The influence of some sympatholytic, parasympatholytic and serotonin-synthesis-inhibiting agents on the ultrastructure of the rabbit pineal organ.

The influence of certain drugs on the ultrastructure of rabbit pinealocytes was studied. The results obtained after administration of p-chlorophenylalanine and p-chloroamphetamine support the hypothesis proposed earlier that the smooth endoplasmic reticulum in the light pinealocytes is involved in indoleamine synthesis. The administration of either one of the sympatholytic agents, 6-hydroxydopamine or alpha-methyl-p-tyrosine, induced typical fine structural changes corresponding to those observed after surgical sympathectomy.


Routine use of the hydrogen platinum electrode system in shunt detection.

Routine use of the hydrogen platinum electrode system (HPES) in 1,375 consecutive cardiac catheterizations facilitated shunt detection in 171 patients, led to the diagnosis of unsuspected shunts in 18 patients, and was of particular value in accurately localizing unusual left-to-right shunts. Left-to-right shunts were detected in 171 patients (12% of the total catheterizations). Eighteen unsuspected shunts (10% of the total shunts, or 1% of the total catheterizations) were found. Atrial septal defect (ASD), partial anomalous pulmonary drainage (PAPVD), ventricular septal defect (VSD), and ruptured Valsalva aneurysm were demonstrated, usually associated with other congenital or acquired lesions. HPES was of particular value in accurately localizing the venous drainage of 38 unusual or complex lesions with left-to-right shunting. Five patients with rheumatic mitral valve disease had PAPVD, a higher incidence (1.2% of rheumatic mitral valve disease) than had previously been reported. The rationale for use of a sensitive shunt detection method as a routine part of the catheterization procedure is discussed.


The external field intravascular electromagnetic flowmeter system as applied to standard arteriographic catheters and conscious humans.

New methodology, utilizing electromagnetic principles, has been developed for the measurement of regional vascular blood flow in intact animals and man. The flow sensor consists of a fine, insulated wire loop which has a small electrode on each side of the loop. This loop-probe, which is inserted like a guidewire through standard cardiac or angiographic catheters, springs open upon emerging from the catheter, and the electrodes are automatically applied to diametrically opposite sides of the inner vascular wall. This miniaturization of the flow sensor has been achieved by imposing the magnetic field which pervaces the artery from a coli located outside the body. As blood flows through the vessel across the magnetic field, the induced voltage across the blood column detected between the electrodes is proportional to the volume rate of blood flow. The loop-probe can be used simultaneously as an arterial diameter gauge. Means are described for achievement of a reliable, nonocclusive zero-flow baseline and flow calibration.


Cytotoxicity, mutations and DNA damage produced in Chinese hamster cells treated with streptozotocin, its analogs, and N-methyl-N'-nitro-N-nitrosoguanidine.

The activities of streptozotocin (SZ), three structural analogs of SZ, and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in producing cytotoxicity, mutations to 8-azaguanine (8-AzG) resistance, and DNA damage (single-strand breaks) in V79 Chinese hamster cells have been examined. These three biological processes appear to be associated. MNNG was about 10(3) times more active on a molar basis than SZ, and the activities of the analogs fell within these extremes.


[Activity of somatostatin-containing cells of the Ilets of Langerhans in experimental diabetes].

Insulin-, glucagon-, and somatostatin-containing cells were evaluated by morphometry in sections of pancreas treated for immunofluorescence. Glucagon- and somatostatin-containing cells were found to be increased in islets of streptozotocin-diabetic rats as compared to control islets.


[Anticonidiogenic effect of hydroxyurea on Neurospora crassa].

Conidiation induced in a low sugar-ammonium medium (or by other means such as full starvation or heat shock) is almost fully prevented by hydroxyurea. In a parallel manner the DNA/RNA and DNA/protein ratios are prevented from increasing.


A study of language skills in severely subnormal children.

A study of 37 severely subnormal children, comparing their language development with their non-verbal ability, is described. The test scores obtained by the 17 children with Down's syndrome were compared with those of the remaining 20 children ("others); a cross-sectional examination of the effects of increasing chronological age was made; and an assessment of speech intelligibility was compared with language scale scores. The results show that the children as a group had a language deficit compared with their non-verbal ability, and that their verbal comprehension tended to be poorer than their expressive language ability. Children with Down's syndrome tended to have inferior language ability through the differences between their scores and those of the "others" were not statistically significant. An association between poor intelligibility of speech and low expressive language scores was demonstrated. The results are discussed in the context of other studies. Possible reasons for the patterns of language development observed are suggested, and the practical implications, particularly the need for careful attention to the language development of severely subnormal children from an early age, are considered.


A study of the psychological effects of facial deformity in children.

Anecdotal reports of the psychological effects of facial deformity suggest that the area around the mouth is of crucial importance. In the first of two studies, children in London and Amsterdam ranked drawings of facially deformed children; their ordering was consistent, with a hare lip or protruding teeth being the most commonly rejected. A second study followed up 24 children aged about 8 years who had had a hare lip repair. The results did not confirm the hypothesis that such children differ from their non-handicapped peers in overt behavior in school.


The education of physically handicapped children in normal schools.

This paper is based on our experience in the Central Remedial Clinic over a number of years that physically handicapped children do not in general do well in ordinary schools. An attempt is made to delineate some of the problems that may confront a handicapped child of generally average intelligence who attends a normal school. These problems are associated with the following conditions: specific learning difficulties, emotional problems, poor school attendance, large classes, limitations in ordinary teacher training and lack of remedial teachers and other special staff. The need for early and continued psychological and educational assessments is emphasized, and it is suggested that most young physically handicapped children of average intelligence would benefit from starting in a special assessment unit, to ensure as far as possible, correct school placement. This view is not currently held by a number of educational authorities who generally advise that physically handicapped children should go to ordinary schools if possible. We feel that this advice is not always in the best interests of the child. There is need for continuing friendly and informal communications between parents and members of the special school team.


The handicapped child.

This article is not about specific conditions such as cerebral palsy, or deafness, or mental retardation, it is about every handicapped child; that is every child whose development and life fulfillment are restricted and who requires help to overcome or to reduce the effects of his handicaps. The picture and principles described below apply to all handicapped children whatever the nature of their basic disorder.


Loreto House: a pattern of care.

This short article is primarily concerned with, what the authors consider to be, two important considerations in any form of residential child care, particularly long-term: 1 The great need for a coherent overall philosophy, which is clearly understood by all members of staff. It is felt that, all too often, assumptions are made about general agreement, which are not necessarily borne out by observed practice. 2 The need for the meticulous selection of primary caring staff, followed by relevant in-service training rather than an overreliance upon, what are sometimes, quite arbitrary qualifications. The article attempts to present a broad profile of a unit which, although it does not claim to represent the ideal, is nonetheless beginning to assume a purposive and identifiable character. The point is made that clinicism, professionalism and academic discussion are important but they are not the only considerations. The children must remain the raison d'etre for such a unit, not the justification. The authors hope to have conveyed their conviction that cooperation and communication between the members of a multidisciplinary team presents the most practical and the most productive approach to the care of profoundly and multiply handicapped children.


Profile: toy libraries, school, hospital and home.

Toy libraries are now a well-established component of the services available to the parents of handicapped children. Difficulties of varying kinds have inevitably arisen in the 5 years' history of the toy library movement, some of which could be resolved by linking developments of new libraries with existing institutions. The advantages of a toy library/institution link accrue to both elements of such a union and it is the purpose of this article to argue the case for an increase in the number of such developments.


The ophthalmologist's role in multidisciplinary assessment of developmentally handicapped children.

Among 200 children who had received routine ophthalmic and orthoptic examinations as part of their evaluation by a multidisciplinary assessment team, it was found that there was a high incidence of ocular defects. These defects included refractive errors (98 children), squint (74 children), nystagmus (15 children), cataract, retinopathy and optic atrophy. This high incidence of ocular defects emphasized the need for the routine ophthalmic examination of developmentally handicapped children in order to detect and treat ocular conditions which might otherwise have gone undetected, and enabled the visual sense of these children to be evaluated in relationship to their general development.


Integrated education of visually handicapped children: lines of communication between the professionals in charge.

The local teacher has the immediate responsibility for the integrated education of the visually handicapped child. He gets frequent information and assistance from the county special teacher who is responsible to the public for the educational progress. When the child has his annual opthalmological examination, his medical history is explained and related to the performance of the child at an informal meeting. At this meeting, the ophthalmologist learns to understand the educational problems and the teachers learn what the pupil can see and the conditions under which he functions. All parties take great interest in the pupil's life after school hours, both as to leisure and to his relations in the family group. The parents are continually informed both by the teachers and the ophthalmologist, and a report of the medico-educational meeting is sent to the child's local physician and local ophthalmologist as well as the National Registry of Blindness.


Special education in Denmark and integration of visually handicapped children in normal classes in the public school.

Experience over the last decade in integrating severely visually handicapped pupils in normal school classes is encouraging. We have learned that a visual handicap, no matter how severe, can be compensated for through materials, educational support, cooperation between the persons involved so that the child can be taught in the local school where he belongs and live as normal a life as possible. We are also aware of how things can be improved, but this is a question of economics and to some extent emotional attitudes in the pupil's environment. Although much is done to inform as many as possible in the child's milieu about what blindness is and what to do about it, we still meet problems of full acceptance of the handicap. It takes more than a decade to change emotional attitudes and because of this and because the first demand to any kind of teaching must be flexibility, the integrated education of the visually handicapped will never be a question of neither/nor but always a question of either/or.


Further characterization of the natriuretic factor derived from kidney tissue of volume-expanded rats. Effects on short-circuit current and sodium-potassium-adenosine triphosphatase activity.

Boiled homogenates of kidneys from volume-expanded and hydropenic rats were subjected to column chromatography. The fraction eluting within the range of partition coefficients (Kav) 0.76-0.89 (fraction III) was lyophilized and the effects of this semipurified preparation were assessed on short-circuit current (SCC) across isolated frog skin, on rat kidney cortex Na-K-ATPase activity, and on sodium excretion by the rat in vivo. At a dose of 500 mug/ml, fraction III from expanded rat kidney inhibited SCC by 21 +/- 5% (P less than 0.01), whereas the same fraction from hydropenic rat kidney produced an insignificant change in SCC of 2 +/- 8 %. In a dose-response study, 50, 150, 500, and 1,500 mug/ml of fraction III from expanded rat kidney inhibited SCC by 4, 8, 19, and 28%, respectively; 500, 1,000 and 1,500 mug/ml inhibited Na-K-ATPase activity by 11, 22, and 49%, respectively. An identical study with fraction III from hydropenic animals showed no significant effect in either assay. Also, fractions from expanded and hydropenic rats, eluted after fraction III (fractions IV and V), had no effect on SCC or Na-K-ATPase activity. Fraction III also produced significant natriuresis in vivo at a dose of 500 mug/ml, confirming our observations that a natriuretic principle may be recovered from the kidneys of volume-expanded rats. We suggest that this natriuretic principle may act by reducing active sodium transport via inhibition of Na-K-ATPase.


Cardiac performance in rats with renal hypertension.

To evaluate cardiac performance in renal hypertension more precisely we determined cardiac function curves for 12 normotensive rats and 11 other rats with two-kidney Goldblatt hypertension. The hypertensive group (BP = 134 +/- 8 mm Hg) showed significant cardiac hypertrophy (44 +/- 1% increased ratio of heart weight to body weight, P less than 0.01) and markedly increased left ventricular stroke work with a moderate but not significant increase in left ventricular end-diastolic pressure (LVEDP) (5.9 +/- 0.8 vs. 4.7 +/- 0.4 mm Hg). We evaluated cardiac function by recording left ventricular end-diastolic pressure, stroke volume (SV), and cardiac output (CO) (by electromagnetic flowmeter) during rapid alteration in venous return. Analysis of variations of stroke volume vs. left ventricular end-diastolic pressure showed that renal hypertension is accompanied by a significant decrease in ventricular performance [SV = 0.0190 + 0.0509 LVEDP - 0.0025 (LVEDP)2 + 0.0001 (LVEDP)3] compared to the normotensive group [SV = 0.0430 + 0.0644 LVEDP - 0.0040 (LVEDP)2 + 0.001 (LVEDP)3]. The alterations in stroke volume and cardiac output were associated with a lack of significant changes in the work performed at matched end-diastolic pressures. The data indicate that chronic renal hypertension is accompanied by a depression of cardiac reserve which is not revealed by measurements of cardiac output and left ventricular end-diastolic pressure at rest. This impairment in cardiac function might be related to either diminished cardiac contractility or reduced left ventricular compliance; the latter possibility is in accord with our finding of a 2-fold increase in the hydroxyproline content (P less than 0.001) and a significant decrease in the DNA concentration of ventricular tissue.


Effect of clofibrate on plasma proteins including components of the hemostatic mechanism.

The effect of clofibrate (1.5 g/day) on different plasma proteins and on components of the hemostatic system was studied in eight men with either mild diabetes mellitus or cardiosclerosis. Before treatment, the subjects were investigated weekly on five occasions. The means of these determinations were compared with the values observed after 2, 6 and 14 weeks of treatment. During the treatment albumin and transferrin increased significantly while orosomucoid, ceruloplasmin, beta1 E-globulin, IgA, IgM and fibrinogen decreased significantly. The decreases of the last proteins in per cent were found to be associated with each other in single subjects, i.e. a subject who reacted with a certain degree of change in one protein tended to react in a similar way with regard to the other proteins. A correlation was observed between the concentration before the treatment and the decrease in concentration during the treatment for ceruloplasmin, IgG, IgA, IgM and fibrinogen. The fibrinolytic activity increased significantly. Plasminogen decreased after 6 weeks and increased after 14 weeks of treatment. Platelet adhesiveness was not influenced.


Television reading system.

The value of the television reading aid system is discussed, in the training of visually handicapped children.


Separation of dermatan sulfate from heparan sulfate in mucopolysaccharidosis urine by chromatography on Sephadex G-75.

Oligosaccharides of testicular hyaluronidase-degraded dermatan sulfate were separated from undegraded dermatan sulfate by chromatography on Sephadex G-75, but not by chromatography on Sephadex G-25. All but the smallest of these oligosaccharides were recovered in excellent yield following dialysis and precipitation with cetyl pyridinium chloride (CPC). G-75 chromatography of dialyzed, concentrated Hunter urine mucopolysaccharides precipitated with CPC resolved most of the large dermatan sulfate into a void volume related peak which was free of heparan sulfate. Decreasing amounts of dermatan sulfate oligosaccharides were eluted with sephadex-retarded polysaccharides, including small amounts which appeared with otherwise pure heparan sulfate.


A review of the medical, educational and social needs of 207 handicapped children.

The Mary Sheridan Centre serves the needs of two health districts with a population of over half a million. The assessment of the handicapped child is combined with a Day Nursery and Observation Unit which provides therapeutic, educational and supportive guidance. During the year May 1973-74, 207 children were referred for assessment of whom only 11 were found to have no handicap. One-third of these referrals were from the hospital follow-up baby clinic and two-thirds came from community and general practitioner sources. The average age of referral was two years for girls and two and a half years for boys. Of the 196 handicapped children, 33 had neurological disorders, 30 congenital anomalies and 50 an adverse perinatal history. Social factors were thought to contribute significantly in 72; 35 children came from single parent families. Behaviour problems were noticed in a high proportion (68). Forty-four children regularly attend the Centre's day nursery whose staff include preschool teacher, occupational therapists and trained nurses for play, speech stimulation and specific therapy; 48 attend for speech therapy and 19 for physiotherapy. The prime aim is to help the parents continue with the therapy and care of their child in their own home.


Psychological responses to genetic counseling for Down's syndrome.

To assess some of the emotional aspects of why parents seek genetic counseling and to measure the effect of genetic counseling in parents of children with Down's syndrome, pre- and post-counseling measures of anxiety, hostility, depression, and self-concept were obtained from 43 parents. Pre-counseling responses were compared with those of normative controls, and pre- and post-counseling scores were compared for areas of significant change. Anxiety, hostility and depression levels were significantly higher in parents seeking counseling than in normative controls (both P less than 0.002). Following genetic counseling, there was a significant lowering of anxiety (P less than 0.0005) and depression (P less than 0.05) along with a significant increase in overall self-concept (P less than 0.01). The study documents the importance of looking at factors related to emotional needs and self-image of parents in genetic counseling.


Trisomy 21 in mother and daughter.

A 28-year-old woman with trisomy 21 had a daughter with trisomy 21. This case brings the total to 23 mothers recorded as having trisomy 21. Their offspring consist of 14 normals and 10 trisomics, 21 born at term, plus 3 abortions. The proportions of normal and trisomic offspring are about equal.


Four cases of omphalocele in two generations of the same family.

A family in which four cases of omphalocele were found within two generations is presented. One of the patients also had Down's syndrome. To our knowledge, this is the first report of such an occurrence in one family.


Clinical and biochemical expression of a unique mucopolysaccharidosis.

A boy who presented with painful joints leading to contractures was found to have a mucopolysaccharidosis not previously described. He had severe dysostosis multiplex of the long bones but nearly normal intellectual development and no involvement of the cornea. Lysosomal storage vacuoles were noted in dermal endothelial cells; these were similar to those seen in the genetic mucopolysaccharidoses. Mucopolysacchariduria was not excessive in amount but it was distinctly abnormal in pattern and his excretion of dermatan sulfate resembled that found in the Hunter and Hurler syndromes. The activities of the lysosomal hydrolases in cultured fibroblasts were normal or increased. The degradation of accumulated 35S-mucopolysaccharide in fibroblasts in culture was typical of a mucopolysaccharidosis. His mother accumulated 35S-mucopolysaccharides in fibroblasts, suggesting an X-linked inheritance of the disorder.


Dermatoglyphics in mosaic Down's syndrome.

To determine whether quanitative dermal indices are useful in ascertaining the liability for or severity of mosaic Down's syndrome (DS), dermatoglyphics of 107 subjects with proven 46/47,+21 DS were scored by four quantitative dermal indices. The distribution of mosaics by weighted mean percentage of +21 cells ranged from 1 to 95 and was bimodal. Mean maternal age at birth of mosaics (32.9 +/- 7.5 years) was elevated when compared with control maternal ages in the literature. The distribution of quantitative dermal indices for the total mosaic population fell roughly midway between those in the literature for normal and full DS individuals: 73% of mosaics were classified as definitively DS, 21% were in the intermediate range, and 6% were normal. For mosaics who were minimally affected, 24% were DS, 53% intermediate, and 23% normal. One can conclude: (1) For any suspect mosaic, a dermal score in the DS range is highly suggestive of karyotypic pathology. (2) The high prevalence of intermediate scores in normal subjects severely restricts their diagnostic value in screening for mosaics in the general population. For a selected population, such as parents of +21 children, the screening value of quantitative dermal indices remains an open question. Weighted regression analyses demonstrate a highly significant correlation (P less than 0.001) of dermal index score with the weighted mean proportion of +21 cells transformed to the logit scale. One may exploit this correlation to predict the ratio of +21/normal cells in infants, in whom early karyotype evolution can preclude an estimate of the ultimate syndrome based on initial degree of mosaicism. Furthermore, this correlation provides additional indirect evidence that dermal microsymptoms in DS are a reflection of the presence of +21 cells.


The scintigraphic findings in Paget's disease of bone.

Bone scans and radiographic skeletal surveys have been done in 41 patients who had Paget's disease. The scintigraphic findings are consistent with what is known of the pathophysiology of Paget's  disease. Diseased bone demonstrates increased vascularity, an increased degree of uptake of bone-seeking radiotracers and, in appropriate bones, evidence of marrow replacement. The bone scintiscan is a more sensitive indicator of the extent of polyostotic Paget's disease than conventional radiograph, demonstrating 34% more lesions. Because it reflects shorter term changes in osteoblastic activity the bone scan is of some value in providing immediate objective evidence of the therapeutic effectiveness of Mithramycin which has been used in this study in the treatment of the minority of patients with pain in Pagetoid bone. A technique for documenting alterations in uptake by diseased bone numerically is presented. Upon treatment with Mithramycin the ratio of abnormal uptake in relation to normal bone fell from 8.7 to 3.9.


The mucopolysaccharidoses and mucolipidoses.

The mucopolysaccharidoses and mucolipidoses are recessively inherited lysosomal storage diseases. Each of the disorders can now be specifically identified in cultured fibroblasts. As a group these disorders clinically present with a Hurler-like phenotype. Genetic heterogeneity and variable expression of the same enzyme deficiency require a combined clinical and laboratory approach to the diagnosis of these disorders. This feature is demonstrated by mucopolysaccharidosis I. This diagnosis refers to a specific deficiency of the lysosomal enzyme alpha-L-iduronidase. Further characterization requires clinical assessment to determine whether the final diagnosis is the Hurler syndrome, the Scheie syndrome or the Hurler-Scheie compound. Clinically each of these three disorders may be difficult to distinguish from other mucopolysaccharidoses or mucolipidoses. There is no specific treatment currently available for any of these disorders. However, a specific diagnosis should be established in each case to insure an accurate prognosis (some of these disorders are compatible with near normal life expectancy and normal intelligence), appropriate genetic counseling for the family and timely use of prenatal diagnosis by amniocentesis which is available for each of these disorders.


Quantification of chorea in Huntington's disease by power spectral analysis.

A spectral analysis technique for quantifying dyskinesia in patients with diagnosis of Hungtington's Disease (chorea) (H.D.) is described. Spectral analysis involves computation of the magnitude of abnormal involuntary movements (AIMS) and of their distribution in frequency. It has the advantage of providing an objective measure of such movements. Three H.D. patients under different drug regimens and three age-matched controls have been evaluated and representative time records and power spectra are presented. Analysis established marked differences in the amplitude and shape of the normal and patient spectra. In addition, spectral analysis proved sensitive to differences in drug treatments among patients suggesting its additional use in evaluating the efficacy of therapeutic agents in the treatment of movement disorders.


Islet transplantation into rat liver: in vitro secretion of insulin from the isolated perfused liver and in vivo glucagon suppression.

Islet isografts were injected into the portal veins of rats made diabetic with streptozotocin. The isografts normalized not only plasma glucose and insulin levels but also the elevated plasma immunoreactive glucagon level. The in vitro basal insulin secretion and prompt sensitivity to glucose were shown directly by perfusing isolated livers containing transplanted islets. In vitro glucagon secretion to an arginine stimulus could not be demonstrated, although it would have been expected demonstrated, although it would have been expected in normal islets. Thus, it appears that insulin derived from transplanted islets is capable of correcting endogenous hyperglucagonemia and of ameliorating the effects of experimental diabetes while transplanted islet glucagon secretion is relatively suppressed.


Electronmicroscopy studies on the exocrine pancreas of Wistar-Rats following treatment with Streptozotocin.

In Wistar rats the intraveneous injection of streptozotocin (65 mg/kg body weight) caused a permanent hyperglycemia. After 5 days there were lesions in the exocrine parenchyme of the pancreas and its nerve fibers. Pathological changes were found in cytoplasm, cell membrane, nucleus and all other cell organelles, too. The zymogen granules remaining after extensive degranulation may disintegrate in two different ways: 1. Shrinking of the granules and formation of a hale between granule membrane and core, the electronic density of which is decreased; indistinct demonstrability of the granule membrane and finally its decomposition. 2. Shrinking of the granules, decrease of the electron density and either homogeneous or mainly peripheral arrangement of the disintegrated material of the granules; irregular shape of the granules and splitting of their membranes.


The binding of lipid to the lipid-free adenosine triphosphatase protein of sarcoplasmic reticulum.

Dinitrophenylated dipalmitoyl phosphatidylethanolamine and its lyso derivative have been shown to bind to the lipid-free ATPase protein derived from the sarcoplasmic reticulum. The binding of these lipids is accompained by the quenching of up to 95% of the tryptophyl fluorescence of the protein. This effect is reversed by 9-10 mM deoxycholate. The solubility of the lipid-free ATPase protein in the absence of deoxycholate and the solubility of submillimolar concentrations of the dinitrophenylated monopalmitoyl phosphatidylethanolamine anion in aqueous media allowed binding experiments using this lipid ligand to be carried out in a simple buffer system. It is shown that in the case of this lipid the initial phase of the binding process displays an apparent positive co-operatively. Data from the second phase in the saturation of the protein with this lipid is consistent with binding to independent, equivalent, non-interacting sites with a microscopic (intrinsic) association constant of 1.63 x 10(6) M-1, the fluorescence being quenched in the geometric fashion. Altogether a total of about 15 molecules of this lipid may be bound by the protein.


Inhibition by triphenyltin chloride of a tightly-bound membrane component involved in photophosphorylation.

At very low concentrations (less than 1 muM) triphenyltin chloride inhibits ATP formation and coupled electron transport in isolated spinach chloroplasts. Basal (-Pi) and uncoupled electron transport are not affected by triphenyltin. The membrane-bount ATP in equilibrium Pi exchange and Mg2+-dependent ATPase activities of chloroplasts are also completely sensitive to triphenyltin, although the Ca2+-dependent and Mg2+-dependent ATPase activities of the isolated coupling factor protein are insensitive to triphenyltin. The light-driven proton pump in chloroplasts is stimulated (up to 60%) by low levels of triphenyltin. Indeed, the amount of triphenyltin necessary to inhibit ATP formation or stimulate proton uptake is dependent upon the amount of chloroplasts present in the reaction mixture, with an apparent stoichiometry of 2-2.5 triphenyltin molecules/100 chlorophyll molecules at 50% inhibition of ATP formation and half-maximal stimulation of proton uptake. Chloroplasts partially stripped of coupling factor by an EDTA was are no longer able to accumulate protons in the light. However, low levels of triphenyltin can effectively restore this ability. The amount of triphenyltin required for the restoration of net proton uptake is also dependent upon the amount of chloroplasts, with a stoichiometry of 4-5 triphenyltin molecules/100 chlorophyll molecules at 50% reconstitution. On the basis of this and other evidence it is concluded that triphenyltin chloride inhibits phosphorylation, ATP + Pi exchange and membrane-bound ATPase activities in chloroplasts by specifically blocking the transport of protons through a membrane-bound carrier or channel located in a hydrophobic region of the membrane at or near the functional binding site for the coupling factor.


Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine.

Administration of p-chloroamphetamine (PCA) (2.5-10.0 mg/kg) or fenfluramine (FF) (5.0-15.0 mg/kg) to rats induces a behavioral syndrome--consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading--which is a reflection of the activity of central serotonin-mediated synapses. The syndrome appears within 3-5 min following i.p. administration of PCA or FF, and the syndrome-inducing effects of PCA and FF are blocked by prior depletion of serotonin with p-chlorophenylalanine. By contrast, the syndrome-inducing effect of 5-methoxy-N,N-dimethyltryptamine (5-M-DMT), which directly stimulates postsynaptic serotonin receptors, is not changed by prior serotonin depletion. Catecholamine depletion with alpha-methyl-p-tyrosine produces essentially no change in the syndrome-inducing effects of PCA, FF or 5-M-DMT. These data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin.


[A study on the ouabain-sensitive (Na+ + K+)-ATPase activities of skeletal muscle and brain membrane fractions from genetically dystrophic mice (author's transl)].

The ouabain-sensitive (Na+ + K+)-ATPase activities of membrane fractions from hind-leg muscle and brain of normal and genetically dystrophic mice (C57BL/6J-dy strain) were studied, and the following results were obtained. 1) The ouabain-sensitive (Na+ + K+)-ATPase activity of frozen muscle sarcolemmal fraction from normal mice was several times higher than that of fresh one. 2) The ouabain-sensitive (Na+ + K+)-ATPase activity of frozen muscle sarcolemmal fraction from dystrophic mice was almost equal to that from normal one. But the muscle membrane yield from dystrophic mice was considerably low compared with the yield from normal one. 3) With brain membrane fractions, no differences were observed between normal and dystrophic mice in the ouabain-sensitive (Na+ + K+)-ATPase activity as well as in the yield of membrane fractions.


Localization of Na+, K+-ATPase in brain.

Enzyme activity, representing the sites of K+-stimulated p-nitrophenylphosphatase, a component of the sodium, potassium-stimulated-adenosinetriphosphatase system, has been localized in the somatosensory cortex of the rat brain. The reaction product is most obviously associated with fibers that are thought to be axons and dendrites. Large dendrite-like fibers appear to arise in layer 5 of the cortex and arborize in layers 1 through 4. Smaller, reactive fibers are found throughout the cortical layers. Neuron cell bodies did not exhibit substantial enzymatic activity. It did not appear that glia contributed significantly to the activity in cerebral cortex.


Cell membrane Na+, K+-ATPase and sarcoplasmic reticulum: possible regulators of intracellular ion activity.

Cardiac muscle requires an external source of calcium for contraction, but current evidence supports an intracellular pool of bound calcium as the primary activator of contraction. The size of this intracellular pool modulates the amount of calcium released to troponin during systole and the resultant contractile response. Proposed mechanisms for modulation of activator calcium include: 1) an alteration in phase II "slow current" allowing increased electrogenic calcium flux; 2) a glycoside independent sodium-calcium exchange across the sarcolemma that can be modulated by changes in the sodium gradient; 3) potassium-calcium exchange system during cardiac repolarization; 4) an augmentation of calcium accumulation by cardiac sarcoplasmic reticulum related to various phosphorylation mechanisms; and 5) an alteration in phospholipid affinity effected by cardiac glycoside at sarcolemmal sites related to the Na+, K+-ATPase.


Cell potential and the sodium-potassium pump in vascular smooth muscle.

An electrogenic sodium-potassium pump appears to contribute materially to the steady-state potential and to certain of the transient potential responses of vascular smooth muscle. Since changes in cell potential in turn can lead to changes in contractile state, the pump is implicated in some of the constriction-dilation responses of blood vessels. The vasodilator action of potassium is explainable, for instance, through an effect on cell potential if (and only if) an electrogenic pump is assumed to be extruding sodium at a faster rate than it takes up potassium. This is supported by the observation that ouabain, an inhibitor of Na,K-ATPase activity, will eliminate or reverse the vascular effect of potassium. Furthermore, when the in vivo and in vitro effects on vascular smooth muscle of altered extracellular potassium concentration are compared to calculated cell potentials based on a model that includes an electrogenic pump, the experimental findings are shown to be logical and predictable.


Structural proteins in the myofilaments and regulation of contraction in vertebrate smooth muscle.

The contractile systems of vertebrate smooth and striated muscles are compared. Smooth muscles contain relatively large amounts of actin and tropomyosin organized into thin filaments, and smaller amounts of myosin in the form of thick filaments. The protein contents are consistent with observed thin:thick filament ratios of about 15-18:1 in smooth compared to 2:1 in striated muscle. The basic characteristics of both types of contractile proteins are similar; but there are a variety of quantitative differences in protein structures, enzymatic activities and filament stabilities. Biochemical and X-ray diffraction data generally support recent ultrastructural evidence concerning the organization of the myofilaments in smooth muscle, although a basic contractile unit comparable to the sarcomere in striated muscle has not been discerned. Myofilament interactions and contraction in smooth muscle are controlled by changes in the Ca2+ concentration. Recent evidence suggests the Ca2+-binding regulatory site is associated with the myosin in vertebrate smooth muscle (as in a variety of invertebrate muscles), rather than with troponin which is the regulatory protein associated with the thin filament in vertebrate striated muscle.


Alaskan malamute chondrodysplasia. II. Urinary excretion of hydroxyproline, uronic acid and acid mucopolysaccharides.

The urinary excretion of free, total and non-dialyzable hydroxyproline appeared to be similar in both chondrodysplastic and non-chondrodysplastic Alaskan Malamutes of ages six and twenty-six weeks suggesting the metabolic defect was probably not related to a gross disturbance in collagen metabolism. Urinary hexuronic acids also appeared to be similar in levels for both populations. A four-fold increase in urinary mucopolysaccharide levels observed at age twenty-six weeks in the chondrodysplastic Alaskan Malamute suggested a deviation from normal. The magnitude and variability of deviation were not sufficient to indicate that this condition could serve as a model for the mucopolysaccharidosis of man but probably indicated a delayed maturation process.


Nutrition in cryptogenic cirrhosis and chronic aggressive hepatitis.

The nutritional status of 80 patients with non-alcoholic chronic liver disease was assessed by determination of various nutritional parameters in body fluids. With the exception of vitamin C there was a higher incidence (40%) of fat soluble vitamin deficiency (vitamins A, E, and carotene) than of the water soluble vitamins. Less than 10% of patients showed evidence of vitamin B12, nicotinic acid, thiamin, or riboflavin deficiency, and 17% had evidence of folic acid deficiency. The presence of deficiency was not related to age of the patient or fat absorption, and an inadequate dietary intake was not a major cause of deficiency. The incidence of nutritional deficiency is less frequent in non-alcoholic as compared with alcoholic liver disease.


[Angiomas and angioma-like changes of the bronchial arteries (author's transl)].

Hyperplastic changes of the bronchial arteries may take the form of a racemose arteriovenous angioma or result from chronic bronchitis. Clinically, recurrent haemoptysis is a striking feature occurring in otherwise fit patients. The two forms can be distinguished by bronchial arteriography because of the difference in the appearance of the vessels. In the one condition there are circumscribed areas of arterial and venous, vascular abnormalities, in the other there is vascular hyperplasia, which is less clearly circumscribed. In both forms, broncho-pulmonary, i.e. arterio-venous anastomoses can be demonstrated; these may be considered as the cause of the haemoptyses.


[Radiological lung changes in progressive pulmonary insufficiency (author's transl)].

Chest radiographs can reflect increasing pulmonary insufficiency of shock lung. In the early and intermediate stages, there is almost pure interstitial oedema which, in the later stages becomes alveolar-interstitial. In addition one may find evidence of broncho-pneumonia. Respiratory insufficiency is due to abnormalities of perfusion and distribution and is aggravated by disturbance of oxygen diffusion. The latter is due to an increase in the alveolo-capillary diffusion distance in the presence of interstitial oedema. It was not possible to demonstrate quantitatively significant precapillary shunts greater than 25 mu.


[The diagnosis of pulmonary calcinosis by scintigraphy (author's transl)].

Three patients are described who were examined with the bone-seeking substance 99mTc-E.H.D.P. The abnormalities discovered were ascribed to metastatic calcification in the lungs. The patients suffered from three quite different conditions, but in each there was hypercalcaemia. One patient had chronic renal insufficiency  with secondary hyperparathyroidism, in the other cases the cause of the hypercalcaemia could not be determined. In one patient, it was possible to confirm the diagnosis of pulmonary calcinosis histologically. Previously published cases indicate that it is possible to demonstrate lung calcification by using Tc-phosphate compounds, particularly 99mTc-E.H.D.P. This is important, since it is often not possible to demonstrate it radiologically. It further demonstrates that the accumulation of 99mTc-E.H.D.P. is dependent on active bone metabolism.


[Pulmonary uptake of 198Au during liver scanning in two patients with amyloidosis (author's transl)].

Lung uptake of 198Au-colloid, injected for a liver scan, is demonstrated in two patients with systemic amyloidosis, The incidence, importance and mechanism of this phenomenon is discussed.


[Scintigraphic findings in amoebic abscess of the liver (author's transl)].

The accuracy, size, localization and course of liver scans of solitary or multiple amoebic liver abscesses was evaluated in 52 patients. The scintigraphic data were correlated with the clinical symptoms. In 47 of the 52 patients it was possible to demonstrate the liver abscess on the scintigram; the right lobe of the liver was involved more frequently than would have been expected simply on the basis of its volume. In most of the patients investigated the abscesses were solitary and in only 28% was it posssible to recognise two or three abscesses occurring simultaneously. Follow-up examinations showed rapid diminution in the size of the abscess furing medical treatment but complete return to normal during the first six months occurred in only 17% of cases. The results are discussed.


[Unusual complication of pancreatitis as seen in angiographic picture (author's transl)].

Selective angiography of pancreas is useful not only to diagnosis of early inflammatory changes but also it is an important exploratory method of pathological processes in later period. By this method it is possible to discover important pathological changes on passing by arteries which can end fataly. In our case the arteriography of pancreas was performed to make clear a subphrenic abscess and at the same time there were discovered inflammatory lesions of splenic artery accompanied by a creation of some pseudoaneurysmas in pancreatic tissue. Their evolution was followed four times by arteriography.


[Catheter embolisation of renal tumours (author's transl)].

Arterial embolisation of renal tumours with foreign particles is described. This involves occlusion of the arteries supplying the tumour through a catheter introduced by the trans-femoral route. Pre-operative and therapeutic embolisation should be distinguished. During pre-operative embolisation, the kidney should be totally occluded by the foreign  particles in order to obtain a bloodless operation zone and in order to avoid the much feared production of tumour emboli. Because of the clinical consequences of renal artery emboli, this procedure should be carried out immediately before the operation. During therapeutic embolisation, which is not followed by an operation, only those vessels supplying the tumour should be occluded in order to avoid the complications of a renal embolus. Ischemia of the tumour and less rapid growth may then be excluded.


[The value of pneumomyelography in the investigation of the terminal theca (author's transl)].

Three hundred lumbar air myelograms were selected from a total of 1,500 examinations and their results analysed. The method described in this paper provides significantly more information than conventional myelograms. In the opinion of the author, lumbar air myelography can replace iodinated oils and esters in the diagnosis of disc prolapse, since its accuracy is not significantly inferior. Because of its lack of toxicity it is to be preferred.


[The widened "empty" internal auditory meatus. A new differential diagnosis of the small acousticus neurinoma].

Six patients with symptoms suggestive of acoustic neuromas showed a wided, contrastfilled internal auditory meatus during positive contrast meatography on tomographic cuts. These results suggest that widening of the internal auditory meatus may not always be due to a space-occupying lesion. The explanation for these findings is not known. No comparable findings have been published in the relevant literature. Surgical intervention, which is frequently harmful and carried out because of a misdiagnosed acoustic neuroma can only be avoided by carrying out cisternography with positive contrast materials and tomography in the Stenvers' and Schüller projection.


[Hyperostosis triangularis ilii -- a sacro-iliac stress phenomenon Part. 2 (Incidence, prognosis, pathogenesis, aetiology, tracer studies, differential diagnosis) (author's transl)].

The anterior iliac margin adjacent to the sacro-iliac joint contains a physiological zone of hyperostosis. Its shape is that of a triangular pyramid. Because of its small size, it is radiological invisible, but is nevertheless an indication of the presence of normal stresses passing from the mass of the trunk to the lower extremities. If for any reason, such as is described in this paper, the stresses on the hyperostosis zone are increased, the latter becomes enlarged, while still keeping its shape. It then appears on the radiograph as hyperostosis triangularis ilii. In approximately 50% of cases there is a simultaneous but variable sacral hyperostosis. Observations on 40 patients, together with two autopsies and radionucleide investigations suggest that hyperostosis triangularis ilii represents a potentially reversible bone reaction of the physiological hyperostosis of the anterior iliac margin. The clinical differential diagnosis raised by the radiological finding of a "triangular ilium hyperostosis" is discussed.


[The inherent dynamics of radiological diagnosis and ways of controlling it].

The persistent increase in the number of radiological investigations, which has been going on for several decades, has been called its "inherent dynamics" by Rausch. An analysis of the figures has shown that it is due not only to increasing use on the part of doctors and hospitals, but is particularly the result of an increase in the number of examinations per patient. Suggestions for limiting the increase are discussed, particularly a more stringent control of the indications by the radiologists, prevention of repetitious examinations and avoidance of qualitatively unsatisfactory examinations.


[Genetic hazards in a technological age (author's transl)].

The maximal tolerable risk for mankind due to radiation and chemically induced mutations has been accepted as an increased mutation rate of 25%. A linear dose-effect relationship has been assumed and from the experimentally obtained mutation rate due to irradiation of mouse spermatogonia, the following risk factors were obtained: 1. The doubling dose for specific locus in the mouse is representative of recessive conditions. 2. The mutation rate depends on dose rate and fractionation of the irradiation. 3. The extrapolation factor for using these mammalial results in man is about 1.2. 4. The results of specific locus investigations are representative of all the mutation-types in a mouse that have been investigated. 5. Both sexes are similarly affected. On the above premises, a radiation dose of approximately 75 mrem per annum would increase the spontaneous mutation rate in man by about 9% per generation. The risk due to chemical mutagens should not exceed that due to radiation. Methods similar to those used for radiation risks are able to estimate the chemical risk to the population. The tolerable risk to the population from chemical mutagens depends partly on the radiation burden, but the extent of the chemical burden is unknown. This can only be estimated if the law provides for measurements of mutagenicity for drugs, food additives, biocydal agents and industrial chemicals. A risk analysis should be carried out for those chemo-mutagens which are essential. The chemical burden of all permitted mutagens should not exceed the spontaneous mutation rate by 10% per generation at the most. The human hereditory stock can be protected from irreparable damage only if one succeeds in establishing norms for the controlled use of chemical mutagens similar to the regulations which already exist for radiation protection.


[Value versus risk judgements in diagnostic radiology. Basic and practical considerations (author's transl)].

The author persues earlier considerations regarding a quantitative evaluation of the usefulness against risks of radiological examinations, with a detailed discussion of the radiological and diagnostic problems. The possibilities of accurately quantifying degrees of urgency are discussed in practical terms, particularly for new forms of investigation in widespread use. In addition to a consideration of the usefulness and risks based on days gained or lost in the life of the patient, it is suggested that the cost of the examination should also be borne in mind. A model is illustrated by a number of examples. Finally, certain psychological problems are outlined which are concerned with the valuation and use of protective measures and with subjective estimates of risks involved.


[Biomedical use and dosimetry of pions of the sin 590 MeV isochrone cyclotrone. VII. Radiation therapy using negative pions (author's transl)].

The scheme of radiation of Schumacher for high energy electrons is investigated. In it 3 high individual doses are given at first. In the second phase which follows immediately, weekly single doses of 500 rad are given until the tumor is completely destroyed. Reoxygenation and transformation of anoxic cells are important here for the number of surviving tumor cells but unfortunately still rather unknown. This uncertainty can be removed with the Pion therapy in which transformation does not take a large part. About 10 single doses of negative pions of 150-200 rad should be clearly superior to 5000 rad electron doses (D1 = 500 rad) and should not exceed the limits of tolerance with a weekly treatment. Finally the importance of contamination with electrons of the pionrays is examined. Exact measurement of this contamination is necessary.


[Noninvasive demonstration of wall movement and stroke volume distribution of the left ventricle after myocardial infarction (author's transl)].

A noninvasive technique, i.e., the intravenous injection of a bolus of 99mTc, allows one to visualize the wall motion and the stroke volume distribution of the left ventricle after myocardial infarction. Thus, in the first weeks after infarction, it is possible 1) to answer the question of the function of the involved wall segment, 2) to detect early complications, 3) to follow-up the course 4) to estimate the patient's functional status for treatment more accurately and 5) to control the result of treatment. Furthermore, one can calculate the ejection fraction, demonstrate other zones of reduced systolic function and evaluate the degree of congestion in the lung and involvement of the right ventricle. The study is based on 42 examinations in 35 patients with proven myocardial infarction. Only three patients presented normal systolic wall motion. In the remaining 32 patients there was hypokinesia of the infarcted segment partly combined with some temporary dyskinesia during ventricular contraction or with localized akinesia. Three patients had an aneurysm, two a ventricular septal defect and 19 some degree of mitral reflux, in seven congestive heart failure was present. Certain technical requirements are essential for this noninvasive technique. They are discussed in detail. Examples of wall motion and stroke volume distribution of a normal left ventricle, anterior and posterior infarction and an aneurysm are illustrated.


[Clinical and experimental investigations with 201tl for noninvasive myocardial scintigraphy (author's transl)].

The biological distribution of 201Tl after intravenous injection was studied experimentally in 42 rats. It was found (see figure 1) that the kidneys showed the greatest affinity for 201Th, reaching an activity concentration of 6.6% per gramme of tissue, almost independently of time. Within the first 30 minutes of injection, myocardial activity exceeds that of the surrounding structures (10 min. p.i.: 4.24%/g; 30 min. p.i.: 2.58%/g). During this time the myocardium can be well demonstrated by "image processing". The relatively fast myocardial kinetics of 201Tl (half value time 33 minutes) make it necessary, strictly speaking, to use a scintillation camera. The clinical value of this method is illustrated by a number of case histories.


[The reliability of myocardial scintigraphy with thallium201, A comparison with lacvocardiography and perfusion scintigraphy (author's transl)].

Eighteen patients were investigated by laevocardiography, perfusion scintigraphy and with a 201thallium scan. In four patients with normal contractility of the left ventricle, normal uptake of 202thalium was found in every patient. Hypokinesia of the anterior wall or apex of the ventricle showed normal uptake on the 201thallium scintigram in four out of five patients. It follows that it is not usually possible to diagnose hypokinetic mural portions on 201thallium scintigrams without quantitative analysis. Our experience up to date with areas of akinesia has shown that it is possible to demonstrate areas of scarring (as negative contrast) in seven out of nine cases.


[Cinematographic and clinical findings from simultaneous two-plane coronary angiography (author's transl)].

Simultaneous cine-angiographic examination of the coronary arteries in two planes is now possible, due to technical advances, without losing any of the information that may be obtained by a single-plane technique. This method shortens the examination, reduces the radiation dose when compared with a large film technique and significantly reduces the risk to the patient. Our experience in 67 examinations is recorded.


[The effectiveness of vasopressors and vasodilators for pharmaco-dynamic renal angiography (author's transl)].

9,450 radiographs of 355 patients were analysed in order to determine the diagnostic values of pharmaco-dynamic renal angiography. In each case renal angiography was performed by a conventional techinique as the basis for a clinical experimental study of the effectiveness of a-renergic and cholinergic drugs. The comparison showed unequivocally that pharmacodynamic methods may increase the value of renal angiography. Vasopressors alter the pressure gradient during the arterial phase and improve filling of neovascular areas, which are themselves unreactive. The value of the vasodilators depends on the increased contrast values during the parenchymatous and venous phases of the angiogram. In this way structural changes in tne renal parenchyma and pathological changes in the veins can be emphasised. The value of adrenergic drugs consists in increasing the vascular supply to various tumours, focal inflammatory disease and renal contusion, whereas cholinergic drugs are suitable for improving the demonstration of parenchymal lesions, such as tumours, cysts, abscesses, tuberculomas and localised renal trauma. The results indicate clearly that pharmaco-dynamic methods represent an integral part of renal angiography.


[Undersirable pharmaco-angiographic effects of adrenaline in malignant renal tumours (author's transl)].

The authors have twice observed undesirable effects of adrenaline during the demonstration of malignant renal tumours. Following adrenaline there was less flow of contrast medium into the tumour vessels than during angiography without the drug. In their opinion, this is due to the fact that constriction of the inter-lobar arteries occludes the vessels supplying the tumour, and that in some cases the new-formed vessels react strongly to adrenaline. In a third case, the tumour vessels reacted much more strikingly to adrenaline than would have been expected from previous experience. They therefore doubt whether pharmaco-angiography with adrenaline is always indicated for demonstrating malignant renal tumours; adrenaline may be expected to produce a positive result only in these cases in which there is a central origin of the artery supplying the tumour. They therefore suggest a change to some other, more suitable drug.


[Catheter embolisation of metastasising renal carcinomas using butyle-2-cyano-acrylate (author's trabsl)].

Embolisation with butyle-2-cyano-acrylate was carried out in four inoperable renal carcinomas. By mixing this tissue adhesive with 50% glucose it remains suitable for embolisation for eight to ten minutes. Contact with blood produces the desired effect of immediate and permanent vascular occlusion. Since the material adheres to the vessel wall, it is not carried to any other vascular areas. No complications due to this material have been observed.


[Supra-renal venography in patients with suspected endocrine hypertension (author's transl)].

In forty patients suspected clinically of having an endocrine cause for hypertension, an adrenal cortical adenoma was confirmed histologically in five. Hyperaldosteronism with enlarged or normal adrenals was demonstrated in three patients. The diagnosis in a further eight patients with an abnormal hormone pattern and/or an abnormal venogram has not yet been confirmed. Adrenal glands show considerable variation in their size, shape and localisation on venography.


[Coeliac angiography with high contrast flow rates (author's transl)].

The coeliac axis can be reliably catherised, using a catheter with a double curve; this can be advanced into the hepatic artery to assume a stable position. The advantages of this catheter can also be utilised by making several side holes and leaving the tip in the coeliac trunk. The side holes permit even filling of all branches of the trunk and because of the stable position, contrast can be introduced at a rate approximating blood flow. The method is easily performed, with excellent results.


[The angiographic demonstration of the arterial component of large meningiomas in the cerebral cortex and medulla (author's transl)].

The arterial architecture of large meningiomas were studied in the cerebral cortex of medulla by selective arteriography of internal and external carotid arteries, or the common care in 12 patients. The findings were compared with operative observations (or in one case with the autopsy result), and were related to the histological and pathological findings. The origin of the supplying vessel was found to be significant in the differential diagnosis.


[A rare anomaly of cerebral vessels (Unilateral aplasia of the internal carotid artery, persistent hypoglossal artery) (author's transl)].

A case of unilateral aplasta of the internal carotid artery is described, and another of a persistent hypoblossal artery. The embryological basis of carotid aplasia and the diagnostic criteria of a persistent hypoglossal artery are discussed.


[An unusual cerebral arteriovenous malformation (author's transl)].

A rare, extensive arterio-venous fistula with cardiac enlargement was found in an infant. Numerous branches from the internal and external carotid artery were disposed in a stellate manner to form a large central vessel, probably corresponding to the inferior sagittal sinus. The brain was grossly abnormal. The embryology, clinical features and diagnoses are discussed.


[Atypical termination of the vertebral artery and of the inferior posterior cerebellar artery (author's transl)].

A rare varient in the termination of the vertebral artery is described associated with a low origin of an unpaired inferior posterior cerebellar artery lying between C. 1 and C. 2. This is illustrated radiographically. An attempt is made to explain this radiologically and to classify it. Possible clinical significant of this anomaly, particularly in relation to subarachnoid haemorrhage, is discussed.


[FMD-manifestation and clinical findings (author's transl)].

FMD, angiographically demonstrated as a string of beads is descripted in etiology, manifestation, clinical findings, proceeding and therapy. Nine cases under 500 unselected cerebral angiograms are reported which means 1.8% of all angiograms we have performed. Another hypothesis to etiology is given.


[Radiogenic carotid stenosis. The problem of radiation induced arterio-sclerosis (author's transl)].

Amongst late radiation damage, lesions of the cerebral arteries are relatively rare. The relationship between the radiation and arterio-sclerosis is discussed in connection with a 63-year old female patient with an atheromatous carotid stenosis; at the age of 5 years she received high dose rate radiation for cervical node tuberculosis. From animal experiments and an increasing number of human observations, it is concluded that radiation may be a predisposing and accelerating local factor in the formation of arterio-sclerosis. Amongst the recognised cases of radiogenic carotid stenosis or occlusion, the latent period averages 30 (9-57) years.


[The value of intensifier photopneumopelvigraphy in the diagnosis of gynaecological diseases (author's transl)].

The diagnostic value of gas contrast examinations of the female genital organs, using a 70 mm. intensifier technique, was evaluated in 625 examinations. Its advantages, particularly with respect to radiation dosage, as well as its disadvantages, are discussed. Photopneumopelvigraphy is recommended for routine use.


[The accuracy of placental scintigraphy (author's transl)].

The results of 150 placental  scans are reported, using 99mTc erythrocytes, 113mIn gelatine and 113mIn tranferrin. Accuracy was checked at surgery and compared with ultra sound findings. In 62% of patients, the indications for placental scintigraphy was suspicion of placenta praevia because of bleeding in late pregnancy. In 38% placental localisation was performed for amniocentesis for Rh incompatibility. Localisation of the placenta was accomplished in 98.6% by scanning and in 95% by ultra sound. Accuracy of scanning was 94% and ultra sound 70%. Placental scanning is at present the most accurate method for a placental localisation and should therefore be used when an accurate diagnosis cannot be achieved by other techniques.


[A comparison of isotope nephrographic examinations during pregnancy and hormonal contraception (author's transl)].

Renal function was investigated by isotope nephrography in 31 pregnant women with normal kidneys during various phases of pregnancy, and in 137 women on continuous contraceptive steroids (up to eight years). The semi-quantitative parameters of zum Winkel were used. It was found that the use of oral contraceptives did not lead to any change in renal function, whereas with advancing pregnancy there was distinct excretion delay on the isotope nephrogram. The results are discussed in the light of the relevant literature. Isotope nephrography appears to be a satisfactory screening test for evaluation of renal function on each side.


[Bacteriological investigations in radiological clinic (radiographic apparatus, rooms and personnel) (author's transl)].

The importance of X-ray departments as a potential source of infection with hospital organisms was investigated by examining a number of radiographic rooms and comparing these with two private dwellings. It was found that there was a higher incidence of organisms than in private homes, but this was considerably less than on wards. Particularly high numbers of organisms, including pathogenic ones, were found on radiographic apparatus which was inaccessible, and on sponge pillows. Regular disinfection reduced the number of organisms almost to the level of an operating theatre. A visit to the X-ray department does not present a significant risk of infection; nevertheless, hygiene can be markedly improved by appropriate changes in the rooms and by carrying out methods of disinfection.


[Focal liver diseases--laparoscopic aspects].

A survey of the laparoscopic findings in such important focal diseases of the liver as metastasis, tumours, cysts and abscesses is given. Among the granulomatous changes, sarcoidosis, lymphogranulomatosis, tuberculosis and reticulosis deserve special attention. Definitive differentiation is, as a rule, only possible after carrying out a histological examination. In numerous infectious diseases, small granulomatous changes can be observed in conjunction with a so-called reactive hepatitis. Industrial noxae (e.g. beryllium, asbestos, silicates, and others) can also induce granulomatosis.


[Failures and hazards of surgical laparoscopy].

During the filling up of the pneumoperitoneum the needle can be put in the wrong direction and so blood vessels , intestinum or adhesions might be punctured. According to the authors procedure the abdominal wall is grasped by one hand or an instrument. This way the umbilicus is placed in the best position for the puncture with the Verresneedle or the trocar. Pulling with the left hand vertically the direction of the needle or trocar consequently will be parallel to the vertebral column. With this procedure, lesions of intestinum or vessels are practically impossible. In more than 4000 personally performed laparoscopies the author never saw adhesions in the region of the umbilicus except in two cases of cancer patients. If the intestinum is adherent to the umbilicus, as in the case of ileus, surgical measures are necessary.


Islet transplantation in experimental diabetes of the rat. IV. The influence of transplantation site and of histocompatibility on islet function.

Experimental islet transplantations in pancreatectomized and streptozotocin-treated diabetic allogeneic and partially inbred rats are considered with respect to transplantation site and immunological factors responsible for survival. It could be shown that transplantation into the liver and into the lung in both systems (allogeneic and partially inbred) was accompanied by longer survival of the islets compared with the following regions: subcutaneous tissue, muscle, epididymal fat tissue, peritoneal cavity. This indicates that not only immunological but also factors of blood supply (oxygen consumption?)play a role in the survival of the grafts. - The success of transplantation depends mainly on histocompatibility. Partially inbred rats showed significantly longer survival of islets than non-inbred rats. The studies of other groups using similar experimental models are reviewed.


Origin of the extra chromosome no. 21 in Down's syndrome.

Eighteen of 38 examined families with children with Down's syndrome showed polymorphisms of chromosome 21 elucidating the origin of the extra chromosome 21. Maternal origin was found in 10 cases and paternal origin in 8 cases. In both sexes errors occurred both in the first and in the second meiotic division.


Maternal and paternal origin of extra chromosome in trisomy 21.

Fluorescence markers were studied in 40 patients with Down's syndrome and their parents. In 11 cases maternal and in 5 cases paternal non-disjunction could be shown. The disjunctional event occurred in the first meiotic division in 5 maternal and in 2 paternal cases. A second division failure was found in 4 maternal and 2 paternal cases. In 3 cases the failure could either be of first or second meiotic division origin.


Antigen in immune complex nephritis. V. Recovery and identification by gel precipitation.

A procedure is described for detection of antibodies and antigens in 'immune complex' nephritis. Kidney tissue is minced, washed and sealed in a well of an agarose or agar plate. Separation of immune complexes is achieved by electrophoresis at 56 degrees. Afterwards, antibody is readily detected in reaction with a proper anti-IgG serum. Antigen is identified by its corresponding antibody, the reaction with which is, in some instances, strengthened by counterimmunoelectrophoresis.


Purification of group C streptococcal extracellular antigens detected with naturally occurring human antibodies: isolation of streptokinase and two previously undescribed antigens.

Twelve antigens were detected in crude group C streptococcal extracellular concentrates, using naturally occurring antibodies in normal human gamma globulin. These group C streptococcal antigens all appeared to be present in crude group A streptococcal extracellular concentrates, although the latter contained additional antigens reactive with the human antibodies. Systematic purification procedures were established for the isolation of the group C streptococcal antigens by a sequence of salting out, hydroxylapatite chromatography, Sephadex G-100 gel filtration, and isoelectric focusing. With such procedures, three of the group C streptococcal antigens were isolated in a relatively pure state. One of the purified antigens was identified as streptokinase on the basis of its fibrinolytic potency, its reaction of identity with two purified streptokinase fractions obtained from other sources, and its high titer in immunodiffusion assays. The most highly purified streptokinase fractions, derived from the 0.1 M sodium phosphate hydroxylapatite eluate, revealed a plasmin-inhibiting effect at high concentrations of streptokinase. This was not seen in the purified streptokinase of equivalent functional and immunological purity that was derived from the 0.2 M sodium phosphate hydroxylapatite peak. Two other streptococcal antigens were also isolated to a high degree during the course of the above study. These were designated antigens X and Y and were found to be unrelated immunologically to each other or to streptokinase. Their isoelectric points were 6.7 and 8.8, respectively, and both were present in group A streptococcal concentrates. Esterase activity was found to be widely distributed in almost all of the fractions obtained in the various purification steps, indicating a high degree of heterogeneity of the streptococcal enzyme. Histochemical staining techniques applied to the immune precipitates formed with human antibodies indicated that none of the antigens detected in crude group C and group A streptococcal concentrates possessed catalase, glucuronidase, glucosaminidase, acid or alkaline phosphatase, arylsulfatase, leucineaminopeptidase, or chymotrypsin enzymatic activities.


Staphylococcal scalded-skin syndrome: development of a primary binding assay for human antibody to the exfoliative toxin.

Exfoliative toxin (ET) from a phage group II Staphylococcus aureus strain causing staphylococcal scalded-skin syndrome was purified by electrofocusing. Ampholytes and salts were removed from the final product by column chromatography on G-50 Sephadex. Sodium dodecyl sulfate-polyacrylamide gels of the final product yielded a single band upon gel electrophoresis, even when 60 mug of protein was placed in the gels. Radiolabeling of the purified toxin with 125I yielded a product that still caused exfoliation of suckling mice, indicating that the toxin was still biologically active. A radioimmunobinding assay was developed and used to test rabbit and human sera for antibodies to exfoliative toxin. Although the maximum percentage of binding was not as high as expected (approximately 40%), it was postulated that either iodination had not been sufficiently vigorous or the toxin had sustained immunological damage. The assay was reproducible and more sensitive than the existing neutralization method and readily applicable to the testing of human sera for exfoliative toxin antibodies.


Glutathione and lens epithelial function.

The relationship of the concentration of glutathione (GSH) in lens epithelium to the transport of cations in the lens was studied by decreasing the level of GSH in the epithelium and monitoring subsequent effects in the lens on the distribution of cations, the activity of Na+-K+ ATPase and the uptake and efflux of 86Rb. Oxidation of GSH in cultured rabbit lenses was accomplished by the use of 1 mM tertiary butyl hydroperoxide (TBHP), a reagent which appears to be suitable for the specific oxidation of GSH in this tissue. The concentration of GSH found in the normal lens epithelium was estimated to be 64 mum per gram wet weight or nearly six times that present in the whole lens. A decrease in the concentration of GSH in lens epithelium of 60 per cent or more leads to an increase in hydration, a shift in the distribution of Na+, K+, and Cl-, a decrease in the activity of Na+-K+ ATPase, and a decrease in the active transport, and an increase in the passive diffusion of 86Rb. In the TBHP-treated lenses there is a rapid decrease in the production of lactate, possibly as a result of the inhibition of Na+-K+ ATPase, but the effect on the level of lens ATP is delayed and less pronounced. It appears that the adverse effect on membrane permeability caused by the oxidation of GSH is partially reversed when a high level of GSH returns to the epithelium. However, the decrease in active transport of 86Rb and the inactivation of Na+-K+ ATPase are not reversed by either regeneration of GSH in the tissue or by treatment with exogenous dithiothreitol and may indicate an irreversible conformational change in the enzyme initiated by the loss of the protective effect of GSH. The data indicate that a critical level of GSH is required in the lens epithelium for the maintenance of normal cation transport.


Thymoxamine hydrochloride: effects on the facility of outflow and intraocular pressure.

Eleven subjects with normal eyes and sixteen subjects with open-angle glaucoma had a selective alpha-adrenergic blocking agent, thymoxamine hydrochloride 0.5 per cent eyedrop, applied to one of their eyes. This consistently produced miosis, but did not significantly alter the intraocular pressure or the tonographically determined facility of aqueous outflow. Because we find that thymoxamine can selectively induce miosis without significant accompanying effect on the ciliary muscle or facility of outflow, we expect that this drug may prove to be a useful diagnostic adjunct to gonioscopy in distinguishing between angle-closure glaucoma and open-angle glaucoma with narrow angle. It seems worthwhile proceeding with clinical evaluation of this possibility.


Resistance of Neisseria gonorrhoeae to antibacterial drugs in Ontario.

Observations on multiple resistance of 227 N. gonorrhoeae strains are presented in this paper. These strains were previously isolated from the urogenital area from patients who did not respond to antibacterial drug treatment. The above-mentioned strains were referred to our laboratory for confirmation and for susceptibility testing. All the N. gonorrhoeae strains showed resistance in vitro to penicillin concentrations between 0.5-2.0 i.u./mi. In addittion to penicillin resistance, 83.7% showed resistance to cephaloridine, 72.2% to kanamycin, 58.1% to spiramycin, 51.5% to erythromycin, 41.4% to sulphadiazine, 37.0% to tetracycline, 29.9% to ampicillin and 25.1% to spectinomycin.


Lysine catabolism in Rhizoctonia leguminicola and related fungi.

The catabolism of lysine was studied in several yeasts and fungi. Results with cell-free extracts of Rhizoctonia leguminicola support a proposed pathway involving (D- and L-) EPSILON-N-acetyllysine, alpha-keto-epsilon-acetamidohexanoic acid, delta-acetamidovaleric acid, and delta-aminovaleric acid in the conversion of L-lysine to shortchain organic acids. Label from radioactive L-lysine was found to accumulate in D- and L-epsilon-N-acetyllysine, delta-acetamidovaleric acid, delta-aminovaleric acid, and glutaric acid in cultures of R. leguminicola, Neurospora crassa, Saccharomyces cerevisiae, and Hansenula saturnus, suggesting that the proposed omega-acetyl pathway of lysine catabolism is generalized among yeasts and fungi. In N. crassa, as is the case in R. leguminicola, the major precursor of L-pipecolic acid was the L-isomer of lysine; 15N experiments were consistent with delta1-piperideine-2-carboxylic acid as an intermediate in the transformation.


Cyanide-resistant respiration of a Neurospora crassa membrane mutant.

Choline starvation of the Neurospora crassa chol-1 mutant leads to a decrease in respiration through the cytochrome chain and a concomitant induction of the alternate oxidase.


Siderophore protection against colicins M, B, V, and Ia in Escherichia coli.

A variety of natural and synthetic siderophores capable of supporting the growth of Escherichia coli K-12 on iron-limited media also protect strain RW193+ (tonA+ ent-) from the killing action of colicins B, V, and Ia. Protective activity falls into two categories. The first, characteristic of enterobactin protection against colicin B and ferrichrome protection against colicin M, has properties of a specific receptor competition between the siderophore and the colicin. Thus, enterobactin specifically protects against colicin B in fes- mutants (able to accumulate but unable to utilize enterobactin) as predicted by our proposal that the colicin B receptor functions in the specific binding for uptake of enterobactin (Wayne and Neilands, 1975). Similarly ferrichrome specifically protects against colicin M in SidA mutants (defective in hydroxamate siderophore utilization). The second category of protective response, characteristic of the more general siderophore inhibition of colicins B, V, and Ia, requires the availability or metabolism of siderophore iron. Thus, enterobactin protects against colicins V and Ia, but only when the colicin indicator strain is fes+, and hydroxamate siderophores inhibit colicins B, V, and Ia, but only when the colicin indicator strain is SidA+. Moreover, ferrichrome inhibits colicins B, V, and Ia, yet chromium (III) deferriferrichrome is inactive, and ferrichrome itself does not prevent adsorption of colicin Ia receptor material in vitro. Although the nonspecific protection against colicins B, V, and Ia requires iron, the availability of siderophore iron for cell growth is not sufficient to bring about protection. None of the siderophores tested protect cells against the killing action of colicin E1 or K, or against the energy poisons azide, 2, 4-dinitrophenol, and carbonylcyanide m-chlorophenylhydrazone. We suggest that nonspecific siderophore protection against colicins B, V, and Ia may be due either to an induction of membrane alterations in response to siderophore iron metabolism or to a direct interference by siderophore iron with some unknown step in colicin action subsequent to adsorption.


Effect of ammonium ions on the induction of nitrite reductase in Neurospora crassa.

Results with strain am-la, a glutamate dehydrogenaseless mutant, showed that ammonium ions must first be metabolized in order to repress nitrite reductase in Neurospora.


Biochemical and genetic studies on galactosamine metabolism in Neurospora crassa.

In Neurospora, galactosamine can be released from the cell wall and from an alcohol-soluble compound by acid hydrolysis. All of the detectable alcohol-soluble galactosamine was present as uridine diphospho-2-acetamido-2-deoxy-D-galactose (UDPGalNAc). The results of pulse-labeling studies and enzymatic assays indicated that UDPGalNAc was synthesized via the epimerization of uridine diphospho-2-acetamido-2-de+xy-D-glucose (UDPGlcNAc). A single-gene morphological mutant, doily (do), which grew at less than 4% the rate of the wild-type strain, had 3% of the wild-type UDPGalNAc content and 0.5% of the wild-type level of cell wall galactosamine but normal levels of UDPGlcNAc and cell wall glucosamine. Cell extracts of the doily cultures containing only 20% of the specific activity of UDPGlcNAc-4-epimerase found in the extracts of wild-type cultures. Two types of faster-growing partial revertants of the doily strain were isolated. One type had an intermediate level of both alcohol-soluble and cell wall galactosamine. A second type had an intermediate level of alcohol-soluble galactosamine but low levels of cell wass galactosamine. Genetic analyses indicated that the reverse mutations had occurred at the do  locus in both types. This finding that cell wall glucosamine synthesis and growth rate can be separated genetically indicates that mutations at the do lucus lead to pleiotropic effects.


Mechanisms of siderophore iron transport in enteric bacteria.

Uptake of 55Fe- and 3H-labeled siderophores and their chronic analogues have been studied in Salmonella typhimurium LT-2 and Escherichia coli K-12. In S. typhimurium LT-2, at least two different mechanisms for siderophore iron transport may be operative. Uptake of 55Fe- and 3H-labeled ferrichrome and kinetically inert lambda-cis-chromic [3H]deferriferrichrome by the S. typhimurium LT-2 enb7 mutant, which is defective in the production of its native siderophore, enterobactin, appears to occur by two concurrent mechanisms. The first mechanism is postulated to involve either rapid uptake of iron released from the ferric complex by cellular reduction without penetration of the complex or ligand or dissociation of the complex and simultaneous uptake of both ligand and iron coupled with simultaneous expulsion of the ligand. The second mechanism appears to consist of slower uptake of the intact ferric complex.


Transient state kinetic effects of calcium ion on sarcoplasmic reticulum adenosine triphosphatase.

A rapid mixing technique was used to investigate the effects of Ca2+ ion on the kinetics of ATP hydrolysis by sarcoplasmic reticulum vesicles. "Basic" ATPase measured in the absence of Ca2+ showed an initial burst of inorganic phosphate production. Similarities in the transient state kinetic properties of basic and "extra" or Ca2+-dependent ATPase suggest that the two activities represent a single enzyme species. At low concentrations of Ca2+ (less than 10(-6) M) the time course of the partial reactions of extra ATPase appeared to fit a simple scheme in which the acid-stable, phosphorylated enzyme (E approximately P) breaks down directly to inorganic phosphate and free enzyme. A similar mechanism seemed to apply to moderate levels of ATP and high external concentrations of Ca2+ known to inhibit transport activity. In the intermediate range of Ca2+ concentrations inorganic phosphate production was resolved into two phases consisting of a fast initial rate (burst) and slow steady state. Acid-stable phosphorylated protein showed a transient decay which coincided with the appearance of the burst. This behavior is consistent with a scheme in which E approximately P breaks down to an acid-labile or noncovalent intermediate state (E-P). A slow secondary increase in phosphorylation followed the transient decay in E approximately P. This late phase of protein labeling was eliminated following pretreatment with Triton X-100, sodium oxalate, or diethyl ether which decrease or prevent the formation of a transport gradient. An analysis of the dependence of the steady state level of phosphorylation and rate of inorganic phosphate production on Ca2+ concentration indicated that the phosphorylation mechanism involves interaction of two Ca2+ ions with the enzymatic carrier. The pathway by which E approximately P breaks down, i.e. whether it goes to E + Pi or E-P, may depend on the extent to which these sites are occupied by Ca2+. The transport of Ca2+ is discussed in terms of a flip-flop mechanism in which E approximately P and E-P represent high and low affinity Ca2+ binding states occurring in separate halves of an enzyme dimer.


Purification and physiological role of a peptide stabilizing factor of rat liver phosphofructokinase.

A substance has been purified to apparent homogeneity from rat liver which, as previously reported (Dunaway, G. A., Jr., and Segal, H. L. (1974) Biochem. Biophys. Res. Commun. 56, 689-696), specifically stabilizes the major liver isozyme of phosphofructokinase (PFK-L2) against thermal inactivation and whose level in vivo changes in parallel with and in precedence to that of the enzyme. Molecular weight determinations gave values around 3,500. Evidence for the peptide nature of the factor includes its correspondence with ninhydrin-positive material on gel filtration and paper electrophoresis and its susceptibility to pronase. Electrophoretic behavior indicated at least one free amino group and several carboxyl groups. Amino acid analysis of the peptide yielded only glutamate, glycine, and half-cystine, in equimolar amounts. However, neither GSH nor GSSG have PFK-L2-stabilizing activity. No free sulfhydryl groups were present. Chemical analysis for tryptophan was also negative. The ultraviolet spectrum confirmed the absence of aromatic amino acids. The spectrum exhibited a characteristic peptide peak at 190 nm with no absorbance beyond 240 nm. The factor is unstable to storage in the cold except in the presence of glucose or dithiothreitol. Sucrose, fructose, and GSH were ineffective in this regard. It was slowly denatured by heat or reduced pH even in the presence of glucose. The factor was induced in fasted animals specifically by glucose, of the nutrients tested, and in diabetic animals by insulin. Induction by both glucose and insulin was blocked by cycloheximide and actinomycin. The time course of the glucose induction was the more rapid of the two with a marked overshoot to 3 times normal levels at 12 hours. Increased levels of the factor preceded the increased levels of PFK-L2 brought about by glucose or insulin administration. Native PFK-L2 was inactivated by lysosomal extracts, and this inactivation was strongly inhibited by the peptide factor. These results are in accord with the proposal that the peptide plays a role in regulating PFK-L2 turnover in vivo. The factor also activated the phosphofructokinase-catalyzed reaction by promoting fructose-6-P binding. This effect is analogous to that of AMP on the kinetics of the reaction; however, the factor effect was additive to that of AMP, and the factor did not reverse inhibition by excess ATP as does AMP. We postulate that the stabilizing factor affects an equilibrium between PFK-L2 conformers in favor of one more resistant to lysosomal and thermal inactivation and with greater affinity for fructose-6-P.


ATPase activity required for termination of transcription by the Escherichia coli protein factor rho.

The relationship between the RNA-dependent beta-gamma ATPase in purified rho preparations and rho-mediated termination of transcription has been investigated. In a purified in vitro system, transcription from lambdagal DNA has been carried out using either ribonucleoside triphosphates (NTPs) or four ribonucleoside 5'-(beta-gamma-imino)triphosphates (NMP-P(NH)Ps) as RNA precursors. In the presence of NTPs, rho termination activity results in (a) the synthesis of rho-dependent transcripts which are of discrete size by polyacrylamide gel analysis and (b) a marked reduction by hybridization assay in RNA transcribed distal to the rho-sensitive termination site tR. In the presence of four NMP-P(NH)Ps, which are not substrates for the beta-gamma ATPase, termination by rho is completely abolished, whereas rho-independent termination occurs normally. Addition of ATP to transcription reactions containing four NMP-P(NH)Ps restores termination, ruling out the possibility that the termination activity of rho is nonspecifically inhibited by the analog preparations. We interpret our data as strongly suggesting that the RNA-dependent beta-gamma ATPase activity of rho is required for rho-mediated termination of transcription.


Potentiation of glucagon secretion by serotonin antagonists in man.

To study the possible implication of endogenous serotonin in the control of glucagon secretion in man, normal volunteers were subjected to alpha-cell stimulation before and after oral treatment with serotonin antagonists (cyproheptadine and methysergide) and with an inhibitor of serotonin synthesis (para-chlorophenylalanine, PCPA). After administration of cyproheptadine (16 mg daily, for two days) the glucagon responses to arginine (N=12) and to insulin-induced hypoglycemia (N=9) were more marked than in the control experiments (differences between maximal elevations: +165 pg/ml, P less than 0.0001, and +197 pg/ml, P less than 0.02, respectively). After methysergide treatment (9 mg daily, for two days), a potentiation of arginine-provoked glucagon secretion was also observed (+260 pg/ml, P less than 0.002; N=7). Similarly, after PCPA administration (2 g daily, for four days) the alpha-cell responsiveness to both aminogenic (N=12) and hypoglycemic (N=7) stimuli was enhanced (+108 pg/ml, P less than 0.05, and +164 pg/ml, P less than 0.05, respectively). Since glucagon secretion is potentiated by treatment with drugs which either antagonize serotonin action or inhibit its synthesis, the suggestion can be made that endogenous serotonin modulates alpha-cell function in man by acting as an inhibitor.


7beta,17alpha-Dimethyltestosterone (calusterone)-induced changes in the metabolism, production rate, and excretion of estrogens in women with breast cancer: a possible mechanism of action.

The metabolism of estradiol, its production rate and the urinary excretion rate of its metabolites were studied in 5 women patients with breast cancer, 2 of whom were postmenopausal and 3 were ovariectomized, both before and after a period of 7beta,17alpha-dimethyltestosterone (calusterone) therapy. In all cases calusterone caused a profound decrease in the transformation to estriol and an increase in the formation of estrone and 2-hydroxyestrone. The production rate of estrogens was diminished by calusterone in the three overiectomized patients but not in the postmenopausal subjects. The possible participation of the above changes in the chemotherapeutic action of calusterone is discussed.


Familial true hermaphorodism in three siblings: plasma hormonal profile and in vitro steroid biosynthesis in gonadal structures.

The in vitro biosynthesis of estrogens and androgens by gonadal tissues of the ovotestes was studied in three siblings with familial true hermaphrodism and correlated with daily steroid and gonadotropin plasma levels. The probands were 15, 13, and 11 years old with normal male phenotype and external genitalia, grade III hypospadias, bilateral scrotal ovotestes, gynecomastia, and no uterus or fallopian tubes. Their karyotypes were 46XX both in peripheral lymphocytes and in gonadal fibroblasts, and no Y chromosome fluorescence was observed. A fusiform biopsy of each gonad was obtained, and the testicular and ovarian structures were excised and incubated for five days at 37 C with 3.8 muCi of 7alpha3H dehydroepiandrosterone, in Eagle's growth media, 95% O2 and 5% CO2. After standard procedures, four extractions with methylene chloride were performed, and the residue was assayed using Sephadex LH no. 20 chromatography. Testosterone (T), delta4androstenedione (delta 4), 5alphadehydrotestosterone (5alphaDHT), estrone (E1), estradiol-17 beta (E2) and estriol (E3) were measured. Also, during 16 consecutive days daily venous samples were obtained, and FSH, LH, E2, progesterone (P), and testosterone (T) were determined. The predominant steroids formed in vitro were estrogens, mainly E1 by either the testicular or ovarian structures. In the 11-year-old subject, the ovotestes were less active than in his oldest siblings. The patterns of androgen production showed that T was the principal androgen formed, followed by delta4 and minimal amounts of 5alphaDHT. The daily plasma hormonal profile resembled more closely a female pattern, specially in the 15 and 13-year-old patients. It is suggested that the ovotestes of these siblings had the enzymatic mechanisms necessary for estrogen and androgen biosynthesis, mainly E1 and T using a preferential metabolic pathway via androstenedione. Furthermore, it seems that the testicular structures had a greater capability to synthesize estrogens than the ovary.


The use of the Minnesota Multiphasic Personality Inventory with low back pain patients.

The MMPI was administered to 36 male low back pain patients at the Seattle Veterans Administration Hospital. The patients were divided into three groups of 12 each. The organic group contained patients who had an organic basis for their pain. The functional group contained patients who had no organic basis for their pain. The mixed group contained patients who had some organic basis for their pain, but one that was thought to be insufficient to account for the pain they were reporting. The mixed and functional groups differed significantly from the organic group on the Hs, Hy, Pt, Sc, Hy-O, D-O, and DOR scales. The mixed and functional groups differ significantly from each other only on the Hy-O scale. The special low back pain scales of Lb and DOR were found to have little utility when used separately. When used in conjunction, however, the scales discriminated correctly 75% of the time.


Asthma: comparative bronchodilator effects of ipratropium bromide and isoproterenol.

The effect of ipratropium bromide administered at two dosage levels, 40 and 80 mug, isoproterenol, 150 mug, and placebo using a metered dose inhaler was evaluated in ten adult patients with asthma in a double-blind, crossover study. The new atropine-like drug proved to be as effective a bronchodilator as isoproterenol in this study, although it had a later peak effect. Ipratropium bromide had a longer course of action than isoproterenol (4 hours compared to 1-2 hours) and was free of significant side effects. The larger dose of the new drug produced a slightly greater and longer-acting effect than the smaller dose. Ipratropium bromide seems to have had bronchodilator effects on both large and small airways.


Surgical methods in the treatment of rhinophyma.

Fifteen patients with rhinophyma were treated surgically by cutting off the hyperplasia nodules with a scalpel followed by shaving with a disposable shaving razor. The cosmetic results were good and no scar formation occurred.


Common plantar hyperkeratoses.

In general, metatarsal bars have provided a simple method of relieving pain and disability caused by plantar hyperkeratoses over metatarsal heads. By spanning the longitudinal arch, the bars effectively relieve pressure from the middle three metatarsal heads and elevate the distal portion of the metatarsal bones. This often results in favorable repositioning of displaced proximal phalanges and eliminates direct pressure exerted by metatarsal heads. Also, by giving more uniform support to the foot, metatarsal bars rearrange the weight-bearing surface in a more even way, which favors resolution of hyperkeratoses by removal of pressure points. The prescription for metatarsal bars must be written for both shoes. Dual bars provide balanced walking surfaces and do not induce asymmetric motion of the lower spine as a single bar would. They can be applied to moderately high-heeled shoes for women and regular oxfords for men. The leading edge of the bar must be properly skived and tapered to provide an even surface with the forward part of the soles of the shoes. If this is not done properly, the bars may strike against uneven surfaces as the foot slides forward in walking or running. The patient should return to the prescribing physician in two or three weeks after the bars have been worn constantly. By analyzing the scuffed surfaces of the metatarsal bars, the physician can determine whether or not the bars are firm and thick enough and in the proper position to relieve and divert pressure from the metatarsal heads. Perhaps two pair of shoes should be thus altered to provide a change of foot gear for ordinary purposes. Unaltered dress shoes may be worn for short periods of time as party or formal occasions demand. Eventually, when the painful processes have subsided, the patient may resume wearing ordinary shoes and use the modified shoes if symptoms recur from time to time.