law enforcement agencies were examined for adverse health effects caused by their activities in firing ranges and exposure to lead. Central nervous system and gastrointestinal symptoms were prominent and correlated with blood lead and zinc protoporphyrin levels. Half the group had blood lead levels exceeding 40 microgram/dL, and four (5%) exceeded 60 microgram/dL. Environmental surveys of three firing ranges indicate that indoor facilities with insufficient ventilation may have considerable air lead concentrations with levels up to 900 microgram/cu m or 4.5 times the current Occupational Safety and Health Administration standard for an eight-hour shift. Evaluation of lead effects should be taken into account in medical surveillance programs of firearms instructors. Zinc protoporphyrin determination has proved a suitable and practical way to assess biological effects among exposed persons and should be available at medical facilities responsible for the health of indoor firing range employees.


Screening for sickle cell hemoglobinopathies. Screening for sickle cell hemoglobin can detect carriers, who can benefit from education and genetic counseling, and can bring about early diagnosis, supportive care, and management for patients with established disease. However, such screening programs should be designed and supervised properly by health professionals to avoid methodological pitfalls and other unfortunate circumstances that have occurred in the past.


The interface between undergraduate and graduate medical education. The principal current problem related to the interface between undergraduate and graduate medical education is the lack of preparation of graduating medical students to assume many of the patient-care responsibilities required in certain graduate programs. There are two sides to the interface, and both require attention if the problem is to be resolved. The educational quality of the generally permissive fourth year of medical school should be examined in terms of the need for medical schools to prepare students for graduate educational programs. An effective broad first year of graduate medical education requires the development of institutional policy by all clinical departmental directors jointly and the delegation of operational responsibility to a small group of professionals.


Toxic effects of isoniazid in tuberculosis chemoprophylaxis. Role of biochemical monitoring in 1,000 patients. One thousand patients receiving isoniazid chemoprophylaxis were prospectively followed up to assess the value of liver function monitoring plus monthly clinical evaluation. Two hundred twenty-two (22.2%) of the patients had at least one elevated SGOT level during the course of treatment, and 47 asymptomatic persons had isoniazid therapy discontinued because of consistent elevations greater than five times normal. Another 17 had symptoms in association with elevated SGOT levels, and therapy was stopped in these patients as well. No patient became seriously ill, and there were no deaths. Biochemical monitoring should be done routinely in patients receiving isoniazid chemoprophylaxis to avoid the development of irreversible hepatic reactions.


Calcium and parathyroid disorders in children. Chronic renal failure and treatment with calcitriol. Progression of renal failure, represented by rising serum creatinine concentrations, was correlated with progressive elevation of serum parathyroid hormone (PTH) concentrations in 23 children. A significant linear relationship was established. Despite normal serum calcium concentrations in 11 children receiving maintenance hemodialysis, circulating PTH concentrations were elevated after six months. Progressive deterioration with time occurred in all variables tested, at six-month intervals. These complications were reversible with kidney transplantation or treatment with 0.25 to 2 microgram/day of calcitriol for four to 20 weeks.


Therapeutic embolization with detachable silicone balloons. Early clinical experience. A recently developed percutaneous transcatheter technique for selectively occluding arteries with detachable silicone balloons was applied in four patients. Uncontrollable hemorrhage from carcinoma of the cervix was controlled by selective uterine artery occlusion in one patient. Life-threatening hemorrhage from cystic fibrosis in another patient was controlled by balloon occlusion of a bronchial artery. A patient with hypernephroma and another with right ischial fibrous histiocytoma each had preoperative occlusion of the arteries supplying the neoplasms to reduce operative blood loss and to obviate the need for surgical ligation of the internal iliac artery in the latter patient. Detachable balloon embolization techniques represent a nonoperative method for permanently occluding arteries without the risks of inadvertent embolization.


Continuing education for the rural physician. A two-day continuing education course in emergency care was presented in small communities of Colorado and Wyoming to 349 rural physicians. Eighty percent of the physicians in those areas participated, indicating the interest of rural practitioners in updating their training if they can do so in their own communities. Continuity of care in the communities was provided by university residents covering local hospitals and clinics. The cost was comparable with other forms of continuing education; there was no tuition fee. The success of the program suggests that the special problems of providing education in rural areas require special solutions. Courses must be designed to reach all rural physicians to satisfy the increasing demand for continuing medical education.


Indomethacin and the nephrotic syndrome. Treatment of membranous nephropathy and the nephrotic syndrome with 2 mg/kg/day of indomethacin resulted in prompt and sustained reduction in urinary protein excretion and the loss of edema fluid, which allowed the withdrawal of diuretic therapy and liberalization of salt intake. The reduction in proteinuria was paralleled by a decrease in urinary prostaglandin E (PGE) and F (PGF) levels. Plasma PGE and PGF levels did not change appreciably. Withdrawal of indomethacin therapy resulted in an increase in urinary protein and urinary PGE excretion. Reinstitution of therapy resulted in reductions in both values. Indomethacin may provide a useful means of reducing proteinuria and controlling edema in some patients with the nephrotic syndrome.


Intravaginal estrogen creams and endometrial cancer: no causal association found. In two case-control studies of estrogens and endometrial cancer, women were asked about previous use of intravaginal estrogen creams. In a set of cases and controls chosen by conventional procedures from a tumor registry, the odds ratio was 0.90. In an alternative set of cases and controls who had all received dilatation and curettage or hysterectomy, the odds ratio was 0.82. Despite the reported relationship between oral estrogens and endometrial cancer and although intravaginal estrogen creams are readily absorbed by the vaginal mucosa, we detect no causal association for their use.


Complete remission of acromegaly with medical treatment. A 40-year-old patient with a ten-year history of acromegaly had persistent disease despite prior treatment with conventional pituitary radiotherapy and two transsphenoidal hypophysectomies. Initial evaluation showed characteristic acromegalic features, hypertension, amenorrhea, inappropriate diaphoresis, and poorly controlled diabetes mellitus despite isophane insulin suspension daily. Growth-hormone levels were high and did not suppress with glucose load. Treatment with bromocriptine was associated with prompt improvement in glucose intolerance, with elimination of insulin requirement within 72 hours of institutions of this therapy. Blood pressure normalized; inappropriate diaphoresis disappeared. Within three months ovulatory menses were noted to resume for the first time in ten years. There was progressive improvement in the soft-tissue changes of acromegaly. The growth-hormone levels fell within three hours after the first dose of bromocryptine and remained suppressed throughout her six-month course of therapy.


Step 2 regimens in hypertension. An assessment. A single-blind clinical trial compared step 2 combination therapy consisting of 50 or 100 mg of hydroflumethiazide plus either 0.125 to 0.250 mg of reserpine, 500 to 2,000 mg of methyldopa, or 80 to 320 mg of propranolol hydrochloride, in 59 patients whose elevated blood pressure (BP) failed to respond adequately to the thiazide alone. After nine weeks of treatment, diastolic BP was reduced below 90 mm Hg in all 20 patients treated with the reserpine-hydroflumethiazide combination, in 13 of the 19 patients treated with methyldopa and hydroflumethiazide, and in 16 of the 20 patients treated with propranolol and hydroflumethiazide. Changes in laboratory values were not substantial; adverse reactions occurred only in the methyldopa group. Although the three treatment regimens were similar with respect to safety and efficacy, the reserpine-hydroflumethiazide combination offers the advantages of more convenient dosage at lower cost.


Incidence and significance of candiduria. The 100,000 colony count has been used without careful evaluation for the diagnosis of renal candidiasis. Therefore, a prospective study was done on 1,004 urine samples from patients without signs of candidiasis to determine the incidence of candiduria and Candida colony counts. These were compared with colony counts from histologically proved cases of renal candidiasis. The incidence of candiduria varied from a low of 4% in men to a high of 39% in girls during their second week of antibiotic therapy. The overall mean colony count was 1,292 +/- 1,500. The mean colony count in clean-catch urine specimens from six proved cases of renal candidiasis was 23,750 +/- 12,311. The difference in colony counts from proved and unproved cases is statistically significant. Counts greater than 10,000 Candida organisms per milliliter require further investigation.


Hepatitis B virus. Inappropriate reactions to transmission risks. Ten patients designated as hepatitis B surface antigen (HBsAg) carriers were screened for inappropriate reactions to their disease. Assessment with a 32-item questionnaire showed three carriers to have underreacted to the risks of HBsAg transmission through misunderstandings or denial concerning the disease. One carrier, through severe social withdrawal, showed overreaction to the possibilities of disease transmission. Counseling was provided regarding the risks of HBsAg transmission. At a one-month follow-up, all carriers appeared appropriately aware of the risks of transmission, and one of two carriers referred for psychotherapy showed greatly improved social adjustment. We recommend that persons treating HBsAg carriers screen routinely for inappropriate reactions to risks of disease transmission and provide counseling as needed.


The care of patients at increased risk of premature pacemaker failure. During 1975 to 1977, a series of advisory notices from a pacemaker manufacturer alerted us to an increased probability of sudden, premature pacemaker failure in 217 patients. Three possible responses to these recalls were used among these patients: prophylactic pulse generator change, increased surveillance without pulse generator change, and routine surveillance with replacement only after pacing failure. During the three years after implantation of these pulse generators, 30 sudden failures and 19 incidents of rate decrease indicating impending failure were observed; all were corrected by pulse generator replacement. Among the 50 deaths were six for whom terminal pacemaker status information was inadequate, but overall mortality was not notably different from other pacing series. Consideration of recalls should include projected frequency of failure, expected mode of failure, patient dependence on pacing, and presence of coexisting diseases.


American foreign medical graduates. Performance after a year of supervised clinical clerkships (fifth pathway). The performance during graduate medical education of Americans who have studied medicine abroad and who have taken a year of intense and closely supervised clinical clerkships (fifth pathway program) was assessed. Only 14% of such house officers were given inadequate or below-average ratings in overall clinical performance by residency program directors. Ninety percent or more received average, good, very good, or excellent evaluations in their ability to take medical histories and perform physical examinations, in their response to instruction, in behavior and interpersonal relationships, and in appearance and emotional stability. Seventy percent were said to be as good as or better than house staff in general. Carefully selected and properly motivated Americans who have studied medicine in a foreign country can become good physicians following a well-organized, comprehensive closely supervised year of clinical clerkship education.