Aspects of suicide and parsuicide.

Aspects of suicide and parsuicide. Five aspects of suicidal behaviour in Edinburgh from 1968 to 1974 were examined. The data referred to 478 suicidal deaths and to parasuicide (attempted suicide) admissions to the Regional Poisoning Treatment Centre (R.P.T.C.). Firstly: 28% of suicides were found to have had a parasuicide admission and there was some evidence of a slight excess of deaths in the years immediately following parasuicide. Secondly: among suicides preceded by parasuicide, those with a recent episode (within 2 years of death) were found to be essentially similar to those with a longer interval. Thirdly: a history of previous parasuicide at any time was found to be important in delineating two groups of suicide. Suicides with prior parasuicide died more often from poisoning with drugs and were more likely to have a history of psychiatric treatment; suicides without prior parasuicide died more often from poisoning with domestic gas or violent means, were older, of higher social class and less often married. Fourthly: parasuicides who killed themselves within 2 years of admission to the R.P.T.C. were compared with a group of (broadly nonsuicidal) parasuicides. And lastly: a scale predictive of repetition of parasuicidal behaviour was used in an attempt to distinguish parasuicides who killed themselves from those who did not. The scale did not discriminate between the two groups.


Primary peptic ulcer in childhood. Psychosocial, psychological and psychiatric aspects. Twenty-five children with radiologically confirmed primary peptic ulcers were investigated. All patients suffered from duodenal ulcer and there was an unexpected female preponderance. The frequency of introverted personalities was greater in the patients than in the controls. Five patients suffered from psychiatric disorders, three had histories of suicidal attempts and three reported homosexual experiences. Six patients had nicknames. Eight patients had been operated on for appendicitis. The above parameters were negative in all control cases. The patients had lower mean IQ, worse adaptation to school, more anxious and overprotective parents, higher frequency of faddiness in food and lower frequency of nail-biting than the controls. The onset of symptoms was preceded by psychotraumatic events in eight cases. The findings suggest that the manifestation of the genetic background of duodenal ulcer is strongly influenced by environmental factors and factors associated with the personality of the patients.


Vascular occlusion with a ferromagnetic particle suspension. An experimental investigation in rabbits. Magnetically controlled iron thrombosis has been attempted in rabbits. A horseshoe magnet across the jugular vein could arrest injected iron particles in the blood stream so that a well localized, solid thrombus developed. The connection between the strength and orientation of the magnetic field and the force developed on the iron particles was also investigated.


Intravenous bolus of 125I labeled meglumine diatrizoate. Early extravascular distribution. A mixture of 125I labeled meglumine diatrizoate and 131I labeled human serum albumin was injected into the femoral vein of 26 anesthetized male rats. Measurements of the activities in cardiac blood and in different tissues of the lower extremity and in the testis were performed at time intervals ranging from 5 s to 5 min after injection. The determination of tissue uptake and distribution volumes of diatrizoate showed widely differing accumulation of contrast medium. Over 50 per cent of the intravenous bolus of diatrizoate was extravascular at 40 s.


Angiography in pheochromocytoma of the urinary bladder. Report of a case. A case of pheochromocytoma of the urinary bladder in a 20-year-old female is reported. This is the 36th reported case in the English language literature. The patient had classical symptoms of vesical pheochromocytoma with sudden onset of headache, palpitations, and blood pressure elevation during voiding. The provisional diagnosis was arrived at on clinical history, laboratory investigations, including the estimation of catecholamines and vanil mandelic acid (VMA). The diagnosis was confirmed and the tumor was exactly localized by means of angiography. The angiographic appearance of pheochromocytoma of the urinary bladder is not pathognomonic and is similar to that previously described for adrenal pheochromocytoma. Angiography is, with adequate precautions, a safe and useful procedure for ruling out synchronous adrenal or extra-adrenal tumors and for exact localization of the bladder tumor.


Phlebographic appearances of the left renal and left testicular veins. The normal phlebographic appearances of the left renal and left testicular veins are described, based upon the findings in 100 patients admitted because of confirmed or possible testicular tumor. The patients had no metastases demonstrated at foot lymphography, urography and phlebography of the inferior vena cava.


Arterial segmental vasoconstriction. Frequency and pathogenetic factors. Frequency and pathogenetic factors involved in arterial segmental vasoconstriction observed in a series of 55 patients are analyzed. A large number presented peripheral nutritional disturbance and these included 5 patients with definite or highly possible Buerger's disease. The possibility that in certain patients segmental vasoconstriction may be an early sign of systemic or local arterial disease is discussed.


Chronic sclerosing osteomyelitis of the mandible. Radiographic differential diagnosis from fibrous dysplasia. Among 13 patients with chronic osteomyelitis of the lower jaw, clinical, radiologic and histologic difficulties were encountered in 5 cases, in the differential diagnosis from fibrous dysplasia. The radiologic, and in some measure the clinical and histologic features typical of the two diseases are described. Variations in the bone structure during the course of the disease, as well as periosteal new-bone formation, are characteristics of chronic osteomyelitis. When problems are encountered in differentiating between fibrous dysplasia with periodical pain and swelling, and osteomyelitis, repeated radiologic examinations are to be recommended.


Xerographic tomography.

Xerographic tomography. Tomographic depiction using Xerox plates was compared with that of screen film tomography. The Xerox plates entail much higher demands as to the quality of tomographic blurring than screen film combinations. Circular or hypocycloid movements give rise to errors of depiction which are more disturbing in xerographic tomography due to the fact that the screen film combination has such properties as to be unable to record certain spurious signals present in the radiation relief, which appear in the higher-precision recording of the Xerox plates. This indicates that these plates are to be preferred if only the spurious signals can be eliminated. Suitable tomographic movements are described. To counteract the high radiation doses in xerotomography, it is suggested that specially constructed cassettes for simultaneous multisection tomography should be used.


Carcinoembryonic antigen in amniotic fluid. Carcinoembryonic antigen (CEA), a substance which is known to occur in high amounts in the fetal gut and also in certain tumors of the gastrointestinal tract, has been demonstrated in amniotic fluids from different stages of pregnancy. Radioimmunoassays of CEA in amniotic fluids of 91 normal pregnancies showed a decrease from a mean of 53 ng/ml at 19 weeks to 25 ng/ml at the end of gestation. The CEA activity in amniotic fluid was eluted in the same volume as a standard 125I-CEA on a Sephadex G200 column. Amniotic fluid therefore contains CEA similar in molecular weight to the CEA purified from liver metastases of colonic cancer. Among 17 cases of abnormal pregnancies, CEA elevations were observed in five with anomalous fetuses.


Hereditary angioneurotic oedema in Finland. Clinical, immunological and genealogical studies. A total of 7 families with hereditary angioneurotic oedema (HANE) have been found in Finland. Six HANE patients have died from laryngeal oedema, 27 patients with diagnosed HANE are alive and 21 members have a haematological abnormality typical of HANE, i.e. a deficiency of the inhibitor of the activated first component of complement (C1-INH), but no manifest symptoms. The largest family has 363 living members, 303 of whom were investigated for C1-INH, C4 and C3. Fourteen patients had HANE, 18 relatives were symptomless but had C1-INH deficiency, and 3 members of the family had died from laryngeal oedema. In two families only one case of HANE was diagnosed, the parents in both cases being symptomless with normal C1-INH levels. All patients who had died from laryngeal oedema and 10 of the 27 HANE patients still alive had a typical triad of paroxysmal abdominal pain, peripheral oedema and laryngeal oedema. Six patients have had abdominal attacks alone, three peripheral oedema alone and two only laryngeal oedema. The age at onset of symptoms was 1-51 years. Three patients, who have received continuous methyltestosterone therapy, had hardly any symptoms during the treatment. Thirteen patients have received tranexamic acid, either during an attack or continuously, with positive effects in all except two. Cinnarizine treatment was beneficial in three out of four cases, both when given continuously or during an attack.


Ultrasound as a complementary diagnostic method in deep vein thrombosis of the leg. The ultrasound method for detection of deep vein thrombosis (DVT) of the leg has been used in a study comprising 47 patients. This method was compared in the same group with a clinical evaluation and was controlled by venography. Clinical evaluation gave a correct diagnosis in 28 (59.6%) of 47 patients, false positive or false negative in 19 (40.4%). With the ultrasound method, the correct diagnosis was made in 41 (87.2%) of 47 patients, false positive in 3 (6.4%) and false negative in 3 (6.4%). No cases were missed of thrombosis situated proximal to the popliteal vein. The method was less accurate in cases of thrombosis situated in or distal of the popliteal vein; the 3 patients in whom a false negative diagnosis was made, belonged to this group. Since the ultrasound method has been shown to give few false positive and false negative results, it should be suitable as a screening procedure in patients with symptoms suggestive of DVT.


Membrane filtration in microscopical examination of urinary sediment. Microscopical examination of the urinary sediment has been performed after membrane filtration and after routine centrifugation, and the results were compared. Various quantities of urine were filtered through a membrane with pore size of 3 micrometer, stained with Shorr stain and made translucent with xylol. All granular and cellular casts were counted on a trimmed membrane, 15 X 20 mm. The routine centrifugation was carried out on 10 ml urine at 1500 rpm for 3 min. Among 11 patients with glomerulonephrits and recurrent hematuria, casts were found in 9 after filtration but in only 2 after routine centrifugation. Casts were detected by the filter method in the urine after angiography of the kidneys in 8 of 12 patients, after centrifugation in only one of them. No casts were found in 6 patients with hematuria due to urological disorders and in 21 healthy persons. The diagnostic sensitivity of microscopical examination of urine was greatly increased by the filter method. This may be due to larger amount of urine examined by the filter method, but an additional cause may be that routine centrifugation destroys red cell casts.


Regulation of plasma aldosterone in anephric and non-nephrectomized patients during hemodialysis treatment. The relationships between plasma aldosterone and changes in plasma potassium, plasma cortisol, plasma sodium, blood volume and body weight have been studied in 6 anephric and 11 non-nephrectomized patients on regular hemodialysis. In all patients, the plasma aldosterone concentration decreased during dialysis. In the anephric patients, a significant correlation (p less than 0.001) was demonstrated between the fall in plasma aldosterone and the fall in plasma potassium (total body potassium depletion). Measurements between consecutive hemodialyses, furthermore, showed a significant correlation (p less than 0.001) in anephric patients between total body potassium repletion (increasing plasma potassium) and the rise in plasma aldosterone. In contrast, the potassium and aldosterone changes did not correlate in the non-nephrectomized group. During dialysis, a decrease was found in all parameters, but no correlation was demonstrable in either group between the changes in plasma aldosterone and the fall in plasma cortisol, sodium, blood volume and body weight. The data in the anephric patients emphasize the important role of potassium in the regulation of aldosterone secretion.


Nephrotoxicity in combined cephalothin and gentamicin therapy. Thirty-two series of treatment with cephalothin and gentamicin for 5-10 days have been administered to 26 patients. An increase in serum creatinine occurred in 6 series. Important factors for the renal damage were elevated pretreatment serum creatinine, elevated serum gentamicin and probably a high serum cephalothin. In 2 patients the nephrotoxicity was fully reversible; the others died before a dicisive improvement in renal function could be expected. In 11 out of 28 treatment series there was a transient drop in serum potassium. Since the combination of cephalothin and gentamicin as the primary treatment of life-threatening infection has often proved effective, and since short-lasting treatment seems to entail only a minute risk of nephrotoxicity in patients with normal pretreatment serum creatinine, we still prefer this treatment in such cases.


Haemodynamics and renal function following injection of bumetanide. Haemodynamics and renal function have been investigated in 12 patients with valvular heart disease before and after injection of 2 mg bumetanide in the right heart catheter. There were no significant changes in oxygen consumption, arteriovenous oxygen difference, cardiac index, heart beats per minute, stroke volume or right and left ventricular stroke work 35 min after the injection, whereas pulmonary and systemic arteriolar resistance showed a slight but insignificant reduction. Mean pulmonary capillary venous pressure, left ventricular end-diatolic pressure, mean pulmonary arterial pressure and mean pressure in the right atrium were highly significantly reduced after injection, systolic left ventricular pressure showing a significant but slight decrease. The creatinine and urea clearances increased considerably during the first 50 min after injection of bumetanide, but diminished during the second period to levels somewhat lower than the initial values. There was also a marked increase in the clearance of sodium potassium, calcium, magnisium and phosphate. It is concluded that bumetanide is a very potent diuretic which changes haemodynamic parameters towards normal values.


Treatment of advanced breast cancer with chemotherapeutics and inhibition of coagulation and fibrinolysis. A case of advanced breast cancer with cerebral metastasis and pleurisy is reported in which irradiation and cytostatics had failed to retard progressive growth and spread of the tumour. Adjuvant therapy with heparin combined with the fibrinolytic inhibitor tranexamic acid was followed by regression of the cerebral metastasis as well as the pleurisy. When last seen one year later, the patient was free from symptoms.


Toxicity of intravenous catheters tested in a human bone marrow culture system. Nine brands of i.v. catheter were tested for toxicity in a human bone marrow culture system, and content and leaching of plasticizers determined. Three catheters showed toxicity to the culture system and three others leached di-2-ethylhexyl-phthalate in appreciable amounts.


Myocardial scintigraphy with 99mtechnetium stannous pyrophosphate in patients with possible acute myocardial infarction. Fifty-six patients with a preliminary diagnosis of possible acute myocardial infarction (AMI) were studied on the second or third day after onset of symptoms by 99mtechnetium stannous pyrophosphate myocardial imaging. The scintigraphy was positive in 25 (44.6%). The final clinical diagnoses upon discharge were: definite AMI in 11 with positive scintigraphy in 9 (82%), intermediate coronary syndrome (ICS) in 37 with positive scintigraphy in 15 (40.5%), postinfarction failure in 4 with positive scintigraphy in 1, no diagnosis of coronary heart disease in 4 patients with negative scintigraphy in all. Of the 37 patients with a final diagnosis of ICS, 25 were admitted to the Coronary Care Unit with chest pain as the only symptom. In this group the mean percentage increase in ASAT was significantly higher in 9 patients with positive scintigrams than in 16 with negative. It is therefore assumed that among patients with ICS, a positive scintigraphy may reflect a more serious myocardial injury than a negative scintigram. Of six patients with an acute tachyarrhythmia and ICS, scintigraphy was positive in the three with the most long-lasting or severe arrhythmmias. False negative scintigrams may be seen in some patients with definite AMI.


Alcohol consumption and hematology.

Alcohol consumption and hematology. A number of hematological variables have been investigated and followed during a hospital stay in a group of 34 non-cirrhotic male alcoholics after acute drinking bouts. The most prominent findings were a rise in reticulocytes, a fall in serum iron and a rise in WBC, especially with respect to the lymphocytes. HB and hematocrit values both fell during hospitalization, while ESR and serum haptoglobin rose. No change was observed in the platelet count. It is concluded that alcohol has marked effects on the hematological system even in subjects without serious liver damage. The results underline the importance of an adequate knowledge of the patient's alcohol habits in the investigation of obscure hematologic abnormalities.


Bioavailability of D-propoxyphene, acetyl salicylic acid, and phenazone in a combination tablet (Doleron): interindividual variation and influence of food intake. The influence of food intake on the bioavailability of three analgesic compounds--propoxyphene chloride, acetyl salicylic acid and phenazone--in a combination tablet, Doleron, has been examined in eight healthy volunteers. A single oral dose was given both on an empty stomach and together with a standardized breakfast meal. The plasma concentrations of propoxyphene, its major metabolite norpropoxyphene, salicylic acid and phenazone were determined by mass fragmentography, spectrofluorimetry and gas chromatography. Concomitant food intake had no consistent influence on the bioavailability of any of the components. Hence, doleron may be taken together with meals as well as between meals. Large interindividual variations in propoxyphene and phenazone concentrations were found, indicating that an optimal effect will not always be obtained by standard doses.


Role of bran in normals. Serum levels of cholesterols, triglyceride, calcium and total 3 alpha-hydroxycholanic acid, and intestinal transit time. After the intake of approximately 24 g wheat bran daily for 5 weeks, 25 trainee nurses showed no changes in the serum levels of cholesterol, triglyceride, calcium or total 3 alpha-hydroxycholanic acid. On the other hand, the study revealed a reduced intestinal transit time with good correlation to an increased frequency of bowel movements. Average body weight fell significantly, by 0.4 kg. The daily caloric intake remained constant throughout the study period, whereas the calcium intake was significantly increased. Among the serum parameters and the dietary constituents, good correlation was found only between serum cholesterol and the dietary cholesterol content. In addition, an inverse relationship was demonstrated between the serum levels of cholesterol and total 3 alpha-hydroxycholanic acid. The significance of this observation is as yet unknown.


Proteinuria following renal arteriography. Report of two cases. Two patients reacting with transitory, massive proteinuria after diagnostic renal arteriography with a commonly used non-ionic contrast medium, metrizoate, are described. One of them developed temporary renal failure; the concentration of urinary albumin reached 330 g/g creatinine. It is suggested that intratubular precipitation of proteins, obstructing urinary flow, might be one factor in the development of her renal failure.


Tachycardia, hypertension and syncope. A case report. A case of orthostatic syncope with tachycardia and hypertension is described. Initially the condition was interpreted as a dysfunction in the neurovascular orthostatic regulation, but extensive physiologic examinations failed to give a comprehensive explanation. A psychiatric examination demonstrated the condition eventually to be hysteriform and the patient was completely cured by psychotherapy.


The effect of 1-alpha-hydroxycholecalciferol on the renal handling of phosphate in parathyroidectomized man. In a previous investigation by our group it was suggested that the stimulating effect of 1-alpha-hydroxycholecalciferol (1-alpha-OH-D3) on the tubular reabsorption of phosphate is mediated via the parallel suppression of the parathyroid hormone (PTH). A direct effect of 1-alpha-OH-D3 on the renal tubule could however not be completely excluded. Therefore, the effect of 1-alpha-OH-D3 was studied in 5 totally parathyroidectomized patients, in whom concomitant suppression of PTH would not occur. TmP/GFR, i.e. the ratio between the maximal tubular reabsorption of phosphate (TmP) and the glomerular filtration rate (GFR), was used as an indicator of the renal handling of phosphate. Estimation of TmP/GFR was performed 1) when the patients were vitamin D depleted and hypocalcemic, and 2) after 14-27 days of treatment with 1-alpha-OH-D3 to obtain stable normocalcemia. In patients with absent parathyroid function, no effect of 1-alpha-OH-D3 on TmP/GFR could be demonstrated. It is therefore concluded that 1-alpha-OH-D3 exhbits no antiphosphaturic effect in the absence of PTH and that the previously demonstrated antiphosphaturic effect of 1-alpha-OH-D3 in man is mediated via a concomitant suppression of PTH.


Bone composition and parathyroid function in chronic renal failure. The development of bone abnormalities has been studied in 24 patients with severe chronic renal failure. The glomerular filtration rate (GFR) was between 5 and 25 ml/min. The mean values of plasma calcium, degree of bone mineralization (P/Hypro) and bone mineral content (BMC) were subnormal, whereas the mean values of plasma phosphorus and serum parathyroid hormone (PTH) were elevated. Analysis of the data revealed that the various parameters became increasingly pathological with decreasing renal function. Serum PTH correlated inversely with both GFR and plasma calcium. The decrease in bone P/Hypro with decreasing renal function could be explained by an inverse correlation to serum PTH. Plasma alkaline phosphatase correlated inversely to both bone P/Hypro and BMC. The present study on individual patients with varying degrees of renal insufficiency shows that the development of secondary hyperparathyroidism correlates with a reduction in the degree of bone P/Hypro and suggests that significant bone changes appear when the GFR falls below 15 ml/min.


Bone, calcium, and hydroxyproline metabolism in hyperparathyroidism and after removal of parathyroid adenoma. Several laboratory parameters have been followed before and after surgery in a 69-year-old woman with parathyroid adenoma and severe skeletal involvement. High preoperative levels of immunoreactive parathyroid hormone rapidly decreased postoperatively, accompanied by a similar fall in the peptide-bound hydroxyproline (HP) excretion in the urine. Renal clearance of free HP was high both pre- and postoperatively, probably because of renal damage associated with the disease. The high serum alkaline phosphatase levels increased slightly after the operation. The patient developed severe postoperative hypocalcaemia, and prolonged calcium supplement therapy was necessary. The results imply a clear correlation between the changes in Ca homeostasis and the breakdown rate of bone collagenous matrix. Postoperative hypocalcaemia was mainly due to the rapid change in the rates of bone formation and destruction.


Bone composition and vitamin D after Pólya gastrectomy. With the aim of evaluating bone phosphorus/hydroxyproline ratio (P/Hypro) as an index of osteomalacia, this bone index and the bone mineral content (BMC) have been investigated together with other indices of calcium metabolism in 27 gastrectomized patients. None of the patients had clinically manifest bone symptoms. The mean values of bone P/Hypro, BMC, plasma calcium and plasma magnesium were subnormal; the mean values of serum parathyroid hormone (iPTH) and plasma alkaline phosphatase were elevated. Mean serum 25-hydroxycholecalciferol (25-OH-D) did not differ from normal. A significant positive correlation was found between bone P/Hypro and serum 25-OH-D, but no significant correlation between bone P/Hypro and BMC. Serum 25-OH-D and bone P/Hypro were significantly lower and serum iPTH was significantly higher in a subgroup of 12 patients with no regular supplementary intake of vitamin D. In conclusion, the gastrectomized patients had blood biochemical evidence of a mild vitamin D insufficiency and the low bone P/Hypro values can be explained by mild osteomalacic changes in bone.


Intermittent melphalan and prednisolone therapy in plasma cell myeloma. Thirty-two consecutive, previously untreated patients with plasma cell myeloma were treated with 4-day courses of melphalan (0.25 mg/kg/day) and prednisolone (2 mg/kg/day) every sixth week. The observation period ranged from 26 to 75 months and the total median survival time was 29 months. 75% of the patients responded to therapy and their median survival time was 42 months. Sex did not influence either the response rate or the survival time. Most patients were treated in an out-patient clinic and required a minimum of check-ups.


Blood pressure and renin during treatment with pindolol. Beta-receptor blocking drugs are known to decrease BP and plasma renin activity (PRA) in hypertensive patients. We treated 31 hypertensive patients with the beta-receptor blocking drug, pindolol, for 3 months. During the first month (mean daily dose 10 mg) and the second month (mean daily dose 14.2 mg) BP and PRA decreased. During the third month of pindolol therapy (mean daily dose 19.0 mg) 16 patients had an unexpected rise of BP towards control levels and PRA levels rose, too. The remaining 15 patients maintained a good antihypertensive drug effect and suppression of PRA. Pretreatment PRA was not related to BP reduction. The change in diastolic BP was not significantly related to that in PRA. The results indicate that low doses of pindolol,10-15 mg daily, will suffice in mild essential hypertension. An increasing frequency of partial drug resistance may be a result of unnecessarily high doses of pindolol.


Renal glucosuria and aminoaciduria.

Renal glucosuria and aminoaciduria. A follow-up examination of five patients in whom renal glucosuria had been diagnosed 7-15 years previously, showed that the condition was unchanged. There was no indication of hormonal abnormalities. Oral glucose tolerance test, with determination of insulin, growth hormone and free fatty acids, showed no difference between the patients and a group of normal subjects. The urinary excretion of insulin and albumin was normal, but two patients turned out to have an increased excretion of certain amino acids, aspartic acid in one and glutamic acid, citrulline and alanine in the other.


Renal excretion of pyruvate, lactate and alpha-ketoglutarate in kidney donors before and after nephrectomy and in patients with terminal uremia. The excretional patterns of lactate, pyruvate and alpha-ketoglutarate have been investigated in 7 patients with terminal uremia and in 10 kidney donors with normal renal function before and after unilateral nephrectomy. Methods for analysis of the three substances in urine were elaborated. In all patients, the levels of renal excretion of lactate and pyruvate were very low, and clearance values were independent of the glomerular filtration rate (GFR). alpha-ketoglutarate clearance varied to some extent with renal function, but no correlation to GFR was found, and exceeded the GFR in uremic patients, indicating that the net result of renal handling of alpha-ketoglutarate may be a tubular secretion.


Relationship between changes in the content of acetylcholine and the activities of acetylcholinesterase and choline acetyltransferase in the hippocampus of the rat after septal lesions. Changes in acetylcholine (ACh) content and acetylcholinesterase (AChE) and choline acetyltransferase (ChAc) activity in the hippocampus were compared after various septal lesions. With the use of a multiple regression model it was shown that the time course of the ACh and enzymic level changes is concordant after total destruction of the septum, but not always after partial damage. Septal lesions produced an effect mainly on bound ACh. The results suggest that the activity of AChE and ChAc is not the rate-limiting factor of the ACh level in the hippocampus. The involvement of other hippocampal neurotransmitters acting through the high-affinity uptake of choline is supposed to play an important role in ACh content regulation.


Differential effects of dorsomedial prefrontal lesions on active and passive avoidance in young and adult rats. In Experiment I, four weanling and four adult rats had dorsomedial prefrontal lesions administered prior to initial 2-way avoidance acquisition, while in Experiment II surgical procedures for eight subjects were interpolated between acquisition and a first generalization test along CS tonal frequency. Results indicated impairment of initial avoidance acquisition following lesions, which recovered after a 30-day interval, permitting generalization testing in extinction. When DM lesions were interpolated between acquisition and testing, the effects on avoidance responding were comparatively minimal, but after 30 days lesioned subjects could not reacquire criterion avoidance levels. In all generalization tests there was little evidence of frequency control in lesioned subjects compared to eight sham operated controls of each age. Age effects in both experiments were confined to somewhat greater deficits and less recovery of responding in the pups. Two additional experiments examined passive avoidance acquisition and retention in 144 rats of 18-20, 30-32 and 100+ days of age after dorsomedial prefrontal lesions administered either prior to (Experiment III) or following (Experiment IV) initial training and testing. These data suggested rather minimal lesion effects since variability in retention was readily attributed to age differences. Data were related to prefrontal deficits that are specific to age and task requirements.


Effects of cardiac vagotomy on heart rate conditioned responses in cats. Normal cats were bilaterally vagotomized at cardiac level and submitted to a classical defensive conditioning using excitatory, inhibitory and differential stimuli. That group was compared with a normal one. Both groups showed an anticipatory bradycardia to the noxious excitatory stimulus and a late deceleration to the inhibitory stimuli. The experimental group presented more variable and labile responses. Basal and intertrial heart rate decreased in normal but not in operated animals. The autonomic regulation of the conditioned bradycardia reflex is discussed according to the hypothesis that both active and passive fear reactions are fundamentally mediated by sympathetic activity.


Auditory intensity generalization after CER differentiation training. Auditory intensity generalization was tested in 32 rats trained in CER (conditioned emotional response) differentiation between the 50- and 70-dB white noise intensities. All generalization gradients showed regular monotonicity across the noise intensity dimension independently on experience with the CS+ value prior to the differentiation training. Two kinds of peak shift were obtained. Stimuli further away from the CS? value and more intense than the CS+ inhibited the on-going food motivated behavior more strongly than the CS+ itself. Stimuli further away from the CS+ value and more intense than the CS? enhanced the on-going behavior more than the CS?. A method of statistical analysis indicated that individual gradients and group data corresponded to the same generalization functions.


New aspects of cerebrospinal fluid dynamics in humans investigated by sequential gamma camera cisternography, with data evaluation by the digital multichannel analyzer. 2nd part: pathology of cerebrospinal fluid flow in the subarachnoid space of the brain convexity. The use of the sequential gamma camera technique with evaluation of the stored information in the digital analyzing system to investigate CSF dynamics quantitatively has given interesting new information about the circulation in the epicortical SA space. The streaming of I131HSA-labelled CSF in a protracted bolus or bulk was submitted to quantitative and temporal analysis by defining the activity maxima and their amounts as well as their times of appearance. Different modalities of activity evolution in various regions make it possible to define three main types of circulatory disturbance, which are: 1. Global epicortical inhibition, 2. circumscribed epicortical inhibition by a) restriction of the SA space, b) dilatation of the SA space, and 3. gamma cisternographic asymmetry, apparently due to restriction, with a fully functioning but dilated SA space and no real inhibition. The pathological conditions in the SA space leading to these different flow disturbance modalities are presented, and the necessity to perform quantitative and temporal analysis for definition of the functional flow conditions is emphasized.


Titanium clips in neurosurgery for elimination of artefacts in computer tomography (ct) a technical note. To eliminate the occurrence of artefacts produced by clips on the CT images, the use of titranium clips is suggested. Tests in vitro and in vivo indicate that clips manufactured from 0.2 mm thick 99.9 per cent titanium do not cause artefacts. They are resistant to corrosion, nontoxic, effective, easy to handle, relatively cheap, and are visible on plain X-ray films.


Suprascapular entrapment neuropathy.

Suprascapular entrapment neuropathy. The unusual syndrome of suprascapular entrapment neuropathy is described with reference to a 19-years-old girl. The most important symptom is pain in and around the shoulder, while wasting of the Spinati muscles is the cardial sign. Surgical decompression of the nerve relieves the pain immediately.


Absent cervical pedicle.

Absent cervical pedicle. Congenital defect of a cervical pedicle produces a rare clinical syndrome with a characteristic X-ray picture associated with vague clinical signs often accentuated after trauma. A careful analysis of the X-ray films, including oblique views, shows the congenital defect of the pedicle and the associated abnormalities which can all be attributed to a defect in the neural arch centre of chondrification. Further X-ray examinations including myelography with or without vertebral angiography as well as surgical exploration should be unnecessary. A case of absence of the right pedicle of the sixth cervical vertebra is described. The symptoms in this patient were not caused by the malformation, but by an associated enlarged seventh cervical transverse process which produced a thoracic outlet syndrome.


[Ventricular fluid pressure measurement by microcatheter and pressure-controlled external fluid drainage (author's transl)]. Long term control of ventricular fluid pressure by means of a ventricular catheter offers the advantage of pressure-controlled external fluid drainage, especially in patients with space-occupying processes which lead to acute disturbances of the fluid circulation. In a measuring system with the possibility of drainage it is advisable to measure the VFP with a microcatheter. The microcatheter is introduced through the drainage catheter. Both catheters are placed in the anterior part of a lateral ventricle. Communication between the drainage system and the transducer is avoided. There is no necessity for frequent disinfection or changing of parts of the system during long term control of the patient. Any occlusion of the drainage system can be recognized immediately because the measuring procedure will not be interrupted by such an occlusion. In 201 patients the ventricular fluid pressure was recorded by the microcatheter method for a total of 1086 days. The infection rate was under 1%. With simultaneous external fluid drainage it rose to 2.2%. For patients with space--occupying processes of the posterior cranial fossa external drainage is recommended for 5--10 days postoperatively as a precaution against rises in CSF pressure.


Functional Queckensted's test in rheumatoid atlanto-axial luxation. Queckenstedt's test was carried out in 15 patients with marked rheumatoid atlanto-axial luxation. The test was done when moving the neck stepwise between flexion and extension, and with the patient in both lateral and sitting positions. The test performed in the sitting position was termed the functional Queckenstedt's test. The flexed position of the neck and the sitting body position, either alone or in combination, were factors contributing to a manometric block. Six more block phenomena were recorded in the sitting compared with the lateral position. As the sensitivity of the test seemed unaffected by body position, this indicated an increased atlanto-axial luxation in the sitting position. This applied to the neutral as well as the flexed position of the neck. There was a fairly good correlation between neurological symptoms and signs and the functional Queckenstedt's test. The use of the test as an aid supplmentary to the clinical and roentgenological findings when deciding on the treatment of patients with rheumatoid atlanto-axial luxation is outlined.


Prostaglandins and the control of muscle tone in the ductus arteriosus. Several lines of evidence implicate E-type PGs in the maintenance of patency of the foetal ductus arteriosus. The PGE mechanism is functional in man, sheep, rat and rabbit, but it is seemingly absent in guinea pig. The role of the PGs in the closure of the vessel at birth is uncertain. Work with different species suggests that as PO2 rises at birth the relaxant effect of PGEs on  the ductal muscle decreases. This decreased sensitivity may facilitate the oxygen triggered contraction. The calf ductus is an exception and its closure may be mediated by PGF2alpha. An important fact emerging from this review is that species may differ with regard to the occurrence and possible function of the PGs in the ductus arteriosus. The significance of these differences to the function of the oxygen-sensing mechanism remains a major question for future research.


Renal handling of sodium, water and divalent ions in patients with primary biliary cirrhosis. 1) Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). In an attempt to clarify this clinical observation, renal handling of sodium, water and divalent ions was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone (ADH) secretion in 5 patients with PBC and 9 normal subjects. 2) Mean fractional excretion of sodium, water, phosphate and calculated fractional distal delivery of sodium were significantly greater in patients with PBC as compared with normal controls. Fractional CH20 for given fractional urine flow was similar in patients with PBC and normals. 3) The data suggest that patients with PBC have a greater diminution of proximal tubular reabsorption of sodium in response to ECVE than controls. This augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this type of cirrhosis.


Minor influence of parathyroid hormone on fractional tubular reabsorption of phosphate in chronic renal failure. In untreated patients with chronic renal failure and glomerular filtration rates (GFR) between 10 and 25 ml/min the decrease in fractional tubular reabsorption of phosphate was correlated to the degree of secondary hyperparathyroidism. This correlation was not found in patients with GFR below 10 ml/min. During treatment with 1alpha-hydroxycholecalciferol for 11 weeks: a) serum parathyroid hormone concentration decreased in all patients on average 60%, and was normal in 5 patients after treatment b) fractional tubular reabsorption of phosphate decreased significantly (on average 0.21) c) glomerular filtration rate decreased significantly (on average 27.5%). Since the reduction (or normalization) of serum parathyroid hormone concentration did not increase the fractional tubular reabsorption of phosphate, other (GFR-related) factors than parathyroid hormone play the major role for renal handling of phosphate in chronic renal failure when GFR is below 25 ml/min.


The maximal tubular reabsorption of phosphate in relation to serum parathyroid hormone. The relation between the renal handling of phosphate and the serum concentration of immunoreactive parathyroid hormone (i-PTH) was investigated in 15 patients with a very wide range of i-PTH, glomerular filtration rate (GFR), maximal tubular reabsorption of phosphate (TmP) and TmP/GFR-ratio. The latter was used as an index of the renal handling of phosphate. Seven patients had well functioning kidney allografts (GFR 43.1-64.9 ml/min), while 8 had varying degrees of chronic nephropathy (GFR 2.3-26.7 ml/min). The TmP, i-PTH, 51Cr EDTA clearance, the extracellular volume and serum concentrations of calcium and standard bicarbonate were estimated. An inverse significant correlation was demonstrated between TmP/GFR and i-PTH (p less than 0.001), while none of the other investigated factors correlated thyroid hormone has a key role in the regulation of the tubular handling of phosphate in patients with impaired renal function.


Inhibition of parathyroid hormone secretion by isoproterenol. Intravenous infusion of the beta-adrenergic agonist isoproterenol produced a fall in the serum concentration of parathyroid hormone. It also produced a pronounced fall in the serum phosphate concentration, and significant increases in blood glucose and serum insulin concentration and in pulse rate. The fall in serum parathyroid hormone was abolished by beta-adrenergic blockage with propranolol. Oral glucose loads produced a pronounced fall in serum phosphate concentration, comparable to the fall after isoproterenol infusion, but no significant changes in serum parathyroid hormone. It is concluded that the fall in serum parathyroid hormone after isoproterenol is due to a beta-adrenergic effect. It is unknown, if isoproterenol acts directly on the parathyroid hormone secreting cell, or the fall in serum parathyroid hormone is secondary to the effect of isoproterenol on other endocrine glands or the cardiovascular system.


Effect of parathyroid hormone and volume expansion on jejunal calcium, sodium, and water transport in the rat. The effects of PTH on jejunal calcium, sodium, and water transport were studied in the rat in situ. In TPTx rats, as well as in normal rats, bovine PTH induced a decrease in net calcium, sodium, and water absorption. Additionally, lumen-to-plasma calcium flux was found decreased in both groups. Stimulation of endogenous PTH secretion by calcium-poor hyperoncotic albumin resulted in a similar decrease in net calcium, sodium, and water absorption. It is suggested that PTH has a direct inhibitory effect on jejunal calcium, sodium, and water absorption.


Influence of vitamin D on bicarbonate reabsorption. The effects of acute administration of 25 hydroxycholecalciferol on bicarbonate reabsorption was studied in dogs. 25 hydroxycholecalciferol infused into the renal artery at a dose of 0.2 microgram/kg/hour led to a small but significant bilateral increase in bicarbonate reabsorption in intact dogs. 25 hydroxycholecalciferol had no effect on bicarbonate reabsorption in thyroparathyroidectomized dogs. The phosphaturia of bicarbonate administration was not altered by 25 hydroxycholecalciferol administration.


Liver endoplasmic reticulum: target site of halocarbon metabolites. Initial injury produced by exposure of rats to carbon tetrachloride, halothane, vinyl chloride or trichlorethylene appears to involve the endoplasmic reticulum. First, there is dispersion of the ergastoplasm, then vacuolization and degranulation of the rough endoplasmic reticulum with concomitant retraction of the smooth endoplasmic reticulum into tightly clumped tubular aggregates. In addition, membranes in these tubular aggregates seem to undergo supra-molecular disassembly. Along with this structural disorganization, functional capacity of the organelle diminishes. Activation of these halocarbons to toxic species by functional elements of the endoplasmic reticulum is indicated by the enhancement of their toxicity by pretreatment with chemicals which induce components of the mixed function oxidase system and by the formation of certain metabolites and/or covalently bound products. Insight into the molecular mechanisms of membrane injury brought about by these halocarbon hepatotoxins has been provided by the characterization of chemical changes produced, such as increased lipid diene conjugate content, and the patterns of enzyme deactivation.


Mechanisms by which small molecules alter ionic permeability through lipid bilayer membranes. Small molecules may be particularly effective cytotoxic agents by way of altering ionic permeability in cell and organelle membranes. The mechanisms by which such molecules may acte on membrane permeability are examined here in light of the rather precise understanding of the mechanisms by which ionic permeability is induced and altered in lipid bilayer membranes. In particular, the influence of specific changes in membrane composition on the kinetics of direct and carrier mediated transport of ions are examined in detail and related to the electrical potentials originating from dipolar residues at the membrane surface.


Altered drug permeability in mammalian cell mutants. The properties of colchicine uptake into Chinese hamster ovary cells were examined and found to be consistent with an unmediated diffusion mode. This uptake was stimulated several fold by metabolic inhibitors. The activation energy of colchicine uptake was found to be 19 kcal per mole; a similar value was obtained in cells stimulated by cyanide. Drug resistant mutants with greatly reduced colchicine permeability have been isolated. They displayed a pleiotropic phenotype, being cross-resistant to a variety of unrelated compounds. The basis of this pleiotropy was due also to reduced drug permeability. Examination of the lipids and fatty acids of parental and mutant cell membranes revealed no major differences. However, a 170,000 dalton surface glycoprotein was observed to be associated with colchicine resistance. This glycoprotein was postulated to be a modulator of drug permeability. All these data are consistent with the concept that mammalian cells are able to regulate the permeation of drugs entering by an unmediated diffusion process.


Lectin receptors and lectin resistance in chinese hamster ovary cells. Chinese hamster ovary (CHO) cells previously selected in a single-step for resistance to one or two different lectins and assigned to individual phenotypic groups on the basis of their unique patterns of lectin resistance, have been examined for their lectin-binding abilites. The lectin-binding parameters of CHO cells were shown to be very complex in a detailes study of the binding of 125I-WGA to wild-type (WT) cells. On the basis of these results, standard assay conditions were established and comparative binding studies between the twenty-two WT and lectin-resistant (LecR) clones were performed. A general correlation of lectin resistance with decreased lectin-binding ability and of lectin sensitivity with increased lectin-binding ability was found, although several exceptions to this trend were observed.


Interactions of acetylcholine receptors with organic mercury compounds. Micromolar concentrations of methylmercury and several organic mercury fungicides were found to block binding of [3H]acetylcholine (ACh) to the ACh-receptor of the electric organ of the electric ray, Torpedo ocellata. The same compounds had little or no effect on the catalytic activity of ACh-esterase of the same tissue. [14C]Methyl-mercury bound to the purified ACh-receptor with high affinity (Kd=7micrometer) and there were 6.5 +/- 0.5 binding sites for each ACh-binding site. Binding of methylmercury was highly cooperative with a Hill coefficient of 2.6. This binding was irreversible by redialysis in methylmercury - free medium, however, the bound [14C]methylmercury was easily displaced from the receptor protein with micrometer concentrations of BAL or penicillamine. Methylmercury also blocked binding of [3H] nicotine and [3H]pilocarpine to the nicotinic and muscarinic ACh-receptors of the rat brain, respectively. The data suggest that the ACh-receptor may be a target for methylmercury and other organic mercury compounds.


Membrane water channels and SH-groups.

Membrane water channels and SH-groups. The transport of water across human red cell membranes is conmonly interpreted in terms of small aqueous channels. This interpretation is based largely on indirect evidence. In this report, two sets of experiments providing more direct evidence for this idea is presented. (1) The effect of various SH-reactive reagents on the movement of water was studied. Using these compounds we attempted to localize and characterize those membrane SH-groups which are important for water transport. (2) Experimental evidence which suggests that these channels are assembled from aggregates of specific membrane protein(s) is presented.


Phenytoin dosage in the elderly.

Phenytoin dosage in the elderly. Measurement of serum-phenytoin concentrations in 17 elderly patients showed that levels of 40 mumol/l or more were not produced by daily doses of less than 300 mg/day, but that doses of 350 mg/day or more produced higher and potentially toxic levels. Determination of mean values for Vmax and Km for phenytoin gave values little different from those for younger patients. The implications of these findings for anticonvulsant therapy in the elderly are discussed.


The effect of ageing on drug absorption from the gut. Single oral doses of aspirin and practolol were given to young and old subjects. The results of the plasma concentration-time curves were subjected to pharmacokinetic appraisal. There was no difference with either drug between the two age-groups in the mean absorption rate constant and the time at which maximum concentration in the plasma occurred. However, the amount of drug in the plasma of the elderly group was the same or higher than that in the younger group. It is concluded that ageing has no significant effect on the rate or amount of these drugs absorbed.


The difficulties of old people taking drugs. There is considerable interest in the problems of the elderly taking drugs correctly and appropriately. A recent survey (Parkin et al. 1976) showed that these problems that have long been known in geriatric practice have now been noted by general physicians. This review was undertaken when an occupational therapist in a geriatric unit team noted that, although patients and their relatives were taught methods of dressing, toileting, shaving, bathing, eating, walking, transferring to a chair, wheelchair mobility and communication by the occupational therapist, physiotherapist and speech therapist, no advice or teaching was given concerning the accurate taking of the drugs prescribed. The results of a detailed investigation are reported elsewhere (Atkinson, Gibson & Andrews 1978). Repeatedly, patients ready for discharge were handed a batch of drugs by a nurse at the last possible moment, even while sitting by their luggage awaiting the ambulance. Following this, special attention was paid to problems such as intellectual impairment, loss of memory and confusion, poor sight, inability to handle containers, failure to take drugs and lack of patient-education. During ward rounds, particularly when a geriatric health visitor was present, attention was drawn to special topics such as the number of patients who inadvertently kill themselves and the numbers needing readmission due to failure to take drugs, overdosage or underdosage or mixing of drugs (Wade 1972). Ferguson Anderson's comment (1974) that 7.15% of hospital admissions are due to drug reactions was also noted.


Thyroid disease in a psychogeriatric population. Over a six-year period, routine biochemical screening for thyroid disease was carried out on 662 patients aged 65 years and older, admitted to the psychogeriatric unit of a major psychiatric hospital. Hypothyroid values were found in 1.2% of the population (8 patients). Hyperthyroid values occurred in 0.76% (5 patients). The thyroid abnormality was considered a significant factor in the psychiatric presentation of only two patients and in both the thyroid disease was clinically apparent. Practical benefits obtained were so disappointing that they did not justify the practice of routine screening in this type of patient.


A simple method of measuring tremor using a variable-capacitance transducer. A simple, inexpensive method of recording tremor, using a variable-capacitance transducer, is described. Technical details of the transducer are given, along with examples of tremor traces illustrating the transducer's ability to monitor parkinsonian patients during drug therapy.


A cheap electro-pneumatic high-low bed.

A cheap electro-pneumatic high-low bed. A cheap, simple high-low bed is described for use in wards without a compressed air supply. A main design feature is ease of operation to ensure that the bed is at the correct height for the patient and nurse and to waste as little as possible of the nurse's time.


Progressive supranuclear palsy.

Progressive supranuclear palsy. In the past four years, four patients with progressive supranuclear palsy have presented to the Department of Geriatric Medicine, Oxford, under the care of one of us (RAG). They were all females whose symptoms began in the sixth or seventh decade. They died from three to six years after the onset of symptoms. All had neuropathological studies which are described. The presenting characteristics included frequent falls, difficulty in walking, nuchal rigidity, abnormalities of gaze, pseudobulbar features and mild dementia. These are features particularly common in the elderly and it is suggested that the condition may be under-diagnosed.


Self-neglect.

Self-neglect. Twenty-five patients suffering from gross self-neglect are described, the majority were discharged home and, while in hospital, appeared to have a good quality of life. These findings are at variance with previous reports.


A histamine-induced decrease of action potential duration in cardiac muscle mediated by the H2 receptors. The effects of histamine (10(-7)--10(-5) M) on the cardiac action potential have been studied in ventricular strips of guinea pig heart, electrically driven at a constant rate. A decrease of action potential was constantly observed at histamine concentrations above 10(-6) M. No significant variations of the other electrophysiological parameters were induced by the amine. The decrease in the duration of the action potential was blocked by burimamide at a concentration (10(-4) M) which induced only a slight changes in action potential outline. It is suggested that the shortening of the repolarization phase induced by histamine is due to the H2 receptor-mediated activation of the calcium inward current, which can increase the intracellular calcium concentration influencing the potassium permeability.


Adrenaline-stimulated, aspirin-sensitive synthesis of histamine in the rat. The intravenous injection of 10 microgram/kg of adrenaline raised total rat lung histamine from 5.3 +/- 0.7 microgram to 8.4 +/- 0.7 microgram and rat skin histamine from 624 +/- 51 microgram to 835 +/- 85 withing 5 min. These changes were no longer apparent after 10 min. Stomach histamine was raised by a statistically non-significant extent, intestinal histamine was unaffected. Blood drawn 2 min after the injection of adrenaline failed to show an increased content of histamine. Rats given 1 mg/kg of compound 48/80, had greatly elevated levels of histamine in blood, but exhibited no increase in lung histamine. This result, as well as the extent of the increase of histamine observed in skin, which cannot be accounted for in any other way, point towards stepped-up local synthesis as the origin of the effect of adrenaline. Aspirin (20 mg/kg, intravenously, 10 min prior to adrenaline), prevented increases of skin histamine. Evidence suggesting mast cells as the site of action of adrenaline, is discussed.


Mechanism for histamine H2-receptor induced cell-cycle changes in the bone marrow stem cell. The treatment in vitro of mouse bone marrow cells with 4-methylhistamine triggered the hematopoietic stem cell (CFU-S) from the G0 state into the S-phase of the cell cycle. In contrast, 2-methylhistamine had no such effect. Metiamide antagonized the effects of low concentrations of 4-methylhistamine. Antagonism by metiamide was reversed by high concentrations of 4-methylhistamine. Imidazole, and activator of phosphodiesterase, also suppressed the cell-cycle effects of 4-methylhistamine. The latter findings suggests that cyclic nucleotides may mediate in the stem cell response to 4-methylhistamine. Blocking the metabolism of endogenous histamine with a combination of aminoguanidine and chloroquine also initiated DNA synthesis in the bone marrow stem cell. Metiamide antagonized the effects of the aminoguanidine/chloroquine combination. These experiments associate a histamine H2-receptor with the hematopoietic stem cell. They also suggest that, if available, endogenous histamine can initiate cell-cycle changes in the pluripotent bone marrow stem cell.


Effect of some central nervous system acting drugs on rat brain and liver monoamine oxidase activity. A number of central nervous system acting drugs were administered to male rats. At certain time intervals after the administration of these drugs, the rats were sacrificed. Liver and brain monoamine oxidase (MAO) activities were determined. The drugs employed were: ethyl alcohol, cognac, hexobarbital, diazepam, imipramine and chloralose. Results obtained indicated that the liver MAO activity was not altered by any of these drugs. Brain MAO activity, contrary to in vitro studies, was increased by alcohol and cognac. The increase was not due to a direct effect of alcohol on the enzyme activity, since the in vitro addition of equivalent concentrations of alcohol, as those calculated to be present in vivo, to brain homogenates resulted in a decrease rather than an increase in activity.


Alteration of Hepatic microsomal enzyme systems and the lethal action of non-steroidal anti-arthritic drugs in acute and chronic models of inflammation. Depression of the hepatic microsomal enzyme system(s) in adjuvant-induced polyarthritis (AIP), a chronic inflammation model, has been confirmed indirectly by the enhancement of hexobarbital Na-induced sleeping time and extended for the first time to zoxazolamine-induced paralysis. In addition, barbital Na-induced anesthesia was increased during the course of AIP development, indicating that the CNS of these rats appears to be more sensitive to drug effects, since this barbiturate is excreted virtually unmetabolized. Most likely because of these effects, LD50 values for acetylsalicylic acid, phenylbutazone and indomethacin in AIP rats decreased in terms of mg/kg (increased toxicity) as the disease became more severe (Day 21) since they are known ultimately to be metabolized by the liver. On the other hand, the toxicity of a new non-steroidal anti-inflammatory agent, meseclazone, was not altered significantly in AIP. This is most likely due to the fact that its near total conversion to 5-chlorosalicylic acid has been shown to occur by hydrolytic cleavage as it pases through the intestinal wall with litter hepatic involvement. Finally, carrageenan edema, a model of acute inflammation, did not affect barbiturate sleeping times of zoxazolamine paralysis, nor were any of these drugs studied more lethal in this disease state.


Activity of various immunosuppressive drugs on tuberculin hypersensitivity reaction in chickens. Drug induced immunosuppression of chicken immune response was studied in F1 hybrids of the CB and IC inbred lines. In tuberculin reaction complete inhibition of wattle swelling was induced by the administration of methotrexate, colcemid (1 mg/KBW), and 6-mercaptopurine. The cellular infiltration was substantially reduced in these cases. Cyclophosphamide and colcemid (0.1 mg/KBW) reduced partially the wattle swelling but had no apparent effect on the cellular infiltration. Acetinomycin D did not affect in measurable degree the wattle swelling. The histologic picture was in this case the same as in the control animals. The same drug administration schedule had less pronounced effect on anti-HSA antibody production. No anti-HSA antibody was found after the 500 mg/animal doses of 6-mercaptopurine. Significant reduction of anti-HSA titres was found after 50 mg/animal doses of 6-mercaptopurine, colcemid (1 mg/KBW), 25 MG/KBW or cyclophosphamide and after the methotrexate treatment.


Smooth muscle sensitization induced by colchicine: is it an in vitro property of antitubulin agents? Colchicine 0.1 microgram/ml induces a reversible increase of guinea-pig isolated ileum contractions (50 to 60% of maximal contractions) to acetylcholine, nicotine and PGE2. At 1 microgram/ml, it induces an irreversible increase of similar contractions to acetylcholine and 5-hydroxytryptamine. Low concentrations of indomethacin are able to reduce or even to abolish this increase. This smooth muscle sensitization could be related to the ability of colchicine to stimulate prostaglandin biosynthesis. Vinblastine has been described to induce a similar in vitro sensitization of guinea-pig isolated ileum. This effect might be also a non-specific property of antitubulin agents. The relationships between such an in vitro sensitization and the clinical effects of colchicine, including diarrhea, remain unclear.


Surgical management of intermittent claudication. The distribution of claudication reflects the anatomic site of stenosis or occlusion. Palpable pedal pulses do not rule out proximal stenosis, nor do weak pulses certify leg pain as claudication. An initial conservative approach is not appropriate for patients with rest pain, ulcers, gangrene, rapid increase in discomfort or dangerous lesions involving major collateral vessels. Early surgical treatment is also advisable for patients whose occupations are in jeopardy. Complete arteriography is essential. Proximal disease must be corrected first.


Giant cell arteritis and blindness.

Giant cell arteritis and blindness. The etiology of giant cell arteritis (temporal arteritis, cranial arteritis) is still obscure. Polymyalgia rheumatica is probably a stage of the same disease. It causes systemic and localized symptoms, usually in patients older than 55 years, and is not uncommon as a cause of loss of vision. The sedimentation rate is unusually high. The diagnosis is defintively established by biopsy. The response to steroid therapy is dramatic.


The tonsillectomy-adenoidectomy dilemma. Tonsillectomy and adenoidectomy (T&A) is the most commonly performed surgical procedure in the U.S. Considerable controversy surrounds this operation because all previous studies have demonstrated experimental flaws that compromise the value of the findings. While an apparent immunologic deficit following T&A has been demonstrated, the clinical significance of this finding is unknown. Normal humoral antibody responses are found after surgery and no increase in clinically apparent viral infection has been shown. T&A consistently normalizes pharyngeal microflora.


When the patient wants facial cosmetic surgery. Cosmetic facial surgery can improve appearance but it cannot make everyone beautiful (or handsome) or solve all problems. The patient must be well motivated and must comprehend the limitations of the procedures. Procedures useful in providing a more youthful appearance include blepharoplasty, browlift and face-lift. Sometimes all three are indicated. Chemical face peeling is used for correction of fine skin lines.


Identifying and treating the drug-misusing patient. The drug misusers whom physicians encounter in private practice are not the stereotypes. Treatment of drug problems is possible on an outpatient basis if physicians are willing to extend their normal role. Overcoming negative feelings toward patients who misuse drugs, employing some basic counseling skills and being aware of the relatively uncomplicated medical procedures involved in therapy can enable the physician to treat certain types of drug misuse in his own office.


Evaluation of the patient with chronic facial pain. A major difficulty in the investigation of chronic facial pain has been a practical classification permitting the selection of appropriate diagnostic procedures to elucidate the etiology of the pain and to provide appropriate therapy. Categorization of facial pain syndromes into vascular, neuritic, muscular, rheumatic, traction and inflammatory and psychogenic groups provides a useful approach to the problem. Despite the utility of this method and advances in noninvasive diagnostic techniques, many pain syndromes remain refractory to full understanding and/or therapy and will test the physician's patience and perseverance.


Alcohol in pharmaceutical products.

Alcohol in pharmaceutical products. Alcohol is the diluent in more than 500 proprietary products and is found in concentrations up to 68 percent. This factor can pose significant problems in patient management; for example, problems can arise in the alcoholic patient under disulfiram therapy, in the patient with active peptic ulcer disease and in the patient under treatment with central nervous system depressants or other substances that interact with alcohol. The alcohol content raises difficulties with abstinence programs and adolescent alcohol abuse. A list of pharmaceutical products containing alcohol is included.


Quieting a wire strander for the tire cord industry. Evaluation of detailed noise and vibration measurements on a wire strander led to the identification of noise sources. The same data were used to optimize the selection of absorption materials while meeting the severe space limitations imposed by the equipment design. The acoustical treatment resulted in a 6-7 dBA noise reduction.


Effects of particle sizes and solubilities of lead sulphide dust on mill workers. A total of 15 mill employees were sampled by means of personal samplers for total airborne lead and respirable air leads while working in a lead sulphide mill. Blood and urine samples were collected from the same workers during the period of the survey. Poor correlations were observed between the total air leads and blood leads for the total subgroups studied as well as between the respirable air leads and blood leads for the smokers. Tests simulating the acidity and retention of lead sulphide in the stomach confirmed the low solubility of this compound.


Loudness Discrimination Index (LDI): a test for the early detection of noise susceptible individuals. Work has been completed at the Environmental Acoustics Laboratory during the past year on developing an industrially feasible Loudness Discrimination Index (LDI) Test. Data obtained on experimental subjects who had been exposed to brief, high-level sound showed that the maximum Loudness Discrimination Index Shift (LDIS-Max.) is a valid and reliable indicator of temporary, noise-induced, hearing change. This test is better suited to industrial usage than the traditional TTS test. Suggestions for the implementation of LDI testing in the industrial setting are discussed.


Chronic inhalation of cobalt oxide and cigarette smoke by hamsters. Exposure of hamsters to CoO aerosol (10 g/L, 7 hrs./day, 5 days/week) caused pneumoconiosis but affected neither the life span nor the incidence of other than pneumoconiotic lesions. No carcinogenic effects of CoO were observed. While cigarette smoke exposures significantly increased the incidence of certain types of other than pneumoconiotic lesions including tumors, they also increased the life span of the smoke-exposed animals significantly. The latter phenomenon may account for the higher tumor incidence in the smoke-exposed animals. No effect of the smoke exposures on incidence and degree of pneumoconiosis was observed. The mean body weights of the smoke-exposed groups were significantly reduced.


An experimental laboratory system to evaluate the industrial fate of toxic volatile inorganic hydrides. This paper reports the development of a gas sampling and static reactor system for identifying potentially toxic volatile byproducts from an industrial process and for characterizing their airborne stability at trace levels. The system has been applied in an exemplary manner to the analysis and fate of diborane and phosphine. The heart of the system consists of a static reactor to which pyrolysis products or other reactants can be added from a flow reactor. The static reactor can be resampled at any time. Methods for identifying and quantifying pyrolysis products by chromatography with multiple detectors and mass spectroscopy are included.


A solid sorbent personal sampling method for the simultaneous collection of nitrogen dioxide and nitric oxide in air. A sampling method is described for the collection of air samples containing both nitrogen dioxide (NO2) and nitric oxide (NO) in the range of 0.5 to 5 ppm NO2 and 9 to 50 ppm NO. These two gases are trapped on a solid sorbent sampling tube which employs the collection of the NO2 on a triethanol-amine (TEA)-impregnated molecular sieve surface; the oxidation of NO to NO2 by a solid oxidizer; and the collection of the converted NO on another section of TEA sorbent. The trapped NO/NO2 on each TEA section is desorbed and the concentrations are determined spectrophotometrically. At all concentrations tested, the collection efficiency for NO2 averaged approximately 96%. The collection efficiencies for NO were as follows: at 9 ppm, 97%; at 11 ppm, 106%; at 24 ppm, 84%; and at 50 ppm, 67%.


Effect of chemical defoliation on leaf and bract content in raw cotton. Chemical defoliants are applied to about 40% of the U.S. Cotton acreage as a harvest-aid practice prior to machine picking. Raw cottons derived from defoliated and nondefoliated fields were examined for content of bract and leaf trash Chemical defoliation lowered, but did not remove, leaf as a major trash component. The content of bract was unaffected by this harvest-aid practice. The histamine content in green leaf trash was 10X that found in nongreen leaf trash.


A new personal dosimeter for the monitoring of industrial pollutants. A new passive sampling device (GASBADGE dosimeter) has been developed for personal/ambient monitoring of industrial air pollutants. Compact and convenient to use (no pump, wet chemicals, or length of stain estimation required, etc.), it may be either worn or used for area monitoring. The operating principle is based upon Fick's first law of diffusion. Analysis of the collection element after exposure yields the time-weighted (TWA) exposure concentration. Promising results have been obtained to date in controlled exposures with sulfur dioxide and nitrogen dioxide. Preliminary data also indicate the applicability of the GASBADGE dosimeter to the monitoring of a wide variety of organic vapors.


Cotton dust sampling, III-estimation of statistical errors with vertical elutriators. Cotton dust levels measured by vertical elutriators have been studied in terms of the variance components associated with statistical errors due to sampling equipment, location, time and repeated sampling. A thumb-rule is proposed for estimating sampling errors of three-hour vertical elutriator samples as a function of average dust level. Relative efficiency of three-hour samples is shown to be superior to that of six-hour samples at moderate dust levels (0.4-0.6 mg/m3) but inferior at low dust levels (0.1-0.2 mg/m3. Errors due to location and equipment are found insignificant from this particular study.


Cotton dust sampling, II--vertical elutriation. Cotton dust sampling by vertical elutriation has existed since 1970. Early medical correlations using this method of sampling used median values instead of mean values because of unexpected high and low values. The methodology necessary to obtain consistent results is difficult to achieve and worthy of review.


Chromatographic determination of aromatic hydrocarbons in ambient air. A gas chromatographic method has been developed for the determination of aromatic hydrocarbons in solvent mixtures. Bulk solvents and charcoal tube air samples may be analyzed. The procedure utilizes the unique separation characteristics of a gas chromatographic column containing a highly selective stationary liquid phase, N,N-bis (2-cyanoethyl) formamide. The interfering oxygenated solvents are extracted using 75 percent H2SO4. An 11-foot, 35 percent CEF column may be used to qualitatively analyze the lower boiling aromatic hydrocarbons (benzene, toluene, xylenes). Total or specific aromatics are then quantitated using a 3-foot, 35 percent CEF column with an internal standard. Applications of liquid chromatographic concepts to this analysis were also investigated.


Clinical experience with the Smeloff-Cutter aortic valve prosthesis: an 8-year follow-up study. A total of 46 patients who survived aortic valve replacement with the present model Smeloff-Cutter prosthesis between 1968 and 1973 were followed up postoperatively. All patients received oral anticoagulant therapy. The average age at implantation was 44 +/- 13 (mean +/- standard deviation) years; 36 patients were male and 10 were female. The valve damage was caused by rheumatic disease in 19 (41 percent), infective endocarditis in 14 (30 percent), congenital heart disease in 7 (15 percent) and other factors in 6 (13 percent). Late death occurred in eight patients (17 percent). All available patients were followed up until December 1976. During the 8 years of follow-up study, seven patients, including four heroin addicts, had postoperative endocarditis (15 percent); five of the seven had cerebral involvement, possibly from septic emboli. Four patients were reoperated on; three had active endocarditis and one had a high transvalve pressure gradient. The mean follow-up time was 4.9 years per patient. Of the 38 living patients, 33 have functional improvement and are still being followed up. Only one patient had a bland embolism to a systemic artery. No ball variance or other types of material failure have been detected. Although the chronic aspects of valve disease remain after prosthetic valve replacement, the Smeloff-Cutter aortic prosthesis deserves strong consideration when selecting a rigid prosthesis for aortic valve replacement.


Significance of subendocardial S-T segment elevation caused by coronary stenosis in the dog. Epicardial S-T segment depression, local ischemia and subsequent necrosis. A model of partial thickness ischemia has been developed using subendocardial S-T elevation without epicardial S-T elevation to detect partial thickness ischemia which is sufficient to cause subsequent necrosis. Subendocardial blood flow in this model (measured with radioactive microsphere techniques) may be reduced to 25 percent of normal (P less than 0.001) by coronary stenosis and tachycardia while subepicardial flow remains normal. Epicardial S-T depression seems to indicate reciprocally subendocardial S-T elevation as long as a layer of nonischemic epicardial muscle is present, but when ischemia becomes transmural, epicardial S-T elevation occurs. Regional pressure-flow relations were determined as distal coronary pressure was reduced at a constant aortic pressure, heart rate and cardiac output. These relations revealed remarkably effective autoregulation of epicardial blood flow concomitant with progressive subendocardial ischemia.


Evolution of regional ischemia distal to a proximal coronary stenosis: self-propagation of ischemia. The temporal evolution of myocardial ischemia was studied in open chest dogs at constant preload, afterload and heart rate. In one group of animals, a variable circumflex arterial stenosis was used to maintain constant distal circumflex arterial hypotension (40 to 50 mm Hg). During a 3 hour period of stenosis, flow in the subendocardial fourth of the ischemic ventricular wall decreased from 0.22 to 0.09 ml/g per min (P less than 0.02), whereas subepicardial flow was not significantly changed. Local vascular resistance, therefore, doubled in the most ischemic area of myocardium. In a second group of animals in which proximal coronary stenosis was held constant and pressure varied, an ischemia-mediated increase in local vascular resistance was also demonstrated. In addition, a reciprocal relation was observed between changes in flow in the left anterior descending coronary region and changes in collateral flow to the region of the circumflex artery. A coronary steal mechanism and an ischemia-mediated resistance increase may be two means by which ischemia is self-propagating.


Cross-sectional echocardiographic features of Ebstein's anomaly of the tricuspid valve. Multicrystal real time-motion echocardiographic studies of 10 patients with Ebstein's anomaly of the tricuspid valve are reported. Eight patients also underwent hemodynamic and angiographic study. All but one of the patients had inferior and leftward displacement of the tricuspid valve. In seven patients multiple echoes were obtained from the tricuspid valve, all seven manifested elongated tricuspid valve leaflets, and in six the leaflets were thickened. Excessive excursion of the tricuspid valve was noted in five patients and a "whipping" motion seen in three. Nonspecific findings in nine patients included an increased right ventricular dimension and systolic anterior septal motion. Thus, cross-sectional echocardiography provides distinctive diagnostic findings that are specific for Ebstein's anomaly.


Atrial defect size after Blalock-Hanlon atrioseptectomy. In transposition of the great arteries, a Blalock-Hanlon closed atrial septectomy is performed to improve intracardiac mixing at the atrial level. Although the Blalock-Hanlon septectomy is a common surgical procedure in cyanotic congenital heart disease, it has not been adequately assessed pathologically. In 14 heart specimens from patients (aged 3 days to 19 years) with transposition of the great arteries and Blalock-Hanlon septectomy, the margins of the septectomy, fossa ovalis and atrial septum were identified. The total area of the septum and its defects was calculated using planimetry. The ratio of defect size to atrial septal area was expressed as percent communication, which ranged from 5 to 39 (mean 18) percent in eight specimens with intact limbus of the foramen ovale and 26 to 57 (mean 42) percent in six specimens in which the limbus had been excised. The finding that specimens in which the Blalock-Hanlon defect extended into the fossa ovalis had the largest total communication emphasizes that to obtain optimal bidirectional atrial mixing the surgeon should extend the Blalock-Hanlon procedure across the limbus into the foramen ovale.


Results and complications of intraaortic balloon pumping in surgical and medical patients. The intraaortic balloon was attempted for therapy in 94 patients and successfully placed in 86. The balloon catheter could not be passed through the femoral or iliac artery in 12 patients (13 percent) of the group; in 4 of these the balloon was inserted through an aortic arch graft. The medical indications were cardiogenic shock and preinfarction angina. Ten of the 14 patients in the group with shock survived when treated with an aortic balloon without emergency surgery. Indications for balloon pumping in the surgical group included inability to wean the patient from the pump-oxygenator, postoperative shock and prophylactic placement of the balloon for poor ventricular function. Inability to remove a patient from pump-oxygenator support was the most common surgical indication, and 47 percent of patients were long-term survivors. Only 1 of the 17 patients for whom balloon pumping was used prophylactically died. Complications occurred in 17 percent of the entire group of 86 patients although the rate for medical patients with cardiogenic shock was 50 percent. The most common complication was arterial insufficiency requiring removal of the balloon. Four patients had permanent damage to the legs from ischemia, one patient requiring bilateral amputation. The overall incidence of serious arterial obstruction was 10 percent. Other complications included balloon displacement with arterial obstruction and pericardial tamponade from anticoagulant agents resulting in death.


Loeffler's endocarditis presenting as mitral and tricuspid stenosis. Loeffler's endocarditis characteristically produces cardiac dysfunction by the combined effects of endocardial fibrosis with restriction to diastolic inflow and intracavitary thrombosis with partial cavity obiliteration. Although valve dysfunction may complicate this condition, it is rarely of primary hemodynamic significance. This report describes an unusual case in which mitral and tricuspid stenosis were the primary cardiac lesions. Because of the critical nature of the valve stenosis, surgical intervention was attempted despite evidence of left ventricular involvement. This case suggests than when significant valve dysfunction complicates Loeffler's endocarditis, surgical revision may be undertaken with at least temporary amelioration of the valve disorder and without apparent adverse effect on the underlying disease process.


Echocardiographic study of malfunction of the Bjork-Shiley prosthetic heart valve in the mitral position. This report presents an echocardiographic study of four cases of malfunction of the Bjork-Shiley prosthetic heart valve in the mitral position. The malfunction was proved in all patients by cardiac catheterization, observation at cardiac surgery or findings at postmortem examination. Two distinctive motion patterns of the malfunctioning valves were detected in the echocardiogram. One was a rounded and slowed pattern of opening and closure that correlated with the presence of abnormal clotting on the prosthesis (two patients). The other was an unusual "hump" during the opening phase that correlated with significant perivalve leak (two patients). These patterns along with other observations appears to be valuable in recognizing mitral valve Bjork-Shiley prosthetic malfunction with echocardiography.


Chest pain and bilateral atrioventricular valve prolapse with normal coronary arteries in isolated corrected transposition of the great vessels. Clinical, angiographic and metabolic features. A man evaluated for disabling chest pain was found to have isolated anatomically corrected transposition of the great vessels. Angiography demonstrated right and left atrioventricular (A-V) valve prolapse and normal coronary arteries. Atrial pacing produced chest pain, ischemic electrocardiographic changes, abnormal myocardial lactate metabolism and marked elevation of the left ventricular end-diastolic pressure; all of these changes returned to normal on termination of pacing. The association of corrected transposition and bilateral A-V valve prolapse and the possible causes of myocardial ischemia in this patient are discussed.


Isolated ventricular discordance and complete atrioventricular canal in situs inversus. Report of successful surgical repair. Isolated ventricular discordance is a very rare malformation, most often lethal in the first months of life. A patient with this lesion survived to age 9 years in spite of the coexistence of a complete form of atrioventricular (A-V) canal. Surgical repair with a Mustard procedure was associated with correction of the endocardial cushion defect. Situs inversus itself caused no problem. Although permanent complete A-V block occurred, the result has been satisfactory so far. This case is thought to be the first successful correction of this malformation.


Mechanism of early "pump" failure of the ischemic heart: possible role of adenosine triphosphate depletion and inorganic phosphate accumulation. A marked reduction in oxygen tension and adenosine triphosphate (ATP) content accompanies the early "pump" failure of the ischemic heart. However, it appears to be unlikely that decreased ATP supplies for energy-consuming reactions in the myocardial cell cause the observed decrease in myocardial contractility because of the high ATP-affinity of the substrate-binding sites of known energy-consuming reactions in the heart. Furthermore, lack of chemical energy for the contractile proteins and known ion pumps would tend to promote rigor and not a decrease in contractility. Recent evidence suggests that ATP at concentrations greater than those needed to saturate the substrate-binding sites of energy-consuming reactions can exert modulatory effects on ion fluxes. These modulatory effects of ATP could allow a less severe decrease in ATP concentration to inhibit both calcium entry into the myocardial cell and calcium efflux from the sarcoplasmic reticulum. In addition, the large amounts of phosphate liberated from phosphocreatine and ATP could, by causing formation of insoluble calcium-phosphate precipitates, trap calcium in the sarcoplasmic reticulum and mitochondria in the ischemic myocardium. These proposed explanations for the early "pump" failure in the ischemic heart, together with other theories such as intracell acidosis, appear to warrant further study.


Prediction of human nitrogen balance from food intake data. Nitrogen balance data from 1,813 nitrogen balance days on adults and 141 nitrogen balance days with young children were compared with that predicted from food intake and body weight data using the equations developed by Miller and Payne. In addition, 14-day growth data from 378 infants were also compared with those predicted assuming a constant relationship between positive nitrogen balance and weight gain. The original Miller-Payne equations were found to predict with poor accuracy, and various modifications have been proposed which include changing of the exponent for body weight, addition of a factor for activity, lowering of the value for endogenous nitrogen losses, and attempting to allow for the nonlinear relationships at low levels of intake. New equations are proposed including these modifications which can significantly improve the accuracy of prediction of nitrogen balance and growth from food intake and body weight data.


Comparison of glucose and fructose tolerance before and after starvation. Glucose and fructose were studied in eight healthy volunteers who fasted twice for 4 days. Before and after the fasts each subject received a 4-hr glucose or fructose infusion providing 0.5 g/kg/hr. Glucose infusion during starvation resulted in a mean maximal plasma glucose rise of 401 +/- 21 mg/100 ml (+/- SEM) as compared to 119 +/- 10 mg/100 ml before starvation. Insulin/glucose ratios were lower than normal in fasted subjects. Fructose infusion during fasting produced a maximal plasma glucose rise of 91 +/- 9 mg/100 ml as opposed to 5+/-1 mg/100 ml before starvation. During fructose infusion in the fasted state, plasma fructose levels were higher than control and the rise in blood lactate and pyruvate was delayed, but finally lactate concentrations were above control values. The antiketotic effects of intravenous glucose and fructose were similar during fasting but fructose was significantly less potent in reducing free fatty acid levels. After starvation, urinary carbohydrate losses during glucose infusion were 5 times higher than those observed during fructose infusion. Thus, fructose utillization was less impaired during fasting than was glucose utilization, although fasting induced abnormalities in both glucose and fructose metabolism.


Intakes and serum levels of protein and iron for 70 elderly women. Calculated protein and iron intakes, serum protein levels, and measurements of iron nutriture for elderly women were related to age, income, education, and type type of residence. Low or deficient levels of total serum protein and albumin were observed for 36 and 20% of the subjects and low hemoglobin and elevated total iron-binding capacity values were recorded for 19 and 40% of the subjects. Values below the acceptable standards for albumin and hemoglobin and above the acceptable range for total iron-binding capacity were greater for nursing home patients than for private home residents. Nutrition intervention appears to be a crucial part of correction of the deficient biochemical measurements which may result from malnutrition and/or pathological conditions.


Effect of severe kwashiorkor on intellectual development among Nigerian children. A study was conducted to investigated the intellectual sequelae of severe kwashiorkor among Nigerian children of school age. The design for the study had an experimental urban kwashiorkor (index) group and four control groups, namely, a sibling group, a lower class group, an upper class group, and a rural kwashiorkor group. Various psychological tests measuring specific intellectual abilities were administered to all of the subjects taking part in the study. The findings showed that the index group had lower levels of certain types of intellectual skill-specifically the higher cognitive skills-at school age than their siblings, and more so than other controls except their rural counterparts; males showed a tendency to be more affected by severe kwashiorkor with regard to mental development than their female counterparts; there was no relationship between scores in the psychological tests and the ages at which the index cases were admitted into hospital; the upper class was clearly superior in performance of the tests and also in measures of weight and head measurements when compared to all of the other groups; there was no relationship between head circumference and scores in the tests among subjects in the five groups.


The impact of infection on vitamin metabolism: an unexplored area. Very little work has been done to answer the question: What is the effect of an infectious process on vitamin metabolism? The few studies that have been done would indicate that in the acute phase of an infection there is a redistribution of vitamins as well as other nutrients; these changes can be interpreted as indicating an adaptive and perhaps beneficial response of the host in meeting the challenges imposed by the infectious agent. It is accepted that chronic infection may lead to nutrient depletion, but it is not clear that in the normal healthy individual the administration of vitamins during an acute infections is of any benefit. One can certainly argue that during the infectious process the administration of vitamins and perhaps other nutrients could conceivably afford some protection were the infectious process to continue for some time. This raises other questions concerning the effects of chronic infection and whether or not they occur in well or malnourished individuals.


Inappropriate secretion of antidiuretic hormone in children with bacterial meningitis. A prospective study of bacterial meningitis in children was initiated two years ago. Serum sodium concentrations below 135 MEQ/liter were noted on admission in 72 of 124 (58.1 %) of patients enrolled in the study protocol. Low initial serum sodium concentration and prolonged depression in serum sodium despite fluid restriction correlated significanly (P less than 0.001 to 0.01) with the presence of neurologic sequelae of the disease. Inappropriate secretion of antidiuretic hormone as the cause of these electrolyte changes could be inferred by indirect measurement of serum and urine solute and volume data and was specifically documented, in patients enrolled most recently, by specific radioimmunoassay of antidiuretic hormone.


Nutritional assessment and support during infection. Protein malnutrition is one of the principal factors relating to morbidity and mortality during infection. Nutritional assessment is required to determine the severity of depletion and degree of hypermetabolism affecting this patient population. Simple anthropometric and 24-hr urine collections together with routine biochemical analyses can readily allow clinical assessment to occur. Optimal utilization of dietary intake is dependent on the degree of protein catabolism and energy expenditure in excess of the basal energy requirement. Urinary nitrogen excretion in 24-hr on a protein-free diet is especially valuable in aiding this assessment. This analysis together with urinary creatinine which provide important estimates of lean body mass and serial measures will allow estimates of the progression of malnutrition. In infected adults optimal protein intake to produce positive nitrogen balance is 1.5 to 2.0 g of protein/kg per day. This would appear to reflect the fact that 16% of the caloric expenditure comes from protein sources during injury. Since this value is approximately twice that seen during nonstress, the reutilization of body protein would appear to be decreased. Careful appreciation of the metabolic response during infection is necessary prior to consideration of the nutritional support plan. Knowledge regarding the phase of infection, severity of nutritional depletion, and degree of hypermetabolism will influence the attainable goals of nutritional support.


Total body protein catabolism in starved and infected rats. The catabolic effects of starvation alone, or starvation in the presence of pneumococcal sepsis, were compared in rats whose skeletal muscle protein had been tagged 14 days earlier with 14C-phenylalanine. In a fed rat, protein catabolism (as estimated by expired 14CO2) is not constant throughout the day but is highest during the dark hours. Starvation is associated with accelerated protein catabolism and a gradual loss of periodicity. Infection increases the rate of catabolism still further and results in a complete loss of periodicity.


Specific metabolic effects imposed by Streptococcus pneumoniae upon the response to femoral fracture in the rat. The possible potentiation of an infection upon the metabolic consequences of trauma was tested in rats using a 2 X 2 block design which included control, femoral fracture, pneumococcal infection, and fracture plus infection groups. Infection introduced unique metabolic effects different from those of starvation, femoral fracture, or both together. Infection-induced effects included an accelerated conversion of 14C-alanine to glucose, higher serum haptoglobin, alpha2-macrofetoprotein, copper, and ceruloplasmin values, and lower serum iron, zinc, and transferrin concentrations. The first three of these infection-induced effects were diminished in rats with a femoral fracture. No measured effect of infection was increased in traumatized rats.


Failure of yellow fever immunization to produce a catabolic response in individuals fully adapted to a protein-sparing modified fast. In previous studies, patients consuming a protein-sparing modified fast (PSMF) did not develop the expected increase in nitrogen excretion following incidental infectious illness. To assess the catabolic response with a controlled infection in such patients, 17-D yellow fever vaccine was administered to four young obese adults after 3 weeks of this hypocaloric regimen (PSMF), essentially carbohydrate-free and providing 1.5 g protein/kg ideal body weight. Average daily nitrogen excretion from the third week of the PSMF was compared to values from the week following immunization. Contrary to the experience with malnourished children being nutritionally rehabilitated or young adults fed an adequate calorie, low (0.1 g/kg body weight) protein diet, neither urinary nitrogen excretion nor nitrogen balance was significantly affected in the study group. In three of the four subjects in the group, average nitrogen balance was positive in the week pre-and post-yellow fever immunization. In individuals fully adapted to a PSMF the metabolic consequences of mild infection on nitrogen metabolism were reduced. This may be because the usual catabolic hormones, glucocorticoid and glucagon, which are elicited by infection fail to increase nitrogen excretion in fasting or whenever dietary carbohydrate is excluded.


Interaction of nutrition and infection: plans for future research. Future research concerning the interactions between infectious disease and nutritional status must extend our available knowledge concerning these two major problem areas. Critical studies must be designed in animal models as well as in man. The effects of malnutrition on immune responsiveness must be studied. Key information is lacking with respect to the utilization of host energy and protein during infection. Alterations in body chemistry are especially important in protracted diarrheal and respiratory diseases of children. A concensus has not yet been reached concerning the optimal approach to iron nutritional needs during infection or to those of other trace nutrients including the vitamins. Research needs in each of these areas are listed.


Carboxyhemoglobin concentrations in flash fire victims: report of six simultaneous fire fatalities without elevated carboxyhemoglobin. Eight people died in a traffic accident involving a tractor-trailer and ten autos. The accident caused a series of flash fires from ruptured gas tanks. Complete autopsies established that six of the victims died exclusively from thermal trauma; none showed an elevated blood carboxyhemoglobin concentration. Flash fire victims are exceptions to the axiom that elevation of blood carboxyhemoglobin is a sine qua non for concluding that a decedent recovered from the scene of a conflagration was alive in the fire.