Deployment, supervision and decision-making of residents in an emergency psychiatric service.

A lessening of personal discomfort felt by residents on-call in the Emergency Psychiatric Service has resulted from changes in the frequency of being on-call, exclusion of beginning residents from duty and arranging for the presence of a faculty psychiatrist for one or two hours during each on-call period. Coincidental significant reductions in the number of cases admitted to hospital and reductions in the proportion of discrepancies between diagnoses made by the emergency resident and those made later by inpatient unit staff have been described. The relationship of the changes in resident experience to the reduction in admissions and decreased proportion of diagnostic discrepancy has been discussed using a model of the process of emergency psychiatric admission described earlier by Bartolucci et al. (1). Less isolation, anxiety and some increased experience on the part of the psychiatric residents on duty in the Emergency Psychiatric Service results in greater awareness and better appraisal of the non-medical aspects of psychiatric emergencies.


"Dislocation of expectations" (management of violence on a general hospital psychiatric unit).

An approach to the management of potential violence on a General Hospital Psychiatric Unit is described as it evolved following analysis of the successful handling of a series of problem patients. The importance of an attitude of acceptance towards potentially violent persons is emphasized as is an orientation towards prevention. An approach of consistency and directness with enhancement of the patient's positive personality features is favoured. The initial assessment is considered important and clues to the prediction of violence are highlighted, as are aspects of the supervision plan. A specific technique for prevention of violence based on the principle of Dislocation of Expectations, or doing differently than the subject expects, is introduced.


A socio-psychiatric profile of emergency service patients.

A study of patients using the psychiatric emergency services of the Royal Ottawa Hospital was undertaken to determine their demographic and clinical characteristics, correlations between the two and comparisons with other studies. Special clinical forms of every fifth patient seen were analyzed and the data presented. These data are useful in the planning of and establishing and operating a psychiatric emergency service with an attached short-term inpatient unit, as well as assessing the feasibility and value of crisis intervention and brief psychotherapy in treating patients quickly.


The syndrome of inappropriate secretion of antidiuretic hormone (SIADH): an overview.

We have reviewed 14 cases of water intoxication in psychiatric patients. In these cases the possibility of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) was suspected or diagnosed. The SIADH should be suspected in psychotic patients who drink water excessively, develop seizures, disorientation and deterioration of mental status.


Insight and hospital adjustment.

The relationship between insight and adjustment in schizophrenics was examined. Subjects who scored higher on a paper-and-pencil insight test were rated by hospital staff as better adjusted behaviourally but described themselves as more psychologically distressed than presumably less insightful subjects. Results were discussed in relation to the notion that insight in schizophrenics may intensify subjective distress while conducing to behavioural adaptation.


The induction of acute psychosis in a group setting.

The case histories of two patients are described, each of whom suffered a severe psychotic decompensation, one apparently schizophreniform and the other affective, after attending a seven day marathon group conducted by a charismatic, aggressive leader. The work of Yalom and Lieberman is reviewed, with regard to leader and participant characteristics in encounter group casualties. Drawing upon the work of Bion and Kernberg, a specific means for the induction of psychosis is suggested, involving primitive splitting and the projection of "all bad" self-object constellations within a group setting.


Names and dream-work.

Four dreams are reported in which associations leading to previously unacknowledged material were elicited by asking about names. Inquiry into names and distortions of names (rhymes, puns, contractions, initials, visual symbols) is a useful technique in the provocation of emotionally-laden connections. A possible explanation lies in the parallel between naturally occurring name transformations and the dream work of regression, displacement, condensation and symbolization.


Manic depressive illness in adolescence and childhood: review and case report.

The literature on this topic from its inception by Kraepelin is reviewed. While Kraepelin and the French school always recognized juvenile mania, the Anglo-American school has no such unanimity of opinion. Less than 100 cases are described in the world literature. In Canada affective psychoses are rarely diagnosed under age 10 and of all affective psychoses admitted to institutions less than 5% are under age 20. The differences between child and adult mania are outlined. It is proposed that manic-depressive illness occurs in children but is not diagnosed more often because of its dissimilar presentation to the adult form and doubts about its existence in childhood. The case history of a 14 year old boy who presented in a hypomanic state is described. There was a strong family history of affective disorder. Both his parents and his half-sister were already on lithium for manic-depressive illness.


A review of pseudorabies (Aujeszky's disease) in pigs.

The main features in terms of etiology, clinical signs, pathogenesis, pathology, diagnosis, epizootiology and control and prevention that are known about pseudorabies are briefly reviewed. Areas still lacking in information which may provide more effective and reliable means of dealing with pseudorabies are mentioned and recommendations using available tools and knowledge to deal with the problem of pseudorabies are given.


Pathological studies of "Sudden death syndrome" in broiler chickens.

Sudden death syndrome usually occurs in heavy, fast-growing and healthy-looking broilers. Most of the affected birds are males. The characteristic necropsy changes are seen in well-fleshed broilers with edema and generalized pulmonary congestion, recently ingested feed in the crop and gizzard, distended intestine with creamy content and empty gall bladder. The liver and kidneys are slightly enlarged and the latter have patchy areas of subcapsular hemorrhage. The heart contains clotted blood in the atria but the ventricles are often empty and the left ventricle in particular assumes a hypertrophied appearance. Microscopic examination of heart muscle reveals degeneration of fibers, separation of cardiac muscle fibers by edema and infiltration of heterophils. The lungs have severe vascular congestion, inflammatory cell infiltration in the mucosa of the secondary bronchi and edema fluid in the tertiary bronchi and interlobular connective tissue. The liver has moderate bile duct hyperplasia, periportal hepatitis and mononuclear cell infiltration adjacent to bile ducts which possibly leads to bile duct constriction. The kidneys have subcapsular and parenchymatous hemorrhage.


Studies on effect of lighting on "Sudden death syndrome" in broiler chickens.

Broiler chicken flocks were studied to determine the mortality from sudden death syndrome occurring in the flocks. The difference in the incidence of the syndrome in pullets and cockerels, and the age at which the most birds are affected were also studied. The weight of sudden death syndrome birds was compared with the flock average and the effect of continuous lighting as opposed to intermittent lighting was examined. The results suggest that; continuous lighting produces more sudden death syndrome deaths than intermittent lighting; that the incidence of sudden death syndrome is higher in cockerels than pullets; that the highest death rate occurred during the third and fourth weeks of life, and that sudden death syndrome birds on the average were heavier than the flock average.


Vascular ring anomalies: case report and brief review.

During early fetal life six pair of aortic arches surround the esophagus and trachea. Normal maturation and selective regression of these structures form the adult vasculature. Abnormal location or development of the aortic arches may result in pressure on adjacent organs. Vascular ring anomalies must be considered with any patient with a history of regurgitating food shortly after eating. Physical examination, test feedings, survey and contrast radiographs may give an accurate impression of the problem but a final diagnosis can only be made following surgical exploration. In the case presented, the dog had all the clinical and diagnostic signs suggestive of a vascular ring anomaly. Thoracotomy and elimination of the vascular constriction around the esophagus was both diagnostic and therapeutic for the condition. It is important that owners be made aware that surgical correction of the stenosis does not guarantee a successful conclusion to the case. If the dilation of the esophagus cranial to the stenosis is severe, accumulation of food with subsequent regurgitation may persist. A dilation of the esophagus caudal to the stenosis is present in a large percentage of cases and this also may result in an unrelenting problem. Unfortunately, the probability of these complications cannot be accurately evaluated prior to treatment.The hereditary potential for this defect must also be considered. Congenital vascular anomalies such as patent ductus arteriosus would seem to have a hereditary basis. Therefore, it is probably correct to advise against breeding affected animals. Further, the inbreeding of nonaffected animals which come from litters containing affected animals should be avoided.


Mushroom poisoning in a dog.

The false morel (Gyromitra esculenta), a mushroom responsible for occasional fatalities in man, caused a fatal hemolytic episode in a ten week old dog. The clinical symptoms observed and the gross and histopathological findings, are discussed.


Ischaemic embolic myelopathy in a Labrador crossbred dog.

A case of ischaemic embolic myelopathy in a dog is described. It was demonstrated histologically that these focal ischaemic lesions were associated with emboli, histochemically identified as fibrocartilagenous.


Blood levels of sulfamethazine achieved in beef calves on medicated drinking water.

Studies on the use of sodium sulfamethazine in drinking water at three levels (572, 1028 and 1848 mg/L) were conducted in healthy weaned beef calves under similar dietary and environmental conditions. Blood sulfonamide levels greater than 5 mg/dl were attained with each treatment level but at different time intervals. The maximum levels in blood were achieved with the highest concentration in the water. However, a reduction in water intake caused a lower than anticipated dose of sulfamethazine. Under the conditions of the experiment the administration of sulfonamide in drinking water may be an effective means of mass medication of cattle.


Topical treatment of experimental ringworm in guinea pigs with griseofulvin in dimethylsulfoxide.

The topical administration of 1.5% griseofulvin in dimethylsulfoxide for five to seven days was a satisfactory treatment regime for experimental ringworm in the guinea pig.


Case report: six cases of verminous pneumonia (Muellerius sp.) in goats.

Six cases of verminous pneumonia in goats due to Muellerius sp. were reviewed. In only one case was the pneumonia diagnosed antemortem. The gross necropsy findings and histopathology revealed a widespread interstitial pneumonia in all the cases. There was variability in the local reaction around the parasites from almost none in the mildest cases to larger focal accumulations of macrophages and mononuclear inflammatory cells. Only in the severest cases were eosinophils seen and even then were scattered and few in number. No nodular lesions were seen associated with the parasites. The pathology of the pulmonary lesions in goats appears to be more commonly of the diffuse type and therefore significantly different from the nodular lesion usually observed in sheep.


Equine respiratory disease on the Western Canadian racetracks.

The serological results from this study clearly show that both equine influenza and equine rhinopneumonitis viruses were present during spring and autumn epidemics of respiratory disease on Western Canadian racetracks. Approximately 11% of the horses showed significant convalescent titres to influenza while 9% showed significant convalescent titres for equine viral pneumonitis. It was noted in our study a positive vaccination history corresponded with a reduction in the severity of the respiratory infection.


[Ecbolic and hormonal action of synthetic prostaglandin F2a in fetal mummification in two Holstein cows (author's transl)].

Ecbolic and Hormonal Action of Synthetic Prostaglandin F(2)a in Fetal Mummification in Two Holstein CowsThe effects of treatment with synthetic prostaglandin F(2)a (500mug i.m.) to correct cases of fetal mummification in two Holstein cows are described.


Transplacental effect of diethylstilbestrol in female rats.

The effect of diethylstilbestrol propionate (DES; 1 mg/kg body wt. was studied in the female offspring of rats exposed subcutaneously on the 19th day of gestation. Examination of vaginal smears showed persistent estrus in adult rats treated prenatally with DES. Compensatory ovarian hypertrophy (COH) induced by hemicastration of these rats was not suppressed by estrogens. A per oral test for glucose-tolerance revealed decreased utilization of glucose in the offspring of DES-treated rats. Preliminary observations demonstrated that tumors developed in 14 of 18 (77.8%) progeny transplacentally expoed to DES and in 9 of 34 (26.5%) intact control rats. Tumors of the ovary and the endometrium were found only in the rats treated prenatally with DES; no tumors of the uterine cervix or vagina were observed in either experimental or control groups. It is suggested that a transplacental effect of DES in the female is impairment of the sex differentiation of the hypothalamus. The resulting hormonal and metabolic shifts might promote tumorigenesis.


Carcinogenic effect of N-bis(2-hydroxypropyl)nitrosamine by a single administration in rats.

The carcinogenic effect of a single intraperitoneal injection of N-bis)2-hydroxypropyl)nitrosamine (BHP) was studied in male Wistar rats. Lung tumors (adenomas and adenocarcinomas) had the highest incidence (100%). Fewer neoplasms were induced in the thyroid (adenomas and adenocarcinomas, 36%), kidney (renal cell carcinomas, 8%), and the sigmoid colon (adenomas and adenocarcinomas, 9%). No pancreatic neoplasms were found.


Enhanced urinary excretion of 7,8-dihydro-6-hydroxylumazine by mice bearing the Ehrlich ascites tumour.

A fluorescent urinary metabolite, excreted by mice carrying the Ehrlich ascites tumour (EAT), has been identified as 7,8-dihydro-6-hydroxylumazine. This finding agrees with other data which show that a disorder in pteridine metabolism is commonly associated with the presence of malignant growth.


N6(Methylnitroso)adenosine: a carcinogenic nitrosamine derived from a naturally-occurring nucleoside.

N6(Methylnitroso) adenosine (M6(NO)Ado) is found readily under acidic conditions by the interaction of nitrite with 6-methyladenosine, a naturally-occurring nucleoside. Swiss mice were treated with M6(NO)Ado by injection (40 mg/kg each treatment) transplacentally and then as newborns and young adults. The incidences of lymphomas, primary lung tumors, and hepatic neoplasms were significantly greater in these treated animals than in controls. These results demonstrate the tumorigenicity of M6(NO)Ado.


Ductular origin of pancreatic cancer and its multiplicity in man comparable to experimentally induced tumors. A preliminary study.

The histologic features of 3 randomly selected pancreatic cancer cases are compared with those found in Syrian hamsters after treatment with N-nitrosobis(2-oxopropyl)amine (BOP). The 3 human cases all exhibited hyperplastic, preneoplastic and malignant changes which were markedly multicentric, and which arose predominantly from ductules, as well as from small ducts. The findings were comparable to those in the hamster mode. Proliferation and malignant alterations of the intrainsular ductules were commonly seen in both human and experimental tumors. The data is consistent with the concept that cells of the small ducts and especially of the ductules represent a potential source of human, as well as experimental, tumors. The small number of human cases studied does not allow generalization, but the marked resemblances in all 3 randomly selected pancreatic cancer cases were remarkable.


Phagocytosis of asbestos fibers by human pulmonary alveolar macrophages.

Human pulmonary alveolar macrophages (PAMs) were cultured for 24--72 h with varying concentrations (0--300 microgram/ml) of amosite asbestos (AS). At lower AS concentrations, (less than 100 microgram/ml) no decrease in cell viability occurred during the first 24 h of culture. Significant cytotoxicity (P less than 0.005 in all instances) was observed, however, following incubation for 24 h with higher AS concentrations (greater than 100 microgram/ml). Even following incubation with lower concentrations of AS, significant cytotoxicity (P less than 0.006 in all instances) was observed after 48 or 72 h of culture. Scanning electron microscopy (SEM) clearly illustrates the various stages of AS phagocytosis by PAMs. SEM also documented morphological changes in PAMs following AS exposure. These included increased zeiosis and the appearance of a fibrous-like material on the surface of AS fibers following initial contact with the PAM cytoplasmic membrane. Further study of the biological interactions between AS and human cells, such as PAMs, might provide valuable information regarding the etiology of AS-related lung disorders.


The detection of various nitrosamines in the hepatocyte primary culture/DNA repair test.

Evaluation of 6 carcinogenic nitrosamines in the hepatocyte primary culture/DNA repair test revealed that all were active. Three non-carcinogenic analogs were negative. This sensitivity to nitrosamines, together with considerations concerning the metabolic capability and end point of this assay, indicates that it will be a useful addition to screening batteries that include bacterial mutagenesis assays.


Induction of unscheduled DNA synthesis in suspensions of rat hepatocytes by an environmental toxicant, 3,3'4,4'-tetrachloroazobenzene.

Unscheduled DNA synthesis was induced by 3,3'4,4'-tetrachloroazobenzene (TCAB)) in freshly isolated suspensions of rat hepatocytes. A dose-dependent response was demonstrated. Hepatocellular DNA was obtained after the chloroform-isoamyl alchohol-phenol extraction of the isolated nuclei. The induction of unscheduled DNA synthesis was measured by the incorporation of [3H]-thymidine in the presence of hydroxyurea as determined by the scintillation counting assay. DNA repair data obtained in this study on benzo[a]pyrene and methyl methanesulfonate are comparable to a previous report using primary cultures of hepatocytes and cesium chloride gradients. Hence, the present method offers promise as a rapid and sensitive screen for chemical carcinogens.


A carcinogenicity study of pesticide dieldrin in hamsters.

Syrian golden hamsters were fed for their lifespan a diet containing 0, 20, 60 and 180 parts per million (ppm) Dieldrin. Tumour-bearing animals totaled 13% among control females and ranged between 3-15% in treated females. Eight per cent of male controls had tumours and between 16-23% of treated males. Incidences of endocrine organ tumours were comparable in all groups. A hepatoma was found in 1 female and 1 male led 180 ppm Dieldrin. The present results show that hamsters tolerate higher doses of Dieldrin than do mice and rats. No significant tumour incidence was observed in treated versus control Syrian golden hamsters.


Methyl glyoxal bis guanylhydrazone abolition of the toxic action of spermidine on cells in culture.

Spermidine inhibits many cells in culture because amine oxidase in the serum converts spermidine to toxic products. Methyl glyoxal bis guanylhydrazone (Methyl GAG) inhibits cells in culture because it is a specific inhibitor of S-adenosylmethionine decarboxylase, preventing the conversion of putrescine to spermidine. When both spermidine and methyl GAG were added together, no inhibition was observed. The effect could be explained by the finding that methyl GAG was a powerful non-competitive inhibitor of the enzymatic oxidation of spermidine to acrolein.


Nicotine and cotinine in breast fluid.

Breast fluid which bathes the mammary ductal epithelium may contain tumorogenic components. In view of the number of tobacco components inhaled during smoking, it was of interest whether nicotine and its metabolites were present in this fluid. Fluid was obtained from the nipple from menstruating women who were smokers and non-smokers. In smokers, nicotine and cotinine were detectable in the fluid 30 min after smoking. Further analysis of breast fluid may give leads as to whether components present are related to breast carcinogenesis.


O6-methylguanine accumulates in DNA of mammary glands after administration of N-methyl-N-nitrosourea to rats.

N-Methyl-N-nitrosourea (MNU) induces mammary carcinoma in female rats when given intravenously. After a single intravenous dose of N-methyl-N-nitrosourea (5 mg/100 g body wt.), we were unable to detect a shift of rat mammary gland DNA on an alkaline sucrose gradient. However, the alkylated products in DNA, 7-methylguanine and O6-methylguanine, were determined at various times following treatment with N-methyl-N-nitrosourea. O6-Methylguanine was removed from the DNA at a slower rate than 7-methylguanine and increased in the DNA with a second injection of N-methyl-N-nitrosourea. 3-Methyladenine was not detected in DNA from the mammary gland of the rat. These data support previous work with brain and bladder that suggest the persistence of O6-methylguanine in DNA might be involved in the induction of cancer by N-methyl-N-nitrosourea.


Investigations on the carcinogenic burden by air pollution in man. Intratracheal instillation studies with benzo[a]pyrene in a mixture of Tris buffer and saline in Syrian golden hamsters.

Syrian golden hamster received intratracheal instillations of 0.125, 0.25, 0.50 or 1.0 mg benzo[a]pyrene (B[A]P) in a mixture of Tris buffer and physiological saline once weekly for life. Papillary polyps, squamous cell papillomas and carcinomas developed in both the larynx and trachea. In addition, bronchiogenic adenomas, adenocarcinomas and squamous cell carcinomas were induced in the lung. The highest incidence of respiratory tract tumours (83%) was seen in hamsters receiving 0.25 mg B[a]P. The results of these investigations are statistically evaluated and discussed.


The binding to mouse skin DNA of benzo[a]pyrene, its 7,8-diol and 7,8-diol-9,10-epoxides in relation to the tumorigenicity of these compounds.

Tritium labelled and carbon-14 labelled benzo[a]pyrene (PB), (+/-)trans 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (PB-7,8-diol), (+/-)-7 alpha,8 beta-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene and (+/-)-7 alpha, 8 beta-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]-pyrene were applied to the shaved backs of mice. After 24 h the DNA was isolated from the treated skin and the extent of hydrocarbon binding was determined. The level of DNA binding is considered in relation to the previously reported carcinogenicity of the various benzo[a]pyrene derivatives.


Sodium lack prevents strophanthidin toxicity in Purkinje fibers.

The effect of strophanthidin on electrical and mechanical activity of canine cardiac Purkinje fibers perfused in vitro was tested in the presence and in the absence of sodium. The following results were obtained: (1) in Tyrode's solution, strophanthidin causes spontaneous fast rhythms; (2) perfusion of a tetraethylammonium (TEA) Na-free solution results in an initial slowing and quiescence followed by the development of spontaneous small potentials; (3) exposure to strophanthidin during the perfusion of the Na-free solution fails to induce an acceleration of spontaneous discharge; (4) on returning from Na-free to Tyrode's solution there is a temporary acceleration of the small potentials and this acceleration is larger and lasts longer when the Na-free solution contains strophanthidin, and (5) in fibers intoxicated with strophanthidin, exposure to Na-free solution stops the fast rhythms. It is concluded that sodium plays an important role in strophanthidin toxicity and no toxicity occurs when sodium is replaced by TEA.


Effect of posture on arterial pressures, timing of the arterial sounds and pulse wave velocities in the extremities.

We have recorded systolic and diastolic blood pressure, and the intervals between the QRS complex of the electrocardiogram and the Korotkoff arterial sound at systolic and diastolic pressure (QKs and QKd, respectively), at the brachial and posterior malleolar arteries, for normal subjects in the supine, standing, or head-down positions on a tilt table. These data make it possible to calculate an apparent mean pulse wave velocity. Results indicate: (1) when the subject is supine (0 degrees), brachial and posterior malleolar artery blood pressures are virtually identical; (2) upon standing (+90 degrees), both systolic and diastolic pressures in the foot are elevated by a mean of approximately 70 mm Hg, whereas brachial artery systolic pressure is unaffected and brachial diastolic pressure is raised 7 mm of mercury; (3) conversely, in the head-down (feet-up) position (-30 degrees) the blood pressure in the foot was decreased approximately 20 mm of mercury, whereas the brachial arterial pressure is again unaffected; (4) as one changes from the head-down to the supine to the standing positions, the mean QKs interval at the brachial artery was increased by 5 and 15 msec, respectively; (5) conversely, the arrival of the pulse wave in the leg was hastened, with QKd decreasing by 7 and then 18 msec. The effects of QKs were slightly smaller in the brachial artery but considerably larger in the malleolar artery, with a decrease of 16 msec and then 48 msec; (6) mean apparent pulse wave velocity increases from 9.1 to 10.9 to 17.6 m/sec, as one changes from -30 degrees to 0 degrees to +90 degrees.


The unbalanced heart. Animal models of cardiac dysrhythmias.

The heart often appears to function independently because it can maintain regular activity even when isolated from the rest of the body. Likewise, it maintains its regularity in the midst of powerful but balanced neural and pressure influences. Experimental situations designed to unbalance these forces produce rhythm disturbances resembling those encountered clinically. Unbalancing of the sympathetic supply with the parasympathetic supply totally obliterated, leads to tachycardias of various origin which are eliminated by adrenergic blockade. Removing the sinoatrial node results in atrial brady-tachyarrhythmia, eliminated by cholinergic blockade. Unbalancing the pressure load results in premature ventricular contractions that are clearly not mediated by external neural controls. Cardiac rhythm disturbances thus result from a variety of forces that may be readily tolerated when balanced by opposing forces but cannot be controlled without that buffer.


Atrial acetylcholinesterase activity in various heart diseases of man.

Distribution and activity of the acetylcholinesterase enzyme in the human atrial myocardium was studied histochemically in a clinical series of patients subjected to cardiac surgery for (1) uncomplicated atrial septal defect (ASD), (2) ischaemic heart disease (IHD), (3) mitral and/or aortic valvular disease (VHD) necessitating replacement with a prosthetic valve, without major symptoms or signs of myocardial incompensation, or (4) clinically overt congestive heart failure (CHF) due to VHD prior to cardiac surgery. In all specimens, a rich distribution of acetylcholinesterase-positive single axons and small fascicles, constituting a three-dimensional nerve net, was observed within the myocardial tissue. This nerve net was obviously mainly parenchymatous, i.e. unrelated to the blood vessels. Small groups of acetylcholinesterase-positive small nerve cells were observed in some specimens, with loosely woven fascicles of axons emerging from one pole of the ganglia. No differences in the distribution of the acetylcholinesterase activity or in the pattern of the inbuilt intrinsic nervous apparatus were observed in the various groups of patients. All specimens were completely devoid of non-specific cholinesterase activity. It was concluded that (I) the human atrial myocardium is richly supplied with cholinergic intrinsic (post-ganglionic vagal) axons and (II) the acetylcholinesterase activity is not a major determinant of the parasympathetic abnormalities associated with cardiac diseases, especially with myocardial pump failure.


Hemodynamic adjustments in hypertensive patients developing circulatory congestion during beta-adrenergic blockade.

In the course of chronic treatment with a cardioselective beta-blocking agent (atenolol) 6 patients out of a series of 38 hypertensives developed signs of circulatory congestion. In spite of this, maximal exercise capacity was maintained. This resulted from hemodynamic readjustments at rest and exercise, where an increase in stroke volume played a major role.


The portal vein as collateral in inferior vena cava obstruction.

In five patients with obstruction of the inferior vena cava, collateral flow to the portal vein was demonstrated. Although there are many reports on caval occlusion, only 21 cases with this collateral circulation pattern have been reported. The reasons for this are most likely technical: To demonstrate this circulation, a large volume of contrast medium must be used and, because of the low flow velocity in the numerous wide collaterals, delayed films are also necessary.


Heparinized catheters for long-term intraarterial infusion of 5-fluorouracil in liver metastases.

A heparinized catheter was used for the regional infusion of 5-fluorouracil in seven patients with liver metastases. The hepatic artery was catheterized from the left brachial artery. The period of treatment varied from one to 13 weeks. Pull-out angiograms, obtained after eight catheterizations, revealed complete occlusion of the brachial artery in five and partial occlusion in three, although no patient had ischemic symptoms in the hand. Thus, heparinization of the catheter did not prevent thrombosis during long-term infusion therapy.


Predictive value of radionuclide methods in the diagnosis of unilateral renovascular hypertension.

The validity of noninvasive (iodine-131 iodohippurate renogram, iodine-131 ortho-iodohippurate clearance, indium-113m EDTA--technetium-99m DTPA sequential renal scan) and invasive (xenon-133 washout) radionuclide screening tests was evaluated in the diagnosis of 105 patients with unilateral renovascular hypertension (RVH) and in 45 patients with essential hypertension (EH). In RVH positive findings on the stenosed side were noted in 73% of renograms, 73% of o-iodohippurate-clearance tests (N = 22), 81% of sequential renal scans, and 90% of xenon-washout studies (N = 67). In a subgroup of 55 retrospectively selected patients with normal or improved blood pressure following renovascular surgery, the preoperative findings had been positive on the stenosed side in 78% of renograms, 75% of o-iodohippurate-clearance tests (n = 20), 85% of sequential renal scans, and 93% of xenon-washout studies (n = 23). The sequential renal scan appears to be a sufficiently reliable method in noninvasive screening for unilateral RVH, although invasive xenon-washout studies show a higher percentage of hemodynamic alterations in the stenosed kidney. o-iodohippurate clearance tests, and in particular xenon-washout studies, can reveal arteriosclerotic lesions in the contralateral, non-stenosed kidney, which may be of importance when the decision for renovascular surgery is pending.


Metastatic renal cell carcinoma to the remaining kidney 14 years after nephrectomy: report of two cases.

In two patients with renal cell carcinoma, late metastases to the remaining kidney were found. The metastases were histologically identical to the primary tumor, and more than one nodule recurred in both cases. Advanced surgical techniques allowing removal of metastases from the sole kidney make diagnosis of these lesions clinically important.


Angiographic appearance of leiomyomas of the small intestine: report of two cases.

Benign and malignant smooth muscle tumors of the small intestine have each been considered as displaying distinct angiographic characteristics. However, as two cases illustrate, the angiographic features of benign and malignant smooth muscle tumors overlpa, and radiographic differentiation of these tumors is not feasible. In most cases angiography can distinguish smooth muscle tumors from other vascular lesions.


Pitfalls in the plain film evaluation of the thoracic aorta: the mimicry of aneurysms and adjacent masses and the value of aortography. Part I. Transverse aortic arch.

In five instances, transverse aortic arch aneurysms were found that had initially, clinically and radiographically, mimicked thoracic neoplasms. Transverse aortic arch aneurysms display a wide spectrum of presentation: they may be asymptomatic, or they may cause symptoms secondary to esophageal, bronchial, vascular, or neural compression within the mediastinum and so mimic neoplasms. Conventional radiography in four projections and tomography are important components of the diagnostic evaluation of middle mediastinal masses. However, because plain film analysis is unable confidently to distinguish selected uncalcified aortic arch aneurysms from neoplasms, thoracic aortography is essential to the diagnosis.


Pitfalls in the plain film evaluation of the thoracic aorta: the mimicry of aneurysms and adjacent masses and the value of aortography. Part II. Descending thoracic aorta.

Distinguishing posterior mediastinal and pulmonary masses from aneurysms and tortuosity of the descending thoracic aorta may be difficult, as five such cases illustrate. Both the neoplasms and the aortic aneurysms or tortuosity can compress the same vital mediastinal structures; thus, they may give rise to the same symptoms. Because the plain film findings may also be similar, aortography is essential to their diagnosis.


The ascending aorta in aortic stenosis.

Dilatation of the ascending aorta, a frequently reported sign of aortic stenosis, was assessed in 47 patients for whom aortic angiograms has been recorded. Twenty-eight of the patients had rheumatic valvar disease and 19 had congenital aortic stenosis. A simple ratio between the maximal width of the mid-ascending aorta and the width of the aortic root was calculated. Patients with congenital aortic stenosis had significantly greater supravalvar aortic dilatation than did those with rheumatic aortic valve involvement. There was no correlation between the pressure difference across the aortic valve and degree of dilatation of the ascending aorta.


Complications of coronary arteriography: a follow-up report.

A nationwide survey of complications due to coronary arteriography during 1973--74 yielded responses from 176 hospitals (89,079 coronary arteriograms). The overall mortality rate was 0.14% (brachial, 0.12%; femoral, 0.16%). In the brachial group, the mortality rate was three times as high for non-heparinized as for heparinized patients. In institutions performing fewer than 100 examinations per year, the combined incidence of death, myocardial infarction, and cerebral embolism was five times higher than in institutions performing more than 400 examinations per year. Left main coronary artery or three-vessel disease was present in most patients who died of the procedure. Compared to a previous survey of 1970--71, there was a profound decrease in significant complications (including death, myocardial infarction, and cerebral embolism) and entry site complications such as thrombosis. A reduction in mortality with the femoral technique since 1971 was not accounted for by heparinization and may reflect increasing experience with the method and shorter angiographic times.


Electron microscopy of the indoleamine-accumulating neurons in the retina of the rabbit.

The recently discovered indoleamine-accumulating retinal neurons were studied electron microscopically after destruction of the dopaminergic retinal neurons and subsequent labeling with 5,6-dihydroxytryptamine. These observations confirm earlier fluorescence microscopical studies on the distribution of the indoleamine-accumulating neurons in the rabbit retina. Their perikarya are known to be located in the inner nuclear layer (INL) among the amacrine cell bodies. Their processes are found only in the inner plexiform layer (IPL), most of them in the innermost third part of that layer. The indoleamine-accumulating terminals are pre- and postsynaptic to bipolar neurons in the innermost sublayer of the IPL. Reciprocal synapses are probably the rule. The synaptic vesicles of indoleamine-accumulating synapses onto bipolar cells are arranged in "globular" clusters around a central electron dense, round body. A number of synapses formed by unlabeled amacrine neurons with postsynaptic indoleamine-accumulating elements were also detected. These synapses were mainly found in the outermost third of the IPL. Synaptic contacts between presynaptic indoleamine-accumulating neurons and postsynaptic unlabeled processes of amacrine cells are very rare.


Electron microscopic study of the termination of the centrifugal fibers in the goldfish olfactory bulb.

The terminals of centrifugal fibers to the olfactory bulbs of goldfish were studied by electron microscopy after transection of the medial, lateral or entire olfactory tract. The centrifugal fibers originate in the telencephalic hemisphere, pass through both the medial and the lateral olfactory tract, and form synaptic contacts with dendrites in the granule cell layer.


Pinocytosis and locomotion of amoebae: XII. Dynamics and motive force generation during induced pinocytosis in A. proteus.

The mechanism of induced pinocytosis was investigated in Amoeba proteus by light and electron microscopy. The application of nine different inducing substances revealed that pinocytotic channel formation, elongation, vesiculation, shortening and disappearance are the result of the successive or simultaneous action of both traction and pressure forces, which are produced by the contractile activity of a plasma membrane-associated layer of filaments ranging from a few hundred nm to several micrometer in thickness. The initial phase of channel formation is caused by traction forces according to the membrane flow concept, whereas channel elongation and vesiculation mainly result from pressure forces in conjunction with the extrusion of small hyaline pseudopodia. Shortening and disappearance of the pinocytotic channels are brought about by local contractions of the cortical filament layer in the basal region of the hyaline pseudopodia. Experiments using latex beads as marker particles together with inducing substances show that a rapid membrane turnover duirng pinocytosis can be excluded, and that the plasma membrane slides as an entire structure over the underlying cytoplasm.


Ultrastructure and cytochemistry of the gastric mucosa of a reptile, Tiliqua scincoides.

The gastric mucosa of a reptile, the lizard Tiliqua scincoides, has been examined by light and electron microscopy. The gastric pits lead into glands that are extensively coiled in the proximal stomach but become progressively shorter and straighter in the distal stomach. The following epithelial cell types have been identified: (i) Surface mucous cells (SMC) line the entire lumenal surface as well as the pits. They contain mucus granules that stain with periodic acid-Schiff and, like the granules of mammalian SMC, commonly contain an electron dense core that appears not to be mucus (periodic acid-chromic acid-silver methenamine nonreactive). (ii) Glandular mucous cells are present in glands throughout the mucosa. They are probably homologous with the mucous neck and antral gland cells of mammals; like SMC their mucus granules contain nonglycoprotein cores. (iii) Oxynticopeptic cells (OPC) are the predominant cell type in the proximal gland but become infrequent distally. Their fine structure resembles that of OPC in other nonmammalian vertebrates, with features like those of both parietal cells and zymogen cells of mammals. (iv) Endocrine cells of three different types have been identified. Two of these show close similarities to the EC and ECL cells of mammals.


Maturation of the hypothalamo-neurohypophysial system. I. Localization of neurophysin, oxytocin and vasopressin in the hypothalamus and neural lobe of the developing rat brain.

Sections of the hypothalamus, median eminence and pituitary from fetal and neonatal rats were examined with the immunoperoxidase staining technique and light microscopy. Purified antisera raised against vasopressin and oxytocin, and antisera cross-reactive with rat neurophysin were used to localize these antigens in the hypothalamo-neurohypophysial system (HNS). Neurophysin was detected throughout the HNS of the 18-day fetal rat. Vasopressin was present in the hypothalamus and pituitary of the 19-day fetus, and in the median eminence of the 4-day neonate. Oxytocin was not detected in the pituitary until 1--2 days after birth, in the hypothalamus after 4 days, and in the median eminence after 8 days. During the first days after birth the supraoptic nucleus was more mature than the paraventricular nucleus. The HNS did not approach maturity until at least 7 days after birth. The relative maturity of the supraoptic nucleus compared with the paraventricular nucleus, and the detection of vasopressin before oxytocin are evidence for the one-neuron-one-hormone theory. The data do not exclude the possibility that the fetal hypothalamo-neurohypophysial system, and perhaps the fetal hormone, vasotocin, affect the initiation and course of parturition.


[The significance of enzyme cytochemical methods in the classification of hemoblastoses].

Selected cytoenzymological methods together with the PAS reaction often permit more precise identifying normal and tumorous blood cells and thus determining the type of hemoblastosis. The cells of the myeloid neutrophil series are characterized by the activity of peroxidase and naphtol-AS-D-chloracetate esterase, monocytic elements by the activity of a nonspecific esterase sensitive to fluoride, the tumorous cells of the red series by the PAS positivity and paranuclear positivity of acid phosphatase. Some tumorous lymphoblasts have gross PAS--positive granules in the plasma, others, probably of T-origin, paranuclear focal positivity of acid phosphatase. Hematological classification of acute hemoblastoses does not exactly correspond to Löffler's cytochemical classification; of diagnostic and therapeutically considerable importance is the synthetic evaluation of the hematological finding and of interpretive possibilities of individual cytochemical methods.


[Ultrastructural cytopathology of plasmocytic myeloma with respect to the so-called maturation nucleoplasmic asynchrony].

On the basis of electronmicroscopic study of 50 cases of plasmocytic myeloma, in part of the cases the maturational nucleoplasmic asynchrony of myelomatous plasmocytes was observed ultrastructurally. The authors discuss its importance for bioptic diagnosos.


[The advantage of combined histological and cytological examination for the early diagnosis of lung tumors].

The authors present an analysis of the results of pre- and postoperative cytohistological examination in patients with suspect bronchogenic carcinoma. The number of falsely cytologically positive findings in a group of 446 patients with non-tumorous affection did not exceeed 2%. In confrontation of 1516 cytological and histological perioperative results the ascertained number of incorrect cytological conclusions was not higher too.


[Pleural and peritoneal cytology].

3857 secretions of the serous cavities were examined in 1964 to 1976. A positive finding from a first examination occurred in 58.8%, after repeated examination in 72.1%. Falsely negative findings formed 6.2%. The diagnostic certainty of examination was 93.4%. 93.5% of all findings were controlled by a bioptic or a necroptic finding and by a clinical finding and its development. In 93.0% histological sections, too, besides spreads, could be made from the sediment. A positive finding in both techniques occurred in 59.0%, in 4.5% the spread was negative and the histological section from the sediment positive; in 8.6% it was the other way round. In 13.1% the diagnosis was thus possible by the combination of spreads with a cytohistological technique. Determination of the primary localization of a malignant tumor was possible in 2/5 of positive cases independently; in the further 1/5 it was possible on the basis of cooperation with a clinician.


[Clear-cell sarcoma with melanin].

Melanin was proved in the tumorous cells in a 62-year-old man who had a malignant tumor with the structure of clear cell sarcoma of tendons on the sole of the foot. Electronoptic examination confirmed the presence of numerous melanosomas and their complexes. Although the tumor may be regarded as a special variant of melanoblastoma from clear cells (7), the authors give reasons admitting an independent position within the clear cell sarcoma of tendons.


[Histochemical diagnosis of Hirschsprung's disease].

Examination of 65 rectal biopsies and 10 resections by the histochemical detection of cholinesterase leads to the following conclusions: 1. Density of the nerve fibers in lamina propria is irregular and the examination of the cholinesterase activity may lead to falsely negative results in aganglionosis. 2. Constant is, in aganglionosis, the finding of markedly increased reaction in the nerve fibers of the muscularis mucosae and submucosa. 3. Biopsy must, therefore, include even muscularis mucosae and the choice of the instrument for biopsy removal must meet this requirement.


[Pulmonary hypertension and fetal circulation after severe congenital diaphragmatic hernia (author's transl)].

The authors present four new born with severe anoxemia after congenital diaphragmatic hernia repair. In three babies' hypoxemia was present from birth. Cardiac catheterization revealed pulmonary hypertension, resulting in a state of fetal circulation. Tolazoline produced an improvement in oxygenation, but became secondary ineffective. In one case ductus arteriosus was occluded during cardiac catheterization, after which immediate improvement in peripheral oxygenation was seen. Ligation of the patient ductus arteriosus was proposed in that case. In the fourth infant, hypoxemia developed secondary and was successfully treated with tolazoline. It is suggested that ligation of the patient ductus arteriosus and administration of pulmonary vasodilatators are both effective in improving oxygenation, in patients who may die an anoxic death after repair of a severe congenital diaphragmatic hernia.


[Meconial peritonitis. Recordings about six observations. Diagnostic and prognostic value of calcifications. Therapeutic given off (author's transl)].

The authors report six cases of meconium peritonitis with intra-abdominal calcifications; surgical intervention was successful in four. In five patients, fibrocystic desease of pancreas was eliminated. Presenting this report, it is their intention to underline the good prognosis of calcifications which generally eliminate the meconium ileus.


[Acute acalculous gallbladder disease in children: acute cholecystitis or acute gallbladder distension (author's transl)].

Acute acalculous gallbladder disease is rarely encountered in children. Two observations permit a review of its clinical, diagnostic, and therapeutic aspects. Acute acalculous cholecystitis and acute gallbladder distension present clinically in a similar fashion, although, in the latter the fever is usually absent and there is a history of episodic pain. The pathogenesis of these affections remains uncertain but generalized infection and anomalies of the cystic duct seem to be favoring circumstances. The diagnosis, rarely initially made, could be confirmed by oral cholecystography showing an non visualized gallbladder. Surgery is necessary in order to confirme or refute the diagnosis. The therapeutic approach can be either the simple drainage of the gallbladder or a cholecystectomy. Due to the risk of allowing a cervicocystic obstacle persist, it seems that a cholecystectomy, which is well tolerated by the child, would be preferable.


[Bronchial atresia of a segment (author's transl)].

Bronchial atresia of a segment in the lung is a very uncommon cause of pulmonary disorder. The diagnosis is very easy. The plain film is sufficient. Distension of a segment with air trapping during the inspiratory phase with one or more tumor in the hile due to the impaction of mucous secretion of the bronchi above the obstruction. Frequently asymptomatic the revelation is accidental during the evolution of a communal upper respiratory tract infection. The treatment is surgical.


[A case gallbladder torsion in a two years child is presented (author's transl)].

For this exceptionnel case seeing the young age of the child, the litterature is reviewed. This disease is seldom diagnosed before the operation but in case of acute abdominal syndrome with palpable tumor in the right subribs area, the diagnosis of gallbladder torsion can be considered. The pronostic is excellent because the quite easy gallbladder oblation brings a quick recovery without after effects.


[Reversed gastric tube oesophagoplasty in children (author's transl)].

Over the last two years the authors performed 6 oesophagoplasties with reversed gastric tube, no splenectomy, retrosternal placement of the gastric tube and cervical termino-terminal anstomosis within a single operating interval. Only one death occurred, independent of the oesophagoplasy technique, as well as two minor complications favourably solved spontaneuosly (cervical anastomosis fistule). The operation was perfectly gone through, post-operation consequences were surprisingly simple and the distant result, in all five cases of survival,--clinically excellent, both oesophagoscopically and radiologically; the children went back to an absolutely normal feeding programme. Though short, this series joins the other papers published of late and indicates oesophagoplasty with reversed gastric tube as a valuable method in reconstruction children's oesophagi.


[Efficiency and limitations of Pickrell's anomyoplasty in treatment of postoperative incontinence in children with anorectal malformations (author's transl)].

Eight children with high or intermediate anorectal malformations and fecal incontinence after primary repair were operated according the Pickrell technique. In 3 patients, the result of the Pickrell plasty was clinically not sufficient and the opposite gracilis muscle was used in addition at a second operative session. The 8 children were studied clinically, radiologically, by electromyography and manometry. The results are presented in detail. All 8 patients had a good passive continence at rest, but an active physiological continence could not be achieved. This seems to be due mainly to the absence of the internal anal sphincter, but partially also to the incomplete or even lacking adaptation of the pulled through bowel, which showed a relative hyperactivity and did not function as a neorectal reservoir. Some therapeutic measures to overcome the problems due to the fact that we deal at the same time with smooth and with striated muscles are discussed in the limelight of the present study.


[Sphincter-oriented gluteal myoplasty, in the treatment of faecal incontinence in sacral agenesis and surgically treated anorectal malformations (author's transl)].

The treatment of anal incontinence associated with anorectal malformations and sacral agenesis uses, in general, the levator ani. The role of the latter muscle can, however, only be passive, since it provides only suspension and angulation of the anorectal junction. Active control of continence may be obtained by means of an operation which encircles the rectum with a contractile muscular ring made up of the gluteus maximus muscles. It reverses the anorectal angulation and ensures effectice daytime continence by voluntary contraction. This control may be lost during sleep but it is felt that rehabilitation exercises can be successful. The technique is described here, detailing the advantages which may be hoped for and the present results.


Immediate effects of hydralazine-isosorbide dinitrate combination on exercise capacity and exercise hemodynamics in patients with left ventricular failure.

Resting hemodynamics improve during vasodilator administration in patients, with congestive heart failure (CHF), but the effects of these agents on exercise is unknown. Twenty-two patients with class II or III CHF performed bicycle exercise to symptomatic maximum before and 90 minutes after random double-blind administration of oral hydralazine (100 mg) and isosorbide dinitrate (40 mg) (11 patients, group 1) or placebo (11 patients, group 2). Exercise duration was unchanged after treatment in either group. Maximal oxygen consumption changed insignificantly in both groups, from 12.6 +/- 1.2 (SEM) to 13.6 +/- 1.6 ml/kg/min in group 1, and from 11.7 +/- 1.4 to 13.4 +/- 1.7 ml/kg/min in group 2. Maximal cardiac index was unchanged in both group 1 (4.00 +/- 0.33 to 4.41 +/- 0.29 l/min/m2) and group 2 (4.11 +/- 0.43 to 4.14 +/- 0.42 l/min/m2). Systemic vascular resistance at peak exercise was also unchanged in both group 1 (14.1 +/- 1.6 to 11.8 +/- 1.0 units) and group 2 (14.7 +/- 1.6 to 13.5 +/- 1.6 units). at submaximal exercise (300 kilopond-meters/min), however, cardiac index after treatment increased in group 1 (0.51 +/- 0.18 l/min/m2, p less than 0.05) and systemic vascular resistance decreased (-3.3 +/- 1.3 units, p less than 0.05), but were unchanged in group 2. Thus, although vasodilators do not improve maximal exercise capacity acutely, they can improve hemodynamics at lower work loads which may, therefore, be better tolerated in patients with CHF.


Amrinone: a new non-glycosidic, non-adrenergic cardiotonic agent effective in the treatment of intractable myocardial failure in man.

Chronic congestive heart failure not controlled by conventional therapy was treated with intravenous amrinone, a new non-glycosidic, non-catecholamine cardiotonic agent. Eight patients with New York Heart Association functional class III-IV symptoms were hemodynamically monitored. At peak effect, cardiac index (CI) increased from 1.84 +/- 0.32 to 2.74 +/- 0.44 l/min/m2 (mean +/- SD) (p less than 0.001) and left ventricular filling pressure (LVFP) decreased from 25.8 +/- 6.2 to 19.5 +/- 6.8 mm Hg (p less than 0.05), while heart rate and mean aortic blood pressure did not change significantly. Mean endocardial circumferential fiber shortening (mean Vcf), determined by echocardiography, increased from 0.61 +/- 0.27 to 0.89 +/- 0.34 cir/sec (p less than 0.05). The duration of action after bolus infusion varied from 60--90 minutes. During continuous infusion of amrinone, sustained increases in CI and reductions in LVFP, similar to those at the time of peak effect after bolus administration, were maintained for 180 minutes. These marked cardiotonic effects of amrinone in patients already taking digitalis for severe heart failure occurred without side effects of arrhythmias or altered arterial pressures. The fact that the drug is orally active makes amrinone a v:ry promising inotropic agent for the treatment of chronic heart failure in man.


Complications of coronary arteriography from the Collaborative Study of Coronary Artery Surgery (CASS).

Data were collected prospectively on 7553 consecutive patients undergoing coronary arteriography. The studies were performed at 13 clinics of the Collaborative Study of Coronary Artery Surgery (CASS) using brachial and femoral techniques. There were eight deaths 0--24 hours and seven deaths 24--48 hours after arteriography (2/1000). There were 15 non-fatal myocardial infarctions (MIs) 0--24 hours and four MIs 24--48 hours after arteriography (2.5/1000). Of 657 cases with left main stenosis greater than or equal to 50%, five died and three had MI. Left main disease increased risk of death by 6.8 times (p less than 0.001). Other factors increasing risk were unstable angina, congestive heart failure, multiple premature ventricular contractions, and hypertension. Of the 1187 patients studied from the brachial artery, six died (0.51%) and five had MIs (0.42%). In 6328 patients studied from the femoral artery, nine died (0.14%) and 14 had MIs (0.22%). The brachial artery technique increased the risk of death 3.6 times compared with the femoral approach (p less than 0.05). This result did not apply when analysis was restricted to laboratories with 80% or more brachial procedures. Risk was not altered by heparin. Thus, a prospective, multicenter analysis of complications reveals low risk of coronary arteriography but significant difference between two techniques.


The quality of resonance of the first heart sound after myocardial infarction: clinical significance.

Frequency analyses of the first heart sound (S1) were performed in 80 normal subjects and 80 postinfarction patients. A readily recognizable frequency pattern characterized by a quality of resonance greater than or equal to 2, as measured by the Q factor at 3 db down, was noted in 78 of the 80 apparently normal subjects. An aberrant pattern with a Q less than 2, often accompanied by a lowering of the frequency content, was found in 78 of 80 postinfarction patients. We propose that the quality of resonance of S1 is a measure of the degree to which the structural homogeneity of the left ventricle as a compliant contractile unit has been preserved after myocardial infarction.


Mechanism of propranolol withdrawal phenomena.

Nine patients on chronic treatment with propranolol for essential hypertension for 3 months or longer were studied after abrupt discontinuation of the drug. Each patient demonstrated transient supersensitivity to the chronotropic effects of isoproterenol, beginning 2--6 days (median 4 days) after propranolol withdrawal, lasting for 3--13 days (median 6 days), with the maximum sensitivity on day 6. A significantly lower dose of isoproterenol was necessary to increase heart rate 25 beats/min on day 6 (median dose 1.2 microgram, range 0.3--3.4 microgram) compared with after day 14, when sensitivity had stabilized (median dose 2.3 microgram, range 1.4--7.6 microgram). Six patients had transient symptoms (headache, chest pain, palpitations and sweating) after abrupt propranolol withdrawal, coinciding with supersensitivity to isoproterenol in five. Transient increases in plasma catecholamines and blood pressures and sustained increases in heart rate occurred during the period of isoproterenol supersensitivity in most patients, and may have contributed to symptoms noted. The delayed onset and potentially long duration of beta-adrenergic supersensitivity after abrupt propranolol withdrawal have important clinical implications.


Effects of amiodarone on cardiac and coronary hemodynamics and on myocardial metabolism in patients with coronary artery disease.

While the antiarrhythmic effects of amiodarone are well-documented, its hemodynamic effects are not. We injected 5 mg/kg amiodarone i.v. in 16 patients undergoing coronary arteriography. Heart rate did not change. Aortic (systolic, diastolic and mean) and left ventricular (systolic and end-diastolic) pressures decreased significantly (p less than 0.01) at 5 and 15 minutes; systemic vascular resistance also fell significantly (p less than 0.05), while cardiac index increased slightly but significantly (p less than 0.05). Coronary vascular resistance decreased significantly (p less than 0.01) and coronary sinus blood flow rose in most patients, from a mean of 138 ml/min to 153 ml/min at 5 minutes (p less than 0.02); it then returned toward the control value at 15 minutes (mean 145 ml/min). Myocardial metabolism of O2 was normal and unchanged. Metabolism of lactate improved in five patients, remained unchanged in seven and deteriorated transiently in four. No undesirable hemodynamic and clinical side effects occurred when the drug was administered slowly. We conclude that amiodarone is a powerful systemic and coronary vasodilator. In addition to its present indications in the treatment of angina pectoris and arrhythmias, the drug might be very useful as an afterload-reducing agent.


Measurement of left ventricular ejection fraction by mechanical cross-sectional echocardiography.

Cross-sectional echocardiography is a new noninvasive technique for imaging the heart. We developed a method for using mechanical cross-sectional echocardiograms (sector scans) to determine left ventricular volumes and ejection fraction. Using left ventricular cineangiography as a standard, sector scan ejection fraction correlated better (r = 0.93) than M-mode echocardiography by any of three established methods, and the sector scan regression line did not differ from the line of identity (p greater than 0.33). Interobserver variability for sector scan ejection fraction was 2.3 +/- 1.2% (mean +/- SD). Variation between two studies performed within 24 hours and analyzed by the same observer was 1.4 +/- 1.5%. However, the sector scans consistently underestimated left ventricular end-diastolic volume. We conclude that sector scan echocardiography is more reliable than conventional M-mode technique for estimating left ventricular ejection fraction, but estimation of left ventricular end-diastolic volume is unreliable with the methods currently available.


The mechanism of apparent right bundle branch block after transatrial repair of tetralogy of Fallot.

The electrocardiographic pattern of right bundle branch block (RBBB) is routinely observed after transatrial repair of tetralogy of Fallot even though no ventriculotomy has been performed. The mechanism of this conduction disturbance was studied in 16 patients with tetralogy of Fallot and one patient with infundibular pulmonic stenosis. Preoperative ECGs and vectorcardiograms showed right ventricular hypertrophy and no RBBB. Epicardial activation maps were obtained before and after total surgical repair in all patients and after infundibular resection but before closure of ventricular septal defect (VSD) in four of these patients. After infundibular resection, RBBB appeared and activation was markedly delayed (greater than 30 msec) over the pulmonary outflow tract, but was unchanged over the body of the right ventricle. No further changes in ventricular activation occurred after closure of the VSD. This study shows that RBBB after transatrial repair of tetralogy of Fallot is usually produced by infundibular resection, but not by VSD closure, and is associated with delayed activation of the pulmonary outflow tract and base of the right ventricle which results from damage to portions of the right ventricular conduction system.


Body surface potential maps in patients with pulmonic valvular and aortic valvular stenosis of mild to moderate severity.

Multiple-lead surface potential maps were compared throughout ventricular activation in nine patients with mild-to-moderate pulmonic stenosis and in 12 patients with mild-to-moderate aortic stenosis. Abnormal patterns of potential distribution were found in aortic stenosis, including three patients without electrocardiographic evidence of left ventricular enlargement. When related to the onset of depolarization, abnormal departures started later, peaked later, lasted longer, and were more intense, more uniform and discrete in aortic stenosis. In pulmonic stenosis, abnormal departures started earlier, but were more dispersed in timing and location than in aortic stenosis. The left ventricle appears to be the more remote, though more powerful and compact, generator. The right ventricular shell, however, is nearer to the surface, and is more anatomically extended in surface area, permitting much wider shifts in wavefront location and orientation as a result of small differences in pressure, or volume, or location of the heart in the thorax.


Familial occurrence of mitral valve prolapse in X-linked muscular dystrophy.

A high incidence of mitral valve prolapse (MVP) has been reported in patients with X-linked Duchenne muscular dystrophy. In our study MVP was present in six of 22 Duchenne dystrophy cases (27%) followed in the Maryland General Hospital Muscular Dystrophy Clinic. In addition, seven carriers of Duchenne and X-linked benign (Becker) dystrophy had evidence of MVP. Autosomal dominant transmission of MVP was present in four families. The unusually high prevalence of MVP in families with X-linked muscular dystrophy may have potential value in the recognition of the carrier trait.


Effects of the Valsalva maneuver on myocardial ischemia in patients with coronary artery disease.

The influence of the Valsalva maneuver (VM) on myocardial ischemia was evaluated in 24 patients with coronary heart disease. Clinical and hemodynamic responses to the VM were studied during acute ischemia manifested by angina pectoris with transient left ventricular (LV) dysfunction and compared with responses during nonischemic intervals. In the absence of evidence for acute ischemia (angina and increased LV end-diastolic pressure), six patients had abnormal hemodynamic responses to the VM. Five had lack of systolic pressure overshoot and in one, systolic pressure did not decline during straining. When the VM was performed during an ischemic episode, 14 patients had abnormal responses (12 with lack of overshoot in phase IV and two with lack of systolic pressure decline in phase II). In 18 patients a prompt decline in LV end-diastolic pressure occurred with the disappearance of angina during the VM. These changes uniformly occurred during the latter part of straining (VM phase II) as cardiac size and systolic pressure declined. No adverse effects occurred when a VM was performed during acute ischemia. Our observations suggest that the VM abruptly reduces determinants of cardiac oxygen demand, relieving acute ischemia without harmful effects.


The conduction system in hypoplasia of the aortic tract complex.

This is a study of the course of the conduction system in two cases of hypoplasia of the aortic tract complex, one with mitral stenosis and the other with mitral atresia. In both there was a posterior atrioventricular (AV) node which formed the AV bundle. In case 1 the bundle was short and bifurcated early. The branching bundle gave off a large left bundle branch (LBB), many Mahaim fibers to the septum and a small right bundle branch (RBB). In case 2 the AV node was divided into two parts which formed two posterior bundles which joined together to form a short branching bundle. Instead of a LBB there were profuse Mahaim fibers passing from the branching bundle to the depths of the ventricular septum. The RBB was large. The abnormalities seen in the conduction system particularly in the LBB are discussed from the embryologic stand-point.


Relative stabilities of purified human mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase in lyophilized materials.

Eight different pools of purified human mitochondrial and cytoplasmic isoenzymes of aspartate aminotransferase were prepared, to examine the effects of the following matrix variables: the matrix support material (bovine serum albumin and polyvinylpyrrolidone), endogenous pyridoxal concentration, and azide as an antimicrobial preservation. Storage temperatures of 25 and 37 degrees C were used as a rapid and convenient means of accelerating the degradation process. Activity of the enzyme was measured with and without pyridoxal in the reaction solution. We found that the mitochondrial isoenzyme was consistently more labile than the cytoplasmic isoenzyme under identical storage conditions. Both isoenzymes were more stable in matrixes containing bovine serum albumin than in those containing polyvinylpyrrolidone. No apparent difference in the stability of either isoenzyme was observed at matrix pyridoxal concentrations of 15 micromol/L and 150 micromol/L. Only the mitochondrial isoenzyme in matrixes containing bovine serum albumin and 15 micromol of pyridoxal per liter had increased activity (about 9%) when pyridoxal was added to the enzymatic reagent. The amount of activity in reconstituted specimens did not apparently change after 72 h at 4 degrees C.


A simple, direct radioimmunoassay for plasma cortisol, featuring a 125I radioligand and a solid-phase separation technique.

A simple, direct radioimmunoassay for cortisol in human serum and plasma is described. An antiserum, raised in sheep to a cortisol-3-(O-carboxymethyl)oxime/bovine serum albumin conjugate, is coupled to microcellulose. No extraction is required because plasma samples and standards are incubated with the antiserum and an 125I radioligand in a low-pH buffer, which denatures cortisol-binding globulins. The assay satisfies accepted validation criteria. In addition, results from the radioimmunoassay compare well with those obtained by a gas chromatographic-mass spectrometric technique (r = 0.968; FRIA = 0.97 FGCMS + 2.0 nmol/L). The latter procedure features the very high intrinsic specificity obtained by selected ion monitoring at high mass-spectrometric resolution (M/deltaM = 8500) with a Varian MAT-731 instrument. The simplicity of the radioimmunoassay procedure, with use of reagents prepared "in house," makes this a very practical and economical assay for use in the medium or large endocrine laboratory.


Predictive values of thyroxine, thyrotropin, and triiodothyronine concentrations in serum.

The predictive values of total thyroxine, thyrotropin, and total triiodothyronine concentrations in serum for clinically apparent and subclinical hypothyroidism and hyperthyroidism were determined by retrospective analysis of clinical cases chosen from the frequency distributions of hormone test results. Very low total thyroxine concentrations, less than 25 microgram/L, were specific for hypothyroidism. Most subclinical hypothyroid cases had intermediate or low total thyroxine concentrations, 35-60 microgram/L, with moderately increased thyrotropin concentrations, greater than 12 milli-int. units/L. Thyrotropin cut-off concentrations were identified that had predictive values greater than 90% for classifying untreated and hormone-treated hypothyroid cases. Above-normal total thyroxine concentrations, regardless of absolute value, were not specific for hyperthyroidism, because binding-protein alterations related to estrogen taking were prevalent and produced occasional marked increases in serum total thyroxine. Nevertheless, cut-off concentrations for serum total thyroxine and total triiodothyronine were identified that had a predictive value greater than 90% for hyperthyroidism, without necessitating measurement of the capacities or concentrations of hormone-binding proteins.


Outliers in clinical chemistry quality-control schemes.

Results submitted to large-scale quality-control schemes are commonly judged against the mean and standard deviation (SD) of the results from other laboratories. It is desirable to ignore outlying values in estimating this mean and standard deviation, and results more than 2.5 or 3 SD from the mean are commonly rejected. I show that an outlier can so inflate the estimated SD that its presence is not detected by this method. Alternative estimators that are less influenced by outliers are described, and their application to quality-control data is discussed.


Method for determining thiocyanate in serum and urine.

We describe a method for rapid and specific measurement of thiocyanate in serum or urine. We separate thiocyanate from interfering compounds by adsorbing it on an anion-exchange resin that has special affinity for thiocyanate, then eluting with sodium perchlorate. The eluted thiocyanate is quantified by a modified König reaction, sodium hypochlorite being used as the chlorinating reagent. Analytical recovery of thiocyanate added to serum and urine was quantitative; the coefficient of variation was 2.3% for both within-day and between-day precision. Cyanide and certain antibiotics interfere, but may be eliminated by including additional washing steps in the usual procedure. The proposed procedure was compared with another method, based on the oxidation of thiocyanate to cyanide. Agreement was satisfactory, both for serum and urine.


Phosphatidylglycerol in 261 samples of amniotic fluid from normal and diabetic pregnancies, as measured by one-dimensional thin-layer chromatography.

We describe a one-dimensional thin-layer chromatographic method for separating lecithin, sphingomyelin, phosphatidylglycerol, and other phospholipids. The occurrence of phosphatidylglycerol in relation to the lecithin/sphingomyelin ratio is reported for 261 amniotic fluid samples. This compound does not consistently appear until the ratio exceeds about 3.1, and occurs less often in samples from diabetic patients than in those from normal patients. The respiratory distress syndrome did not occur when phosphatidylglycerol was present in amniotic fluid although the reverse was not necessarily true. Thus the presence of phosphatidylglycerol offers additional assurance of pulmonary maturity.


Microchemical analysis for 13 constituents of plasma from healthy children.

Normal values for 13 chemical constituents of plasma were estimated from results for 837 presumably healthy children. Ninety microliters of specimen was analyzed for lactate dehydrogenase, aspartate aminotransferase, alkaline phosphatase, inorganic phosphorus, total calcium, total cholesterol, total proteins, albumin, uric acid, urea nitrogen, alanine aminotransferase, total bilirubin, and glucose. We used two Abbott ABA-100 Bichromatic Analyzers interfaced directly to the ABA Data Management System. For each test age- and sex-related variations were assessed and normal values were estimated for six different age groups.


Elemental composition of platelets. Part I. Sampling and sample preparation of platelets for trace-element analysis.

Sampling of platelets for trace-element analysis poses special problems: obtaining adequate sample material, achieving a sufficient cell purity, preserving viability (integrity), correcting for trapped plasma, and controlling contamination. We used a blood-cell separator for the primary isolation of platelets from blood, and differential centrifugation in natural plasma to further isolate them. The pyrimidopyrimidine RA233 was used as a stabilizer to maintain viability. 131I-labeled human serum albumin was used to estimate trapped plasma. Contamination was controlled by using five-times-distilled water to simulate donor's blood in the system and by comparing three fractions: the serum, the first portion of the platelet-rich plasma, and the supernatant plasma after the final centrifugation. Neutron activation analysis was used for the elemental analysis. A single differential centrifugation of the platelet-rich plasma from the blood-cell separator at 400 x g for 8 min was optimum (mean mass fractions:erythrocytes/platelets less than 5 mg/g and leukocytes/platelets less than 20 mg/g). The trapped plasma in the wet platelet samples amounted to about 0.40 g/g. No appreciable contamination from the sampling system was found for the elements Ag, Cd, Co, Cr, Cs, Cu, Fe, Mo, Rb, Sb, Se, and Zn.


Elemental composition of platelets. Part II. Water content of normal human platelets and measurements of their concentrations of Cu, Fe, K, and Zn by neutron activation analysis.

We determined the elements Cu, Fe, K, and Zn in normal human platelets by neutron activation analysis. The platelets were obtained from seven donors and treated as described in Part I. The elemental composition is expressed on a wet-weight basis for plasma-free platelets. The following results were obtained (+/- values are 1 SD); "Pure" platelets: trapped plasma = 378 +/- 35 mg/g, water content = 715 +/- 15 mg/g, mean weight of the single platelet (by two different methods) = 9.9 +/- 1.1 pg and 11.2 +/- 1.7 pg, K = 4.39 +/- 1.06 mg/g, Zn = 49.23 +/- 10.97 microgram/g, Fe = 12.28 +/- 2.94 microgram/g, and Cu = 1.39 +/- 0.25 microgram/g. "Impure" platelets: trapped plasma = 349 +/- 31 mg/g, water content = 736 +/- 12 mg/g, K = 3.26 +/- 0.78 mg/g, Zn = 35.71 +/- 7.99 microgram/g, Fe = 17.11 +/- 5.10 microgram/g, and Cu = 1.39 +/- 0.21 microgram/g. To our knowledge, no data on Fe and Cu in platelets have hitherto been reported.


Elemental composition of platelets. Part III. Determination of Ag, Au, Cd, Co, Cr, Cs, Mo, Rb, Sb, and Se in normal human platelets by neutron activation analysis.

The elements Ag, Au, Cd, Co, Cr, Cs, Mo, Rb, Sb, and Se were determined in platelets from seven normal donors. The results, in ng/g wet weight, for plasma-free platelets follow: "Pure" platelets: Ag = 29 +/- (18), au = 0.22 +/- (0.22), Cd = 6.2 +/- 3.4, Cs = 54.8 +/- 19.2, Cr = 6.1 +/- 2.5, Co = 7.5 +/- (5.0), Mo = 3.4 +/- 1.3, Rb = 10400 +/- 3000, Sb = 18 +/- (26), and Se = 782 +/- 127. "Impure" platelets: Au = 0.23 +/- (0.28), Cd = 6.4 +/- 2.6, Cs = 35.2 +/- 13.8, Cr = 8.2 +/- 2.9, Co = 2.9 +/- (3.0), Mo = 3.2 +/- 0.8, Rb = 8700 +/- 1700, Sb = 13.2 +/- (8.7), and Se = 679 +/- 57. To our knowledge, none of these 10 trace elements has been determined in platelets before. The selenium concentration in platelets exceeds that in other tissues (e.g., liver). We suggest that glutathione peroxidase or other unknown selenoenzymes are particularly important in platelet metabolism. Platelets are crucial for triggering thrombosis, and so may be involved as links between selenium deficiency and the concomitant increased death rate from cardiovascular disease.


Significance of "high" acid phosphatase activity in the serum of normal children.

Serum acid phosphatase activity in normal children (newborn to 18 years) is several fold that in normal adults. Activity is age-related but not sex-related. The isoenzyme pattern in children is similar to that in adults and contains no prostatic fraction. Quantitatively, most of the enzyme activity in the serum of children is tartrate-resistant and correlates well with heat-labile fractions of alkaline phosphatase activity in serum, suggesting that the source of the higher acid phosphatase activity in children is bone. Significant tartrate-resistant acid phosphatase activity was demonstrated in the giant cells in three patients with giant-cell tumors, but not in the "osteoblasts" in six patients with osteogenic sarcomas and many other normal or abnormal tissues. This work suggests that the higher enzyme activity in the serum of children represents a normal physiological phenomenon resulting from their greater osteoclastic activity.


Anaphylaxis in the mouse--a model for using two-dimensional electroimmunodiffusion to study pathological changes in multiple serum proteins simultaneously.

Two-dimensional electroimmunodiffusion is rarely used in clinical chemistry, because its potentialities are not yet widely appreciated. Studying mouse anaphylaxis, we observed with this technique certain striking short- and long-term pathologic changes in several important serum antigens, which aptly demonstrate its uniqueness and potential clinical usefulness. We present some of these observations here, for illustration. We analyzed sera from CF-1 female mice that had been anaphylactically shocked with chicken conalbumin antigen and bled 45 min to 22 days afterward. In three separate experiments, with samples of serum being analyzed only once each, this technique easily and surely detected quantitative and (or) qualitative changes in several serum antigens. We discuss here the changes in 7S gamma1 immunoglobulin, C3 globulin, hemopexin, and alpha lipoprotein, and explain how some of these changes would have been difficult and others impossible to detect by currently routine tests. We urge the adoption of two-dimensional electroimmunodiffusion for frequent use in the clinical laboratory for diagnosis, prognosis, and monitoring pathological conditions.


Serum ferritin compared with other indices of iron status in children and teenagers undergoing maintenance hemodialysis.

To determine how best to assess iron status, I studied 12 young renal patients (ages 5.5 to 20 years) undergoing regular hemodialysis treatments. Iron balance was estimated by monitoring iron loss ascribable to blood loss during dialysis and diagnostic testing, and iron intake in the form of oral and intravenous iron supplements and blood transfusions. Traditional methods of evaluating iron status--measurement of hemoglobin, erythrocyte indices, reticulocyte count, iron, and transferrin--were compared with measurement of serum ferritin. The serum ferritin measurements provided superior information. In three cases this method was superior to visual assessment of bone marrow stained for iron.


Electrolytes of breast-cyst fluid.

We constructed an electrolyte balance sheet for 11 individual specimens and two pooled specimens of breast-cyst fluid. Na+ and K+ ranged in concentrations from those representative of extracellular fluids (147 and 9 mmol/L, respectively) to those of intracellular fluid or a high K+ secretion (23 and 168 mmol/L, respectively). Cl- concentrations ranged from 9 to 98 mmol/L (mean, 31), bicarbonate concentrations from 0 to 34 mmol/L (mean, 16). Ca2+ concentrations did not exceed 2.1 mmol/L. Total protein ranged from 14.7 to 35.8 gL. Fluid osmolality ranged from 249 to 300 mOsm/kg of water (mean, 280). The difference between measured cations and anions indicates an "anion gap" of 140 mmol/L, which must be carried by 46 mOsm/kg of water. We suggest that tricarboxylic acids of the Krebs cycle may account for the missing trivalent anions.


Limitations of immunochemical measurement of ceruloplasmin.

We describe a quantitative immunochemical method for the nephelometric measurement of ceruloplasmin. Results are compared with those from a radial immunodiffusion technique. We examine factors affecting the results, such as antiserum source and calibrators, and list reference limits for a pediatric population.


Double-antibody method and the protein-A-bearing Staphylococcus aureus cells method compared for separating bound and free antigen in radioimmunoassay.

We compared the protein-A-bearing Staphylococcus aureus immunoadsorbent to the double-antibody precipitation method for separating bound and free radiolabeled antigen in a radioimmunoassay. With human albumin (antigen) and rabbit anti-human albumin (antibody) as a model, our results indicate that formalin-fixed, heat-killed S. aureus cells could be substituted for the double-antibody precipitation method. Ease of preparation and high adsorption capacity of protein-A-bearing S. aureus for most mammalian IgG make this method economical and time saving.


Direct determination of mercury in blood by use of sodium borohydride reduction and atomic absorption spectrophotometry.

A method is presented for the rapid determination of total mercury in blood. The reagent used is alkaline sodium borohydride, and no digestion of the sample is needed. The detection limit and sensitivity are 1.15 and 1.59 ng of Hg, respectively. The method gives reproducible results (the CV ranged from 5.3 to 6.7% for low and high mercury blood samples, respectively), comparable to those obtained by the digestion method. The mean analytical recoveries of added mercuric chloride and methylmercuric chloride were 106.65 and 99.02%, respectively. Other advantages of the method are freedom from contamination encountered with digestion methods and elimination of matrix effects.


Extraction of human plasma or sera by heat treatment for a solid-phase radioimmunoassay of carcinoembryonic antigen.

Heat treatment and a solid-phase radioimmunoassay are combined to give a relatively simple and rapid procedure for assay of carcinoembryonic antigen in plasma or serum. The new way we describe to extract this antigen is an alternative to the conventional method of extraction with perchloric acid. Heating plasma or serum samples in acetate buffer (0.16 mol/L, pH 5.0) at 70 degrees C for 15 min precipitates out most of the heat-labile, nonspecific plasma proteins, but leaves most of the antigen in solution, with its immunochemical properties apparently unaffected. Comparison between the heat treatment and the perchloric acid extraction yielded comparable values when tested either by solid-phase radioimmunoassay or by the zirconyl phosphate precipitation method. An added advantage of our method is that it gives the same assay values for both plasma and serum. Results for a group of pathological plasma samples, assayed by both our method and the perchloric acid-zirconyl phosphate precipitation method, gave a correlation coefficient of 0.90.


Improved liquid-chromatographic determination of propranolol in plasma, with fluorescence detection.

We describe an analysis for propranolol in plasma, with use of reversed-phase "high-pressure" liquid chromatography and fluorescence detection. Pronethalol is used as the internal standard. The procedure, which involves extraction into an organic solvent, evaporation, and clean-up by micro-scale back extraction from hexane into an aqueous phase, is specific and sensitive. The detection limit is less than 6 microgram/L (2.3 X 10(-8) mol/L). Within-day and between-day coefficients of variation are 1.8 and 4.4%, respectively. Commonly used drugs, including procainamide, N-acetylprocainamide, and quinidine, do not interfere.


Alanine aminotransferase and aspartate aminotransferase measurements with two automated analyzers, SMAC and the ABA-100, compared.

Measurements of alanine aminotransferase and aspartate aminotransferase with the SMAC were evaluated for correlation with the ABA-100, precision, linearity, and carryover. We assayed 200 specimens with normal and abnormal aminotransferase activities with both the SMAC (y) and the ABA-100 (X). Linear regression analysis of the data yielded the following: alanine aminotransferase (r = 0.9732, y = 0.96x + 3.8); and aspartate aminotransferase (r = 0.9892, y = 0.90x + 2.1). Both aminotransferases demonstrated acceptable intra- and inter-assay variations with the SMAC and ABA-100. With the SMAC the upper limit of linearity for alanine aminotransferase was 350 U/L; that for asparate aminotransferase was 450 U/L. Carryover studies for SMAC indicate that specimens immediately following specimens with alanine aminotransferase activities greater 400 U/L and (or) aspartate aminotransferase activities greater than 500 U/L should be re-analyzed.


Positive interference of catecholamine metabolites with quantitation of urinary uric acid by the direct acid ferric-reduction method.

We report the effect of major catecholamine metabolites such as homovanillic acid and vanilmandelic acid, normally present in urine, on quantitation of urinary uric acid by the direct acid ferric-reduction procedure [(Am. J. Clin. Pathol. 60, 691 (1973)]. When aqueous uric acid standards containing a mixture of these two metabolites, in concentrations comparable to those in a normal human 24-h urine, were added to Fe3+-phenanthroline or Fe3+-2,4,6-tripyridyl-s-triazine reaction mixture, the resulting absorbances at 505 or 593 nm considerably exceeded those of standards without such additions. Moreover, quantitation of urinary uric acid by the direct acid ferric-reduction procedure gave values that significantly exceeded those determined by the uricase method. Interference by the two metabolites was eliminated by extracting urine specimens with ethyl acetate before quantitation. Spectral scans revealed that homovanillic acid or vanilmandelic acid alone could also effectively reduce Fe3+-chelator complex and that the effect of these compounds on the analytical reaction was additive.


A simple method for the intravenous fat-tolerance test.

A simple method for measuring intravenous fat tolerance with an artificial fat emulsion (intralipid) was studied and compared with the currently used method of Carlson and Rossner [J. Lab. Invest. 29, 271-280 (1972)]. The proposed method uses as little as 3 mL of whole blood to follow, by nephelometry, the elimination of intravenously administered fat emulsions. There is a high correlation between the K2 values obtained by the current method for plasma and those obtained by the proposed method (r = 0.903). The latter is simpler, quicker, and more acceptable to patients.


Assessment of fetal lung maturity by colorimetric phospholipid determination without digestion.

A previously described method for the determination of phospholipid concentration in amniotic fluid without digestion has been modified to make it more suitable for use in a routine laboratory. Results compare well with those by the original procedure. Results from nearly 70 amniotic fluids, collected at delivery, were compared with lecithin/sphingomyelin (L/S) ratios determined on the same fluids. Statistical analysis of these data showed that for the prediction of lung immaturity, determination of total phospholipid concentration was at least as good as the L/S ratio.


A simplified assay method of superoxide dismutase activity for clinical use.

A simple and inexpensive assay method of superoxide dismutase (SOD) activity of various biological materials has been developed. SOD activity can easily be measured by reading the medium's intense absorbance directly, and many samples can be treated in a short time using a reaction stopper which acts for a long time. Reproducibility of the assay method was excellent for the sample from an individual estimated at two different times (a week to a month) and the coefficient of variance was 5.1%. The mean and standard deviation of SOD activities of 45 blood samples from normal Japanese males 32.9 +/- 10.5 microgram per ml of blood; estimated using bovine SOD standard. The SOD activity of the fluid from lavaged lungs was 15.7 +/- 1.8 microgram/ml, and that of lung tissue homogenates from rats was 2.85 +/- 0.66 microgram/mg of protein.


The effect of sex, deviation from ideal weight and sampling time on blood constituents in presumably healthy subjects.

In order to verify the influence of sampling time on blood constituents, populations of supposedly healthy subjects were grouped according to age, sex, deviation from their ideal weight, state of fasting or nonfasting, and time of sampling. Each fasting subject in one group underwent two samplings during the course of a morning: the first at 08.00 and the second between 09.00 and 12.00. In the second group, the first was taken at 13.00, and the second between 14.00 and 16.00. Subjects in the second group had eaten a standard meal of 700 calories at 12.00. Differences between the paired samples from a given individual are discussed with respect to the time of sampling for plasma urea, creatinine, proteins, albumin, calcium, sodium, potassium, cholesterol, uric acid, chloride ions, phosphate, bilirubin, aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine phosphokinase, alkaline phosphatase, hemoglobin and erythrocyte and leukocyte counts. Variations due to the time of sampling were large for phosphorus, bilirubin, and leukocyte count.


A sensitive fluorimetric method for determination of platelet-bound and plasma free serotonin.

A sensitive and specific fluorimetric assay for blood platelet-bound and plasma free serotonin is described. Serotonin is concentrated and purified on Amberlite CG-50 resin, eluted by 0.15 mol/l HCl and its native fluorescence is read at 295/350 nm. The good recovery (90% about), reproducibility and sensitivity (the smallest amount detectable is 5 ng) make the assay particularly useful for the detection of free serotonin in plasma. The whole procedure is rapid enough to permit the analysis of 15--20 samples within one working day and thus the method is suitable for routine determination of serotonin in biological specimens.


Calibration drift in the automated determination of calcium and magnesium by atomic absorption.

Calibration drift was studied in the automated on-line determination of calcium and magnesium by atomic absorption over periods of up to four hours. Automatic correlation for drift improved the precision of results.


Urinary excretion of hydroxyproline, hydroxylysine and hydroxylysine glycosides by patients with Paget's disease of bone and carcinoma with metastases in bone.

Patient's with carcinoma metastases in bone and Pagent's disease of bone have different patterns of collagen metabolite excretion. Both forms of bone disease resulted in an increased excretion of total hydroxyproline and the ratio of glucosylgalactosylhydroxylsine to galactosylhydroxylysine was below normal. The excretion of glucosylgalactosylhydroxylysine and galactosylhydroxylysine was increased in all patients with carcinoma metastases in bone while the excretion of glucosylgalactosylhydroxylysine in patients with Paget's disease. The ratio of total hydroxylysine (free hydroxylysine + glycosylated hydroxylysines) to total hydroxyproline was normal in patients with carcinoma metastases in bone and below normal in patients with Paget's disease bosne. The pattern of urinary collagen metabolite excretion is a more specific indicator of the presence of bone disease than is the measurement of the excretion rate of any individual collagen metabolite. Bone diseases of different etiologies may result in different patterns of urinary collagen metabolite excretion.


Reflux of billiary components into blood in experimental intrahepatic cholestasis induced in rats by treatment with alpha-naphthylisothiocyanate.

The sera of rats treated with alpha-naphthylisothiocyanate, an agent reported to cause intrahepatic cholestasis, and of rats treated with carbon tetrachloride, are examined for evidence of leakage of bile into blood. The levels of the four bile components assayed, namely IgA, free IgA secretory component, the biliary isoenzyme of 5'-nucleotidase and of direct reacting (conjugated) bilirubin, were all elevated in the sera of rats treated with alpha-naphthylisothiocyanate. No change in any of these components was found in rats treated with carbon tetrachloride, indicating that their appearance in serum is not an inevitable consequence of damage to hepatocytes. As the bile components assayed reach bile by three different routes. their rapid appearance in the sera of rats treated with alpha-naphthylisothiocyanate indicates reflux of bile into blood, presumably as a result of mechanical obstruction of intraheptic bile ducts.


Appearance of creatine kinase BB isoenzyme in the serum of a patient suffering from infarction of the colon.

A case is described of multiple pathologies which was associated with very high levels of total serum creatine kinase activity. Electrophoretic analysis showed the circulating enzyme to be made up of all three isoenzyme fractions; MM, MB and BB. Acute necrosis of a portion of large intestine seems the most likely explanation for the transient appearance of the BB fraction. The implications of these findings with regard to creatine kinase isoenzyme analysis techniques are discussed.


Factors in the choice of detergent in automated oestriol estimation.

Detergent must be added to the strongly acidic Kober reagent to obtain reproducible and well separated peaks in continuous flow analytical methods for oestriol in pregnancy urine. Brij 35 and other polyether detergents are not satisfactory because they or their impurities interfere in the reaction causing high blank response in colorimetric reactions and diminished fluorescence responses. In a single phase fluorometric method these detergents also caused turbidity or phase separation in the solution which passed through the fluorometer. Some anionic sulphate and sulphonate detergents were also unsatisfactory being immiscible with Kober reagent. Selected cationic and betaine detergents are shown to be possible alternatives, although one which is satisfactory in the kober reagent may be unsuitable for a dilution reagent. The betaine Empigen BB was found to be suitable for inclusion in both of these reagents.


Peptide analysis as amino alcohols by gas chromatography-mass spectrometry. Application to hyperoligopeptiduria. Detection of Gly-3Hyp-4Hyp and Gly-Pro-4Hyp-Gly.

A method for the qualitative analysis of oligopeptides in human urine in cases of peptiduria is described. After sample precleaning on a strongly acidic ion exchanger, the trifluoroacetyl/methyl esters were formed and the peptide derivatives were transformed into trifluoroethyl oligoamino alcohols according to Nau and Biemann. It was found that oligoamino alcohols could be isolated selectively on a weakly acidic ion exchanger. The O-trimethylsilylated trifluoroethyl oligoamino alcohols were separated on a SE-30 glass capillary column and analyzed by computer-assisted gas chromatography-mass spectrometry. In order to increase specificity and to facilitate mass spectrometric interpretation, aliquots of the sample were reduced separately with lithium-aluminium deuteride and hydride. Each peptide gave a pair of derivatives with characteristic mass differences of the ions, namely 2 mass units per reduced oxo group (deuterium-hydrogen-labelling of oxo groups by reduction). Correct identification is assumed only if both mass spectral patterns fit the theory. Sample volumes of 5--100 ml of urine are needed. About six samples can be derivatized per week. Three cases with suspected peptiduria were investigated and the following peptides were found: Gly-Pro-4Hyp-Gly; Gly-Pro-4Hyp; Gly-Hyp-Hyp (postulated isomer Gly-3Hyp-4Hyp); Pro-4Hyp and Gly-Pro. With exception of the tetrapeptide, these compounds could be detected also in the urine of a healthy child.