Quantitation of the beta-elimination reaction as used on glycoproteins. The carbohydrate side chains of mucus-type glycoproteins are O-glycosidic bonds between N-acetylgalactosamine to the hydroxyl groups of serine and threonine in the protein core. The alkaline catalyzed beta-elimination reaction, in the presence of sodium borohydride, is used for determining the number of side chains. The present paper presents a study of the quantitativeness of the alkaline borohydride procedure, using four parameters: the loss of seryl and threonyl residues, the formation of alanine and 2-aminobutanoic acid; the decrease in N-acetylhexosamine and the recovery of the amino sugar alcohols. Bovine, ovine and porcine submandibular glycoproteins were studied. Evidence is presented for the existence of N-acetylglucosamine involvement in O-glycosidic linkages to serine and threonine. Results for the relative rates of beta-elimination indicate that serine-linked glycosides are released more rapidly than threonine-linked glycosides.


Cyclic peptides. II. Synthesis of AM-Toxin I. To confirm the structure of AM-toxin I (a phytotoxic cyclotetradepsipeptide) the proposed peptide was prepared by a conventional method. The synthetic peptide and natural AM-toxin I were identical as regards t.l.c., u.v., mass spectra and biological activity in causing necrosis on apple leaves. A prepared dimer of AM-toxin I showed extremely weak activity; the relationship between the ring size and biological activity of AM-toxin I is discussed.


On some methods for EEG pattern discrimination. Two methods of statistical inference for EEG pattern discrimination are described with examples of their application. One concerns whether an arbitrary EEG pattern belongs to a standard EEG group or not, and the other concerns whether a group of EEG belongs to the standard EEG group.


D-Amphetamine thermal effects, metabolic rate and motor activity in rats. The effect of d-amphetamine-induced hypothermia among rats maintained at a cold ambient temperature is related to its ability to release dopamine in the dopaminergic neurons in the mesolimbic pathway. However, the physiological mechanisms which mediate the hypothermia (heat loss or a decrease in heat production) are not known. Since we have failed to demonstrate effects induced by d-amphetamine on food intake or on heat sensors on the rat's tail we conclude that these are not the mechanisms involved in hypothermia. Effects of d-amphetamine on O2 consumption and CO2 production of rats kept at various ambient temperatures were investigated in order to find out if there is any relation between a decrease in body temperature and a decrease in the Basal Metabolic Rate. Neither such relations nor any relations between levels of body temperatures and levels of motor activity were found. The problem of the peripheral mechanisms involved in d-amphetamine-induced hypothermia remain as yet unidentified.


A configuration of cortical coupling differentiating good from poor readers. Thirty-one children, aged 8-5 to 10-11 years, were divided into three groups according to reading levels (poor, borderline, and good), and EEGs were recorded during conditions of rest, light flash, click, and flash/click. The hypothesis that cortical coupling patterns in the left angular gyrus differentiate good and poor readers was supported.


Neural modeling of human behavior: a proposal for a new type of modifiable synapse. Presently published neural models for the stimulation of human behavior have reached a limit in terms of their ability to account for the complexity and magnitude of such behavior. In this paper, these limitations are explored, and a new model is presented which overcomes them. The model employs a new type of modifiable synapse which allows for the integration of three separate bits of information rather than the conventional two bits.


The effects of d-amphetamine and temperature on p-cresol and pentylenetetrazol induced convulsions. Each of twelve (12) rats were subjected to temperatures of 37c, 20c, and 4c in an environmental chamber. Seizure responses to p-cresol injections produced a U-shaped function, with minimal seizures occuring at 20c. Subsequent administration of d-amphetamine eliminated seizures, except at 4c, at which temperature only stereotyped behavior was observed. Environmental temperature effects on metrazol injections in a second group (N=72) seemed to increase linearly with respect to seizure susceptibility and mortality, although latency to first seizure was also a U-shaped function. The findings are discussed in the context of developing a model of epilepsy appropriate for behavioral research.


Effects of light-deprivation on visual discrimination in adult rats. The effects of light-deprication on light flux discrimination by adult rats were tested by a conditioned lick-suppression technique. Total binocular light-deprication for a period of 37-38 days leads to decreased discrimination of the CS (a reduction of 0.64 log units in illumination) by adult rats. The argument is made that these data indicate sensory deficit in the adult animals resulting from binocular light-deprivation.


Ocular-motor effects on the human electroencephalogram. In response to the findings that gross vertical and horizontal eye deviation can be associated with facilitation of the human EEG alpha rhythm, an hypothesis is suggested that the deviation of gaze which exceeds a critical angle and results in a loss of subjective ocular stability is related to the occurrence of the paradoxical alpha effect.


Characterization of self-stimulation elicited from rat dorsolateral pariaqueductal gray. Rats were stereotaxically implanted with chronic bipolar electrodes aimed at the periaqueductal central gray (PCG) and were subsequently tested for intracranial self-stimulation (ICSS) behavior. Consistent and reliable ICSS behavior was elicited from both the midventral and dorsolateral portions of the PCG, the latter result occurring in loci previously reported as predominantly aversive. Midventral PCG ICSS rates were significantly higher than dorsolateral PCG ICSS rates. The higher rates were not accounted for by either current intensity used or motor artifacts. Moreover, both sites displayed reliable ICSS behavior characterized by regular low-variability rates and no seizure activity, seen with other brainstem ICSS sites, but unlike diencephalic and telencephalic ICSS behavior which is characterized by irregular bursts of responding which are highly variable and sometimes accompanied by seizures. The differential ICSS responsivity between PCG structures suggests that they may be mediated by different anatomically-localizable substrates.


Component activities in the autoregressive activity of physiological systems. The higher-order autoregressive (AR) activity of a physiological system (Sato 1975a,b; Sato et al., 1977) was decomposed into first- and second-order activities. The former time-pattern displays a fast rise and an exponential decay, while the latter exhibits a damped sine wave. Application of this component analysis to EEG showed the first-order activity to coincide with the nonoscillatory delta component. The frequency distribution of the natural, damped and resonance frequencies of the second-order activities was found to show one, two or three modes in each frequency range of the delta, theta and beta rhythms in ninety normal adult EEGs. Hence, the second-order activities agree with the oscillatory delta, theta, alpha and beta rhythms. Some changes were induced not only in the frequency of theta and beta rhythms but also in that of alpha rhythm by over-breathing for about three minutes.


Effect of ethanol administration on thiamine metabolism and transketolase activity in rats. To clarify the effect of ethanol on thiamine metabolism and activity of transketolase, a thiamine dependent enzyme, in vivo and in vitro experiments were carried out. For the in vivo experiment, rats were separated into four groups: Group 1, thiamine sufficient diet with no ethanol administered; group 2, thiamine sufficient diet and ethanol administered by stomach tube; group 3, thiamine deficient diet with no ethanol administered; group 4, thiamine deficient diet and ethanol administered. After three weeks, the rats were killed, then thiamine levels and the activity of transketolase were assayed. Thiamine concentration in brains and livers of ethanol fed rats were lower than that in control rats. Urinary thiamine was higher in ethanol administered rats than in controls. The increase in the liver transketolase activity by the in vitro addition of cocarboxylase (TPP effect) was higher in group 3 than in group 4 although original transketolase activity was lower in group 4. For the in vitro experiment, various amounts of ethanol or acetaldehyde were added to the supernatant of brain and liver of intact rats, and transketolase activity was determined. Inhibition by acetaldehyde to transketolas was about 10 times higher than that by ethanol.


Thiamine status of institutionalised and non-institutionalised aged. Thiamine status of 196 institutionalised (in hospital, residential accommodation and sheltered dwelling) and non-institutionalised Caucasian aged subjects was assessed by combined dietary, biochemical and clinical studies. Fourteen subjects (7.1 per cent) consumed less than two-thirds of recommended vitamin B1/DAY. Erythrocyte transketolas activity coefficient (a) test indicated biochemical deficiency of thiamine in 17.6 per cent males and 12.5 per cent females. The incidence of deficiency was highest in subjects of sheltered dwelling. Multivitamin supplementation failed to raise the biochemical thiamine status to normal in 2.9 per cent subjects. No characteristic clinical features of thiamine deficiency were noted, though extreme loss of appetite was reported by 3 subject with activity coefficient greater than 1.30. Dietary intake was not always associated with deficient biochemical indices. The possible factors such as alcohol intake and low folate status affecting the biochemical status of thiamine are discussed.


Riboflavin status of institutionalised and non-institutionalised aged. A combined dietary, biochemical and clinical study was carried out on 196 aged subjects residing at home and institutions (hospital, residential accommodation and sheltered dwelling) to evaluate the nutritional status of riboflavin and to assess the effect of regular vitamin supplementation. The dietary intake of vitamin B2 was below two-thirds of the recommended in 33.3 per cent males and 17l9 per cent females. Biochemical deficiency of riboflavin was noted in 7.1 per cent subjects by erythrocyte glutathione reductase (EGR) activity coefficient (AC) test. An association between activity coefficient and low intake was found when the coefficient was greater than or equal to 1.30. There was no significant correlation between activity coefficient and dietary vitamin B2/day or vitamin B2/100 g protein. Regular oral administration of multivitamin (containing 2.5 mg vitamin B2) prevented biochemical deficiency of the vitamin. Clinical signs of riboflavin deficiency were not seen except in one female subject of sheltered dwelling.


Effect of riboflavin deficiency on the 32P turnover in the macromolecular phosphate compounds of the rat lens. In order to clarify the role of riboflavin in phosphorylation in the lens, the authors have attempted to investigate the 32P turnover in the macromolecule fraction in the lens supernatant from riboflavin deficient rats. 32P turnover in the macromolecular phosphate compounds was reduced remarkably. The macromolecular phosphate compounds in the lens supernatant which was separated by Sephadex G-50 was identified as RNA. These findings reveal that there are close relationships between reduced RNA turnover in the lens and riboflavin deficiency. This concept may contribute greatly to clarifying the pathogenesis of ariboflavinosis in general.


Effect of riboflavin deficiency on the metabolism of the red blood cell. Red blood cells from control and riboflavin-deficient rats were separated into fractions of different mean age. Measurement of haemoglobin in the red cell fractions showed a progressive reduction in the number of young cells as the severity of deficiency increased and a corresponding increase in the old cells. The red cells from the deficient animals were significantly more fragile in all fractions than their comparable fractions in the control animals when exposed to a peroxide generating system. The increased fragility of the red cell in the riboflavin deficient rat may be due to the reduced level of red cell reduced glutathione since this substance is a necessary substrate for flutathione peroxidase which functions to destroy peroxides. Reduced glutathione is also necessary to convert methaemoglobin to haemoglobin and methaemoglobin levels were increased in red blood cells from deficient animals. Thus riboflavin deficiency through its control of the activity of glutathione reductase appears to influence red cell fragility in the rat but there is no evidence yet to suggest that the life span of the erythrocyte is reduced.


A photodecomposition fluorimetric method for determination of riboflavin in the various constitutents of blood. The photodecomposition fluorimetric method has been modified for determination of small quantities of whole blood, erythrocytes, leucocytes, platelets and plasma. The method is accurate in each constituent and contains a test of specificity in each determination. Automation of the method is described. In 13 normal subjects riboflavin in whole blood was range 14.5-24.2, mean 17.7 +/- 2.7 microgram %, in corresponding erythrocytes was range 21.0-44.0, mean 33.7 +/- 6.6 microgram%.


Distribution of riboflavin in blood: in women and in prenates. The reliability of the photodecomposition method for riboflavin in various constituents of blood is demonstrated by recovery tests in vivo. In normal subjects no significant rise in whole blood, erythrocyte or plasma riboflavin is detected 2 hours after oral treatment. With intervenous therapy a rise occurs in plasma riboflavin and not in erythrocytes. In kidney disease after oral riboflavin unusually high sustained plasma levels are recorded with no change in erythrocyte levels. Correspondingly higher erythrocyte riboflavin concentration in cord blood as compared to that of maternal blood may indicate greater avidity of new fetal cells for riboflavin.


Vitamin B6 status of institutionalised and non-institutionalised aged. The vitamin B6 status of 196 aged subjects living at home and institutionalised in hospital, residential accommodation and sheltered dwelling was studied. Subjects receiving multivitamins were grouped separately and the effect of regular vitamin supplementation on the vitamin B6 status was assessed. The mean dietary intake of vitamin B6 was less than 2 mg/day in all the groups. The biochemical deficiency, as evaluated by erythrocyte glutamic pyruvic transaminase (EGPT) index, was observed in 42.3 per cent of the total subjects; the highest incidence was in subjects of sheltered dwelling. Twenty per cent of the subjects receiving multivitamin also had deficient biochemical levels. Anaemia was noted in 1.3 per cent of the vitamin B6 deficient subjects. Clinical signs of deficiency were noted in one female subject of sheltered dwelling.


Stabilization of flow properties of blood with phenylbenzo-gama-pyrone derivatives (flavonoids). An investigation conducted on erythrocytes suspension in plasma revealed an instability caused by apparent sensitivity of erythrocytes to aggregation due to slight changes in normal plasma constituents. There is evidence that low level intravascular aggregation and so-called normal erythrocyte sedimentation rate (ESR) of apparently healthy people may be caused by undue sensitivity of erythrocytes to aggregation by plasma constituents as they vary within accepted normal ranges. Certain flavones, particularly methoxylated compounds, which may occur in the diet, increase resistance of erythrocytes to aggregation by shifts in plasma constituents. The stabilizing and apparent regulatory action of flavonoids on parameters important in the rheology of blood supports the concept that these compounds are necessary in the diet.


On the absorption of ascorbic acid in man. The daily intake of ascorbic acid with the diet was strongly restricted in seven healthy non-smoking males and 90 to 180 mg of ascorbic acid were orally supplemented. After an equilibration period of three weeks about 5 muCi of (1-14C) ascorbic acid was orally administered with carrier (30 mg or 60 mg). The daily intake was then increased to 4 X 1000 mg and the cumulative excretion of radioactivity in the urine measured over a period of 10 days. The average absorption was estimated to amount to 80-90% of the dose.


Hematological studies in vitamin A deficient children. Hematological studies were carried out in 110 children with varying levels of plasma retinol to investigate the relationship between vitamin A deficiency and anemia. In children with plasma retinol levels below 20 microgram/100 ml, the mean levels of hemoglobin and hematocrit were lower than those in children who had retinol levels above 20 microgram/100 ml. Following supplementation of vitamin A, there was a significant increase in the levels of hemoglobin, hematocrit and plasma iron. These findings suggest that apart from deficiency of iron, vitamin A deficiency may also have a contributory role in the development of anemia in children.


Abdominal complications of ventriculoperitoneal shunts in Nigerians. During a period of 12 years, 154 hydrocephalic children were treated with ventriculoperitoneal CSF shunting operations. The abdominal complications thus far encountered include development of a peritoneal fibrous pouch, deliberate extraction of the tube by mothers who mistook it for an Ascaris worm, failure of CSF absorption by the peritoneum giving rise to ascites, spontaneous extrusion of the abdominal tube, bowel perforation and volvulus.


Effect of estrogen therapy on metastatic carcinoma of the prostate. Forty-one patients with metastatic carcinoma of the prostate (stage IV) were treated with diethylstilbestrol or bilateral orchidectomy or both and followed for a period of two years. The effect of treatment was determined every six months and was based on the size and consistency of the primary lesions on rectal palpation, the effects on pain, obstructive symptoms, osseous metastases, level of serum prostatic acid phosphatase and on the overall clinical evaluation of the patient. Bilateral orchidectomy was as effective as a combination of bilateral orchidectomy and diethylstilbestrol therapy. Diethylstilbestrol given alone was less effective. The poorer results obtained were attributed to the failure of many patients to adhere strictly to their estrogen regimen. Rectal digital palpation of the prostate as well as an estimation of the level of serum prostatic acid phosphatase is recommended in developing countries for all male patients over 50 years of age seen at the hospital.


Urogenital tuberculosis in Israel.

Urogenital tuberculosis in Israel. Forty-four patients were treated for urogenital tuberculosis in our ward from 1956 to 1975. Four patients were Israeli born and all the others were immigrants, mostly from Eastern Europe. Immigration greatly influences local morbidity, and tuberculosis is no exception. The highly developed preventive and social medicine of Israel has excellent results, and prognosis is more than favorable. Only one death was registered in our material, and this was due to renal failure of long duration.


Benign perineal masses in the male.

Benign perineal masses in the male. Benign perineal masses in the male are rare. To date 11 cases of benign tumors of the male perineum have been reported. Two unusual cases, both benign tumor masses, are reported. A brief review of the pertinent pathology is included. No similar encapsulated lesions have been previously reported.


Congenital arteriovenous fistula of the kidney. A patient with a congenital arteriovenous fistula has been presented. The peculiar anomalous vascular pattern is the first to be described in the literature.


Evaluation of bacteria and biliary tract diseases. Bile specimens were taken for culture from 100 patients who had disease originating in the biliary tract. Routine cases of chronic cholecystitis with cholelithiasis were found to have a low incidence of infected bile. An acute process appears to be needed in order to produce infected bile, and an acute obstruction of the bile duct due to gallstones produced infected bile. An effort should be made to select these patients and begin antibiotic therapy as soon as possible.


Thyroid lymphography.

Thyroid lymphography. We have presented the lymphographic findings in 13 patients with thyroid enlargement due to various disorders and discussed the diagnostic accuracy of this procedure. It is possible to diagnose uncommon thyroid diseases such as Hashimoto's disease and retrosternal goiter by thyroid lymphography. We recommend more regular use of this useful diagnostic aid.


Teratoma of the thyroid gland.

Teratoma of the thyroid gland. A case of teratoma of the thyroid gland in a 3-month-old child is reported. Present since birth, it presented as an acute respiratory emergency. This was relieved by surgical removal. The tumor showed normal thyroid tissue flanking the mass and at surgery was seen to derive its blood supply from the main thyroid vessels.


Operative treatment of megaureter in adults. After a general outline of ideas about surgery of the megaureter, the author presents one-year postoperative results for 3 adult patients with megaureter, operated on by Prof. Hardy Hendren during his visit to Warsaw. The tapering of the ureters and reimplantation were done in all 3 cases. Though the presented material is too small to draw a definite conclusion, the results obtained in adults by a world-renowned specialist of surgery of megaureter in children can be helpful in the choice of a line of conduct in this difficult urological problem.


External carotid ligature: posterior approach (behind the sternocleidomastoid muscle). Because of difficulties encountered in the ligation of the external carotid artery, both anteriorly and retrovascularly (internal jugular vein), we propose a posterior approach based on anatomic principles. This approach to the external carotid artery is especially useful when structural alterations of the anterolateral neck are present. Surgical details are presented in three patients and the results demonstrate its practicability.


Simultaneous double contrast cystography and modified polycystography in the evaluation of bladder carcinoma. Accurate knowledge about the morphology and degree of infiltration of a bladder tumor is an essential prerequisite to correctly plan, and forecast the results of, the treatment of these tumors. Among the radiological investigations double contrast cystography is superior to excretory cystogram or conventional cystogram in delineating the morphology of bladder tumors. Polycystography demonstrates, radiologically, the degree of infiltration of a bladder tumor. By simultaneously performing these procedures, the information necessary for planning the treatment is obtained in a single sitting, with one catheterization. This procedure was performed in 15 patients, in good correlation with other parameters such as cystoscopy, bimanual examination under general anesthesia and biopsy.


Contribution to the etiopathogenesis of orthostatic proteinuria in children. The results of sequential scintigraphy of the kidneys of 22 children with orthostatic proteinuria and of 25 patients with nephritis or nephrotic syndrome, respectively, have been evaluated. At particular time intervals significant differences have been found between the two groups. On the basis of the visual method of evaluation of scintiscans and by bilateral comparison the authors conclude that in children with orthostatic proteinuria the frequency of asymmetry of the kidneys was significantly higher. These changes were most likely due to spasms or other disturbances of the function of excretory urinary passages in the calyx-pelvis system as responses to unfavourable emotional inpulses (intravenous application of the substance, etc.) and to the sitting position during the examination.


Transerythrocytic concentrations of urea and creatinine in normals and in azotemic patients. Preliminary studies in our laboratory suggested alterations in the distribution of urea and creatinine between red cells and plasma in azotemic patients, as compared to normal controls. The present studies compare plasma erythrocyte concentrations of urea and creatinine in azotemic patients and in control subjects. Effects of adding exogenous urea and creatinine to the blood of control subjects were also studied. The findings suggest alterations of solute distribution patterns in azotemic blood. Specifically, the proportions of the solutes in cells appear reduced in azotemia.


Ureteroneocystostomy without dissection of the submucosal tunnel. A technique of ureteroneocystostomy with fixation of the ureter to the bladder musculature denuded from the mucosa was studied in dogs. The intravesical portion of the ureter shrank to half its original length after the operation. This portion preserved its muscular structure and was overgrown by the bladder mucosa to more than half its circumference. The submucous canal thus formed for the ureter prevented reflux in every animal. The technique avoids the formation of strictures. It is recommended if direct dissection of a submucous canal is impracticable.


Plasma renin substrate during lithium treatment. Inspired from experiments in animals, plasma renin substrate was determined in patients given lithium treatment. In a longitudinal study, renin substrate was determined in 9 patients before the start of lithium treatment and at intervals during 3 months of treatment. In a transversal study, 18 patients on lithium treatment for 2--20 years were compared with 11 control persons. In the longitudinal study, plasma renin substrate values did not, during lithium treatment, deviate significantly from pretreatment values. In the transversal study, values in the lithium-treated patients did not differ significantly from values in the control group. There were no correlations between serum lithium concentrations and plasma renin substrate values. Our study indicates that plasma renin substrate remains unaffected by lithium treatment of manic-depressive patients.


Rupture of a hydatid cyst of the liver into the biliary tract. Rupture of a hydatid cyst into the biliary tract occurs in 5% to 10% of patients with hydatid disease of the liver. The communication between the hydatid cyst cavity and the biliary tree may produce intermittent or progressive obstructive jaundice. The presence of such jaundice complicates the diagnosis since it resembles other biliary disorders such as stone or infection. We treated six patients with hepatic hydatid cysts, four with minute fissures and two with wide ruptures into the biliary tract. The pathophysiologic mechanisms, diagnostic procedures and treatment are discussed.


Umbilical adenoma.

Umbilical adenoma. Sixteen cases of umbilical adenoma have been presented. Surgical exploration revealed significant intraperitoneal findings (various yolk-stalk anomalies) in six of ten patients. There were no postoperative complications. Hence, we recommend complete surgical exploration of patients with umbilical adenomas. Anything less usually results in recurrence.


The effect of acute pulmonary edema on pulmonary vascular resistance: significance for the interpretation of dilated upper lobe vessels on chest radiographs. Dilation of upper lobe pulmonary vessels is an important radiographic sign of acute, left heart failure. A prominent theory is that perivascular edema causes increased resistance at the lung bases and inverts the normal perfusion gradient such that upper lobe blood flow exceeds lower lobe flow. This theoretical increase in flow is thought to cause dilatation of upper lobe vessels. Previous experimental studies determined indirectly changes in resistance from changes in the perfusion gradient: Results were contradictory. We measured directly the effect of edema on resistance in isolated canine lungs. Resistance increased linearly with edema. The magnitude of increase was small, however, and insufficient to cause inversion of the perfusion gradient. Our data indicate that interstitial pulmonary edema does not cause significant redistribution of blood flow. We suggest that dilated upper lobe vessels are veins acting as pulmonary venous manometers, reflecting elevated left atrial pressure, not increased blood flow.


Clinical experience with saralasin infusion in hypertensive patients. Renal arteriography gives a reliable anatomic delineation of the renal vasculature. However, the presence of renal arterial disease does not determine the physiologic significance of the lesion. The intravenous  infusion of saralasin, a specific angiotensin II antagonist, has been investigated as a method for identifying patients with hypertension dependent upon excessive angiotensin II activity. Correlations between the blood pressure response to saralasin infusion, peripheral and differential renal vein plasma renin levels and renal angiography have been obtained in 35 hypertensive patients. The results suggest that a hypotensive response to saralasin infusion provides an adjunct to renin determinations for recognizing angiotensinogenic renovascular hypertension. However, false negative responses to saralasin occur. The reasons for these negative responses need to be determined before saralasin infusion can be employed as the sole screening test for renovascular hypertension.


Successive abdominal roentgenograms: a new method of evaluating postoperative small bowel activity. The technique of two successive abdominal roentgenograms at a five minute interval is proposed as a new method of evaluating small bowel activity in the presence of postoperative intestinal distention. One hundred and forty-four cases of postoperative small bowel distention were studied with this technique and correlated with the clinical evaluation of the bowel sounds and with the development of a variety of postoperative complications. Correlation with the bowel sounds was fairly good, except in the presence of a clinical description of hypoactive sounds. Reduced activity on the successive roentgenograms after the third postoperative day was frequently associated with postoperative complications, while persistent small bowel distention in the presence of significant roentgen activity usually indicated mechanical small bowel obstruction. This method for determination of small bowel activity thus appears to be useful in evaluating postoperative problems.


Transluminal dilatation and stent placement in obstructed ureters in dogs through the use of percutaneous nephropyelostomy. Through an artificially created ureteral obstruction in the dog, a ureteral stent was placed with the aid of a percutaneous nephrostomy tube. The stent was removed after two weeks. This resulted in permanent relief of the obstruction in the treated animals. In contrast to this, the control animals remained completely obstructed with resultant hydronephrosis and loss of kidney. It is proposed that this method can be used in humans where nephropyelostomy had been placed and where surgical correction of the obstructed ureter is not feasible.


Recirculation of iopanoic acid after conjugation in the liver. The purpose of the investigation was to determine if an enterohepatic recirculation occurred for the metabolite of iopanoic acid. The major metabolite of iopanoic acid (Telepaque) in dog bile is the glucuronide conjugate. The identification and quantitation of glucuronide conjugate was accomplished by elemental analysis, paper chromatography, thin layer chromatography, fluorescent excitation analysis, and high pressure liquid chromatography. The stability of iopanoic acid glucuronide in refrigerated dog bile was confirmed. Known amounts of the glucuronide conjugate were instilled into the duodenum of 8 awake adult dogs, and bile collected for 8 hours. Between 19% and 53% (average 31%) of the administered dose was recovered in bile, thereby documenting the presence of an enterohepatic recirculation of conjugated iopanoic acid. The slow rise and plateau of the excretion curve suggests that either the compound is absorbed slowly, or that absorption depends upon deconjugation in the gut. The implications are discussed.


Comparison of CT scanning with photon absorptiometric measurement of bone mineral content in the appendicular skeleton. Traditional methods of bone mineral analysis were compared to a new technique using computerized tomography (or CT scanning). The correlation between the CT values for long bones in the dog and actual calcium content was 0.9942. The correlation between two photon absorptiometric techniques and CT values were also 0.9981 and 0.9962. The precision of repeated scans was +/-2%. It is suggested that the CT scanner will allow bone mineral analysis to be performed with accuracy and precision.


Reaction of the vesical wall to bacterial penetration: resistance to attachment, desquamation, and leukocytic activity. To determine the contribution of the bladder wall to defense against infection we designed a series of experiments wherein movement of introduced bacteria and inflammatory processes (cystitis) were observed by autoradiographic technique. As a first defense line, the bladder mucosal surface showed strong resistance against bacterial attachment and penetration. Moreover, epithelial cells gripped and penetrated by bacteria were desquamated and eliminated through voiding, thus arresting deeper invasion into the bladder wall. When organisms did penetrate the bladder wall, they were phagocytized by polymorphonuclear leukocytes and macrophages in the submucosa and muscularis. In contrast, once leukocytes had migrated into the urine within the bladder, they no longer participated in phagocytosis. Organisms also entered the veins, or the lymphatics, or both, and disappeared rapidly from the local site through the action of the reticuloendothelial system. These observations indicate that--in addition to mechanical emptying--resistance to bacterial attachment, desquamation of invaded cells, activity of leukocytes and macrophages, and disappearance of bacteria from local site are four mechanisms whereby the bladder resists and fights infection.


Quantitative bone mineral analysis using dual energy computed tomography. This preliminary evaluation indicates that CT scanning permits measurement of cancellous, cortical or integral bone. With the single energy technique, precision is high and with mode, CT scanning may prove an important tool for assessing the axial skeleton is osteoporotic conditions.


Morphologic changes in the arterial bed of the penis with aging. Relationship to the pathogenesis of impotence. The arterial vascular bed of the penis has been studied histologically in postmortem material from 30 males in the age range 19 to 85 years, mean 57. Fifteen of these propositi had had diabetes mellitus of average duration of 13 years. In all males more than 38 years old, there was fibrous substitution of the longitudinal smooth muscle in the Ebner pads. Later this was complemented by fibrous proliferation of the intima, medial fibrosis, calcification, and narrowing of the lumen to obilteration from thrombi. The extent of the pathology was apparently related to both age and diabetes mellitus. The nature and extent of the changes indicate that they must necessarily lead to a limitation of the basic function of this arterial tree, i.e., to increase essentially the flow of blood to the cavernous bodies at the time of the erection. These changes can play a decisive role in explaining impotence that occurs with aging, particularly in diabetics.


The effects of vasectomy on the testis and accessory sex glands of the Hartley strain guinea pig. The short term effects of bilateral vasectomy on the testis and the accessory sex glands of the guinea pig were compared with the effects of sham operation and unilateral vasectomy at 3, 5, 7, and 9 weeks after operation. The testis weights, sorbitol dehydrogenase activity, histology, epididymal sperm number, and motility were recorded. Accessory sex glands were weighed and chemically analyzed for fructose and citric acid content. The citric acid concentration of the dorsolateral prostate of the bilateral vasectomy group was significantly higher than concentrations in sham-operated and unilateral vasectomy groups at 3 weeks only. This may indicate transient hormonal derangement as a result of vasectomy. No significant differences were noted between testes of vasectomy and sham-operated groups. The unligated side testes of the unilateral vasectomy group were different from the testes of vasectomy and sham-operated groups. We conclude that interruption and ligation of the vas deferens itself has no effect on the testis of the guinea pig. Furthermore, all vasectomy experiments should include sham-operated controls.


Androgen concentrations in prostate and serum of the male and female Praomys (Mastomys) natalensis. The levels of androgens in the male prostate, seminal vesicles, and serum, as well as in the female prostate and serum, were measured in the rodent Praomys (Mastomys) natalensis. Measurements were made in different age groups of both males and females using a sensitive radioimmunoassay. The results showed that the values for serum testosterone were 10 times greater in the male than the female. The concentration of serum dihydrotestosterone in the male was approximately one-tenth of the concentration of testosterone. The recovery of dihydrotestosterone from the prostate in the female and seminal vesicle in the male was low and these values were not considered. The concentrations of testosterone and dihydrotestosterone in the male prostate were 8.3 +/- 0.5 and 20.0 +/- 2.4 ng per g of wet tissue, respectively. The concentration of testosterone in the female prostate, 7.1 +/- 0.5 ng per g of wet tissue, was similar to that in the male. These studies have shown that the female Mastomys has a prostate which exists in a low androgen environment; it is suggested that this could be used as an experimental model for studying hormonal effects on the prostate.


Evaluation of cerebrospinal fluid flow through a Pudenz 12 mm or a standard Rickham reservoir: phantom experiments. We have investigated the assessment of fluid flow through a Pudenz and a Rickham shunt using radioactive tracer. Experimentally, the radioactivity clearance curve obtained, using either shunt, is defined by two exponents. The relationship between flow-rate (F) and clearance half-time (T1/2) of the first component is identical with the clearance formula (formula: see text) or log10(F) =-LOG10(T1/2) + LOG100.693V using the physical volume. The value of the second component in a Pudenz 12 mm and a standard Rickman reservoir is log10(F) = -1.3LOG10(T1/2) + 0.087 and log 10(F) =-1.8log10(T1/2) + 0.019 respectively. In clinical practice, the first component may not be recorded adequately because the interval between appearance of the first and second components is very short. To calculate the CSF flow, we recommend referring to the line of "radioactivity clearance half-time and flow-rate" of the second component instead of the calculation based on clearance formula using a physical volume.


Treatment of oral estramustine phosphate (Estracyt) in prostatic carcinoma: influences on lipid and carbohydrate metabolism. Estramustine phosphate (Estracyt), a combination of estradiol and nitrogen mustard given to males with prostatic carcinoma, had the same effect on serum lipids, lipoproteins, and serum phosphoglyceride fatty acid composition as ethynyl estradiol (Etivex). The characteristic effects on serum lipids caused by both drugs, i.e., a reduction in serum cholesterol and an increase in serum phospholipids, were apparently expressions for reduced low density lipoproteins and increased alpha-lipoproteins. Serum lecithin fatty acid composition revealed during the administration of both drugs a characteristic increase in palmitic acid (16:0) and a decrease in stearic acid (18:0), interpreted as evidence for a cholestatic, although subclinical, liver involvement. Similar changes have earlier been revealed in women given ethynyl estradiol; however, the increase in serum triglycerides and very low density lipoprotein cholesterol in young women was not duplicated in aged males with prostatic carcinoma. Furthermore, in aged males, the administration of these estrogens did not change carbohydrate metabolism but did produce an increase in adipose tissue lipoprotein lipase.


Ex vivo perfusion of the canine and human prostate gland. It has been shown that the perfused canine prostate is capable of responding to pilocarpine stimulation in vitro producing prostatic secretions similar in quantity and quality to those observed in the living dog with a prostatic fistula. Furthermore, the perfused gland is capable of metabolizing testosterone. This perfusion technique has been extended to a human prostate gland harvested from a beating heart cadaver and shows the feasibility of this procedure for future studies in the human.


Development of the ureterovesical junction in human fetus: in consideration of the vesicoureteral reflux. The ureterovesical junctions in human fetuses from 11 to 27 weeks of age were studied histologically. Anatomical relationships and origins of the periureteral sheaths, intravesical ureteral muscles, and trigonal muscles were shown. The superficial periureteral sheath arising from the vesical wall was not the source of the trigonal muscles; the deep periureteral sheath arising from the intravesical ureteral wall formed the deep trigonal muscles. The muscles of the intravesical ureter were differentiated longitudinally and formed the superficial trigonal muscles. The development of the two trigonal muscles--superficial and deep--depends on the development of the deep periureteral sheath and the intravesical ureteral muscles. From the finding that both trigonal muscles are present in fetuses compared with both periureteral sheaths or intravesical ureteral muscles in the latest stage, the ability to maintain the valve mechanism in the ureterovesical junction in the human fetus is based on the periureteral sheaths and intravesical ureter--not on the trigone.


Experimental study with the Scurasil ureteral prosthesis. The latest generation of Scurasil (dimethylpolisoxane) ureteral prosthesis was used in six dogs as a model for internal urinary diversion in patients with metastatic disease. It was found to cause minimal reaction but carried a high complication rate, including stone formation, end-stage pyelonephritis, and hydronephrosis. Although technically easy to use, modifications in design are necessary prior to use in humans.


Gated computed tomography of the human heart. Production of in vivo images of the human heart, with delineation of the individual cardiac chambers and myocardial wall thickness, was accomplished by coupling a relatively simple electrocardiographic gating device to a translate-rotate type of computed body tomographic scanner. Differentiation between the myocardial wall and the intracardiac blood pool was attainable in the patient with a normal hematocrit only when intravenous iodinated contrast media was used.


Control of ureteral peristalsis during changes in intravesical pressure. Studies of the ureteral response to changes in intravesical pressure (IP) have been conducted by surgically altering the neural and hydrodynamic integrity of canine ureters. Ureteral function was assessed by acute and chronic recordings of ongoing electrical activity. Intact control ureters responded (acute to 56 per cent; chronic to 83 per cent) to elevated IP with immediate increases and to decreases in IP with slowing or cessation of activity. Acute ureteral ligation mimicked the effects of increased IP, except the responses were much slower. Ureterotomy and the resultant extravasation of urine did not alter the ureteral response. Disruption of renal nerves, whether by selective sectioning or by nephrectomy, was associated with exaggerated ureteral frequency responses which were delayed in onset. Ureters lacking neural connections with the bladder responded with bursts of multiple spikes and increases in the force of peristalsis. These observations are discussed in terms of the myogenic and neurogenic control of ureteral peristalsis.


The use of the CO2 laser for partial nephrectomy: an experimental study. The CO2- laser knife was used for partial nephrectomy in an experimental study of 20 mongrel cats. Of these, 16 survived, two died of peritonitis, and two died of unrelated causes. The inherent characteristics of precision and hemostasis of this modality, already found useful in controlling complications in other fields of surgery, proved to be a safe and effective method for partial nephrectomy as shown by angiography and histopathologic examinations of the operated kidneys at 0, 7, 14, 21, and 90 days after surgery. Complications such as hemorrhage or urinary fistula were nonexistent.


Syndrome of hyporeninemic hypoaldosteronism. Study of two cases and review of the literature. Two patients with chronic mild to moderate renal failure presenting with unexplained hyperkalemia were studied, and found to have hyporeninemic hypoaldosteronism. Hyperkalemia, generally uncommon in nonoliguric stable renal failure, resulted from the combination of apparent insensitivity of the diseased kidney to aldosterone and variable degrees of impairment in the reninaldosterone axis. The clinical picture, the methods of establishing the diagnosis, the therapeutic alternatives and the possible pathogenetic mechanisms involved are described.


Viroimmunoassay utilizing a synthetic peptide: a test equivalent to the carcinoembryonic antigen radioimmunoassay. A recently developed immunoassay which utilizes the synthetic fragment CEA(1-11), corresponding to the N-terminal segment of carcinoembryonic antigen (CEA), was used for the evaluation of human sera. The various sera were tested for their capacity to inhibit the inactivation of the modified bacteriophage preparation CEA(1-11)-T4 by antiserum prepared against the bovine serum albumin (BSA) conjugate CEA(1-11)-BSA. In this immunological system both the free synthetic peptide and a semipurified preparation of intact CEA serve as inhibitors. Sera from a large proportion (85%) of patients with adenocarcinomas of the digestive tract, including the pancrease, gave 50 to 88% inhibition. Sera from patients with other cancers, particularly of breast and ovary, also caused inhibition, although it was less marked in both incidence and level. Most normal sera gave less than 40% inhibition, which was considered as the cutoff point. This assay, like the CEA radioimmunoassay, is not suitable for mass screening nor can it be the primary criterion for diagnosis of cancer, but it might be of value as a follow-up procedure for postoperative diagnosis and prognosis.


"Coronary" T waves in the presence of complete left bundle-branch block: a normal variant? The case report of a patient with an ECG pattern of intermittent left bundle-branch block, presenting inverted and symmetric ("coronary") T waves in leads V1 to V3 during periods of normal intraventricular conduction, is presented. The patient was followed up for eight years during which time no relevant symptoms appeared while extensive noninvasive investigations repeatedly failed to reveal any organic basis for the ECG changes. It is stressed that inverted, symmetric T waves in right-sided chest leads may be encountered in young, otherwise healthy subjects with intermittent left bundle-branch block during periods of normal intraventricular conduction. Knowledge of this fact is important in order to avoid iatrogenic cardiac invalidism in such cases.


Role of synovectomy in hemophilic arthropathy. Fifteen knee synovectomies performed in severe hemophiliacs between 1969 and 1971 were reevaluated after a follow-up period ranging from five to seven years. In the majority of cases (53%) there was no recurrence of hemarthrosis; in the others the condition was reduced (40%) or unchanged (7%) and joint scintiscans carried out with 99mTc showed a significant uptake of the tracer. Joint motion was markedly impaired in eight cases despite prolonged and intensive physiotherapy. The majority of patients expressed satisfaction with the operation, which had reduced the frequency and severity of joint bleeding and allowed them to lead more active lives. It is suggested that the possibilities of the conservative treatment presently available should be more extensively explored before establishing the indications for synovectomy.


Reconstructive surgery in the lower limb in hemophiliacs. During the years 1973-76, we performed 76 operations on the lower limbs of hemophiliacs in an attempt to correct the disability due to intraarticular hemorrhages. The ways in which rehabilitative surgery can improve function and retard further damage are discussed in the light of the pathogenesis of disability due to intraarticular and intramuscular hemorrhage. Three particularly successful operative procedures are discussed: 1) supracondylar correction of knock-knee, 2) intertrochanteric correction of coxa valga, and 3) evacuation of iliacus hematoma in patients with paralysis of the femoral nerve.


Drug utilization and adverse drug reactions in medical patients: comparison of two periods, 1969--72 and 1973--76. A study of drug usage and adverse drug reactions was carried out on 2,771 hospitalized medical patients during 1969--76. Comparison of data between 1969--72 and 1973--76 shows an 11% reduction in the average number of drugs per patient, and a 59% decrease in the incidence of adverse effects, calculated as percent of all exposures. The number of patients affected by adverse reactions during the second period fell by 61%. These data seem to indicate that there was considerable improvement in habits of drug usage in the monitored ward.


The Jerusalem perinatal study: the first decade 1964--73. This paper summarizes the main findings concerning Jewish births in the record-linked Jerusalem Perinatal Study. In the decade 1964--73 there were 63,638 births in which the birth weight was at least 1,000 g. The late fetal mortality rate was 9.1/1,000, and the neonatal and infant death rates were 10.1 and 15.5/1,000, respectively. The demographic characteristics of births changed over the decade, with a decrease in the proportion of high birth orders, of mothers with little education, of immigrants from Asia and North Africa, and of marriages within the same group of origin. Fertility fell, especially at the extremes of reproductive life. Illegitimacy was 1.2%. Year-by-year variations in mortality are discussed and the relationship of mortality to maternal age and education, birth order, social class, group of origin and birth weight are described. Frequencies of specific congenital malformations, infant and child admissions to hospital and various obstetric complications are also reported. Changes in obstetric interventions over the decade included an increasing proportion of induced labors, cesarean sections, forceps and vacuum deliveries, and interventions in the third stage of labor. The paper briefly indicates ways in which the data bank of the Jerusalem Perinatal Study is being exploited for a wide variety of health studies.


Relationship between food intake and insulin response to oral glucose tolerance test in short lean children. Based on diet questionnaires and food intake analysis, a study was made of the eating habits of 35 lean children and adolescents with constitutional familial short stature. The children were divided into four groups according to their plasma insulin response to an oral glucose tolerance test (normal or low) and to the season during which the test was given. No statistically significant differences in caloric intake were found. The overall total caloric intake in all groups was 166 to 190% of the recommended dietary allowances set by the U.S. National Academy of Sciences. It is concluded that the insulin response to the oral glucose tolerance test is not related to caloric intake.


Semiquantitative cytochemical estimation of beta-glucuronidase activity in peripheral lymphocytes in healthy human subjects. A semiquantitative cytochemical evaluation of beta-glucuronidase activity in peripheral lymphocytes in 123 normal sybjects was made. It was found that the enzymatic activity was influenced by age but not by sex. Activity was weak in newborn infants but increased with age and reached maximal values in old subjects. Age should therefore be taken into consideration when the enzyme activity is evaluated.


Renal amyloidosis: immunofluorescence and electron microscopy studies. Renal biopsy specimens of 15 patients with renal amyloidosis were studied by immunofluorescence microscopy. The amyloidosis was associated with chronic pulmonary disease in five, rheumatoid arthritis in one, chronic lymphocytic leukemia in one, and familial Mediterranean fever in five patients. In three patients no associated condition could be determined although the pattern of organ involvement resembled that of secondary amyloidosis. IgG and complement (C3) were demonstrated in the glomerular capillary walls and in the mesangium in all patients. The pattern of the deposits was neither granular nor linear. Ig and C3 appeared as large confluent masses or broad ribbon-like segments. In the six patients studied by electron microscopy the fibrillary formation of amyloid was seen in the mesangium and the glomerular capillary walls corresponding to the Ig deposits. No immunofluorescence or ultrastructural differences were observed among the patients with secondary, inherited and leukemia-associated amyloidosis included in this study.


Self-poisoning with digitalis glycosides: successful treatment of three cases. Three patients who attempted suicide with massive digoxin overdoses are described. Peak plasma digoxin levels in the three patients reached 21, 8.2 and 6.2 ng/ml. The clinical condition of the patients was correlated with their plasma digoxin levels. Control of digitalis-induced arrhythmias was achieved with i.v. diphenylhydantoin.


Physician productivity and returns to scale. Cobb-Douglas production functions are used to estimate returns to scale in a sample of solo and group medical practices stratified by size and type of practice. Solo practices and small single-specialty groups are stratified by specialty, and large multispecialty groups are stratified as general practice-general surgery or comprehensive-care groups. Output measures used are gross revenue, total patient visits, and office visits; input measures reflecting practice scale are number of physicians, number of rooms, and number of nonphysician office personnel. Results indicate increasing returns to scale for solo and small group practices but decreasing returns to scale for very large groups. Possible reasons for inefficiency in large practices and the implications of the findings for public policy on health maintenance organizations are discussed.


Implementation of a model for census prediction and control. A model is described that predicts hospital census and computes, for each day, the number of elective admissions that will maximize the census over the short run, subject to constraints on the probability of overflow. Where a computer is available the model provides detailed predictions of census in units as small as 10 beds; used with manual computation the model allows production of tables of the recommended numbers of elective admissions to the hospital as a whole. The model has been tested in five hospitals and is part of the admissions system in two of them; implementation is described, and the results obtained are discussed.


A unified model for scheduling elective admissions. A model is presented that deals with two problems not previously solved: it handles the random arrival of requests for admission and permits continuous updating of scheduling decisions in a dynamic process, and it provides global long-term optimization of patient census rather than a series of suboptimal short-term solutions. The model can be used either for continuous dynamic scheduling or for periodic static scheduling. It is usable with many different system objectives and levels of computer resources, although an on-line computer is needed for its most effective use in the dynamic mode.


Level-load retrieval time: a new criterion for EMS facility sites. A new optimization criterion for locating emergency medical care facilities, level-load retrieval time, is described and applied to Los Angeles County. Results are compared with those obtained by optimizing mean retrieval time. The new cirterion combines retrieval times from demand points served by each facility and patient load on each facility; it yields facility sets with average retrieval times 5 to 10 percent longer, but with much more uniform patient loads, than the sets obtained by optimizing mean retrieval time. The new criterion can be used as a complement to other planning criteria and may help reduce excessive demand on the emergency care services of overloaded facilities.


Psychometric modeling of consumer decisions in primary health care. A psychometric technique, functional measurement, was used to measure the preferences of 77 persons for hypothetical health care providers identified by various levels of cost, travel time, and waiting time; responses were subjected to analysis of variance and graphic analysis to determine the functional relation by which respondents combined the three attributes in arriving at their preferences. Both modes of analysis suggested multiplicative decision models, but these yielded lower values of R2 than did linear models derived for comparison. Respondents were grouped by the proportion of response variance that was explained by each of the three attributes, and decision models were derived for each group. Discriminant analysis of socioeconomic characteristics of the respondents identified the variables that distinguished the groups and contributed to forming their preferences.


Temporomandibular joint dysplasia and open-mouth jaw locking in the dog. In 2 Basset Hounds, the condyloid processes of the mandible became subluxated when the mouth was opened widely, resulting in repeated episodes of locking of the coronoid process lateral to the zygomatic arch. Locking was prevented by osteotomy of a ventral portion of the zygomatic arch.


Black-hair follicular dysplasia in dogs. Black-hair follicular dysplasia in dogs of mixed breeding was delineated by hypotrichosis and dullness of most black regions of the coat. White regions remained full and lustrous. The abnormality was not grossly visible at birth but became evident after the 1st month of life. Among 15 offspring from 2 matings of an affected pair of dogs, each of 12 spotted pups developed the disorder in black regions; the remaining 3 were all white and appeared normal.


A numerical relationship between chromaffin-positive and small intensely fluorescent cells in sympathetic ganglia. A statistical analysis of counts of small intensely fluorescent (SIF) and chromaffin-positive (CH+) cells in superior cervical, thoracic and coeliac-mesenteric ganglia of rats at various ages (Santer et al. 1975) has been carried out. The results indicate that the numerical distribution of CH+ cells closely follows that of yellow SIF cells but not that of green SIF cells. This relationship holds both for different ganglia and for different ages.


Syncytial knots and intervillous bridges in the human placenta: an ultrastructural study. An electron microscopic study has shown that the syncytial knots of the villi of the human placenta contain aggregated nuclei which exhibit marked degenerative changes; within the cytoplasm there is an abundance of cytoplasmic filaments and many stacks of annulate lamellae. It is suggested that syncytial knots are a sequestration phenomenon in which senescent nuclear material is aggregated and removed from metabolically active areas of the syncytiotrophoblast. Intervillous bridges appear to be formed chiefly by fusion of syncytial knots from adjacent villi, and it seems reasonable that the effete material in a syncytial knot should be used for this purpose. The intervillous bridges hava a fine structure which suggests that they have a mechanical function, and this lends support to the theory that they form an internal strut system within the placenta.


The sheep trophoblast and placental function: an ultrastructural study. Both the uninucleate cubiodal epithelial cells and the binucleate giant cells of the sheep trophoblast undergo marked structural modifications during pregnancy. Uninucleate epithelial cells show ultrastructural features which may be correlated in temporal order, with the secretion of steroid hormones, the production of ovine placental lactogen, and the performance of normal non-endocrine placental activities. The binucleate cells appear to be of two main types, one concerned with glycogen storage, and the other with the synthesis of a glycoprotein secretory substance. The binucleate cells are always enclosed by a thin continuous lamina of cuboidal cell cytoplasm which separates them completely from the maternal syncytium and the fetal connective tissue. The cuboidal epithelial and binucleate giant cells may either be closely apposed or else separated by canals or spaces of varying complexity. The presence of these interfacial canals indicates that the ovine trophoblast is another example of an epithelium in which the local movement of water and solutes is mediated by standing gradient osmotic flow systems. Such flow systems may well be an integral part of eutherian placental transport mechanisms.


Diaphysial nutrient foramina in human metacarpals and metatarsals. 728 metacarpals and 691 metatarsals of unknown sex, and 120 metacarpals and metatarsals, each of known sex, were studied for the number, position, direction and symmetry of the diaphysial nutrient foramina. It was found that, in general, these bones had one nutrient foramen which was situated in the middle third of the shaft (over 90%). Few bones had no foramina and some had two. In the first and second metacarpals the foramina were mostly situated on the medial surface, and in the other metacarpals mostly on the lateral surface; whereas in the first three metatarsals the foramina were mostly situated on the lateral surface and in the remaining metatarsals mostly on the medial surface. There was a good deal of bilateral symmetry in the foramina. Without any exception, the foramina were directed away from the growing end. The various theories put forward to account for the direction of the nutrient foramina have been considered. The findings favour the 'growing-end' theory.


Stereological analysis of the mitochondrial compartment of the rabbit parotid gland before and after isoprenaline-induced degranulation. A stereological analysis of the mitochondrial compartment of the rabbit parotid gland has been carried out before and after isoprenaline-induced degranulation. Normally, mitochondria constitute about 5% of acinar cell volume, 6% of intercalcate duct cell volume and 16% of striated duct cell volume. The ratio of inner electron transport membrane to outer limiting membrane is in the range 2.3:1. Two hours after the induction of secretion by isoprenaline a significant (P less than 0.10) increase in the volume fraction of mitochondria in acinar and intercalated duct cells was noted and this may reflect increased oxidative phosphorylation at this time. Other parameters measured suggest that there is some rounding up of mitochondria Another significant feature was an increase in the number of damaged mitochondrial profiles (+80% to +250%, P less than 0.05) after isoprenaline treatment. This finding is discussed in the context of changes in mitochondrial enzyme levels which have been reported in similar situations.


Structure of the intra-chorionic blood sinus in the chick embryo. Portions of the chorio-allantoic membranes from 15 day old chick embryos were processed for electron microscopical examination. The analysis of both 1 micrometer thick sections stained with toluidine blue, and of thin sections stained with uranyl acetate and lead citrate, showed that the lumen of the intraepithelial vascular spaces in the chorion constitutes a single cavity extending over the whole membrane. The vascular arrangement can thus best be described as a single blood sinus, and not as a network of capillaries or sinusoids. The large lumen of the sinus is interrupted by cylindrical columns connecting its floor with its roof. Each column is enveloped in a layer of endothelium, a basal lamina intervening. The core of the column is formed by cytoplasm from two to five different cells ('villuscavity' cells, 'capillary-covering' cells or various combinations of both).


Cutaneous arteriovenous anastomoses present in the tail but absent from the ear of the rat. Histological evidence has been presented for the existence of arteriovenous anastomoses in the rat tail. Similar structures, however, could not be found in the rat ear. The validity of the histological techniques was proved by the demonstration of an abundance of arteriovenous anastomoses in the rabbit's ear. In view of this and other recent evidence, it is concluded that the rat could be a useful model for comparative studies of blood flow in skin with and without arteriovenous anastomoses.


Formation of concentric whorls of rough endoplasmic reticulum in the adrenal gland of the Mongolian gerbil. All cortical cells appeared alike in fetal gerbils of both sexes though glomerulosa cells were distinguishable at the time of birth. Fenestrated cisternae of rough endoplasmic reticulum were observed in all cortical cells of fetal gerbils, but smooth endoplasmic reticulum predominated. Concentric whorls of rough endoplasmic reticulum first appeared in adrenocortical cells at 42 days of age. The whorls developed within cells having abundant smooth endoplasmic reticulum and which were located in the region between the zona fasciculata and zona reticularis. Cells with whorls possibly serve as reserve cells which transform into actively secreting steroid cells in times of stress.


Cytochemistry of blood cells in peripheral smears of some West African reptiles. The distributions of lipid, glycogen, peroxidase, acid and alkaline phosphatases, beta-glucuronidase and naphthol AS-D chloroacetate esterase have been studied in the cells of peripheral smears from the wall ghecko and the crocodile. The erythrocytes react differently from those of mammalian erythrocytes with regard to peroxidase reactivity. The need to take such species differences into consideration when engaged in histochemical investigations is stressed.


The proliferation of elastic fibres after skin incisions in albino mice and rats: a light and electron microscopic study. The replacement of elastic fibres in healing skin wounds in mice and rats was studied with light and electron microscopy. New elastic fibres were seen 1 week post-wounding in the deepest regions of the scar. By 3 weeks post-wounding they could be found in the regenerating dermis. There followed a proliferation of these fibres to numbers far greater than those in unwounded skin. These elevated numbers persisted for the duration of the experiment (4 months). The common notion that elastic fibre formation is not a component of the repair of skin wounds is clearly erroneous.


Subsegmentation of the human liver.

Subsegmentation of the human liver. Subsegmental patterns in 85 human livers have been studied after preparing corrosion casts of the hepatic duct, hepatic artery and portal vein by injecting coloured butyl butyrate solution. A subsegment was identified by the independence of its vessels and ducts from those of its neighbours. In the present study nine hepatic subsegments have been observed: (1) posterior superior, (2) posterior inferior, (3) anterior superior, (4) anterior inferior, (5) medial superior, (6) medial inferior, (7) lateral superior, (8) lateral inferior, (9) caudate (the caudate lobe and process form a spearate subsegment on the basis of the pattern of their blood supply and biliary drainage). The sizes of the subsegments were very similar in 41 cases (48.23%). In the others, some increase or decrease in the size of one or more subsegments at the expense of neighbouring subsegments was observed. These variations are illustrated.


Observations on the fusion of chick embryo myoblasts in culture. Chick embryo myoblasts were grown as monolayers in culture. The formation of myotubes from myoblasts occurred over a 15 hour period in vitro. Time-lapse cinemicrography was used to study the behaviour of myoblasts during fusion and particular attention was paid to the way in which myoblasts aligned themselves. It was found that fusion tended to follow end-to-end rather than side-to-side alignment of myoblasts. This observation suggests that cell orientation is an important factor in myogenesis. Branched myotubes were frequently observed in culture; an explanation of this is offered.


A reappraisal of the ultrastructure of the human respiratory nasal mucosa. A study of the ultrastructure of human respiratory nasal mucosa using specimens of simple mucous polyps showed features essentially identical to those described in the lower respiratory tract. Minor forms of epithelial specialization seen in the nasal lining of the other mammalian species are not demonstrable in man. Inflammatory cells, especially lymphocytes, form an integral constituent of the epithelium, and are in close apposition to the epithelial cells. A marked increase in the epithelial surface area is achieved through ridging and clefting, irregularity of the cell's surface and the presence of microvilli. Branching microvilli are admixed with more conventional structures.


Growth pattern of the rabbit snout dorsum: a serial cephalometric radiographic study with radiopaque implants. Two radiopaque implants were inserted into each (left and right) frontal bone in five female rabbits. Ventrodorsal cephalometric radiographs were then taken in a specially designed head holder at 6 and 16 weeks of age. From these radiographs separate tracings were made on matte acetate paper of the left and right snout including the radiopaque implants. Since the implants maintained the same relationship to each other in each frontal bone, they served as stable reference sites. The markers of the 16 weeks tracing were superposed on the markers of the 6 weeks tracing. The difference in the two established outlines of the snout represented the changes in size and shape in two dimensions that had occurred during the 10 weeks period. The mean increase was 17.91 mm at the distal (anterior) border, 4.95 mm at the lateral border, and 1.22 mm at the medial border. Thus, growth at the lateral border of the snout was about 3 1/2 times that of the lateral border.


Tallysomycin, a new antitumor antibiotic complex related to bleomycin. I. Production, isolation and properties. The unusual actinomycetes strain No. E465-94 produced a complex of new glycopeptide antibiotics tallysomycin, which was separated by CM-Sephadex chromatography into two major components, A (C68H107N21O27S2) and B (C62H95N19O26S2). They were isolated first in a copper-chelated form and showed physico-chemical properties similar to those of the bleomycin-group of antibiotics. Tallysomycin exhibited broad antibacterial and antifungal activity, and was highly active in vivo against bacterial infections in mice. Tallysomycins A and B demonstrated potent activity in the prophage induction of lysogenic bacteria.


Tallysomycin, a new antitumor antibiotic complex related to bleomycin. II. Structure determination of tallysomycins A and B. The structures of tallysomycins A and B, two major components of a new antitumor antibiotic complex, have been determined. They are glycopeptide antibiotics structurally related to bleomycin: four amino acid moieties and a disaccharide fragment which are the constituents of bleomycin molecule are also present in the tallysomycins. Tallysomycins A and B contain two new amino acids and a unique amino sugar, 4-amino-4,6-dideoxy-L-talose, which have not been hitherto found in the phleomycin-bleomycin group of antibiotics. In addition tallysomycin A has an additional amino acid, L-beta-lysine, and thus a longer peptide chain than bleomycin or tallysomycin B. Tallysomycins A and B have the same terminal amine moiety, spermidine.


Reverse phase high speed liquid chromatography of antibiotics. II. Use of high efficiency small particle columns. Improved methods for the separation and quantitation of cephalosporins, penicillins, tetracyclines and several miscellaneous antibiotics by reverse phase high speed liquid chromatography are presented. The methods have been improved significantly by the substitution of high efficiency, small particle (approximately 10 micrometer reverse phase columns in place of the previously used medium efficiency, pellicular columns. The conditions and procedures described here illustrate that considerable improvements in separation and sensitivity of detection of antibiotics are achieved. Pure compounds, complex mixtures of antibiotics in a variety of dosage forms and fermentation broths are routinely analyzed by the described procedures.


The aminoglycoside antibiotics. I. Synthesis and biological evaluation of an analog of gentamicin. The synthesis of 2-deoxy-4-O-(2,6-diamino-2,3,4,6-tetradeoxy-alpha-D-erythrohexopyranosyl)-6-O-(3-deoxy-3-methylamino-alpha-D-xylopyranosyl)-D-streptamine (1), an analog of gentamicin A, from diideoxyneamine and methyl 3-methylamino-3-deoxy-beta-D-xylopyranoside is described. The product was characterized by its 13C nmr spectrum and was found to exhibit broad spectrum antibacterial activity.


Synthesis and antibacterial activities of 1-N [(S)-omega-amino-2-hydroxyalkyl] kanamycin A derivatives. Four 1-N-aminohydroxy-alkyl derivatives of kanamycin A were prepared and their in vitro activities against aminoglycoside-sensitive and aminoglycoside-resistant organisms were compared with amikacin. 1-N-[(S)-4-Amino-2-hydroxybutyl] kanamycin A (Fig. 1, compound 2, code no. UK-18,892) was equipotent to amikacin in all these tests and in mouse protection studies.


Ring formation in a pentapeptide with alternating L and D residues: an analogy to cyclization in the biosynthesis of peptide antibiotics. Acetylation of L-isoleucyl-D-alanyl-D-alanyl-L-valyl-D-leucine with acetic anhydride followed by methylation with diazomethane yielded the expected acetylpentapeptide methyl ester with molecular weight 541, but also resulted in the formation of a by-product with molecular weight 555. The incorporation of the mass corresponding to CH2 seems to be due to ring closure--via a mixed anhydride--and methylation of the cyclol derivative thus formed. A preferred, ring-like conformation stabilized by intramolecular hydrogen bonds that in turn are the consequences of the alternation of D- and L- residues in the sequence, is invoked as explanation for the unexpected cyclization. This assumption is supported by the conversion of the pentapeptide methyl ester to desthiomalformain in molten imidazole.


Mutalomycin, a new polyether antibiotic taxonomy, fermentation, isolation and characterization. Mutalomycin is a new metal-complexing polyether antibiotic produced by a strain of Streptomyces mutabilis NRRL 8088. The metabolite, a monocarboxylic acid, was isolated as the sodium salt C41H69NaO12. The structure of this polyether was established by X-ray analysis of its potassium salt C41H69KO12. Mutalomycin contains six heterocyclic rings and is structurally related to nigericin. The metabolite is active against gram-positive bacteria and Eimeria tenella (chicken coccidiosis).


New antitumor antibiotics, OS-4742 A1, A2, B1 and B2 produced by a strain of Streptomyces. New antibiotics, OS-4742 A1, A2, B1 and B2, were isolated from the culture broth of the strain OS-4742, which was designated as Streptomyces matensis subsp. vineus. These compounds have anthracycline chromophores and sugar moieties, but do not contain nitrogen. They possess antimicrobial activities against Gram-positive bacteria and antitumor activities against S-180 solid tumor on mice.


Nocardicin A, a new monocyclic beta-lactam antibiotic VI. Absorption, excretion and tissue distribution in animals. The absorption, excretion and tissue distribution of nocardicin A, a new monocyclic beta-lactam antibiotic, were studied in various animals. When nocardicin A was given intramuscularly in single doses of 20 mg/kg to rats, rabbits, and dogs, the peak serum levels of nocardicin A were about 1.6 similar to 2.8 times higher than those of carbenicillin in all animals though the levels varied among the species tested. The serum half-life of nocardicin A in these animals was about twice that of carbenicillin. The 24-hour urinary recovery rate of nocardicin A after intramuscular injection was 68.5 percent in rabbits and 77.0 percent in dogs, but was low in rats; i.e., 0.7 percent. When nocardicin A was given intravenously in single doses of 20 mg/kg to these animals, the peak serum levels varied widely among the test species; i.e. about 3 times higher than those of carbenicillin in rabbits and dogs, similar to those in rats. The peak serum and tissue levels of nocardicin A after intramuscular to intravenous injection were the highest in the kidneys, followed by the liver, serum, lungs, heart and spleen. The levels in the liver were prolonged. Nocardicin A, and traces of unknown substances less active than nocardicin A were observed as active substances in the urine recovered after injection of nocardicin A.


Metabolites of gentamicin-producing Micromonospora species I. Isolation and identification of metabolites. From the cultural broth of a Micromonospora species 25 aminocyclitol antibiotics were isolated by repeated ion-exchange chromatographic processes. The main components of the metabolites were identified as gentamicin C1, C2, and C1a. The other previously reported gentamicin type antibiotics and some other degradation products including gentamicin A, B, B1, X2, sisomicin, garamine, gentamines etc., were identified by chemical, PMR, and mass spectroscopic studies. Besides these, seven new gentamicin type antibiotics were isolated and characterized.


Synthesis of a 125I-labelled derivative of the antibiotic griseofulvin. A derivative of griseofulvin has been synthesised, in which the 2'-O-methyl group is replaced by a 2'-(2-iodoethoxy), 125I-labelled group. This derivative is at least as potent as griseofulvin itself, when assayed for inhibition of growth on the Myxomycete Physarum polycephalum.


The enhancement of beta-lactam antibiotic therapy by novobiocin. Novobiocin demonstrates an effect similar to that of probenecid (the "probenecid effect") in enhancing the therapeutic efficacy of antibiotics excreted mainly by the renal tubules. The ability of cefoxitin, cephalexin, cephalothin and penicillin G to protect mice against infection with Salmonella schottmuelleri was enhanced 2- to 3-fold when the animals were given oral doses of either probenecid or of novobiocin. The efficacy of cephaloridine, excreted mainly by glomerular filtration, was not enhanced by either probenecid or by novobiocin.


Studies on mycobacillin derivatives. IV. O-methylation of the antibiotic and identification of the active tyrosine residue. Methylation of myocobacillin with dimethyl sulfate and methyl iodide produced respectively mono- and di-methyl derivatives. the products were inactive against fungal spores and erythrocytes. Tyrosine hydroxyl groups only were methylated; in the monomethyl derivative, the hydroxyl of the tyrosine residue in position 6 is methylated, whereas the hydroxyl of the tyrosine in position 4 remains free; both hydroxyl groups are methylated in the dimethyl derivative. The results indicate that the hydroxyl group of the tyrosine residue in position 6 is essential for the biological activity of mycobacillin.


Synthesis of carbon-14 and tritium labeled sagamicin. Sagamicin, an aminoglycoside antibiotic, was labeled with tritium by means of a platinum catalyzed hydrogen exchange reaction and by carbon-14 in two biosynthetic procedures. 14C-Methyl-L-methionine was used as the radioactive precursor in these biological processes involving Micromonospora sagamiensis. The distribution of radioactivity in 14C-sagamicin and gentamicin C1 was studied by mild acid hydrolysis and Hofmann degradation. The results showed that both C- and N-methyl groups were derived from methionine. One of the biosynthetic processes involved the conversion of gentamicin into sagamicin with resting cells and labeled methionine.


Anti-G suit effect of cardiovascular dynamic changes due to +GZ stress. Lightly anesthetized dogs underwent 1-min exposure to +Gz acceleration without and with a bladder-type anti-G suit. Prior chronic instrumentation permitted through evaluation of cardiac dynamics. During +3 Gz acceleration all recorded dynamic variables were lowered and transient tachycardia occurred. After acceleration ceases, all pressures and dP/dt exceeded control levels. Inflation of the anti-G suit during +3 Gz eliminated the dramatic effects observed during and after acceleration stress. During +6 Gz with the anti-G suit inflated, arterial pressure and dP/dt were maintained whereas left ventricular end-diastolic pressure and total peripheral resistance were much elevated and heart rate was lower. At the onset of G stress, internal diameter of the heart always fell transiently. Otherwise, diameter was not significantly affected by any of the experimental conditions. The results suggest that the anti-G suit maintains perfusion pressure at high sustained G; however, with the anti-G suit inflated at +6 Gz, central venous pressure is dramatically elevated and heart rate depressed. Thus, beneficial effects which provide tolerance to high G are accompanied by potentially detrimental effects.


Hypothalamic thermoregulatory pathways in the rat. The cutaneous blood flow (mbl), rate of oxygen consumption (Vo2), rectal (Tre) and cutaneous (Tsk) temperatures, and shivering activity were measured in unanthetized male rats during a 2-h exposure to 26, 33, or 5 degrees C 2 wk after selective bilateral hypothalamic microknife cuts. Animals with preoptic-anterior hypothalamic (PO/AH) junction cuts 1.5 or 3.0 mm lateral to the midline, as well as parasagittal cuts which separated connections between the PO/AH and medial forebrain bundle exhibited a higher mbl at 26 degrees C than did sham-operated rats. At 5 degrees C the extended (3.0 mm) PO/AH cuts as well as the parasagittal cuts prevented cutaneous vasoconstriction but had no effect on shivering activity; hence Tre was not maintained. None of the cuts demonstrably impaired thermoregulation in the 33 degrees C environment. These results suggest that different sites in the hypothalamus may separately control cold-induced skin vasoconstriction and shivering activity, as well as heat-induced skin vasodilation. It would seem therefore that the integrity of the PO/AH is indispensable in rats for cold-induced cutaneous vasoconstriction but not for cold thermogenesis, and also not for heat-induced cutaneous vasodilation.


Cardiopulmonary function in dogs during lung lavage and unilateral hypoxia. Changes in cardiopulmonary function in Beagle dogs were studied during two methods of lung lavage and during unilateral hypoxia. In one method of lavage, dogs were hyperventilated and saline was instilled relatively rapidly through a single-lumen tracheal tube. In another lavage method, a double-lumen tube separated right and left bronchi and saline was instilled more slowly into the dog's right lung. Unilateral hypoxia was produced by directing right lung airflow to a rebreathing bag. Few blood gas or venous admixture changes occurred during single-lumen lavage, but blood oxygen decreased and venous admixture increased during both double-lumen lavage and unilateral hypoxia. Heart rate, cardiac output, and systemic arterial pressure decreased during single-lumen lavage, but not during double-lumen lavage or unilateral hypoxia. Apparently, most alveoli were gas filled during single-lumen lavage and unilateral hypoxia was not imposed. Similar changes during double-lumen lavage and unilateral hypoxia suggested that unilateral hypoxia was a major change-producing factor during double-lumen lavage.


Effects of acute prolonged hypoxia on cardiovascular dynamics in dogs. Intact anesthetized dogs were exposed for 75 min to either 5.75, 9.0, or 12.0% oxygen in nitrogen. Although pulmonary artery pressures were significantly elevated in all hypoxic exposures, systemic hypertension occurred only at the onset of severe hypoxia(5.75% O2). Coronary blood flow increased from an average of 130 during normoxia to a peak of 400 ml/100 g per min during inhalation of 5.75% O2, and coronary sinus oxygen tensions of 8 Torr and oxygen contents of 1.1 ml/100 ml were sustained for 75 min without biochemical, functional, or electrophysiological evidence of myocardial ischemia. Cardiac index (CI) increased significantly only during severe hypoxia (5.75% O2) with the greatest elevation after 30 min. Subsequently, CI decreased concomitantly with a 27% elevation in arterial hemoglobin concentration and oxygen-carrying capacity. It is concluded that the hypoxic threshold for significant elevations of cardiac output is between 6.0 and 9.0% O2.


Altered control of skin blood flow during exercise at high internal temperatures. We have investigated further the behavior of skin blood flow (SkBF) as internal temperature (measured as esophageal temperature (Tes)) rises in a heated exercising man. A previous study showed that when skin temperature (Tsk) is driven up in exercising men, the increase in SkBF is less than that found for the same Tes and Tsk in a resting man. In this study, we extended our observations into the range of higher Tes to see if SkBF (measured plethysmographically as changes in forearm blood flow) could be driven to higher levels despite competition with skeletal muscle for cardiac output. After Tsk was elevated to 38 degrees C by means of water-perfused suits, subjects exercised at 525-900 kp.m/min (86-147 W) for 17-30 min while Tsk was held at 38 degrees C. We found that SkBF increase per unit increase in Tes is attenuated at higher Tes. In seven men, the average slope obtained from linear regression of FBF on Tes below 38 degrees C was 7.6 flow units/degrees C. Above 38 degrees C, the average was 2.12 flow units/degrees C. In some subjects, the FBF response appeared virtually saturated at a plateau despite a steady rate of increase in Tes with time. Clearly, SkBF does not increase in direct proportion to Tes without bound. Other stimuli (presumably related to blood pressure regulation) interact either to reduce the rate of SkBF increase or to prevent any further increase after Tes exceeds 38 degrees C.


Catecholamines in coronary sinus during exercise in man before and after training. Coronary patients exercised on an ergometric bicycle before and after physical training. Plasma catecholamines were sampled simultaneously at the arterial and coronary sinus levels and assayed with a radioenzymatic method. The increase in the level of coronary sinus catecholamines exceeded the increase in the arterial level, indicating a liberation of catecholamines by the myocardium and an activation of the peripheral sympathetic fibers during exercise. With high work loads, these values no longer differed, suggesting that the additional increase in circulating catecholamines originate from extra-myocardial stores, presumably the adrenal medulla. Arterial catecholamine levels were significantly correlated with work loads, heart rate, changes in systolic blood pressure, and rate-pressure product. After physical training, arterial catecholamine increases for various work loads were lower; these lower elevations were associated with diminished responses in heart rate and systolic blood pressure, resulting in a lower rate-pressure product. Physical training results in diminished sympathetic responses for a given level of exercise, which could be associated with the clinical improvement of these patients.


Volume of isoflow: effect of distribution of ventilation. Volume of isoflow was determined in smokers and nonsmokers following one (VisoV1) and three (VisoV3) inhalations 80% helium 20% oxygen. In addition, distribution of ventilation was measured by single breath nitrogen washout and end-tidal helium concentration was determined following 1-3 breaths of a helium-oxygen mixture. In all subjects (smokers and non smokers), VisoV1 was significantly higher than VisoV3. Furthermore, VisoV1 was abnormal in 55.6% of smokers, whereas VisoV3 was abnormal in only 38.9%. Differences between VisoV1 and VisoV3 (VisoV1 - VisoV3 = deltaVisoV) were significantly larger in smokers. Non-uniform distribution of ventilation was associated with larger values of delta VisoV and lower end-tidal helium concentrations. VisoV1 is a more effective method than VisoV3 in distinguishing smokers with small airways obstruction from nonsmokers. This enhanced sensitivity can be explained by the observation that the effects of maldistribution of ventilation upon helium concentration in the late expirate are minimized after three breaths of a helium-oxygen mixture.


Response of medullary respiratory neurons to hypercapnia and isocapnic hypoxia. Single-unit activity was monitored extracellularly from medullary respiratory neurons and nonspecified neurons of decerebrate cats which were paralyzed, vagotomized, and artificially ventilated. Hypercapnia consistently resulted in increased discharge frequencies and decreased modal interspike intervals for respiratory units; peak integrated phrenic discharge heights increased concomitantly. Although isocapnic hypoxia usually resulted in comparable changes, the firing frequency of some respiratory units was depressed. Moreover, this depression was frequently observed simultaneously with a hypoxia-induced increase in phrenic discharge. Nonrespiratory unit discharge was mainly unaltered by hypercapnia or hypoxia. Following bilateral carotid sinus nerve section, hypercapnia-induced increases in respiratory neuronal and phrenic activities were still obtained; hypoxia depressed these activities. It is concluded that central chemoreceptor afferent influences are ubiquitously distributed to the medullary respiratory complex whereas peripheral chemoreceptor afferents produce only a discrete and unequal excitation of respiratory units. Hypoxia-induced ventilatory changes are further concluded to be the net result of peripheral chemoreceptor excitation of respiratory units and a direct depression of the brain stem respiratory complex by hypoxia.


Increase in sweating sensitivity by endurance conditioning in man. Sweating sensitivity has been evaluated at rest in 10 competitive athletes (cross-country skiers and swimmers). Three sedentary men underwent a 3-mo period of endurance training in a temperate climate, (dry bulb temperature (Tdb): 18 degrees C) and had their sweating sensitivity measured before and after the training period. Mean maximum oxygen uptake (Vo2max, ml.min(-1).kg(-1)) was: skiers: 66.5; swimmers 65.8; sedentary men, pretraining 40.9; posttraining: 48.3 (+18%). Sweat output of athletes under a given stress (passive heating) was markedly higher than that of sedentary men. Skiers exhibited a high level of heat tolerance and were better acclimatized than swimmers, although they had never experienced exposure to heat. The increase in Vo2max of sedentary men was accompanied by 1) an increase in sweating sensitivity with a decrease of body heat storage at steady state (pretraining: 5.4 kJ.kg(-1); posttraining: 3.5 kJ.kg(-1); P less than 0.05); 2) significant shift down the temperature scale with reduced rectal temperature (Tre) for sweat onset; 3) an increase of gain constants of sweating (W.m-2 degrees C(-1) (pretraining: 168; posttraining: 269; gain constant of swimmers: 222). It was suggested that endurance training in cold or temperate conditions with significant increase of Vo2max could act on the thermoregulatory function in a way similar to body heating procedures, such as work in heat, and could contribute to heat acclimatization.


Effects of increased plasma fatty acids on glycogen utilization and endurance. The purpose of this study was to test the hypothesis that increased availability of fatty acids could increase endurance by slowing the rate of glycogen depletion. Rats were given corn oil by stomach tube, and 3 h later an injection of heparin was given to raise their plasma free fatty acids (FFA). The rats with raised FFA were able to run approximately 1 h longer than otherwise comparable control animals before becoming exhausted (181 +/- 8 vs. 118 +/- 8 min, P less than 0.001). At the point of exhaustion, both groups were hypoglycemic and had low muscle glycogen concentrations. The fall in blood glucose occurred less rapidly in the animals with raised FFA; these rats also had significantly higher blood glycerol and beta-hydroxybutyrate concentrations than the controls. Glycogen concencentration decreased less rapidly in all three types of skeletal muscle and in liver in the animals with raised FFA than in the controls. We conclude that increased availability of fatty acids delays the development of exhaustion in rats subjected to prolonged running. It appears likely that the carbohydrate-sparing effect of fatty acids is largely responsible for the increase in endurance.


Factors relating to the strength of male adolescents. Factors relating to the strength of 53 postpubertal adolescent males have been examined. A strength index, composed of left and right handgrip and back strengths, was related to the following: anthropometric measurements and their derivatives; level of habitual activity; body shape as characterized by Heath-Carter and Sheldonian somatotype ratings; and anthropometric ratios. Strength was found to be positively related to all anthropometric measurements with the exception of skinfold thicknesses. When body weight was held constant, strength was positively related to arm circumference, bicondylar diameters of the humerus and femur, thigh volume, and biacromial diameter, and negatively related to percentage of fat. Strength was not related to the level of habitual activity. The relative contributions of overall body size and body shape to predictions of strength are approximately 57 and 47%. Measures of overall size appear to make no independent contribution to strength, beyond that contributed by limb segment volumes, or a combination of linear limb dimensions and measures of body shape.


Effect of SO2 on control of breathing in anesthetized cats. In seven anesthetized tracheotomized cats we studied the acute respiratory effects of SO2 inhalation at different steady-state levels of arterial CO2 tension (Paco2). During room air breathing, SO2 (0.05%) addition caused a progressive reduction in tidal volume (VT) and increases in both respiratory frequency (f) and pulmonary resistance (RL). Atropine sulfate abolished the bronchoconstriction response to SO2 and thus permitted the study of the influence of SO2 on VT and f in the absence of constricted airways. Despite marked reductions in the VT VS. PaCO2 relationships with SO2 exposure after atropine, the relationship between pulmonary ventilation (VE) and PaCO2 was not signifcantly altered. This was the case since SO2 caused solely a reduction in inspiratory duration (Ti), affecting neither the mean rate of rise of inspiratory activity (i.e., VT/Ti) nor the relationship between Ti and breath duration. Thus, airways irritation with SO2 produced rapid, shallow breathing characterized by a shortening of inspiratory and total respiratory cycle times with no change in the rate of development of inspiratory activity. The findings suggest an influence exclusively concerned with the timing of inspiration. Perhaps premature onset of inspiratory activity accounts for the observed effects.


Saturation kinetics for steady-state pulmonary CO transfer. Steady-state diffusing capacity of the lungs for carbon monoxide (DLCO) was measured in 13 anesthetized, paralyzed dogs ventilated at constant tidal volume and rate, using four different inspired CO levels (190, 600, 1,110, and 2,000 ppm). DLCO increased and reached a maximum as the inspired CO level was raised from 190 to 600 ppm. Further increases in inspired CO concentration were accompanied by a decrease in inspired CO concentration were accompanied by a decrease in DLCO. CO dead space and Pao2 remained constant at all inspired O2 levels. In some experiments a second set of measurements was made, the results of which were similar to those of the first set. The results cannot be explained by changes in CO back pressure, pulmonary capillary volume, or reaction rate of CO with hemoglobin, but can be explained if there is carrier-mediated CO transport in the alveolar capillary membrane.


Placental diffusing capacity for carbon monoxide and oxygen in unanesthetized sheep. We measured placental diffusing capacity for carbon monoxide (DpCO) in 10 unanesthetized sheep with catheters chronically implanted in maternal and fetal vessels. Serially measured DpCO during the last third of gestation averaged 0.55 +/- 0.02 (SEM) ml.(min.Torr.kg fetal wt)-1, essentially the same value as that previously reported in anesthetized, acutely operated animals. While placental CO diffusing capacity increased as a function of gestational age when expressed as ml.(min.Torr)(-1), it remained constant when calculated per kg fetal wt. In eight experiments, DpCO showed no change following the administration of several drugs which combine with cytochrome P450. We interpret this as evidence against the carrier hypothesis for placental CO exchange. We calculated the placental diffusing capacity for oxygen to be 0.68 ml.(min.Torr.kg)-1 and the mean maternal-to-fetal capillary Po2 difference to be 10 Torr. Caculations predict that maternal and fetal oxygen partial pressures equilibrate in end-capillary blood during the course of a single transit in placental exchange vessels; thus placental oxygen exchange is not limited by diffusion.