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The distribution and excretion of different body burdens of methylmercury (MeHg) have been investigated in the squirrel monkey. In monkeys given weekly 0.8 mg/kg doses, orally, of 203-MeHg, a linear correlation was observed between the concentrations of radioactive Hg in the blood and brain to as much as a blood concentration of 1 mug/gm. Above this level, the ratio of concentration in the brain and blood was increased. The total Hg concentration in bile collected from the bile duct was 10% to 30% of that in blood, while the concentration in bile from the gallbladder approached that in the blood. The total Hg concentration in feces was always more than ten times that in urine. Biotransformation of MeHg to inorganic mercury has been demonstrated; in the liver about 20% of the total mercury was inorganic, in the kidney 50%, and in the bile 30% to 85%. In the brain less than 5% of the total mercury was inorganic. After a single 0.8 mg/kg dose, orally, of 203-MeHg, the halftime for total Hg in blood was 49 plus or minus 2.8 days, and in the whole body 134 plus or minus 2.7 days. During the first four days after dosing, the decrease in blood concentration was more rapid than that occurring later, due to a redistribution within tissue compartments. A differential distribution of MeHg within the brain has been demonstrated in animals that showed clinical signs of intoxication.

(1) An epidemiological study of an urban South African Negro community has been carried out in Johannesburg. Altogether 964 respondents were examined and in each case radiographs of the hands and feet were obtained. Rheumatoid factor tests were carried out on 404 serum samples. (2) Rheumatoid arthritis (RA) was graded 'definite' or 'probable' on the basis of a modification of the Rome criteria (Kellgren, Jeffrey, and Ball, 1963a). (3) In marked contrast to the findings in rural Africans the prevalence of RA in this community was similar to that in Caucasian populations. Five respondents (all elderly women) had 'definite' RA, giving a prevalence of 1.4% of the females and 0.9% of the total population sample over 15 years old. The prevalence of 'definite' and 'probable' RA combined was 2.6% for males, 3.7% for females, and 3.3% for all individuals over 15 years old. Prevalence increased with age, reaching a maximum in the 65- to 74-year cohort. (4) The form and severity of the clinical and radiological features were unlike the mild manifestations seen in rural African peoples and closely resembled the usual clinical picture of rheumatoid disease. (5) The latex fixation test was positive in 12.1% of the sera tested, which is similar to the high titres found in other African populations. No obvious cause for this phenomenon was found. (6) Several reasons for the marked difference in prevalence of RA between this urban African population and a rural African population are considered. Marked intraracial differences such as this point to the importance of sociological and environmental factors in the pathogenesis of rheumatoid arthritis.

(1) An epidemiological study of a rural African community has been carried out in the Western Transvaal. Altogether 801 respondents over 15 years old were examined; radiographs of the hands and feet were obtained in all these individuals. Serological tests for rheumatoid factor were carried out on 516 blood samples. (2) The diagnosis of inflammatory polyarthritis was based on a modification of the Rome Criteria of 1961. Two categories were defined: 'definite' and 'probable' rheumatoid arthritis. (3) In this population inflammatory polyarthritis was much less common and much milder in its manifestations than in European and American peoples. The prevalence of 'definite' rheumatoid arthritis was 0.12% and of 'definite' and 'probable' rheumatoid arthritis combined, 0.87. Such changes as were encountered on clinical and radiological examination were invariably mild; no respondent in the entire survey had clinical features that would have been accepted in the ordinary way as those of rheumatoid arthritis. (4) The latex fixation test (LFT) was positive in 8.9% of the sera tested; the modified LFT aftaer inactivation of the serum at 56 degrees C was positive in 15.1% of cases. Similar findings in West African populations have been explained on the basis of alteration of the immune response by widespread parasitic infections. No obvious aetiological factor of this type was found in the present survey.

Data have been analysed from a retrospective review of 151 patients with monarthritis of more than 3 months' duration, usually involving the knee joint. The largest group, 49 patients (32%), had synovitis of unknown cause, 44 (29%) had synovitis probably associated with osteoarthrosis and 13 (9%) were diagnosable at presentation as having rheumatoid arthritis according to American Rheumatism Association (1959) criteria, which include serological and histological findings. There was only one case of tuberculous synovitis. Twelve of the thirteen patients diagnosed as rheumatoid arthritis developed involvement in other joints. In most other conditions, however, including synovitis of uknown cause, the prognosis was favourable, with either improvement or complete remission.

A survey of joint mobility was conducted in 295 healthy children between the ages of 5 and 10 years who attended a London primary school. Estimates of the commonly used measurements, that is passive dorsiflexion of the wirsts and ankles, passive hypertension of the elbows and knee, were too insensitive to detect any age effect. However, a method of estimating extensibility of the 5th metacarpophalangeal joint in response to a standard load detected a highly significant inverse correlation between joint mobility and age in the samples significant inverse correlation between joint mobility and age in the samples tested ( r = -0.586; P less than 0.0001). There was no apparement sex difference. Skinfold thickness using the Harpenden caliper over the 3rd metacarpal bone and the in vivo skin elasticity measured using a suction cup device performed on a sample of 78 of the children revealed no influence of either age or sex on these parameters. This is in sharp contradistinction to the effect of both age and sex in these two parameters in adults...

Case notes of the last 67 patients to present at the Brompton Hospital with nontuberculous empyemas, and without malignant disease, have been examined. Three cases of empyema in association with rheumatoid arthritis (RA) were found, and these cases are reported. Previous literature concerning this association is reviewed. It is concluded that two types of empyema may occur in patients with RA. Some develop in association with nodular pleuropulmonary disease and the formation of pyopneumothoraces; in other cases large, recurrent, primary empyemas build up in the presence of active rheumatoid disease alone. As with rheumatoid pleural effusions, middle-aged men seem to be particularly susceptible.

Recordings of pressure within the bladder, urethra, rectum, and external anal sphincter with image intensification and videotaping were carried out in spinal cord injury patients with complete and incomplete lesions, during spinal shock and in the chronic stage. The behavior of the external urethral sphincter and the somatic and visceral motor reflexes of the sacral segments were studied, during and after spinal shock. During spinal shock the majority of patients retained sacral somatomotor activity, in the absence of visceromotor activity, and resistance values at the external urethral sphincter remained high. Vascular oscillations were recorded in the membranous urethra. The highest resistance found in the membranous urethra was at the distal part of the external sphincter.

Experiments designed to examine the relationship between electrical and mechanical events in voluntarily contracting human muscle were performed. Experiments reported in the literature, as well as our own, were categorized according to technique into one of four types: (1) isometric-isotonic, (2) isometric-anisotonic,(3) anisometric-isotonic or (4) anisometric-anisotonic. A general relationship between the absolute value of the surface electromyogram (the absolute value of E and the force (F) generated by the contraction is proposed. This is the integral of the absolute value of E dt = k-1integralF dx i-2integralF dt, where k-1 and k-2 are constants. In the isometric-isotonic condition, this equation reduces to a linear relation between the average electromyogram and the force of contraction. A quadratic relation exists in the isometric-anisotonic, constantly increasing contraction, between the integrated electromyogram and the force of contraction. Also, this equation predicts linear relations for anisometric-isotonic contractions, and quadratic relations for an accelerated rate of contraction, between the average electromyogram and force of contraction. Both the data reported in the literature and our data provide confirmatory evidence for the unifying theory offered in this paper.

Infrared thermography contributes to the care of insensitive limbs. The inflammatory response of near damaged or damaged tissue presents areas of increased heat on the surface which can be detected and followed. Thermography was found to be a valuable aid to the established management methods used for insensitivity problems including management of healing and freshly healed ulcerations, management of neuropathic bone and joint problems and fitting of prosthetic devices and custom shoes. The most important contribution thermography offered was the detection of irritated tissue prior to frank breakdown often in time to prevent permanent injury if quick and effective management followed.

Profound membrane irritability localized primarily to the paraspinal muscles was the major electromyographic criterion proposed by LaBan and associates to predict the early presence and localization of spinal metastatic disease. A retrospective review was recently conducted to determine the accuracy of this interpretation and the effect of the electromyographic report on the attending physician's subsequent workup. In an analysis of 1800 electromyograms at Riverside Hospital, 91 cases were found which met the following criteria: (1) three or more paraspinal segments involved, (2) little or no membrane irritability in the anterior rami, and (3) no previous surgery on the paraspinal area. The proven discharge diagnoses were carcinoma in 24%, herniated nucleus pulposus in 28%, degenerative disc disease in 16%, diabetes mellitus in 9% and miscellaneous in 8%; in 15% no diagnosis could be made. We were unable to differentiate some cases of herniated nucleus pulposus from carcinoma using such criteria as profoundness of levels or number of spinal segments involved. There are partial explanations of why only paraspinal segments may be involved with profound changes in the diseases mentioned, but no explanation for the widespred involvement in localized disease such as a herniated disc. At our hospital it was interesting to note that internists infrequently order myelography or cerebrospinal fluid analysis while orthopedists, neurosurgeons and neurologists rarely order metastatic surveys.

The effectiveness of biofeedback training was compared to conventional physical therapy training in 20 adult hemiparetic patients with chronic foot-drop. They were randomly placed into two groups of ten patients each: the first group treated over five weeks with therapeutic exercise and the second group treated over five weeks with therapeutic exercise plus biofeedback training. In the second group receiving the biofeedback training the increase in both strength and range of motion was approximately twice as great as in the first group. The improvement displayed by even the first group of patients suggests that a potential for functional improvement exists that is often unexploited. The addition of biofeedback facilitates the process. Four patients in the biofeedback group achieved and retained conscious control of dorsiflexion; three of them are now able to walk without the use of the short leg brace.

The degree of pain reported by ten volunteers upon electrical stimulation of their peroneal nerves was measured while stimulus parameters were varied. The responses were compared for stimulations, all of which produced the same amount of ankle torque. The stimulation parameters examined were pulse duration, 0.3 and 1.0 msec; repetition frequence, 20, 50 and 100 hertz; pulse shape, square wave and exponential wave; impedance of stimulator output, constant voltage and constant current; direct current bias, positive or negative to the stimulus; and wave phase, uniphasic and biphasic. Pulse duration of 0.3 msec and constant voltage output were the only two parameters significantly associated with minimum pain response. Analysis of voltage and current wave forms for the different stimulus parameters indicated that the sensation of pain was dependent upon the total amount of electrical charge delivered to the tissue with the pulse.

The purpose of this investigation was to assess the adaptations of middle-aged women and men to a ten-week physical training program. Before and after training on a treadmill maximal oxygen uptake (VO2 max), heart rates and blood lactate were measured. Also, heart rates during submaximal exercise were observed. Additional measurements were made for body fat (skinfold method), resting blood pressure, heart rate and vital capacity. The training program consisted of a 30-minute walking and jogging exercise, three to four days per week. As a result of the training, oxygen consumption at exhaustion increased from 1.72 to 2.18 liters-min (29.2 to 37.4 ml/kg times min) for the women; 2.78 to 3.42 liters-min (33.7 to 41.8 ml/kg times min) for the men. The mean weight loss for the groups (0.7 kg and 0.8 kg) was negligible. Estimates of body fat (skinfold method) showed a significant loss of maximal exercise decreased significantly. No significant decreases in basal heart rate, blood pressure or vital capacity were observed. These data suggest that sedentary middle-aged women respond to vigorous physical training much like sedentary middle-aged men do.

Physical conditioning using weighted ankle spats was evaluated in eight men in the age range 33 to 45 years (mean, 38.4). Evaluation consisted of pretraining and posttraining heart rate (HR) and oxygen uptake (VO2) responses to five submaximal work loads: cycling six minutes at 600 kilopond meter per minute (kpm/min); level walking for ten minutes at both 4.0 and 5.6 km/hr with and without a 1.5-kg weight spat added to each ankle. After the initial baseline evaluation, subjects wore 1.5-kg weight spats on both ankles for three weeks and were reevaluated; during the next three-week period weight was increased to 2.25 kg per ankle. Following the six-week evaluation period, subjects did not wear ankle spats, and detraining was evaluated after three weeks. A control group of four subjects was evaluated at these same submaximal work loads on three different occasions with three-week periods between evaluations. The experimental group wore the spats about 13.5 hours per day and averaged 6.85 km/day (4.25 miles per day) during training. After six weeks of training, submaximal HR decreased 6 to 9 beats per minute (P smaller than 0.05) from pretraining values for all five submaximal work loads; predicted VO2 max and predicted work capacity to achieve a HR of 170 beats per minute increased by approximately 10%. Detraining submaximal HR responses increased slightly, but not significantly, from post six-week training responses. Control group submaximal responses were unchanged between evaluations. It was concluded that individuals who initially possess a low level of cardiorespiratory fitness may have a low threshold for training. Thus, leg weight conditioning may be extremely useful for rehabilitation of patients and for sedentary middle-aged men as special adaptation prio to more high intensity training.

Twenty-four male volunteers took part in four different leg-lift strength tests to study the effects of (a) holding bar in hands, (b) lunging, (c) belt slippage and (d) changes in knee angle. Test method A involved the use of the traditional bar and belt with no restriction of lunging. Test method B was the same as test method A with the exception that lunging was controlled. Test method C involved the use of experimental bar and belt with lunging controlled. Subjects were not allowed to hold the bar in this test. Test method D was the same as test method C except that the subjects were instructed to grasp the bar with their hands. The results showed that most accurate strength scores were obtained with test method C in which experimental belt and bar were employed to eliminate the use of hands, minimize belt slippage and control lunging.

Sexual functioning in patients with spinal cord injury has been the subject of considerable research interest in recent years. There have been numerous studies of both physiological and psychological aspects of sexual functioning, but only the physiological part of this literature has been organized in a systematic fashion. This paper reviews 33 articles that deal mainly or exclusively with psychosocial aspects of sexuality. It is observed that the psychosocial literature in this area is relatively diffuse, dealing with concepts that are inadequately specified and validated.

Three groups of four dogs each underwent proximal gastric vagotomy, truncal vagotomy, or truncal vagotomy with pyloroplasty. Two dogs had sham operations. Gallbladder bile was aspirated and measured. Aliquots were cultured and assayed for cholesterol, phospholipid, and bile salts initially and at subsequent laparotomies. Both truncal vagotomy groups showed marked increases in aspirate volume at subsequent laparotomies. The sham and proximal gastric vagotomy groups showed a small initial decrease in mean aspirate volume without further significant changes. When the bile assay data were plotted on triangular coordinates, all point for all groups remained well within the area of cholesterol solubility. Nevertheless, two dogs in each truncal vagotomy group were found to have gallstones. No stones were found in the sham and proximal gastric vagotomy groups. Proximal gastric vagotomy appears to preserve fasting gallbladder bile volume and does not alter bile composition in the dog.

Clearance of a parenchymal injection of xenon Xe 133 from the jejunum was used to asses changes in tissue perfusion produced by variations in superiorr mesenteric artery flow resulting from partial aortic occlusion. Disappearance of xenon from submucosa and muscularis was similar and reproducible. The biexponential function of the isotope clearanc exhibited a rapid initial component representing mean flow. Calculated xenon clearance rates, expressed as half-times for isotope disappearance and plotted as a function of decreasing superior mesenteric artery flow, were characteristically rapid for a broad range of superio mesenteric artery flows (90 to 600 ml/min). With reduction of superior mesenteric artery flow beyond 80 plus or minus 10 ml/min, tissue clearance of xenon was markedly prolonged. Adequate perfusion of the vascular compartments of the small bowel as measured by xenon clearance was maintained until 80% reduction of superior mesenteric artery flow.

Two patients with spontaneous aortocaval fistulas are described and compared with 67 cases reported in the English literature. Symptoms may vary widely; however, the presence of an expansile abdominal mass with a continuous bruit is usually diagnostic. The only successful management is promt repair of the vena caval defect and the aortic aneurysm. A third patient with spontaneous rupture of an abdominal aortic aneurysm into the left renal vein is alos described. Only five similar cases could be found in the work literature. Left flank pain, pulsatile abdominal mass, continuous bruit, and hematuria is the usual clinical picture. All of these cases involved an anomalous left retroaortic renal vein and all patients survived the necessary surgical correction. The operation of choice is closure of the defect in the retroaortic left renal vein and repair of the aneurysm.

The indirect measurement of ophthalmic arterial blood pressure is an important index in the understanding of cerebral vacsular hemodynamics. Ophthalmodynamometry (ODM), the prototype for such measurement, is, however, replete with difficulties that have limited its widespread use. A preliminary evaluation of a new technique for ODM identified as ocular plethysmodynamography, has yielded accurate opthalmic blood pressure data without the attendant problems. Reproducible values for bilateral ophthalmic arterial pressure levels have been determined in 30 normal volunteers and the levels correlated to brachial arterial pressure levels. In a series of patients with arteriographically demonstrable carotid obstructive lesions, the preoperative and postoperative ophthalmic arterial blood pressure relationships exhibited excellent correlation with the roentgenographic and intraoperative data.

Two hundred sixty-five patients who underwent vagotomy and pyloroplasty for duodenal ulcer disease were observed postoperatively, 220 for two to ten years, with an average follow-up of five years. Vagotomy and pyloroplasty carried a higher overall recurrence rate (3.6%) than did subtotal gastrectomy and vagotomy (1%), largely because of the high ulcer recurrence rate more than two years after operation for massive bleeding (9.2%) rather than that following elective operation (1.8%). Thirty-five percent of these patients with recurrent ulcers did well with medical management and did not require a second operation. The mortality of vagotomy and pyloroplasty for a massively bleeding ulcer (11%) was less than that following subtotal gastrectomy (21%). The mortality of elective vagotomy and pyloroplasty was 1%.

Esophagogastric fistula developed in two patients following operations combining fundoplication and other operative procedures on the esophagus. To our knowledge, this complication has not been previously reported or described. Accurate endoscopy and appropriate barium roentgenographic studies provided the definitive diagnosis. A second reconstruction was successful in one patient; conservative treatment was sufficient in the other.

Diarrhea, often profuse, accompanied by skin excoriation and nutritional and electrolyte depletion is a major complication of ileostomy. In an attempt to improve the course of these patients, an experimental study using dogs was undertaken to investigate an antiperistaltic ileal segment for the prevention of ileostomy diarrhea. Ileostomies were created in dogs. All the dogs with ileostomies died within nine days of weight loss and massive electrolyte and water depletion. A second group of animals underwent creation of an ileostomy simultaneously, with an antiperistaltic ileal segment placed 30.5 cm proximal to the ileostomy. These dogs maintained their weight and electrolyte and water balance. The stools in the group with the reversed ileal segment became semisolid to solid, compared to the watery diarrhea of dogs with ileostomies only.

A 51-year-old man was hospitalized and operated on for gastric carcinoma with widespread metastases and died two months after the laparatomy and biopsy examination. Two years prior to the operation, he deveoped nephrotic syndrome. Anaplastic carcinoma, linitis plastica form, of the stomach was found in the tumor biopsy examination and at autopsy. Light and electron microscopical studies of the kidney biopsy specimen taken at laparatomy confirmed the presence of membranous glomerulopathy. An immunologic basis of the concomitant appearance of malignant neoplasms and nephrotic syndrome is possible, based on reported cases. There is also a possibility that renal damage occurs more commonly in malignant neoplasms, but is not recognized clinically.

Minor technical errors may jeopardize the patency of femoral-popliteal bypass grafts. In an attempt to detect such errors, intraoperative arteriography has been routinely employed. It allows immediate recognition and correction of the most common abnormal findings: intraluminal debris, intimal dissection, distal thrombosis, arterial spasm, and kinking of the graft.

A technique of intraoperative arteriography for evaluating the technical construction of femoral popliteal bypass involves dierect injection of contrast material into the vein graft after construction of the distal anastomosis. This allows full assessment of the anastomosis and of graft position prior to transection of the graft or proximal femoral arteriotomy.

A transverse incision is reported with an oblique counterincision performed in such a manner as to satisfy all Halstedian criteria for tissue removal and to allow as little as possible skin incision to approach the clavicular area. Closure is planned so that there is no tenting of skin or limitation of shoulder motion.

Analyses of the polypeptide composition of influenza B viruses by 13 per cent SDS-polyacrylamide gel electrophoresis are reported. The viruses contained polypeptides of eight species ranging in molecular weight from 27,000 to 78,000. Four of them were glocypeptides and were selectively removed from the surface of the virion by Bromelain treatment. One of the blycopeptides was identified as viral neuraminidase. Three antigenically distinct strains of influenza virus, B/Lee/40, B/Massachusetts/1/71 and B/Hong Kong/5/72, showed an essentially identical electrophoretic picture, although strain-to-strain difference was observed in the migration rate of HA1 and HA2 polypeptides.

Antibody and cell-bound immune response were assessed in rabbits inoculated by the intravenous route with Cenedehill or with wild rubella virus. Our results suggest that wild or attenuated live rubella virus induce a transient unresponsiveness of the lymphocytes to PHA stimulation in vitro and suggest also that this immunosuppression was due to the persistence of rubella virus in the lymphocytes.

Young rats 6 to 22 days of age are extremely susceptible to the neurotoxic effects of hexachlorophene given as a daily bath of undiluted antiseptic detergent containing 3% hexachlorophene (pHiso-Hex). At this age, most rats are clinically and histologically damaged by as few as two daily baths. Younger rats are relatively resistant, probably because they have less myelin to be affected; older rats cannot be poisoned by this route, probably because the more mature liver excretes the drug more effectively. Age-dose-response curves in rats are similar to those in humans. This experimental model is potentially useful in defining other characteristics of this drug.

To assess neurotoxic effects of hexachlorophene in the human population previously shown to be most at risk, a blind clinicopathological analysis was made of all premature infants under 1,400 gm birth weight who survived at least four days and were examined by autopsy over a 7.5-year period. Repeated whole-body bathing of premature newborn infants in 3% hexachlorophene-bearing soap (undiluted pHisoHex) shows a significant statistical association with a vacuolar encephalopathy of the brain stem reticular formation. The prevalence of the vacuolar encephalopathy in premature infants on whom we have adequate brain stem histological information appears to be related to the number of exposures to hexachlorophene, the concentration of hexachlorophene, the thoroughness of rinsing, and other factors (including exposure to ultraviolet light).

Twenty-seven asymptomatic children with confirmed chronic increased lead absorption were compared with 27 matched control children for evidence of neuropsychological impairment. Evaluation of each child included a complete history, physical examination, quantitative neurological tests, and comprehensive psychological tests. There was significantly increased incidence of hyperactive behavior in the subjects with increased lead levels, but there was no significant difference in any of the quantitative test results. Uncontrolled variables, especially lead absorption in infancy and adverse environmental pressures other than lead, still leave questions about the relationship between chronic lead exposure and behavior of intelligence.

The literature concerning cerebral vasospasm associated with subarachnoid hemorrhage (SAH) due to ruptured intracranial aneurysm contains no definitive study of patients to determine whether there is (1) any clinical picture consistently present coincident with known cerebral vasospasm, (2) any relationship between mortality and known vasospasm, and (3) any relationship between serious brain damage (morbidity) and known vasospasm. To answer these important questions, experience with 198 consecutive acute SAH patients (every patient had a cerebral angiogram demonstrating one or more intracranial aneurysms) was studied. The experience with these 198 consecutive patients led to the conclusions that (1) there is no clinical picture consistently present coincident with known cerebral vasospasm; (2) cerebral vasospasm has no effect on the mortality from SAH due to ruptured aneurysm; and (3) there is no relationship between the frequency and severity of the complications from surgical or conservative treatment and the presence or absence of vasospasm.

Cerebral ischemia was induced in gerbils by bilateral carotid ligation for periods of 10 to 40 minutes. Cerebral blood flow (CBF) was measured by hydrogen clearance. Following ischemia, ultimate clinical and electroencephalogram recovery could be predicted in every case within the first five minutes by recovery could be predicted in every case within the first five minutes by recovery of CBF to at least 100% of the control level. In animals without EEC recovery, the postischemic CBF was always less than 80% of control and progressively declined to zero. Residual flow during ischemia appeared to minimize the likelihood of brain death. The determination of ultimate brain death appeared to coincide with a major circulatory abnormality that is probably microvascular.

The state of water in three types of brain edema and in normal brain of the rat was studied by the pulsed nuclear magnetic resonance (NMR) technique. In cold-induced edema and in osmotic edema both in cortex and in white matter, the water protons have longer nuclear magnetic relaxation times than in normal brain. The observed changes correlate with the water content of the brain tissue. In triethyltin induced edema, no change was found for relaxation times in the cortex, whereas in the white matter, an additional fraction was observed with much longer relaxation times, attributable to fluid within the vesicles in the myelin sheaths. Since the NMR technique is non-destructive, it is potentially applicable in the living patient as a method for the detection of brain lesions that are accompanied with changes of brain water.

The vascular hypothesis of the cause of muscular dystrophy suggests that ischemia is responsible for the muscle fiber necrosis. A xenon 133 clearance study of muscle blood flow in Duchenne and other muscular dystrophies showed no obvious difference between the response to exercise and arterial occlusion compared with control subjects. Radioautographic study of distribution of 4-125l-antipyrine in skeletal muscle of mice with muscular dystrophy showed no abnormal areas of ischemia. A statistical examination was also made of the grouping of damaged fibers, one of the observations on which the vascular hypothesis was based. Only 0.9% of fibers undergoing phagocytosis occurred in groups of four or more fibers in greater frequency than would have been expected by chance, and 70% of such fibers were isolated. These studies argue strongly against the vascular hypothesis of the cause of muscular dystrophy.

In a single monkey, the surface of the cerebellum was stimulated electrically for 205 hours with electrodes and parameter values similar to those currently used in humans for treatment of epilepsy. Im pedance of stimulating and nonstimulating control electrodes remained unchanged throughout an observation period of six months. Potentials evoked by cerebellar stimulation could be recorded from the cranium, providing a noninvasive technique of determining the level of current delivered to cerebellum. Examination of the implantation site showed marked meningeal thickening surrounding the stimulating electrodes. Such thickening was not observed surrounding a control set. Light and electron microscopical examination revealed severe loss of Purkinje cells in tissue near the stimulating electrodes. There was also a moderate loss in other parts of cerebellar cortex down to a depth of about 1 mm from the exposed surface. Biochemical analysis revealed metabolic abnormalities consistent with the morphologic evidence of widespread tissue damage.

Two patients with severe idiopathic polyneuritis demonstrated marked bilateral limitation of upper lid descent during the acute phase of their illness. Accompanying facial weakness does not adequately explain this phenomenon and the possibility of supranuclear levator dysfunction is raised.

Forty-six patients with enlarged sella turcica and pneumographic evidence of an intrasellar mass were initially untreated. The courses were variable, and 50% did not require subsequent treatment. All patients with initial visual involvement developed progressive visual impairment. Of patients with clinical evidence of pituitary insufficiency, 66% developed visual field defects and required treatment. Only one patient, whose sole symptom was headache, was subsequently treated, and no asymptomatic patient developed subsequent symptoms and required treatment. Asymptomatic patients with an enlarged sella turcica should have an air study to exclude an "empty sella" syndrome or primary hypothyroidism.

The influence of experimental hyperthyroidism (intraperitoneal injection of crystalline L-thyroxine 1 mg/kg/day, 8-18 days) on cardiac mechanics in contractility in situ were studied in 30 hyperthyroid cats and compared with an euthyroid control group (n equals 30). 1. In hyperthyroidism left ventricular weight was considerably increased. Hypertrophy in hyperthyroidism represents a special case of myocardial hypertrophy, associated with an increase of myocardial performance. 2. Heart rate, systolic pressure, cardiac index, external cardiac work and tension time index were increased by 60-180 per cent. 3. Indices of contractility (dp/dtmax, t-dp/dtmax, dp/dtmax/IP) as well as isovolumetric force velocity relationships and VCE-max and Vmax demonstrated a considerable increase of contractility. Maximum rate isovolumetric pressure fall was increased by 120 per cent. Experimental hyperthyroidism is characterized by hypercirculation associated with increases of pressure, volume and velocity factors. The results are discussed with regards to the effects of increased cardiac mechanics on myocardial energy balance.

The effect of experimental hyperthyroidism on myocardial mechanics was examined on isolated ventricular myocardium (right ventricular papillary muscle) of cats. 1. Isotonic muscle contraction and isometric tension development were largely unchanged compared with euthyroidism. 2. Isotonic contraction velocity and maximal isometric tension rise velocity showed considerable rises of between 41 and 78%. 3. Force-velocity relations of contraction showed changes with increases of contraction velocity with every degree of load. 4. Force-velocity relations of isotonic relaxation showed increases of isotonic relaxation maxima with comparable loads without any alteration of the typical course of the relaxation curves compared with euthyroidism. 5. Lowering the temperature (from 34 to 24 degrees C) produced a considerable fall of the raised contraction and relaxation velocity in hyperthyroidism whereas the values of muscle contraction and tension development important for the pump function were largely unchanged. It is concluded that the myocardium in experimental hyperthyroidism is characterised by a primarily velocity-related increase of inotropy. Lowering the temperature produces an effective fall of the raised velocity values. The mechanisms of the increase of inotropy and significance of the findings are discussed.

The local dilatory reserve of the canine coronary vasculature was studied with the particle distribution technique. Normal ventricles and hearts with slowly progressive narrowing of both the left circumflex coronary artery and the right coronary artery were studied. In spite of chronic occlusion of 2 coronary arteries myocardial infarction did not occur in the majority of animals because of collateral development. Coronary reserve was determined by producing graded to maximal coronary vasodilation. In normal hearts flow increased homogeneously over the entire left ventricle. In hearts with chronic coronary occlusion coronary vasodilation produced non-homogeneous increases in flow: collateral dependent myocardium received less blood flow than myocardium supplied by normal coronary arteries. Early after coronary occlusion the total coronary reserve was less than normal and the dilatory reserve of collateral dependent vessels was markedly diminished. Late (6 months) after coronary occlusion the total coronary reserve was still below normal but the dilatory reserve of collateral dependent vessels had improved. A new quantitative index of collateral function is defined as the level of coronary flow (delivered through normal coronary arteries) at which collateral flow deviates from homogeneous perfusion. Collateral function, when so defined, increases by a factor of almost 6 times between 4 weeks (early after coronary occlusion) and 6 months (late after occlusion) after the implantation of occluding devices.

In the chicken population at large, three electrophoretically distinct pancreatic alpha-amylase isozymes were discovered. The isozymes were designated Pa 1, Pa 2, and Pa 3. The local population of chickens, however, possessed only isozymes Pa 2 and Pa 3 present as three phenotypes: Amy-2 B, consisting of isozyme Pa2; Amy2 BC, consisting of isozymes Pa 2 plus Pa 3; and Amy2 C, consisting of isozyme Pa 3. Pancreatic biopsy permitted the establishment of a breeding flock with defined amylase phenotypes. Matings of this flock established that amylases are inherited as codominant alleles at a single genetic locus. Further, there was no evidence of ontogenetic modification of the amylase isozymes. It was observed that amylase isozymes Pa 2 and Pa 3 each generated a family of at least three faster-migrating amylolytic proteins. These post-translationally modified amylases were designated Pa Xa, Pa Xb, and Pa Xc, where X represents the number of the progenitor amylase. Structural analyses of purified amylases demonstrated that all amylase isozymes are nonglycosidated, monomeric molecules of molecular weight 55,000. In addition, the data are consistent with the hypothesis that the faster-migrating amylases are produced by deamidation of asparagine and/or glutamine residues.

A fast-migrating F' zone of the prealbumin serum esterase system of rabbits is demonstrated in low frequency in the breed Vienna White (stock Cpb:VW). Evidence is given that this zone is controlled by a third allele of the Est-2 locus. The zymotypic expression of this allele (Est-2-F') shows codominance in combination with the Est-2-F allele and complete dominance in combination with the Est-2-F' allele. In contradistinction to the F zones of the Est-2-F allele, the F' zone possesses no atropinesterase activity.

In phylogenetically diploid and tetraploid Cyprinid fish species, erythrocyte volumes, protein contents, and mean activities of the enzymes LDH, 6PGD, and PGI per cell per active gene locus decline with increasing DNA contents. These findings are assumed to reflect an evolutionary tendency of polyploids to regulate their genic activity down to the level of the diploids.

The effect of 0.1 mg/kg Verapamil on the extent of the ischemic area following ligation of a branch of the left descending coronary artery was studied in anesthetized open chest dogs. The sum of the ST-segment elevation during the entire period of occlusion in the epicardial ECG was 15 mV in control infarction compared to 9 mV (p smaller than 0.0005) when Verapamil was infused after ligation. Mean flow in the left descending coronary artery was reduced by coronary ligation alone on the average by 23%, but augmented by Verapamil for 5% above pre-occlusion control flow. Corresponding to the rise in the coronary flow and the drop in perfusion pressure under the influence of Verapamil, the increase of left coronary artery resistance induced by coronary occlusion was diminished. The positive effect of Verapamil on the size of myocardial infarction as estimated from the epicardial ST-segment changes is probably not induced by coronary vasodilatation, but by the Ca-antagonizing effect of this drug, as described by other authors.

Arrested rabbit hearts were perfused in normothermia for up to two hours by a cardioplegic erythrocyte-containing solution having an increased Mg++-, procaine-, and a reduced NaCl-content. After this time, hearts did not reveal any sign of anoxic or toxic damage in their metabolic pattern, in their ultrastructural picture, and in their functional capacity after reanimation. Despite a small loss in adenine nucleotide content, the ATP/ADP ratio and the PC content were raised. The contents of glycogen and glycolytic intermediates were normal or slightly reduced. After two hours of perfusion mitochondria showed no swelling, their membrane structure was unaltered. The myofibrils were well aggregated. The number of glycogen granules was increased. Hearts were reanimated after two hours of cardioplegia and could be loaded by pressure and volume.

The ontogeny of lactate dehydrogenase (LDH) isozymes was examined in avian hybrids and compared with the isozyme patterns of the parental species. Hybrids were obtained by crossing female Japanese quali (Coturnix coturnix japonica) with male domestic chickens (Gallus gallus domesticus). By use of starch gel electrophoresis and an enzyme-specific stain, traces of embryonic paternally derived LDH were detected in unincubated hybrid eggs. It was concluded that the embryonic genes coding for the B subunits of LDH are activated during the hours between fertilization and oviposition. In early blastoderms, a great excess of maternally stored LDH is present. In the hybrid, the predominantly maternal pattern of isozymes shifts during embryogenesis to a predominantly paternal pattern. This was considered evidence for differential allelic regulation of LDH inactivation. A progressive trend toward the establishment of the adult distribution of isozymes in various tissues was also observed in the hybrid and quail, and found to be similar to chicken LDH isozyme ontogeny.

Malate dehydrogenase (MDH) of larval, pupal, and adult stages of Culex p. quinquefasciatus has been characterized by electrophoresis, isoelectric focusing, and other physicochemical means. It exists as a multiple molecular form possessing a large number of isoenzymes, from a minimum of three in early instar larvae to as many as 14 in adults. The isoenzyme pattern changes during development with respect to both relative activity and the appearance of some new forms and disappearance of others. Each developmental stage possesses a characteristic electrophoretic and gel isoelectric focusing pattern. MDH isoenzymes differ in their response to heat and thiol reagents. Similar electrophoretic variants from larvae, pupae, and adults show great differences in their response to heat treatment at 50 C and 56 C, indicating some differentiation of isoenzymes in each stage of development. Homogenization of whole mosquitos in mercaptoethanol solution results in a sharp increase in the activity of the principal bands and a decrease or disappearance of minor ones. The possibility of some minor bands being "conformers" arising due to nongenetic factors is discussed.

Stretching of K-depolarized contracted helically cut strips of pig coronary arteries produced a delayed increase in tension. The influence of temperature and extracellular calcium on this active response to stretch was investigated. Reference for all tension values was the amplitude of contraction (induced by K-depolarization) starting from the high resting tension. 1. The mean amplitude of the delayed tension increase after stretch amounted to 27.5 plus or minus 4.8% (x plus or minus SEM, n equals 9); lowering the bath temperature from 37 degrees C to 27 degrees C caused a drop to 10.8 plus or minus 1.5% (n equals 9; P smaller than 0.0025); increasing the calcium concentration of the bath solution from 2.7 to 6.9 mM produced negligible effects on both the amplitude of the delayed tension increase (24.6 plus or minus 1.0%; n equals 9), and the amplitude of contraction after depolarization. 2. The peak tension time of the active response to stretch was not changed by the 6.9 mM calcium, but prolonged from 27.9 plus or minus 4.0 to 40.7 plus or minus 4.4 minutes (P smaller than 0.025) by lowering the bath temperature to 27 degrees C. At the high calcium level the preparation contracted faster after depolarization than at the normal calcium level. 3. The experimental results correspond with the conception of the sliding filament mechanism as the basic process of contraction also in vascular smooth muscle preparations. The delayed tension increase after stretch may be caused by a recruitment of interaction sites between contractile proteins.

An analysis of age of onset in juvenile rheumatoid arthritis was performed in the last 300 children seen in our clinic. There was a peak age of onset in girls at 1 to 3 years. Distribution of age of onset in boys was bimodal with the first peak at 2 years of age and the second at 9 years. There was no accentuation of frequency in either sex in the 10- to 14-year age group. The distribution of age of onset was bimodal in both monarticular and polyarticular onset of disease, but no particular modal age of onset was seen with systemic onset of disease. It is possible that these data reflect that JRA is not a homogenous disease, or that there are age-sex related differences in host susceptibility or pathogenic agents.

The biomechanical changes in rabbit knee contractures were measured after 9 weeks of immobilization. These results were correlated with the biochemical composition of periarticular connective knee tissue of the same knees. The loss of total hexosamine correlates significantly with joint stiffness on an animal-to-animal basis. Total hexosamine also correlates with the energy required cyclicly to flex and to extend the experimental joints. Of the individual glycosaminoglycan fractions, only hyaluronic acid showed significant correlation with the biomechanical data. The possible mechanism of contracture formation was postulated based on these results.

Rabbit articular chondrocytes produce a chondroid matrix in subculture. This tissue was compared to articular cartilage by histochemical and electron microscopic techniques. Although both tissues were similar, the cytology of chondrocytes and the matrix structure of chondroid tissue appeared less mature.

Four patients are described with a recently recognized variant of double outlet right ventricle. Clinical examination favoured tetralogy of Fallot, but the chest X-ray suggested corrected transposition. Catheterization and angiocardiography showed that the aorta was to the left of the main pulmonary artery, and both arose from a normally positioned morphological right ventricle. Egress of blood from the left ventricle was through a subaortic ventricular septal defect. In all patients severe pulmonary stenosis was present and the right coronary artery ran an anomalous course anterior to the pulmonary valve ring. Two children had successful total correction, and one a palliative Blalock-Taussing shunt. Necropsy material from the fourth patient allowed confirmation of the ventricular morphology and the conducting tissued was examined. In corrective surgery, blood from the left ventricle was rerouted into the aorta by an intraventricular baffle. Pulmonary stenosis was relived by infundibulectomy and outflow tract patch.

The present study represents an attempt to correlate the electrocardiogram and coronary arteriogram in patients with an inferior transmural infarct - or total occlusion of the right coronary artery. The influence of the collateral circulation on these findings was also evaluated. Fifty patients with a total occlusion of the right coronary artery had characteristic electrocardiographic changes of an inferior infarct in 44 per cent, very suspicious changes in 32 per cent, and no changes suggesting an inferior infarct in 24 per cent. However, in this latter group who had no evidence of an inferior infarct, we were able to recognize a small number who showed an anterior wall infarct. Collateral circulation was more frequently present and more extensive in those patients whose electrocardiograms did not show changes typical of inferior transmural infarction. This suggested that collateral circulation might minimize some of the electrocardiographic abnormalities which would normally result from occlusive disease of the right coronary artery. Another 50 patients, selected because of definite electrocardiographic evidence of typical inferior transmural infarction, were evaluated by coronary arteriography. Severe obstructive disease of the right coronary artery was present in 86 per cent of the group. In the remaining 7 patients (14 per cent) minimal or no disease was found. Infarction of the inferior wall may have resulted from occlusive disease of the anterior descending artery or have been the result of a right coronary artery occlusion with subsequent recanalization. We conclude from our study that a careful analysis of electrocardiographic abnormalities in theinferior leads will, with certain limitations, permit us to estimate the likelihood of a severe lesion in the right coronary artery, and, in the face of definite electrocardiographic evidence of an inferior infarct, to predict the diseased artery.

Three cases of acute inferior wall myocardial infarction associated with complete atrioventricular block and junctional escape rhythm showing left posterior hemiblock are presented. The triad appears to consitiute a distinct syndrome. It is postuated that the subsidiary pacemaker is situated either in the bundle of His or the proximal part of the anterior division of the left bundle-branch.

This report describes an unusual hemolytic transfusion reaction. A group O donor was inadvertently transfused with 100 ml of group A red cells during the course of plasmapheresis. Granulocytopenia, thrombocytopenia, hypofibrinogenemia and low levels of factors V, VIII, and IX developed immediately after the infusion. The levels of the cellular elements and coagulation proteins returned to normal in less than an hour; too rapid for a de novo synthesis after consumption of coagulation proteins. We postulate that activation of the kinin system was responsible for the phenomena rather than intravascular coagulation with secondary fibrinolysis.

The occurrence of severe aortic regurgitation in two patients with typical findings of osteogenesis imperfecta is described. Both patients manifested severe haemodynamic abnormalities and underwent successful aortic valve replacement. The operative and pathological findings are discussed.

Twenty-one patients, 11 with normal pulomonary artery pressures and 10 with pulmonary hypertension, had haemodynamic measurements performed before and during dopamine infusion while undergoing cardiac catheterization, in order to evaluate the circulatory effects of dopamine in pulmonary hypertension. In both groups on average, heart rate, pulmonary artery mean pressure, aortic mean pressure, and cardiac index increased significantly, while systemic vascular resistance fell significantly during dopamine administration. In neither group did the average pulmonary vascular resistance or right ventricular end-diastolic pressure change significantly. We conclude that dopamine is a safe and potentially useful drug for the treatment of reduced cardiac output, even in patients with pulmonary hypertension.

In order to determine whether the development of myocardial infarction in different countries is associated with different risk factors, 240 male survivors, aged 40 or less, were studied in nine countries. In the seven centres in developed countries (Auckland, Melbourne, Los Angles/Atlanta, Cape Town, Tel Avic, Heidelberg, and Edinburgh) there was a high procedure of risk factors, particularly of hyperlipidaemia and cigarette smoking. The prevalence of hypertension, obesity, hyperglycaemia, and hyperuricaemia varied from centre to centre. Risk factors were less prevalent in Bombay and Singapore: the most common risks operating in Bombay seemed to be cigarette smoking and hyperglycaemia, while in Singpore cigarette smoking was the commonest. The mean age of the whole group was 35.4 years. Serum cholesterol levels of 7.25 mmol/l (280 mg/dl) or more were present in 25 per cent of all patients, serum triglyceride levels of 2.26 mmol/l )l200 mg/dl) or more in 35 per cent. 80 per cent of the patients were smokers, and 15 per cent were either for hypertension before myocardial infarction or had a raised blood pressure after myocardial infarction. Obesity was found in 19 per cent of all patients and serum uric acid levels over 0.5 mmol/l (8.5 mg/dl) in 17 per cent. 10 per cent of all patients were either treated for diabetes mellitus before myocardial infarction or showed an abnormal glucose tolerance after myocardial infarction. This collaborative study may help, by showing differences in the prevalence of risk factors, to indicate to each centre and to national and to international organizations, the direction for their future studies into the causation and prevention of myocardial infarction in young men.

Published values for the diastolic closure rate of the normalmitral vary and reflect diffference in methods of recording and measurement. From strip chart records it was concluded that the form of the recorded mitral diastolic closure slope can vary, that reproducible measurements of the closure rate can be made from echograms in which diastolic closure approximates closely to a monophasic form, that the amplitude of these echograms is maximal, and that their closure movements remain essentially monophasic at chart speeds up to 100 mm/s. Measuring only complexes with essentially monophasic closure movements, the within and between-subjected variation of the normal mitral diastolic closure rate was investigated. The ranges obtained from multiple measurements in a single subject and from a group of 45 normal subjects were comparable but the distribution of the results differed. It was concluded that there was a real between-subject variation in the normal mitral diastolic closure rate and that the diastolic closure rate in a single subject should be determined by measurement of a series of complexes. The accuracy of measurement of the diastolic closure rate of the normal mitral valve has been improved by using strip chart records and by measuring only echograms in which diastolic closure approximates closely to a monophasic form.

Atrial pacing to the point of angina or up to a maximum rate of 166/min was carried out in 37 patients during coronary angiography. In 9 patients with normal coronary arteries both the right and left ventricular end-diastolic pressures fell remained steady with increasing heart rate. The same response was observed in 14 patients with angiographically proven coronary artery disease. In the remaining 14 patients with provencoronary artery disease the end-diastolic pressure in the left ventricle rose at the point when the patient experienced angina. In 10 of this latter group there was a simultaneous rise in the right ventricular end-diastolic pressure. In 4 patients the rise in end-distolic pressure was seen in the left ventricle only. The haemodynamic events in the right ventricle during angina appeared in most cases to mimic the events occurring in the left ventricle. There was no correlation between the angiographic findings and the changes in end-diastolic pressure in the two ventricles during angina.

A new performed, semi-rigid, polyethylene catheter, with built-in torque control, has been devised for entry to the pulmonary artery in complete transposition of the great arteries. It has been used 19 times in 17 patients: 18 times the pulmonary artery was entered from the right atrium (via the left atrium and ventricle) in a time between 40 s and 15 min (median 5 min); the patients' ages were 2 days to 6 years (median 8 months) and their weights were 3.1 to 13.3 kg (median 6.9 (kg: in the remaining 1 day-old patient, the procedures was terminated because of atrial flutter. The catheter was introduced into the axillary vein in 3 patients and thesaphenous or femoral vein in the remainder. It is suitable for angiocardiography, and the other heart chambers and vessels were easily entered. Thus the catheter has certain advantages over previously described methods for entry to the pulmonary artery, particularly when there is inferior vena caval thrombosis, or when angiocardiography is necessary. Its use does depend on the presence of an interatrial communication, so a method for entry to the pulmonary artery by retrograde catheterization from the axillary artery using a different catheter is also presented; this was successful in 2 patients with ventriculal sepatal defect.

Forty-nine patients admitted to a Coronary Care Unit with myocardial infarction complicated by left ventricular failure, were treated with 1.75 mg Lanoxin over 36 hours. Serum digoxin levels were measured by radioimmunoassay at 8, 24, and 48 hours. No difference in serum levels was observed between those patients who received 'old' (reduced bioavailability) and those who received 'new' Lanoxin. Serum levels were significantly higher at 8 and 24 hours in those patients who received their first dose intramuscularly compared with those who received their first dose orally, irrespective of the bioavailability of the oral preparation used. No correlation was observed between serum digoxin levels and serum urea or creatinine during the 48-hour period of study. The incidence of arrhythmias is reported, but no conclusion can be drawn as to whether or not the glycoside contributed to this in any way. The use of digoxin in patients with acute myocardial infarction complicated by left ventricular failure is justifiable in the light of available evidence. However, in view of the possible predisposition of such patients to toxicity, lower serum levels than were achieved in many of our patients seem desirable and a modified dosage schedule is suggested.

The clinical, laboratory, and necropsy findings in a patient with massive eosinophilia and fatal cardiac failure are reported. Necropsy revealed partial obliteration of the lumen of the left ventricle with dense white thrombus, and fibrous infiltration of the myocardium. An additional finding, not hitherto described in Löffler's endocarditis, was massive enlargement of the mesenteric lymph nodes.

A case is presented in which transient left anterior hemiblock masked the electrocardiographic signs of old inferior wall infarction. The electrocardiographic features are correlated with the anatomopathological findings. This case re-emphasizes the need for careful evaluation of patients with chest pain and left anterior hemiblock.

Since 1969 it has been the policy of this department to perform regular cardiotocograms on all patients admitted during the antenatal period for severe hypertension, with or without proteinuria, and on those in whom poor intrauterine fetal growth was suspected. In five such patients where the fetus died in utero, beat-to-beat variation was reduced and late decelerations were observed. In a further twelve patients similar changes made delivery by elective Caesarean section appear advisable. Half of the infants so delivered had severe metabolic acidosis at birth.

Tubular reabsorption of glucose has been measured during glucose infusion in 29 healthy women during and after pregnancy. All the women had normal glucose tolerance to an oral load, and normal glucose excretion when not pregnant, but exhibited a wide range of daily glucose excretion in pregnancy. Throughout pregnancy the renal reabsorption of glucose is less effective than in the non-pregnant state and, in general, the greater the amount fo glycosuria which develops in pregnancy, the less effective is the reabsorption during infusion. Post partum, women with minor degrees of glycosuria during the preceding pregnancy return to a normal highly efficient reabsorption performance during infusion, but women who exhibit greater degrees of glycosuria have a reduced capacity to reabsorb even though they are no longer glycosuric after the pregnancy. It is concluded that pregnancy imposes some specific change in the glucose reabsorptive capacity of the proximal tubule and that women with more than usual degrees of glycosuria in pregnancy may, in addition, have an element of tubular damage. This is discussed in relation to other renal function changes in pregnancy in an attempt to explain the characteristic intermittency of clinical glycosuria in pregnancy.

Of 173 eclamptics admitted to the only public maternity hospital in Cali, Colombia 44 had stillbirths making a rate of 25-4 per cent. Fetuses delivered before 32 weeks had nearly four times the stillbirth rate of those delivered at term. Those weighing less than 1600 g. had stillbirth rates about six times higher than those weighing above 2500 g. An attempt was made to divide the risk conveyed by low birthweight into two components; that which was due to low gestational age, and that which was due to an abnormally low rate of growth during the gestational time available. Deviation of birthweight below that expected for age (retarded fetal growth, RFG) was used as a measure of the latter component. RFG became more common as gestation progressed and was associated with fetal death only in the latter part of gestation and with marginal statistical significance. After 35 weeks, fetuses at or below two standard deviations from Gruenwald's mean weight for gestational age (Gruenwald, 1966) had a fetal death rate five times higher than those at the mean. The risk of fetal (intrauterine) death conveyed by low gestational age has not been definitively explained. Alternative pathophysiological mechanisms are discussed.

The ability of 15 variables to predict fetal death is examined among 173 eclamptic women admitted to the only public maternity hospital in Cali, Colombia, between 1st Janurary 1964 and 31st December 1970. In addition to low gestational age and retarded fetal growth, high systolic pressure and the unmarried status carried excess risk. Primiparae appeared to be of lower risk because their eclampsia tended to occur late in gestation and was characterized by less retarded fetal growth. Older women and women with a history of abortion appeared to be of higher risk because they tended to have higher systolic pressures. A discriminant function risk formula is presented which generated groups with a nine-fold difference in fetal death rates. This formula could be used to standardize for relevant non-therapeutic factors which meant vary between patient groups who had received different therapeutic regimens.

The hormonal criteria of a "normal" or "ovulatory" response, and three grades of subnormal anovulatory responses, were defined during a first course of treatment with clomiphene citrate in twenty patients with amenorrhoea for which no organic cause could be found. The hormonal responses were estimated by frequent serum measurements and by the menstrual response. Seven patients had a normal or ovulatory response with a late rise of serum progesterone and subsequent menses. Their serum luteinizing hormone (LH) and oestradiol (E2) responses were greater than in spontaneous menstrual cycles. Five patients gave only partial responses, with menstruation and no prior rise of progesterone, Their serum LH and E2 responses were generally lower than in the normal group but had the same pattern except for an absence of the luteal phase rise in E2. Five patients who did not menstruate showed smaller and more variable responses. The remaining five showed no hormonal responses. The second and third groups had ovulatory responses on subsequent clomiphene courses, whereas no improvement was shown by the last group. The serum E2 responses offered the most sensitive index of the responsiveness to clomiphene. Response values in our normal group suggested that higher progesterone levels need to be reached after clomiphene administration than in spontaneous cycles for ovulation to be inferred. The serum prolactin showed no consistent response during the clomiphene test; three patients with moderately raised basal prolactin levels had "normal" responses.

From 291 cases of malignanat disease of the ovary in the North East Metropolitan Region of London, 250 have been classified as of epithelial origin. Of these, 44 have been designated as endometrioid carcinoma. The recognition and features of endometrioid ovarian carcinoma are discussed.

Curettage carried out during the third week of treatment of ethinyl oestradiol in 14 patients with gonadal dysgenesis showed cystic glandular hyperplasia in seven patients developed a large endometrial polyp and in one atypical changes were found in the hyperplastic endometrium. In seven patients treated by an oestrogen-progestogen combination normal secretory endometrium was seen in five, proliferative change only in one (thought to be due to incorrect timing of the curettage) and a small proliferative polyp in association with secretory endometrium elsewhere in the uterus in the seventh. In view of these changes and report of adenocarcinoma of the endometrium in patients with gonadal dysgenesis treated with oestrogens alone it is suggested that a regime of low dose oestrogen therapy for 21 days accompanied by a progestogen on days 15 to 21 is preferable to oestrogens alone.

This case report describes the genesis of endometrial carcinoma after prolonged stilboestrol therapy in a patient with gonadal dysgenesis (Turner's syndrome). The varied histological appearance included the presence of cartilage-like material. A review of the literature reveals the need to treat these patients with combined oestrogen/progestogen preparations rather than with continuous unopposed oestrogens.

Young adult rats, either control or essential fatty acid deficient, were administered either [3-H] oleic acid or [3-H] arachidonic acid by stomach tube. In addition, a group of control rats was given [3-H] palmitic acid. The rats were killed at various times therafter, and the radioactivity of the lipids of brain and plasma was examined. In confirmation of previous work, the blood lipid label was found to rise rapidly and then fall, wheras the activity of brain lipids increased slowly and did not show a decline through the 24-h period studied. Analysis of the brain uptake data according to first-order kinetics confirmed the impressions gained from visual inspection of the data. The initial rate of uptake of arachidonic acid was about 4.5 times that of oleic acid in control animals and in deficient animals. Essential fatty acid deficiency, however, did not induce an altered rate of uptake for either oleic acid or arachidonic acid. The rate of uptake of palmitic acid by control rats was not significantly different from that of oleic acid. Even though the initial rates of incorporation of oleic and arachidonic acids were not changed during essential fatty acid deficiency, the final levels of radioactivity obtained in brain lipids were higher in deficient rats with both fatty acids. The plateau value obtained with oleic acid was 1.5 times higher in deficient animals, while the plateau value for arachidonic acid was 1.7 times higher. An experiment in which deficient animals were allowed access to a control diet for 12 or 24 h prior to the labeling experiment suggested that the higher levels of radioactivity found in brain lipids of deficient animals was not due to an isotope dilution effect. Such animals still displayed the labeling pattern of deficient animals with arachidonic acid, while the results with oleic acid varied somewhat. Our results suggest that essential fatty acid deficiency does not alter the ability of the brain to take up the fatty acids studied. However, the fatty acids, especially arachidonic, are retained in the brain to a greater extent in the deficient animals.

The effects of supplementation of a complete diet with ethyl arachidonate and with ethyl dihomo-gamma-linolenate (20 : 3Omega6) on the fatty acid composition of plasma and tissue lipid classes were studied in normal rats. 2. These prostaglandin precursors were incorporated in varying degrees into all lipid classes of the tissues that were investigated. The largest elevations were seen in plasma and tissue triacylglycerols. Significant increases were also observed in phospholipids, cholesteryl esters and the free fatty acid fraction. 3. Following the feeding of the ester of 20 : 3Omega6, arachiodonate levels also rose in the lipids of some tissues. In others, such as the renal medulla and platelets, and increase in 20 : 3Omega6 content occurred without a rise in 20 : 4. 4. Platelet aggregation is known to be stimulated by 20 : 4 (via active metabolites), but not by 20 : 3Omega6. The ability to modify 20 : 3Omega6 levels selectively in certain tissues is of interest in light of such pharmacologic differences from 20 : 4.

1. Ceramide aminoethylphosphonate was isolated from the adductor, gills, mantle and viscera of oysters. 2. After drastic acid hydrolysis of the lipid, aminoethylphosphonic acid was the only water-soluble carbon-phosphorous compound detected. 3. The main fatty acids of ceramide aminoethylphosphonates were hexadecanoic acid (77-90%) and 2-hydroxy hexadecanoic acid (13-15%). 4. Hexadeca-4-sphingenine, octadeca-4-sphingenine and octadeca-4,8-sphingadienine were identified as the major long chain base components. However, the ratio of the three bases was characteristic for each tissue; the adductor muscle contains primarily hexadeca-4-sphingenine, and the viscera, octadeca-4,8-sphingadienine. The gills and mantle contain the three bases in approximately equal concentration. 5. The main molecular species in the adductor muscle was hexadecanoyl-hexadeca-4-sphingenyl 2-aminoethylphosphonate, while in the viscera hexade-canoyl-octadeca-4,8-sphingenyl 2-aminoethylphosphonate predominated.

Raman spectra of dipalmitoyl phosphatidylcholine and structurally related molecules are examined and vibrational transitions assigned for the C-C, phosphate and C-H stretching modes of these molecules. Particular emphasis is placed on the characteristics of the Raman spectra in the 2800-3000, 1000-1150 and 700-800 cm-minus 1 regions. It is found that hydrocarbon transitions dominate the spectra at the expense of those of the phosphate and choline groups. The methyl and methylene C-H stretching assignments have been clarified for the Raman spectra of phospholipid systems.

Sterol balance measurements using isotopic and chromatographic techniques were carried out in rats fed diets containing beta-sitosterol (0.8%) and cholesterol (1.2%). The activities of the rate-limiting enzymes of cholesterol synthesis (beta-hydroxy-beta-methylglutaryl-CoA reductase, EC 1.1.1.34) and bile acid synthesis (cholesterol 7 alpha-hydroxylase) were determined in the same animals. Cholesterol feeding increased cholesterol absorption from 1.2 to 70 mg/day. The increased absorption was compensated for by inhibition of hepatic cholesterol synthesis, enhanced conversion of cholesterol to bile acids (from 13.7 to 27.3 mg/day) and a slight increase in the excretion of endogenous neutral steroids (from 7.7 to 11.2 mg/day). Despite the adaptation there was accumulation of cholesterol in the liver (from 2.2 to 9.2 mg/g). Beta-Sitosterol feeding inhibited cholesterol absorption (calculated absorption was zero). In these rats there was enhanced cholesterol synthesis (from 20.0 to 28.8 mg/day, but no change in the rates of bile acid formation. Measurements of the activities of the rate-limiting enzymes showed fair correlation with cholesterol-bile acid balance. In cholesterol fed animals, beta-hydroxy-beta-methylglutaryl-CoA reductase was inhibited 80% and cholesterol 7 alpha-hydroxylase was enhanced 61%. In beta-sitosterol-fed animals, the reductase was increased 2-fold and cholesterol 7 alpha-hydroxylase was not significantly different from controls.

Diffusion coefficients of bile salts, lecithin, and cholesterol above the critical micelle concentration have been measured with the diaphragm cell at varying concentrations of bile salts, lecithin, and added electrolyte. The diffusion of the bile salt can be five times faster than that of the solubilized lipids. This is shown not to be an artifact of multicomponent diffusion, but a result of a different transport mechanism of the bile salt. As a consequence, the concentration of bile salt and lipids at the surface of a cholesterol gallstone can differ from those in the bile solution. The effects of this upon growth and dissolution in detergent solutions are discussed.

1. The mechanism of the inhibitory effect of erucylcarnitine on palmityl-carnitine oxidation in rat heart mitochondria was studied. 2. Erucylcarnitine inhibited in the same time the oxidation of [U-14-C]-palmitylcarnitine and the total rate of oxygen uptake. Other acylcarnitines competed as well for the oxidation with radioactive palmitylcarnitine, but they were well oxidized themselves, so that the total oxygen uptake did not decrease. 3. The presence of erucylcarnitine did not change the distribution pattern of Krebs cycle intermediates derived from [U-minus 14 C] palmitylcarnitine except that succinate/malate ratio increased. 4. The presence of erucylcarnitine did not lead to the formation of any beta-oxidation cycle intermediates from [U-minus 14 C] palymitylcarnitine. The formation of beta-hydroxy-palmityl derivative when rotenon was included into the incubation medium, decreased in the presence of erucylcarnitine. 5. It is postulated, that the inhibited entrance of palmityl groups into the beta-oxidation cycle is due to the fact that erucylcarnitine and palmitylcarnitine behave as substrate-competitive inhibitors for long chain acyl-CoA dehydrogenase. 6. There was observed a latency of 1-2 min in the effect of erucylcarnitine on the palmitylcarnitine oxidation, which seems to correspond to the time required for the formation of high amounts of intramitochondrial erucyl-CoA. 7. Erucylcarnitine inhibited the total oxygen uptake with long, medium and short chain acylcarnitines, pyruvate and alpha-ketoglutarate as substrates, while the oxidation of succinate was not affected. 8. Sequestration of free CoA in the form of very slowly metabolized erucyl-CoA is proposed as the partial explanation of the observed inhibitory effects of erucylcarnitine on the oxidation of CoA-dependent substrates (alternatively to the inhibition at the level of acyl-CoA dehydrogenases in case of acylcarnitines).

The hopes raised by the finding of differential Concanavalin A (Con A) agglutinability of normal and transformed cells in efforts to quantify differences between these cell lines seem not to have been justified. In this paper, the development of information on the mechanism of action of Con A on the cell surface, as well as the theories put forward at each stage of this development are surveyed. In this respect, investigations on Con A constitute a case history in biological research. The involvement of glycoproteins and galactosyltransferases in cell-cell interactions and their relations to Con A are also reviewed.

Among 5 families with SBH of Neapolitan origin, herediatry glyco-lipidosis was accompanied in one by beta-thalassemia. All 10 members of this family, namely parents and 8 siblings, were investigated. The mother and two children were found to be carriers of both SBH and beta-thalassemia, while three other siblings were carriers of SBH alone. None of the six patients conformed the classic clinical picture often observed in genotypical SBH. The present state of genotypic transmission of the stigma is discussed on the basis of the author's experience as well as the data in the literature. As for the combination SBH-thalassemia in the same individual it may be concluded that the two genes are most likely independent and certainly not linked.

1. In unanaesthetized pigeons the effect on cloacal temperature was studied of acetylcholine (ACh), carbachol, atropine and (+)-tubocurarine injected into a cannulated lateral cerebral ventricle. The experiments were carried out at an ambient temperature of 19-25 degrees C. 2. ACh or carbachol injected intraventricularly produced hyperthermia, and in larger doses hyperthermia followed by hypothermia. These were central effects because they were not obtained when these drugs were injected in the same doses intravenously. 3. Atropine injected intraventricularly produced hypothermia which was greater and longer lasting than the hypothermia produced with the same dose of atropine injected intravenously. After the intraventricular injection of atropine the hyperthermic effects of ACh and of carbachol were abolished. 4. (+)-Tubocurarine injected intraventricularly produced a long-lasting hyperthermia in doses which had no effect on temperature when injected intravenously. After the intraventricular injection of tubocurarine the hypothermic effects of ACh and of carbachol were abolished. 5. It is concluded that the effects of ACh had carbachol imitate the effects of ACh released from cholinergic neurones in the central pathway involved in temperature regulation. The hypothermic effect of atropine is attributed to unmasking the activity of continuously released ACh acting on nicotinic receptors, and the hyperthermic effect of tubocurarine to unmasking the activity of continuously released ACh acting on muscarinic receptors.

1. Tachyphylaxis to heart rate and bronchodilator effects of (plus or minus)-isoprenaline was studied in anaesthetized open-chest dogs by 5 procedures. 2. Heart rate responses to a series of intravenous injections of isoprenaline were essentially unchanged before and after a 15 min infusion of isoprenaline (at 3 doses). 3. Heart rate and bronchodilator responses in the same animal to an intravenous injection of isoprenaline were not significantly different before and after a 30 min infusion of isoprenaline (at 2 doses). 4. Heart rate responses were relatively constant to an isoprenaline injection given every 30 min during a 4 h infusion of isoprenaline (at 3 doses), but the magnitude of the response was smallest for the largest infusion dose (highest background heart rate) and greatest for the smallest infusion dose (lowest background heart rate). 5. Heart rate and bronchodilator responses in the same animal to isoprenaline were relatively constant during a 5 h infusion of isoprenaline (at 2 doses). 6. Bronchodilator responses to intratracheally administered isoprenaline aerosol were essentially unchanged during a 4-5 h period using various doses and procedures. 7. Tachyphylaxis to the heart rate of bronchodilator effects of isoprenaline was not observed. The present data give no support to the hypothesis that tachyphylaxis to isoprenaline aerosols is an important mechanism in asthma mortality.

1. Isoprenaline, 3.5-20 ng, injected intracerebroventricularly in atropinized mice under pentobarbitone anaesthesia produced a dose-dependent tachycardia. 2. Pretreatment with either reserpine or pempidine blocked nervously-mediated tachycardia as shown by marked reduction of that due to stimulation of the spinal outflow in pithed mice. After pretreatment with these drugs, intracerebroventricular isoprenaline caused tachycardia of a similar degree and time course to that in mice not so pretreated. 3. Pretreatment with either reserpine or pempidine caused supersensitivity to the tachycardia due to intravenous isoprenaline. 4. When allowance was made for this supersensitivity in the effect of intracerebroventricular isoprenaline in pretreated mice, a small dose-dependent residual effect remained that could be attributed to leakage of isoprenaline into the peripheral circulation. 5. This was confirmed by the appearance of a late-developing tachycardia on intracerebroventricular injection of isoprenaline in spinal mice. 6. It is therefore concluded that the tachycardia caused by intracerebroventricular isoprenaline in mice is, at least initially, of central origin.

1. Reserpine administration resulted in a larger initial decline in adrenal catecholamines in spontaneously hypertensive rats (SHR) than in normotensive Wistar rats (NWR); the difference was eliminated by pretreatment with cholisdondamine. 2. Reserpine also produced a larger increase in SHR catecholamines and dopamine beta-hydroxylase several days later; chlorisondamine pretreatment did not prevent the increases, although it did slightly slow the increases. 3. Vesicles from SHR, or NWR incubated with reserpine in vitro demonstrated equivalent inhibition of adenosine 5'-triphosphate (ATP)-Mg-2+-stimulated adrenaline uptake. 4. Recovery of uptake was more rapid in SHR than in NWR after reserpine inhibition, and this was associated with a burst of new vesicle synthesis in the SHR; chlorisondamine pretreatment reduced the number of new, immature vesicles in reserpine-treated SHR. 5. Both SHR and NWR secreted equal proportions of their adrenal catecholamine contents after nicotine administration. 6. These data suggest that the sympatho-adrenal system of the SHR exhibits an enhanced reflex response to reserpine but that reserpine is equally effective in SHR and NWR in producing blockade of vesicular catecholamine transport; these alterations can affect markedly the actions of autonomic drugs in the SHR.

1. Acetylcholine mustard (N-2-chloroethyl-N-methyl-2-acetoxyethylamine), a potent muscarinic agonist, binds virtually irreversibly to muscarinic receptors in longitudinal muscle strips from guinea-pig small intesting, as shown by the inhibition of the binding of E13-H]-propylbenzilycholine mustard ([3-H-PrBCM), an affinity label for the muscarinin receptor. 2. A value for the apparent binding affinity of acetylcholine mustard and a value for the rate constant for the receptor alkylation reaction have been deduced from the rate of onset of the inhibition of [3-H]-PrBCM binding. 3. The kinetic constants obtained may refer largely to the interaction between acetylcholine mustard and the desensitized receptor. 4. At high concentrations acetylcholine mustard practically abolishes the contractile response to carbachol. At the concentrations acetylcholine mustard appears to have multiple actions on the tissue.

The intravenous administration of theophylline to ten healthy human subjects produced either an increase of circulating plasma dopamine-beta-hydroxylase or no change. The rise of plasma enzyme activity may reflect the increased peripheral catecholamine release induced by theophylline.

Segments of ileum from newborn rabbits contracted in response to histamine but sensitivity declined from age 11 days. Intestine from adult animals barely contracted to histamine, even in a concentration of 3 times 10- minus 3 M. Such variation with age was not observed with acetylcholine. The response to histamine was effected by mepyramine-sensitive receptors which appeared to decrease in number as the animals aged.

A statistical significance test to detect seasonality of epidemiological events is described. The method is similar to that of Edwards, but makes it possible to allow for an arbitrary pattern of variation in the population risk, and also for the unequal lengths of time sectors of a cycyle of seasons (e.g., months of a year). From the test it is possible to estimate the amplitude of seasonal variation and the time at which the maximum occurs in a postulated simple harmonic fluctuation; the adequacy of the description of the data by a curve of this kind may be evaluated using a goodness-of-fit test. A numerical example of the calculations is given using some anencephalus data, and the results are compared with those of alternative tests.

A study of the monthly numbers of stillbirths and of deaths due to anencephalus in Canada from 1954 to 1962 showed a weak tendency to a winter excess of affected births. The seasonal trend was more marked in the Prarie provinces and in Quebec than elsewhere; the maximum rate of anencephalus occurrence was in October to December in the Prairies and in British Columbia, and in January to March in other regions.

Data on menarcheal age were collected on girls admitted to the University College of Swansea over a 12-year period. It appears that the downward trend in menarcheal age ceased in girls born about 1946 (the 1965 student intake) and that an upward swing may have since occurred. This change in the secular trend is not due to the association of menarcheal age with family size or of position in sibship, or to changes in the regional composition of the student intake. The well established effect of physique remains, but there is no effect of socio-economic status as assessed by the Registrar-General's classification of the father's occupation.

Three years after a normal cervical smear, 1,007 women were followed up to see how they responded to a computer-generated recall letter. Seven women had died and 150 had had interim smears (mainly in association with regular contraceptive or postnatal examination). Of the remaining 850, low response was not related to lower social class in the way initial recruitment to screening is. Working outside the home was more obviously associated with lower response, as wass full-time compared with part-time work. Response was also related to where the first smear was taken (61% of women first examined at a local authority clinic, but only 29% of those from a mobile industrial clinic) and was related to repetition of a familial routine which favoured permanent rather than mobile facilities. Interviews with returners and non-returners showed that over 90% remembered receiving recall letters, so non-response was a conscious decision not to attend. When a first test originated at work, response to recall tended to be poor. Of the non-returners 42%, but only 24% of the returners, had found the first test unpleasant or embarrassing. One-third of non-returners claimed difficulties in finding time, which is in accord with the lower response from full-time workers. Over 90% of those interviewed gave fear or modesty as the reasons why other women had not had a repeat smear. In general, differences in response to a letter inviting women to have a repeat smear are unlike those which characterize recruitment for a first smear. Consistency of experience appears to be strongly favoured in the regular use of cytological screening.

A self-administerd questionnaire was posted to 1 129 medical general practitioners in an urban and in a rural area of England. The prevalences of headache, and of the features of migraine, in the year immediately preceding the survey were similar in the two areas. After allowing for the different age and sex composition of the populations, these prevalences were also similar to those found in the general population during an early survey in Wales. About 13% of the male and 25% of the female general practitioners thought that they had had migraine in the previous year. There was little evidence that doctors with 'classic' migraine differed from those with 'common' migraine in the proportion who experienced other migrainous features (unilateral distribution of headache and accompanying nausea) or in their response to treatment with ergotamine.

A study in Derbyshire showed that there are wide variations in the populations served by individual home nurses. These variations are difficult to reduce. To assess the quantity and quality of home nursing that is provided more sophisticated formulae than the nurse/population ratio are necessary. For these data derived from output of work are inadequate; studies of need are required in each locality.

Deoxycytidylate (DCMP) deaminase was assayed at various times during and after normal and abnormal pregnancies. The level in amniotic fluid was assessed at induction and at caesarean section, and cord blood levels were estimated after normal delivery and at caesarean section. A rise occurred during labour and after hysterectomy and caesarean section--returning to normal after 2-3, and 12 days respectively. Levels above 4.8 X 10-minus 4 ml-minus 1 were found in cases of preeclamptic toxaemia and early intrauterine death and in twin pregnancies over 36 weeks' gestation. It is suggested that because of its low incidence of false-negative and false-positive results this test is far superior to other enzyme tests in pregnancy, and a further trial is in progress to assess its role.

The behavior of 12 adult ring doves [a small-brained species of Columbidae] was compared with that of 12 adult pigeons [a large-brained species of Columbidae] in a detour problem to see if Rensch's hypothesis of increased brain size being correlated with increased capability can be extended to a perceptual problem-solving task. Three detour dependent variables were intercorrelated with seven gross brain indices obtained from each bird. There were no species differences in terms of detour behavior, and no correlational trends of brain-behavior relationships were discernible. It was concluded that Rensch's hypothesis may not be generalizable to all types of behavior capabilities.

The differences in the cytoarchitectonic organization and the thalamocortical projections to the anterior and posterior cortical fields in cats provide the basis for judgements about their unequal roles in entire behavior acts. Extracellular recordings of anterior frontal neuronal activity have revealed the predominance of the nonspecific type of afferent activation of gyrus proreus neurons; complex integrative properties of gigantopyramidal neurones [posterior frontal regions] have been observed. Participation of the posterior frontal fields in afferent synthesis and in programming motor activity has been shown in behavioral studies. The phlogenetically younger anterior frontal fields are considered to be yet nonspecialized structures; posterior gigantopyramidal fields in cats are considered as the highest apparatus of programming complex motor activity in an experimental situation.

The development of the extrastriate visual system relative to the striate system was estimated indirectly by measuring the volumes of the lateral posteriorpulvinar complex and lateral geniculate nucleus in six varieties of mammals selected on the basis of their propinquity with Anthropoidea [oppossums, hedgehogs, rats, squirrels, tree shrews and bushbabies]. The same animals were tested on two related behavioral tasks [spatial and visual reversal learning] whose successful achievement requires a simple sort of abstraction. The results show that the ability to learn visual reversal, but not spatial reversal, corresponds closely to the relative degree of development of the extrastriate system. Since the variation in both these behavioral and morphological characteristics also parallels the phylogenetic dimension, the recency of common ancestry to anthropoids, the evolutionary origin of the anthropoid capacity for visual abstraction is suggested.