Dietary management of the pregnant diabetic.

The tendency of the pregnant diabetic to fasting ketosis limits the extent to which calorie restriction (particularly negative calorie balance) can be used in the treatment of the obese, adult-onset, pregnant diabetic. In addition, the vagaries of measuring excess weight gain and detecting extraneous sources of weight gain in diabetic pregnancy, and the difficulty of accurately enforcing a caloric prescription without forcing the subject to weigh her food, make the determination of an accurate degree of caloric limitation difficult at best. A greater reliance on the mother's appetite center may be more accurate and rewarding in most instances than any devices available to the clinician. Important considerations in the diet of the pregnant diabetic are adequate protein, minerals, and vitamins, an amount of carbohydrate that is constant from day to day but not necessarily restricted, carbohydrate intake in an unrefined form that maximizes the intake of associated fiber, and a reproducible meal and snack schedule which complements in insulin regimen. Insulin must remain the primary therapeutic tool if the effects of maternal diabetes on fetal morbidity and mortality are to be minimized.


[Anastomosis prolapse of the gastric mucosa].

X-rays of 91 patients who underwent gastric surgery between 1973 and 1977 were retrospectively evaluated. We found 16 large mucosal prolapses through the gastroduodenal anastomosis and another six with a so-called anastomosis bulge. Of these patients, 77% presented complaints in relation to delayed gastric emptying. When analyzing the prolapse frequency, patient age at the time of surgery, type of surgery, and suture technique, we found that mucosal prolapse occurred mostly in older patients with an extensive gastric resection after oralis-partialis anastomosis and after employing the two-layered suture technique.


[Boeck's disease with spinal involvement and retroperitoneal fibrosis].

Sarcoidosis (Morbus Boeck) is a frequently found disease of the reticulohistiocytic system. Etiology and pathogenesis were mostly unknown until today. Histologic study of sarcoidosis shown granuloma with epitheloid cells similar to tuberculosis, often with hyalinization but without cheesy necrosis. The disease mostly starts with a mediastinal and cervical lymphadenopathy. Radiographically, the disease shows three typical stages when spreading to the lungs. Bone involvement in lymphomas, especially vertebral involvement, is found to be rare. A case with an additional retroperitoneal fibrosis is reported from our own hospital.


The bactericidal activity of sera of healthy neonates and newborns with hyperbilirubinaemia to E. coli.

Cord and newborn sera were found to possess a significantly decreased in vitro bactericidal activity to E. coli as compared to sera of adults. Hyperbilirubinaemia in neonataes suffering from both Rh and ABO incompatibility results in a further significant impairment of bactericidal activity of their sera in comparison to healthy newborn infants. Exchange transfusion considerably improved this serum antibacterial activity. The possible mechanism of toxic action of unconjugated bilirubin on the cells of the immune system is discussed.


Cartilage and osteoarthrosis: changes of collagen and proteoglycans.

The authors discuss changes of proteoglycans and collagen in osteoarthrotic cartilage, based on their own results. During osteoarthrosis the proteoglycan molecule diminishes in size, mainly due to a diminution of the carbohydrate portion. The diminution of binding glycoprotein leads to changes in the interaction with hyaluronic acid. Collagen is more soluble and has a reduced resistance to proteolytic enzymes. In the osteoarthrotic cartilage also collagen type I and III is present.


[Aanalysis of nursing in Latin America].

The article presents a comprehensive analysis of health and nursing practices and their relationship to the economic structure and dominant means of production in Latin America. The analysis stems from a division of economic history into the following periods: 1900 to 1930, 1930 to 1960, and from the end of 1960 to present. The writer examines the characteristics of economic and social development in each of those periods and correlates them with health and nursing practices. She delves particularly into the predominant forms of nursing practice and the various approaches to training for auxiliary, technical, and professional staff. She seeks to show that both practice and knowledge in the field of health and nursing are related to the process of economic production. She suggests that recognition of this fact would contribute to a better understanding of the problems confronting the health and education sectors and would permit a search for more realistic solutions to the problems.


[Social security nursing in Costa RICA].

This article reviews the development of social security in Costa Rica throughout the various stages of its growth starting in 1941, with special reference to the scope of the health and maternity insurance system and to disability, old-age, and life insurance. After describing the institutional setting of the social security system, the authors analyze the changes that have taken place in the training and performance of duties of nursing staff in the health services, all of which are now part of the Costa Rican Social Security Fund. Lastly, they present the two-year curriculum for training the graduate nurse, and refer to the practice of nursing in the social security system and to the duties performed by the nurse in health education, the actual care of the well and the sick, administration, and research.


[Development of nursing education in Boliva].

The authors analyze the various stages in the evolution of nursing education in Bolivia. The article begins with 1938, when the first Nursing School was established in the country, and ends at the present time. It emphasizes the series of national and institutional events leading up to the current curricula for the professional nursing and nursing auxiliary programs, which give special attention to the training of personnel to serve under programs of primary health care with community participation.


[Community health as a determinant of the nursing curriculum].

This paper summarizes the experience acquired under the first university-level program for the basic training of nurses in Peru. It describes the gradual refining of the academic curriculum, which was designed not only to train people as competent professionals, but also to acquaint them with the country's basic social problems. Four levels of teaching-learning were defined in wide-ranging discussions in which various academic and professional sectors connected with the health field participated. Establishing a process of steps of increasing complexity has considerably facilitated the integration of community health, the scientific method, and mental health into the structure of the curriculum. The practice of community nursing was heavily emphasized, and it was endeavored to strike a balance between hospital experience and work in communities themselves. The program includes specific studies community groups spanning such aspects as control of the more common disease, epidemiologic surveillance, and accident and disaster prevention. Practical work in community health care earns the same credit as hospital internship. The paper closes with a description of the experience of a specific program conducted in the self-managed city of Villa El Salvador under an agreement between the community and the university. The writer also notes that the intense campaign to publicize the program is having an effect because most nurse-training institutions in Peru are tending to add community nursing to their curricula.


[Liability claims for prosthetic treatment].

Liability claims of 153 patients receiving prosthetic treatment were organized according to damage and were discussed on the basis of the known decisions and judgements of the courts.


[Does traumatic occlusion change the jaw relations?].

Jaw relations were established via squashbites, and the deviations from habitual intercuspidation were measured. The evaluation of 252 squashbites indicated that 1. The mandible deviated as a result of the squashbite. The deviations are not related to the side and almost always lead to an increase in vertical jaw relations. 2. Primarily lateral deviations of the mandible are observed with unilateral squashbites. 3. Simultaneous bilateral squashbites, on the other hand, lead to left as well as right lateral deviation of the mandible. 4. The absolute values of the deviations in the sagittal direction are lowest in the middle; those directed ventrally are slightly more predominant. 5. Compared with materials containing siloxane, squashbites with plaster casts revealed no significant alterations in the qualitative deviations. 6. In terms of direction and extent, deviations of the mandible (primarily sagittal) depend on occlusal factors.


[Compressibility of the tegumentum of the frontal maxillary crest with reference to the extent of model etchings].

Using a measuring technique developed by the authors, the compressibility of the tegmental ridge in the region of the center incisors was acertained. The indentation depth was determined at which blood circulation was disturbed and total anemia and/or pain was produced. Based on the measurements obtained, recommendations were made for the admissible and/or inadmissible extent of model etchings for the reception of bridge components.


[Comparative measurements of standard drills and turbines].

Standard electric micromotors as well as accessory handpieces and right-angle handpieces were subjected to technical tests. Turbines with and without traction power (bearing power) were also studied. The rotational speed could be regulated on one turbine. Normal to high rotational speeds were obtained with electric micromotors when used in conjunction with the transferance attachment. The motors functioned well in terms of the linearity of rotational speed. The study of the rotational speed, regulation of rotational speed, and traction power of the turbines showed that the rotational speed and the possibility of so-called contact grinding of the turbine is equal to that of micromotors. In terms of grinding trauma to the pulp and gingiva, the indications shifted in favor of the turbine.


[Plastic bonding material as the origin of mucosal disorders].

A case reported in which the patient complained of sensations in the musoca over a period of one year. Various other specialists were consulted, but the cause of these sensations could not be established. When the plastic facing on the upper anterior crowns was removed, the sensations disappeared. A metal-ceramic bridge was inserted, and the patient was fitted with a removable dental prosthesis containing teeth made of mineral substance and a base of injection moulding (Copodon). The patient is still free of complaints.


[Denture stomatitis: results of a follow-up study].

Elimination of mechanical and traumatic factors, consistent oral hygiene, and local antimycotic therapy led to rapid healing of the inflammatory alterations in most cases of stomatitis prothetica. Long-time observations showed a high frequency of recurrence; the way in which the prosthesis was worn was apparently a major contributing factor. These alterations often appeared as spotty or flat inflammatory red patches (i.e. denture stomatitis) and were sometimes combined with inflammatory granular or papillary hyperplasia and angular cheilitis. The associated subjective symptoms were slight or entirely absent.


Changes of serum insulin level in lethally irradiated rats.

The levels of serum immunoreactive insulin and blood glucose were measured at 1, 6, 24, 48 and 72 h after the exposure to irradiation (387 mC kg-1 (1500 R) x-rays in male Wistar rats weighing about 200 g and fasted overnight before the irradiation. At 6 h a significant decrease of serum insulin was found which was parallel in both irradiated animals and sham-irradiated controls. This was presumably due to the handling during the irradiation procedure. At later time intervals, the level of insulin in irradiated animals appeared to be relatively stable, while that in controls was significantly increased at 24 h and later showed a steep decline resulting in a significantly decreased level at 72 h. The level of blood glucose was significantly increased in irradiated animals at 6, 24 and 48 h, the average increase at 72 h being about 300 per cent of the level in controls.


Technique for study of hypothalamus (-) pituitary (-) testis function in vitro.

An in vitro system consisting of the rat hypothalamic tissue, the collagenase-digested isolated anterior pituitary cells and the Leydig cells, has been employed, where the testosterone production of the incubated Leydig cells was measured as the end point. The method appeared to be highly sensitive and specific in studying the functional interrelations of hypothalamus-pituitary-testis system. The sensitivity of the Leydig cells to hCG was 0.1--1.0 mU per 10(6) cells, and that of the anterior pituitary cells to LHRH responding with LH release was in the range of 0.1--1.0 ng per 10(6) cells. Two hypothalamic blocks can release a sufficient amount of LHRH to produce LH secretion in the pituitary cell preparation. The described technique seems to be a suitable in vitro approach for measuring the functional activity of the system studied and for evaluation of the sites of response to various external agents.


Prolonged pseudoaldosteronism induced by glycyrrhizin.

We describe the natural recovery from the aggravated hypertension, hypokalemia and suppression of the renin-aldosterone axis after the glycyrrhizin discontinuation in two mild hypertensive women aged 71 and 68 years, who had been administered 273 to 546 mg glycyrrhizin daily for 1.5 and 6 months, respectively, for the treatment of liver disease. About one month after the glycyrrhizin discontinuation, acceleration of hypertension, hypokalemia and suppression of the renin-aldosterone system still continued in both patients. At this stage, sodium restriction resulted in the normalization of blood pressure with weight loss and the subsequent sodium repletion produced a rapid increase in blood pressure to hypertensive levels observed before sodium restriction, with weight gain. Plasma renin activity and plasma aldosterone were low and did not respond to sodium restriction. Inappropriately excessive amounts of potassium were also excreted in the presence of hypokalemia. About one and a half months later, the improvements of aggravated hypertension, hypokalemia and suppressed renin-aldosterone system gradually occurred in both patients. Sodium restriction performed about three months later in case 2 no longer produced the changes in blood pressure and body weight. Plasma renin activity and plasma aldosterone responded subnormally to sodium restriction. These results demonstrate that both patients had a prolongation of the syndrome resembling primary aldosteronism except the low plasma aldosterone level about one month after the glycyrrhizin discontinuation. The possible mechanisms by which this prolongation was caused are discussed.


Effect of somatostatin on glucose-induced 45Ca uptake in the pancreatic islets.

This study was designed in an attempt to elucidate a mechanism of somatostatin inhibition of glucose-induced Ca+ uptake by rat pancreatic islets. Rat pancreatic islets were perifused with Krebs-Ringer bicarbonate (KRB) buffer containing 16.7 mM of glucose with somatostatin (2 micrograms/ml) or/and diltiazem HCl (2 x 10(-5) M). Somatostatin inhibited preferentially the early phase of glucose-induced insulin release, whereas diltiazem HCl inhibited the late one. And the concomitant presence of the submaximal concentration of somatostatin (2 micrograms/ml) and diltiazem HCl (2 x 10(-5 M) provided the completely additive inhibition of glucose-induced insulin release. Rat pancreatic islets were incubated with KRB buffer supplemented with 16.7 mM of glucose and 45CaCl2 (10 muCi/ml) for 5--60 min and the biphasic 45Ca uptake by pancreatic islets was obtained. Somatostatin (500 ng/ml-4 micrograms/ml) gave the suppressive effect on the early phase of glucose-induced 45Ca uptake, but the higher concentration (2 micrograms/ml) of somatostatin did not impair the late phase of 45Ca uptake by pancreatic islets. On the other hand, diltiazem HCl did suppress the late phase of glucose-induced 45Ca uptake dose-dependently, but did not suppress the early phase (2 x 10(-5) M). These data indicate that somatostatin suppresses the early phase of glucose-induced Ca2+ uptake preferentially to the late one and has a different action mechanism from Ca antagonist on glucose-induced insulin release.


Effects of an angiotensin II antagonist; [sarcosine 1, isoleucine 8] angiotensin II, on blood pressure, plasma renin activity and plasma aldosterone concentration in hypertensive and normotensive subjects taking oral contraceptives.

To examine the involvement of renin-angiotensin-aldosterone system in the etiology of oral contraceptive induced hypertension, normal women (Group I), normotensive (Group II) and hypertensive (Group III) women taking Ovulen (R) were infused with a competitive angiotensin II (AII) antagonist, [1-sarcosine, 8-isoleucine] angiotensin II. The angiotensin II antagonist was infused at a rate of 600 ng/kg/min for 30 min 1.5 hrs after intravenous injection of 40 mg of furosemide. Blood pressure was monitored and pre-infusion and post-infusion plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Pre-infusion PRA and PAC showed no significant differences among these three groups. In response to the AII antagonist infusion blood pressure rose in Groups I and II, but blood pressure responses in Group III were variable. Four out of the total 6 subjects had pressor responses and only one subject had a significant blood pressure reduction. In both Groups I and II, PRA decreased and PAC rose after infusion of the antagonist. In Group III, PRA decreased to a lesser degree and PAC showed no consistent change. These data suggest that the renin-angiotensin-aldosterone system in hypertensive women or oral contraceptives is different from that of the normotensive users. However, the pathophysiology of oral contraceptive induced hypertension is not homogenous and angiotensinogenic hypertension is uncommon.


Antimicrosomal antibodies, gastric parietal cell antibodies and antinuclear factors in insulin dependent diabetes mellitus.

Thyroid antimicrosomal antibodies, gastric parietal cell antibodies (PCA) and antinuclear factors were studied in 208 insulin dependent diabetic (IDD) according to the duration of diabetes and patient's age at the time of testing. Antimicrosomal antibodies were found in 11 out of 47 (23.4%) IDD with the duration of less than one year, however this value declined to 13.1% at 1 to 3 years, 15.3% at 4 to 5 years, 10.8% at 6 to 10 years and 5.8% at more than 10 years. Of the 47 IDD, 7 (14.8%) were positive for gastric parietal cell antibodies. The prevalence of PCA declined with increasing duration of diabetes. However, this decrease in the prevalence of antimicrosomal antibodies and PCA was not so extreme as that of pancreatic islet cell antibodies. Antinuclear factors did not reveal a significant correlation with the duration of diabetes. In normal controls, the prevalence of antimicrosomal antibodies, PCA and the antinuclear factors increased progressively with age. In IDD, the prevalence of the antinuclear factors was also progressively greater with age. However, the prevalence of antimicrosomal antibodies in IDD decreased with age and those of PCA showed the lowest percent in the 40-69 year-age group.


Uncoupling action of amytal in membrane vesicles from Escherichia coli.

The barbiturate amytal (5-ethyl-5-isopentylbarbituric acid) has been shown to inhibit amino acid transport in membrane vesicles from anaerobically grown Escherichia coli. Amytal has no effect on the activity of the enzymes of the nitrate respiration system, nor on electron transfer in this system. However, addition of amytal to the membrane vesicles results in a decrease of the membrane potential from -90 mV to -72 mV, and to a decrease of the pH-gradient of -61 mV to undetectable values. Furthermore, amytal causes an increase in the rate of ferricyanide reduction in liposomes, indicating that amytal increases the proton permeability of phospholipid membranes. These results demonstrate that amytal acts as an uncoupler in membrane vesicles from anaerobically grown E. coli.


Isolation and characterisation of peptide hydrolases from the maize root.

The maize root has two main proteinase and carboxypeptidase components. Proteinase I and carboxypeptidase I, which predominate in older plants, appear to have a serine group at their active sites and have been estimated to have molecular weights of approximately 54000 and 77000 respectively. Proteinase I, which has been purified up to 500-fold, degrades haemoglobin and azocasein with maximum activity at pH 4 and 9--10 respectively, while on maize root protein it gives most hydrolysis in the neutral pH range. The main portion of the nitrate-reductase-inactivating activity in the maize root extract is due to proteinase I. Carboxypeptidase I, like several other plant carboxypeptidases such as carboxypeptidase C which have now (IUB Recommendations 1978) been classified as serine carboxypeptidases (EC 3.4.16.1), has maximum activity around pH 5 and has esterase activity. A second group of proteases, proteinase II and carboxypeptidase II, separated from the above on carboxymethyl-cellulose, were shown to have different molecular weight properties and be equally sensitive to serine and thiol group inhibitors. Proteinase II degrades haemoglobin, but not azocasein and does not mediate nitrate reductase inactivation. Associated with this second group of proteases was a macromolecular component which inactivated nitrate reductase but, unlike the action of proteinase I, was not inhibited by phenylmethylsulphonyl fluoride or casein. It was inhibited by metal chelating agents which were without effect on nitrate reductase inactivation due to proteinase I.


On the structure of the teichoic acid from the cell wall of Streptomyces antibioticus 39. Localization of the phosphodiester linkages and elucidation of the monomeric units structure by means of 13C-nuclear-magnetic-resonance spectroscopy.

The cell walls of Streptomyces antibioticus 39 contain a glycosylated poly(glycerol phosphate), in which the repeating monomeric unit is O-alpha-D-galactopyranosyl-(1--3)-O-2-acetamido-2-deoxy-beta-D-galactopyranosyl-(1--1)-glycerol monophosphate. The localization of the phosphodiester linkages between hydroxyl groups at positions 2 and 3 of the adjacent glycerol residues and the structure of the glycoside were established by 13C nuclear-magnetic-resonance spectroscopy. The spectral data are also in accordance with the results of the methylation analysis and enzyme degradation of the glycoside.


A method for the estimation of esterase synthesis and degradation and its application to evaluate the influence of insulin and glucagon.

The irreversible reaction between liver esterases and the active-site-directed inhibitor bis(4-nitrophenyl)phosphate can be used in vivo both for the estimation of the esterase contents and for the measurement of the esterase degradation rates. A method based on this reaction is described which allows the simultaneous estimation of the rate constants of degradation and synthesis of esterases during a period of change in protein concentration. Rat liver was found to contain about 1 mg of organophosphate-binding esterases per g of fresh tissue while the microsomal fraction contains about 30 mg of esterases per g of microsomal protein. Esterase degradation and de novo synthesis were shown to remain in equilibrium for a period of at least five days following the injection of 10 mg bis(4-nitro-[14C]phenyl)phosphate per kg. The decrease of the relative amount of labeled esterases with time was found to follow first-order kinetics yielding an average esterase degrading constant of 0.0165 h-1 which corresponds to a half-life of 42 h. These data were confirmed by an independent experiment using one of the standard procedures for the estimation of degradation rates: [14C]leucine was incorporated and one of the esterases was subsequently isolated by immuno-precipitation. Using isoelectric focussing and dodecyl sulfate electrophoretic methods, the various esterase isoenzymes appeared to have very similar, if not identical turnover rates. This method for the estimation of the turnover characteristics was applied to evaluate hormone effects on liver esterases. The time course of the contents and the turnover of liver esterases was measured under the influence of glucagon treatment in diabetic rats and under the influence of high doses of insulin. The esterase content decreased faster than the average content of microsomal protein under the influence of glucagon. The reverse effect was observed with insulin-treated rats. Both insulin and glucagon apparently reduced the intracellular esterase turnover in rat liver. Kinetic analysis of the results revealed that insulin mainly lowered the esterase degradation rate, though the rate of esterase synthesis might also have been restricted. In the glucagon-treated rats the de novo synthesis of esterases was strongly reduced.


The 5-S RNA binding protein from yeast (Saccharomyces cerevisiae) ribosomes. Evolution of the eukaryotic 5-S RNA binding protein.

The ribonucleoprotein complex between 5-S RNA and its binding protein (5-S RNA . protein complex) of yeast ribosomes was released from 60-S subunits with 25 mM EDTA and the protein component was purified by chromatography on DEAE-cellulose. This protein, designated YL3 (Mr = 36000 on dodecylsulfate gels), was relatively insoluble in neutral solutions (pH 4--9) and migrated as one of four acidic 60-S subunit proteins when analyzed by the Kaltschmidt and Wittman two-dimensional gel system. Amino acid analyses indicated lower amounts of lysine and arginine than most ribosomal proteins. Sequence homology was observed in the N terminus of YL3, and two prokaryotic 5-S RNA binding proteins, EL18 from Escherichia coli and HL13 from Halobacterium cutirubrum: Ala1-Phe2-Gln3-Lys4-Asp5-Ala6-Lys7-Ser8-Ser9-Ala10-Tyr11-Ser12-Ser13-Arg14-Phe15-Gln16-Tyr17-Pro18-Phe19-Arg20-Arg21-Arg22-Arg23-Glu24-Gly25-Lys26-Thr27-Asp28-Tyr29-Tyr35; of particular interest was homology in the cluster of basic residues (18--23). Since the protein contained one methionine residue it could be split into two fragments, CN1 (Mr = 24700) and CN2 (Mr = 11300) by CNBr treatment; the larger fragment originated from the N terminus. The N-terminal amino acid sequence of CN2 shared a limited sequence homology with an internal portion of a second 5-S RNA binding protein from E. coli, EL5, and, based also on the molecular weights of the proteins and studies on the protein binding sites in 5-S RNAs, a model for the evolution of the eukaryotic 5-S RNA binding protein is suggested in which a fusion of the prokaryotic sequences may have occurred. Unlike the native 5-S RNA . protein complex, a variety of RNAs interacted with the smaller CN2 fragment to form homogeneous ribonucleoprotein complexes; the results suggest that the CN1 fragment may confer specificity on the natural 5-S RNA-protein interaction.


Crystallization of bacteriophage MS2.

Crystals of bacteriophage MS2 have been obtained by slowly cooling a 1% virus solution from 23 degrees C to 0 degrees C in the presence of poly(ethylene glycol) 6000. The crystals were colorless, needle-like, anisotropic and very fragile. Electron microscopic observation of the crystals revealed a two-dimensional lattice of particles with RNA phage morphology and dimensions. Preliminary X-ray examination of the crystals confirmed their viral nature.


Methodological aspects of the evaluation of the binding of drugs to plasma and tissue proteins.

This paper describes the methodological aspects of the evaluation of the binding of drugs to plasma and tissue proteins. The relevance of the procedures employed to certain problems in clinical-pharmacology as well as the role of plasma binding in drug distribution and pharmacokinetics are discussed. The possibly important role of plasma protein binding of some drugs is emphasized. The incidence of plasma binding on drug distribution and pharmacokinetics are developed and the possible incidence of pathological states on drug plasma binding are considered.


In vitro evidence of cellular and humoral immune responses following lung allotransplantation in canine recipients with and without immunosuppressive treatment.

Using donor lung antigens as targets, two test methods, a rosette-forming cell test (RFC) and indirect immunofluorescence test (indir. IF), were applied to focus on the first set lung allograft rejection in canine recipients with and without immunosuppressive treatment. In both groups the first sign of humoral or cellular sensitization became evident on the 4th postoperative day, which might answer some unsolved problems in early lung graft damage, recently discussed as a manifestation of certain immunologic reactions. The tests used, indir. IF and RFC, revealed a steadily climbing tendency of immunization in untreated recipients and more variable and reversible positive results in the immunosuppressively treated group. No correlation between cellular and humoral immunity could be proven by our tests. The fact that we found no incorrect positive results in RFC suggests that this test provides important hints for the diagnosis of lung allograft rejection.


Double-blind comparison of metoprolol, alprenolol, and oxprenolol in hypertension.

A double-blind comparison of the beta-blockers metoprolol, alprenolol and oxprenolol was carried out to evaluate their antihypertensive effect and tolerability. 105 patients with previously untreated hypertension entered the trial and 72 completed it. Side-effects were infrequent and were never the reason for drop-out. All three drugs caused a statistically significant reduction in blood-pressure at the lower of the two doses used during a dose-finding period. At the higher dose employed in this period, metoprolol caused a significantly greater reduction in diastolic blood-pressure than did alprenolol or oxprenolol. All three drugs caused a significant reduction in heart rate. During the following period, the beta-blockers were supplemented if necessary with hydrochlorothiazide. This was required less frequently in the metoprolol group than in the other two groups.


Hypotensive action and side-effects of flutonidin in normal subjects. A double-blind controlled trial.

In a double blind study, planned as a 7 x 7 latin square, three oral doses of flutonidin (0.5, 1, 2 mg), of clonidine (0.0075, 0.150, 0.300 mg) and of a placebo were administered to 7 normal volunteers on 7 different treatment days, with an interval of 3 days. On each treatment day sitting blood pressure, heart rate and reaction time were measured, and sedation and dry mouth evaluated before the 1, 2, 3, 4, 6, and 8 h after administration. The placebo did not modify the basal value of any variable. Flutonidin and clonidine produced dose-related effects on blood pressure, heart rate, sedation and dry mouth, but did not influence reaction time. Analysis of the dose-response curves demonstrated that the effect of flutonidin was one-fifth to one-twelfth that of clonidine, depending on which variable was considered.


Selective reduction of adrenal medulla response to angiotensin induced by suppression of renin-angiotensin.

Angiotensin II (AII) induced an increase of adrenaline (A) release from rat adrenal glands in vitro. The response of the adrenal glands was completely abolished 22--24 h after bilateral nephrectomy. Adrenal glands from DOCA-salt-treated rats did not respond to AII as well, whereas adrenal glands from rats treated with furosemide and a low salt diet retained this response. High potassium in the medium increased significantly the release of A from in vitro incubated adrenal glands of nephrectomized rats from 0.43 +/- 0.04 to 0.63 +/- 0.06 microgram/gland and salbutamol (in calcium-free medium) increased the release from 0.34 +/- 0.03 to 0.43 +/- 0.03 microgram/gland. These results indicate that the adrenal medulla develops subsensitivity to AII in vitro, following a reduction in levels of this agonist in vivo.


Prevention of the development of spontaneous hypertension in rats by captopril (SQ 14,225).

Indirect systolic blood pressure (SBP) was monitored in male, weanling, spontaneously hypertensive rats (SHR) maintained on water for 16 weeks (group A) or on captopril therapy (100 mg/kg/day in drinking water) for 4 (group B), 8 (group C), 12 (group D), 16 (group E) weeks. Weanling SHR of group A developed typical, time-related hypertension over a 16-week observation period. In marked contrast, SHR receiving captopril did not develop hypertension. Discontinuation of captopril after 4, 8, 12 or 16 weeks resulted in the usual development of hypertension. There was a transient increase in water consumption of drug treated rats which returned to normal by 8 weeks of dosing. Conversely, when captopril therapy was discontinued after 4, 8 or 12 weeks, there was a transient decrease in water intake, the magnitude of which was inversely related to the duration of drug therapy. These results demonstrate that daily captopril therapy was able to completely prevent the development of spontaneous hypertension. Explanations for the mechanism(s) underlying the influence of captopril on blood pressure and water intake remain speculative.


Structural specificity of nucleotides for insulin secretory action from the isolated perfused rat pancreas.

The study concerned the effects of variuos nucleotides on the insulin secretion from the isolated perfused rat pancreas. ATP, the first nucleotide studied, increased the insulin release induced by glucose 1.5 g/l. There was a first immediate peak followed by a second significant and durable increase. The log dose-response curve was linear for concentrations ranging from 0.825 microM to 330 microM. The effects of natural adenine derivatives (ATP, ADP, 5' AMP, cAMP and adenosine) were compared. ATP was the most active compound; ADP had nearly the same activity as ATP (relative potency ATP/ADP = 3.2); 5' AMP, cAMP and adenosine displayed a very weak activity (about 100 fold less active). Adenylimido-diphosphate (AMP-PNP), a non-phosphorylating structural analogue of ATP, clearly stimulated insulin secretion and its effect was concentration-related. It was about 10 fold less active than ATP. The comparison of triphosphorylated derivatives from various purine nucleosides (ATP, GTP, ITP) or pyrimidine nucleosides (CTP and UTP) showed that only the purine derivatives had a strong insulin secretory effect with, in order of decreasing activity: ATP greater than GTP greater than ITP. These results show that certain structural features (purine basis and di- or triphosphate groups) are essential to elicit an insulin secretory effect.


Characterization of furosemide-induced activation of the renal prostaglandin system.

A detailed time course of changes in plasma renin activity (PRA), urinary prostaglandin (PG) E2, PGF2 alpha, thromboxane (TX) B2 and sodium excretion rates following furosemide was obtained in 7 women. PRA increased within the first 15 min and remained elevated all through the experiment. PGE2, PGF2 alpha, TXB2 and sodium increased simultaneously, reached a peak between 15 and 45 min after furosemide and declined thereafter. It is concluded that furosemide induces a generalized activation of the renal PG system temporally related to the increase of renin release and natriuresis.


6-Keto-prostaglandin E1 inhibits the aggregation of human platelets.

6-Keto-prostaglandin E1 (6-keto-PGE1) was found to have a similar potency to prostacyclin (PGI2) as an inhibitor of platelet aggregation. It caused a time and concentration dependent inhibition of ADP, collagen and epinephrine induced platelet aggregation, the dose ratios for 70% inhibition by 6-keto-PGE1, PGI2 and PGE1 being approximately 1 : 1 : 13. In doses similar to those of PGI2, 6-keto-PGE1 partially inhibited the release of [3H]-serotonin from platelet-rich plasma induced by collagen.


Proliferation kinetics of early hemopoietic precursor cells with self sustaining capacity in the mouse, studied with 125-I-labeled iodo-deoxyuridine.

With a new labeling technique in radiation chimeras, an attempt was made to determine the duration of the phases of the stem cell cycle including shortest and mean generation time and to estimate the number of hemopoietic stem cells per unit of bone marrow cellularity. The DNA of bone marrow cells in DNA synthesis was labeled with 5-125I-2'-deoxyuridine. The labeled cells were followed after being transfused into fatally irradiated mice. The stem cells were found to have a half-time of about 4.3 days in the donor mice. The average time in the population, i.e. the turnover time of the stem cells, was 6.2 days. The half-time did not change significantly even after transfusion of bone marrow into lethally irradiated recipient mice. Tritiated thymidine (3H-TdR) suicide technique revealed that bone marrow stem cells seeding to the spleens and to the femurs of lethally irradiated recipients behaved differently--S-phase in cells seeding to femurs being shorter. The radiosensitivity of stem cells in S-phase had a D0 of 80 rad whereas stem cells distributed throughout the whole cell cycle had a D0 of 185 rad. The respective extrapolation numbers were 1.23 and 1.14. It is calculated that 2--7% of all nucleated bone marrow cells belong to self renewing stem cell populations. The method described provides a new approach for the study of hematological stem cells.


Is human arterial smooth muscle cell proliferation regulated by prostacyclin?

Activated smooth muscle cells exhibit a statistically significant (p less than 0.025) higher prostacyclin production than the contractiles. It is concluded, that the proliferation of the metabolically activated cells, which is an early event in atherogenesis, could be due to prostacyclin regulation.


[Prostaglandins in skin blisters of bullous erysipelas, dermatitis herpetiformis and herpes gestationis (author's transl)].

The PGE2 and PGF2 alpha content of bullae developing spontaneously on the skin was investigated by radioimmunoassay in 12 patients with different skin diseases. The PGF2 alpha level was also established in the plasma and urine. In herpes gestationis, dermatitis herpetiformis and bullous erysipelas the PGE2 and PGF2 alpha content of the bullae considerably exceeded the plasma and urinary PG levels. The findings were thought to be in relation with the acute inflammation of the skin, the mechanism of bulla formation as well as with pruritus.


[Psoriasis vulgaris: immunologlobulin binding to human epidermis after limited proteolysis].

Immune complexes isolated from sera of psoriatic patients and healthy controls show an identical pattern in sodiumdodecylsulfate polyacrylamide gel electrophoresis. And so it seems to be unlikely that the increased provable serum immune complexes by psoriatics contain specific protein antigens.--Following to limited proteolysis of normal human epidermis, antibodies which solely are provable in sera of psoriatic patients could bind to proteolytic altered structures. For achieving a similar process in vivo, the following conditions are to be discussed: (1) an elevated concentration of certain autoantibodies in the sera of psoriatic patients and a temporary increased vessels permeability for antibodies, (2) the availability of structures in the epidermis of psoriatics with increased affintiy to certain antibodies. These structures may be produced by limited proteolysis or as a result of the disturbed differentiation of epidermal cells.


[Cutaneous foreign body granulomas caused by aluminium-hydroxid after desensitization with h Mischpollen-Depotallergen (author's transl)].

Report on a 16 years old female patient suffering from pollinosis and asthma. After desensitization with Mischpollen-Depotallergen foreign body granulomas developed in the injection areas. By fluorescence histochemical examination aluminiumhydroxid was found as cause. The increasing possibility of this side effect by more frequent employment of aluminium-hydroxid, for example in the production of vaccine, is directed on.


Studies on circulating soluble immune complexes of the liver disease. 1. Inhibition assay of polyclonal rheumatoid factor binding to IgG-sepharose.

Polyclonal rheumatoid factor (pRF) was isolated from sera seropositive for RF and it was radioiodinated with lactoperoxidase method. Using the 125I-pRF and IgG-p-azobenzamidoethyl Sepharose 6B, a competitive inhibition radioassay for detecting immune complexes is described. The assay can be performed in 90 min utilizing 10 microliter of serum with good reproducibility and endogenous RF in test serum did not interfere the reaction. The test can detect complexes nearly to 8s and as low as 0.1 microgram/ml of aggregated human IgG. Decomplementation by heating test sera is unnecessary. The assay was performed at 4 degrees C but less inhibition activity was obtained when it was carried out at 24 degrees C.


Effect of proximal gastric vagotomy and anticholinergics on the acid and gastrin responses to sham feeding in duodenal ulcer patients.

Plasma gastrin concentrations and gastric acid output after modified sham feeding were determined in 20 duodenal ulcer patients. Sham feeding produced an acid response corresponding to 40-68% of the maximal acid output after pentagastrin stimulation, with no significant increase of plasma gastrin concentrations. In eight patients proximal gastric vagotomy almost abolished the acid responses to both insulin hypoglycaemia and sham feeding. Sham feeding in the vagotomised patients did not change the gastrin concentrations in plasma. After pretreatment with benzilonium, an anticholinergic with minimal central nervous effects, plasma gastrin concentrations increased after sham feeding. The study confirms that sham feeding is a poor stimulus for gastrin release in duodenal ulcer patients and supports a cholinergic inhibition of gastrin release. Intravenous injection of benzilonium bromide in a dose close to 70 micrograms/kg, and atropine in the low dose of 30 micrograms/kg inhibited the acid response to sham feeding by about 65%. Atropine in a dose of 50 micrograms/kg virtually abolished the acid sham feeding response, possibly owing to ganglionic or central nervous blockade. Vagal activation of the acid secretory glands does not seem to involve a purely cholinergic neurotransmission.


Zymogram studies of human intestinal brush border and cytoplasmic peptidases.

Zymogram studies of peptide hydrolases from the human intestinal brush border and cytoplasmic fractions produced multiple bands--that is, up to seven--while the brush border membrane produced only a single band of enzyme activity. With all of the substrates tested except L-leucyl-L-leucyl-L-leucine, a band having anodic mobility identical with that produced by the brush border enzymes was produced by the cytoplasmic enzymes. With L-trileucine as a substrate, no overlapping band was produced. This band in the cytoplasmic fraction was heat sensitive, while that in the brush border fraction was not. Thus it would appear that there is a single human intestinal brush border peptide hydrolase capable of hydrolysing a variety of di- and tri-peptides. This peptide hydrolases of the brush border and the cytoplasmic fraction of human intestine are distinct.


Salt, diuretics and pregnancy.

This article reviews the homeostasis of water and salt in normal and pre-eclamptic pregnancy. During pre-eclampsia there is a decrease in circulating plasma volume, which the administration of diuretics reduces still further. There is no proof that diuretics have a beneficial effect on prevention or treatment of toxemia of pregnancy. They should thus be regarded as contraindicated, except in cases of cardiac insufficiency and certain renal diseases.


Gossypol--a new antifertility agent for males.

Gossypol is capable of inhibiting the fertility of male rats. On administration of gossypol the spermatids are damaged first. With the increase in dosage and duration of treatment the spermatocytes are also damaged. In the epidymis there are exfoliated spermatids and spermatocytes with numerous dead spermatozoa many of which had their heads and fails separated. The sperm count gradually decreases until azoospermia. Electron microscopic examinations reveal changes in the acrosomes and mitochondrial spiral sheath. Interstitial cells of the testis seemed to be unaffected. Over 4,000 healthy men have been on gossypol for more than 6 months. The antifertility efficacy evaluated by semen examination is 99.89%. Side effects are mild and of low incidence. A few of the subjects are found to be hypokalemic. However, it remains to be elucidated if gossypol is related to the development of hypokalemia.


[Synthetic resorbable and synthetic non-resorbable suture materials in microvascular surgery. Animal experimental study].

In a series of experiments on the aorta of the rat, the behaviour of an absorbable monofilament suture VICRYL (Polyglactin 910) was compared to that of a non-absorbable suture ETHILON (Polyamide 6/6). A total of 86 rats was operated upon and examined over a period of 70 days. The report includes a complete description of experimental procedures and techniques used during the operations. The evaluation of the experiments took place after completion of the mechanical, histological and scanning electron microscopical tests. It has been proven that under similar conditions, the 0,2 metric suture VICRYL has adequate tensile strength to withstand the intravascular pressure in a vessel with an outer diameter of approx. 1,5 mm. Aneurysm, stenosis and dehiscence of the anastomosis did not occur. The VICRYL suture showed no reactive processes after a period of 42 days. With the suture ETHILON the inflammation of the media and the hyperplasia of the intima persisted even after 70 days, at the end of the experiment. It is therefore shown in microsurgery, the monofilament absorbable suture VICRYL and the non-absorbable monofilament suture ETHILON are equal in their mechanical qualities, but that the suture VICRYL has by far the better tissue compatibility.


[Nerve regeneration by means of the effect of an intermittent electromagnetic field. Experimental study on a rabbit].

An experiment on healing of transected nerves of rabbits was carried out. Under microsurgical techniques continuity of the nerve was reestablished by end-to-end coaptation without creating a defect, so only the elasticity of the nerve tissue had to be overcome, and by nerve grafting. In both cases treatment with intermittent high frequency magnetic field was applied continuously. Histologic studies revealed that the scar at the suture site matured more quickly than usually and that distal to the site of transection the normal calibre of regenerated axons was reached within a shorter time than previously.


[Direct flexor tendon suture in the digital sheath].

From 1976 to 1976 in 44 fingers (41 patients) flexor tendons within the digital sheath (zone I and II) were repaired by direct suture. A modification of KESSLER's "grasping" suture was employed. In 21 fingers only the deep flexor and in 23 fingers both flexor tendons were divided; in these cases a repair of both tendons was carried out whenever possible. In cases of delayed repair, however, secondary changes of the gliding apparatus often prevented a repair of the superficialis tendon. Tenolysis was proposed in one half of the cases. It was done not earlier than 3 months after tendon suture. After division of both flexor tendons we obtained in cases with good preoperative conditions (21 fingers) 66% of good and excellent results, according to BOYES' classification, and 75% according to BUCK-GRAMCKO's classification.


[Surgical treatment of the ruptured ulnar collateral ligament of the metacarpophlangeal joint of the thumb].

The diagnosis of ruptured ulnar collateral ligament of the metacarpo-phalangeal joint of the thumb is made from characteristic findings and special radiograms. Without treatment, impairment of hand function will result. Only in a few cases will conservative treatment be successful; the reasons are explained. 26 cases of total rupture of the collateral ligament and their surgical treatment are reported. 16 fresh ligamentous injuries were treated by suturing directly (n = 2), by pull-out wire technique (n = 10), and by screw osteosynthesis (n = 4). The ligament was reconstructed with a free tendon graft in 8 cases of old ligamentous injuries, while the remaining 2 cases were repaired using a pull-out wire. After treatment, all metacarpo-phalangeal joints showed full stability and all patients without discomfort. Restriction of mobility results much more from secondary than from primary treatment. Therefore, we recommend primary surgical treatment of the ruptured ulnar collateral ligament of the metacarpo-phalangeal joint of the thumb.


Propagation of Toxoplasma gondii in suspension cultures of HeLa cells.

A novel method of Toxoplasma gondii cultivation in suspension cultures has been introduced using silicone-coated glass vessels (working volume 100 ml). The cells were kept in suspension by a magnetic impeller at 75 rpm at a temperature of 37 degrees C. HeLa cells grown on MEM with calf serum were used as host substrate. The HeLa cells were infected with zoites of Toxoplasma gondii virulent P strain. After seven days the host cells were destroyed by the toxoplasmas and the number of zoites was up to 24 x 10(6)/ml.


An antigen from Eimeria tenella merozoites for the indirect fluorescence antibody test.

The suitability of the antigen prepared from second generation merozoites of Eimeria tenella for the IFAT was confirmed. In comparison with other two antigens used until now in routine work, i. e., that prepared from histological sections of infected organs or that from in vitro released sporozoites, the merozoite antigen has the advantage of easy preparation in large quantities.


Physiological characteristic and energy balance of Klebsiella aerogenes in a multistage tower fermentor.

Biomass growth, consumption of carbon and energy source, specific rates of formation of metabolic byproducts, biomass yield referred to the C-source and to oxygen, respiration rate and the value of RQ were studied in Klebsiella aerogenes CCM 2318 (on a synthetic glucose medium) at different specific growth rates. Maintenance coefficients and the total energy balance of the cultivation process were evaluated for a multistage tower fermentor with a defined interstage mixing. The results pointed to changes in both glucose metabolism and the physiological state of the population, brought about by changes in specific growth rate. As compared with a chemostat, the culture was found to exhibit a different physiological character is stages 1 and 4 despite a considerable interstage mixing.


The effect of ultrasound on genetic instability in diploids of Aspergillus nidulans.

Ultrasonication at 20 kHz and intensity of 59 W/cm2 of a diploid strain of Aspergillus nidulans was ound to lead to a significant increase in haploidization of germinating conidiospores. In a preliminary study ultrasound was found not to have an effect on the rate of reverse mutation in conidiospore suspensions of auxotrophic mutants.


Skin-window study on the migration of leukocytes of newborns and infants.

Migration of leukocytes of newborns and of infants up to the age of 6 months was studied using the in vivo skin-window technique according to Rebuck. Using the non-specific stimulation (abrasion of the skin only) a slight age-dependent physiological increase of migration of cells was observed within the observation period; after a strong local irritation with diphtheria-tetanus-pertussis vaccine (Alditepera) there was a vigorous migratory response of cells in the skin lesion. Both quantitatively and qualitatively, the migration pattern (i.e. shift from PMN leukocyte to mononuclear cells in the exudate within a 1 d period after abrasion) was not influenced by immunization of infants with Alditepera, suggesting thus the nonspecific nature of this cellular response. The "normal" values of the chemotactic response of leukocytes of newborns and infants are given as a basis for evaluation of defects of this functional activity of leukocytes.


Effect of scarlet fever toxin on the phagocytic activity of the reticuloendothelial system.

In normal rabbits and mice, one i.v. injection of scarlet fever toxin (ET) (30 000 STD per kg of rabbit weight or 20-g mouse) elicited a similar biphasic change in carbon clearance rate - early depression followed by a stimulating phase - as has been described for Gram-negative endotoxins. Prolonged depression without a subsequent stimulation phase was obtained in mice by raising the ET dose. The reasons of the discrepancy between these findings and those of Hanna and Watson (1965b) are discussed. Pyrogenic tolerance to ET is not accompanied by accelerated carbon clearance and is not impaired by RES blockade. A possible mechanism of ET tolerance is suggested.


Influence of antilymphocyte and antipolymorphonuclear sera on the pyrogenic effect of scarlet fever toxin.

The role played by lymphocytes in the pyretic response to scarlet fever toxin (ET) was studied in vivo using antilymphocyte serum (ALS). Two i.v. injections of ALS inhibited the pyretic response to a subsequent ET injection in rabbits. The course of endotoxin fever remained uninfluenced by ALS. Antipolymorphonuclear serum had no effect on the pyretic response to either of the toxins. Pretreatment with ALS also inhibited the skin reaction after i.d. injection of ET. These findings are further evidence a mediating role of lymphocytes in the biological effects of ET, among other things in the release of endogenous pyrogen.


New discoveries of fossil primates from the type Torrejonian (Middle Paleocene of New Mexico).

For the first time in almost 30 years, new Middle Paleocene primate specimens have been discovered in the San Juan Basin, New Mexico. They are from the 'Pantolambda zone' in the type area, Arroyo Torrejon, and are referable to Palaechthon woodi and Torrejonia wilsoni. The only other known association of these two species is in the Shotgun Local Fauna from Wyoming.


[Thirty years of Radiology Department in Hokkaido University Hospital (author's transl)].

Thirty year's history of the Radiology Department of the Medical School of Hokkaido University, the first department of its kind in Hokkaido, is shortly reviewed. Statistics include the number of staff, equipment and patients diagnosed or/and treated in the department. Sections have been formed in the department since several years ago and are functioning to a certain extent independently in order to keep pace with the development of modern medicine and to meet the needs of our hospital. These sections are mainly radiation therapy, nuclear medicine, neuroradiology, X-ray diagnosis in angiology and for the digestive tract. Diagnosis based upon ultrasonography and CT are also becoming recognized sections in the department recently. Further more data processing and statistics seem to grow to become a section in the near future. In conclusion the number of staff, equipment and patients has been and perhaps will be growing increasingly fast. The increasing number of sections which resulted from the establishment of new specialities makes us to anticipate the new and independent departments in addition to the existing one.


Kinetic properties and regulation by L-ornithine of chicken liver arginase induced by insulin.

After injection of insulin into chickens, a new form of arginase with a 16-fold increase of activity appears in the liver. The new form has a different chromatographic behaviour on DEAE-cellulose. The low activity enzyme has a very high Km value (60mM), and is poorly inhibited by L-ornithine. The induced form of arginase is strongly inhibited by L-ornithine and has an allosteric behaviour which can be described by a Monod-Wyman-Changeux model. 1,4-Diaminobutane, spermine have practically no effect on either form of arginase.


[Preparation of N,N-bis(methylsulphonylethoxycarbonyl)insulins (author's transl)].

The preparation of N,N-bis(methylsulfonylethoxycarbonyl)insulins is described. In an aequeous buffer at pH 5.8 selectivity of the reaction of insulin with 20 equivalents of N-(methysulfonylethoxycarbonyloxy)succinimide (Msc-ONSu) leads very specifically to N alpha A 1,-N alpha B 1-(Msc)2 - insulin. The product can be isolated in a yield of 60%. Using N alpha A 1-citraconylinsulin the N alpha B 1, NEB29-(Msc)2 -insulin can be prepared in a yield of 40% based on insulin.


Isolation of basic acrosin inhibitor from bull seminal plasma (BUSI II).

An acrosin inhibitor was isolated from bull seminal plasma by gel filtration on Sephadex G-50 fine and ion-exchange chromatography on CM-Sephadex. The inhibitor is a basic polypeptide (pl greater than or equal to 10.5) of molecular weight 6 200 (calculated from amino acid composition). Its N-terminal amino group is blocked. The inhibitor is not strictly specific in its effect since it also inhibits trypsin and to a lesser degree chymotrypsin, in addition to bull and boar acrosin.


Isolation of acidic acrosin isoinhibitors (BUSI I A, BUSI IB1 and BUSI I B2) from bull seminal plasma.

Three natural proteinase isoinhibitors with low isoelectric points BUSI I A (pI = 3.9), BUSI I B1 (pI = 3.4 and BUSI I B2 (pI = 3.7) were isolated from bull seminal plasma by gel filtration on Sephadex G-50 and ion exchange chromatography on DEAE-Sephadex and SE-Sephadex. Isoinhibitors Bl and B2 have identical amino acid composition. Isoinhibitor A contains six amino acid residues less than isoinhibitors B1 and B2. Since sugars have been detected in the isoinhibitors, heterogeneity may also be due to the sugar component. The isoinhibitors show the same inhibitory properties; all of them inhibit acrosin, trypsin and chymotrypsin. Glandular kallikrein is also inhibited, but to a very low extent only. The molecular weight (Mr approximately 8 900) was determined by gel filtration.


Synthesis of the C-terminal decapeptide of bovine insulin B-chain.

The liquid-phase synthesis of a decapeptide corresponding to the last 10 amino acid residues of bovine insulin B-chain is described. Modified monofunctional polyethylene glycol containing benzyl bromide functional group was used as the soluble polymeric support. Cleavage of the fully-protected peptide from the polymer was achieved with 1N NaOH in dioxane. The protected peptide was purified by chromatography on Sephadex LH-20. The protecting groups of a sample were removed with anhydrous HF, and the unprotected crude decapeptide was purified by ion-exchange chromatography on carboxymethyl-cellulose. Both peptides were tested for the racemization of individual amino acids by the gas chromatographic method. The results showed that no residue had been significantly racemized.


[Rule of antibody structure. Primary structure of a human monoclonal IgA-immunoglobulin (myeloma protein Tro). VII. Purification and characterization of the disulfide bridges].

Myeloma Protein Tro has been isolated from the plasma of a myeloma patient. Monomeric IgA was separated from its polymer (by chromatography on Sephadex G-200). Both the forms were split with pepsin or cyanogen bromide and, if necessary, with thermolysin and subtilisin. The cystin-containing peptides were isolated from the hydrolysates by chromatography on Sephadex, ion-exchange columns, preparative paper chromatography, thin-layer chromatography, electrophoresis or by a combination of these methods. They were characterized by amino acid analyses and by determination of the N-terminal amino acids using the Dansyl-Edman procedure. Thus all the disulfide bridges of an IgA1 immunoglobulin could be established. The monomer has all together 48 cysteins, seven in each L- and seventeen in each H-chain; all these are covalently bonded by SS-bridges. Free SH-groups were not detected. The J-chain could only be identified serologically in the polymeric form of the protein. It is shown that the subunits of the polymers are covalently attached through either Cysl3, Cysl7 or both these residues of the H-chain.


Acid phosphatase: new developments.

Acid phosphatase was the first "tumor marker" to be measured in the blood, and over 40 years have passed since an elevation of the serum acid phosphatase level was observed in patients with prostatic carcinoma. However, significant elevations in the level of this enzyme have been observed in other diseases, as well as elevations of other tissue phosphatases. Many improvements in the colorimetric technique have been introduced, but none has been used successfully to detect the tissue origin of this ubiquitous enzyme. The finding that prostatic acid phosphatase is antigenically distinct from acid phosphatase of other tissues opened a new horizon in the measurement of acid phosphatase in prostatic cancer. On the basis of this immunochemical specificity, several immunoassays have been employed for determining the prostatic acid phosphatase level.


Chronic hereditary nephritis. A clinicopathologic study of 23 new kindreds and review of the literature.

Thirty-three patients with chronic hereditary nephritis, obtained from 23 unrelated families, were evaluated with respect to clinicopathologic features. Renal tissue was examined by light microscopy in 25 cases, immunofluorescence in 19 cases, and electron microscopy in 16 cases. The light microscopic findings varied, and foam cells were present in only four cases. Immunofluorescence was negative in all but four cases, and in these the immunomicroscopic pattern was compatible with the findings of end stage glomeruli and hyaline arteriolar sclerosis. Although electron microscopy uniformly showed marked thinning or splitting of the glomerular basement membrane, parallel splitting of the glomerular basement membrane with interposition of electron dense granular particles was seen in only eight cases. Association of glomerular basement membrane splitting with granular particles was observed in four of six patients with IgA nephropathy, in two patients with benign familial hematuria, and in a normal kidney donor. Eleven patients, seven men and four women, had chronic renal failure requiring dialysis. Of five patients who received renal allografts, three are alive, with post-transplant survival ranging from 24 to 70 months. The other two died of septicemia.


Pathways of urinary backflow in obstructive uropathy. Demonstration by pigmented gelatin injection and Tamm-Horsfall uromucoprotein markers.

The exact pathways of urinary reflux into the renal veins were studied in four cases of clinical obstructive uropathy and in 50 normal human cadaver kidneys. In the four clinical cases Tamm-Horsfall uromucoprotein was used as a marker for location of urine. Routine light microscopy and indirect immunofluorescence for Tamm-Horsfall uromucoprotein using rabbit antiserum showed tubular backflow up to the glomerulus. Dilated tubules filled with Tamm-Horsfall uromucoprotein ruptured into thin walled veins, forming tubulovenous anastomoses with extrusion of their contents into veins. The uromucoprotein was present in interlobar and arcuate veins with superimposed thrombosis and thrombophlebitis. Injection studies using pigmented gelatin in 45 normal cadaver kidneys and pigmented vinylite with corrosion casts in five additional kidneys complemented the clinical studies. Two types of urovascular communication were produced: the less frequent direct pyelovenous communication between a rupturing fornix and an adjacent small vein, and the more common indirect pyelovenous communication in which a ruptured fornix produced a sinus extravasate, which extended along the perivenous spaces of interlobar and arcuate veins. This extravasate gained access into the veins at points of rupture where venous tributaries joined the major veins in the renal medulla. The clinical implications of these tubulovenous and pyelovenous pathways of urinary reflux include backflow of whole urine and continued nephronic function in obstructive uropathy, "reverse backflow" of blood and hematuria, and a direct access for infectious agents into the circulation. These channels provide anatomic correlates for radiologic findings of extravasates and some backflow patterns of contrast material in pyelograms of clinical obstructive uropathy. The possible immunologic consequences of refluxing Tamm-Horsfall uromucoprotein gaining access to tissues and circulation are speculative.


A highly sensitive peroxidase-antiperoxidase method for detection of H-Y antigen on cultivated human fibroblasts.

A peroxidase-anti-perioxidase method for the detection of H-Y antigen at the single cell level is described. The efficiency of the test was examined in cultivated fibroblasts derived from control subjects and from XX males and a true hermaphrodite. For comparison, H-Y antigen was determined in blood cells of the same probands using the cytotoxic test. The finding of H-Y positive fibroblasts in the intersex patients has implications for the origin of these disorders.


Genetics of retinoblastoma.

The genetic basis of retinoblastoma is reviewed and the following conclusions are drawn: 1) The mode of inheritance of the hereditary variety of retinoblastoma (R) is autosomal dominant with about 90% penetrance. 2) About 68% of inherited cases are bilateral, and about 32%, unilateral. There is an intrafamilial correlation between penetrance as measured by segregation ratio and expressivity as measured by the fraction of bilaterally affected patients. 3) The vast majority of all R patients are sporadic cases, i.e., they are the only affected members of otherwise unaffected families. The porportion of bilateral cases is much lower among sporadic than among hereditary cases. 4) All bilaterally affected patients with sporadic R and patients with unilateral sporadic R with more than one primary tumor have to be regarded as germ cell mutants; they will transmit the gene to 50% of their offspring. Only 10%-12% of unilateral sporadic cases are germ cell mutants; 88%-90% are nonhereditary; in these cases the tumor is probably caused by a somatic mutation. 5) In a minority of cases, deletion of the chromosome segment 13q14(=intersitital deletion of the long arm of chromosome 13) has been observed. In addition to R, the patients show a variable degree of general or mental retardation; often there are few external indications of a chromosome aberration. Other chromosome studies suggest anomalies of chromosome 13 in tumor tissue even in cases not showing an anomaly of this chromosome in blood cultures, and possibly a slightly increased chromosome instability. 6) Patients with bilateral, and possibly in general with hereditary, R run an increased risk of becoming affected with other tumor diseases, such as osseous sarcomas, in later life. 7) Knudson's hypothesis of two mutational steps leading to both the hereditary and the nonhereditary variants of R is discussed critically, and the alternative possibility is suggested that in the nonhereditary variant a single mutational step--possibly a small chromosome aberration--could be enough to produce a tumor. 8) Evidence indicating a possible viral origin of R is cited, and animal experiments are mentioned in which R-like tumors have successfully been produced by local DNA virus inoculation. 9) As a consequence of improved survival and reproduction of R patients, an increased in the incidence of R and in the proportion of bilateral cases among all R patients must be anticipated. 10) Detailed rules for genetic counseling in families affected by R are given.


Endocrine pancreatic cells of postnatal "diabetes" (db) mice in cell culture.

Ultrastructural characteristics as well as secretory and biosynthetic behavior of monolayer pancreatic cell cultures established from 4-day-old C57BL/KsJ misty diabetic (m db/m db) mice have been studied in comparison to normal littermate controls. Hypersecretion of glucagon by alpha-cells from BL/Ks misty diabetic mice after 2 days in vitro was found to precede any hyperfunction of the insulin-secreting beta-cells. The increased level of glucagon-release in BL/Ks cell cultures from diabetic mice was accompanied by a greatly enhanced level of incorporation of [3H]tryptophan into glucagon-like molecules whose specific radioactivity was up to 15-fold higher than that observed in cultures from genetic controls. The finding of an alpha-cell dysfunction in cultures established from preweaning diabetic BL/Ks mice suggests that glucagon could play an early role in shaping the events that culminate in the expression of frank diabetes in this inbred strain.


Effect of chlorpromazine on the secretory activity of Escherichia coli heat-stable enterotoxin.

The effect of chlorpromazine on the net intestinal accumulation of fluid induced by Escherichia coli heat-stable (ST) enterotoxin in an infant mouse model was examined. Chlorpromazine, when administered with ST enterotoxin, caused a highly significant decrease in net intestinal fluid accumulation. The inhibition of ST activity was dose dependent with various concentrations of chlorpromazine (P less than 0.001). A significant inhibition of toxic activity was also observed when chlorpromazine was administered before (P less than 0.02) or after (P less than 0.05) ST enterotoxin challenge. No significant differences in fluid accumulation were observed between control mice treated with buffer alone and those treated with only chlorpromazine. These data indicate that chlorpromazine markedly decreases the net intestinal fluid accumulation induced by E. coli ST enterotoxin. Further studies on the potential use of chlorpromazine in both the prophylaxis and the treatment of diarrheal diseases appear warranted.


Neutrophil chemotaxis in patients with Staphylococcus aureus furunculosis.

Neutrophil chemotaxis was evaluated in patients with staphylococcal furunculosis using a modified Boyden chamber assay. Neutrophil chemotactic response to Staphylococcus aureus-derived chemotactic factor was compared with response to Escherichia coli-derived chemotactic factor and zymosan-activated serum. Twenty-one patients with active furunculosis were compared with 29 patients with a history of furunculosis but no recent infection and with 29 healthy control subjects. Chemotactic response to the staphylococcal chemotactic factor was significantly higher in patients with active furunculosis (mean 61.6) than in patients with a history of furunculosis (mean 36.4) or controls (mean 31.4), P less than 0.001. Neutrophils from patients with active staphylococcal infections also had higher chemotactic activity toward E. coli chemotactic factor, but not significantly so (P = 0.09). Chemotactic response to zymosan-activated serum and background neutrophil motility was comparable among the three groups. The increased neutrophil chemotactic response of patients with active infection to bacterial factors, but not zymosan-activated serum, may represent a specific neutrophil response to products of infecting organisms. The differential response of the patients' neutrophils to these attractants supports evidence for the presence of separate categories of chemotaxin receptor on the surface of neutrophils.


Physiological and metabolic alterations accompanying systemic candidiasis in mice.

Mice challenged intravenously with 10(6) viable Candida albicans died between 1 and 16 days after infection. Near the time of death, over 98% of the recoverable fungi came from the kidneys. Physiologically, animals were in renal failure near the time of death as evidenced by elevated blood urea nitrogen (BUN) and blood creatinine levels and a creatinine clearance rate which was about one-half normal. No abnormalities in liver glucogen and blood glucose levels were detectable. When mice were challenged with 4.5 X 10(6) viable C. albicans, they all died within 12 h. Near the time of death they had normal BUN values and were hyperglycemic. In mice receiving 4.5 X 10(6) heat-killed C. albicans, no deaths occurred and liver glycogen, blood glucose, and BUN levels all remained within a normal range and were different from responses to bacterial endotoxin. Cumulatively, the results demonstrate two distinct syndromes for the pathogenesis of experimental C. albicans infections. At the lower dose, mice were in renal failure associated with progressive renal infection. At the higher dose, renal failure was not observed. If a toxin was associated with death from the latter dose, it was not similar to bacterial endotoxin.


Characterization of colonization of the rabbit gastrointestinal tract by Escherichia coli RDEC-1.

We have reported previously the isolation of an Escherichia coli strain (RDEC-1) that in rabbits is able to colonize the gut, adhere to mucosal epithelial cells of the ileum, cecum, and colon, and cause diarrhea by a novel mechanism. The purpose of the present study was to characterize more fully the colonization of the rabbit gut by strain RDEC-1. Colonization reached a maximum 3 to 4 days post-inoculation with strain RDEC-1 and did not decrease until 15 days post-inoculation. Diarrhea occurred 3 to 4 days after colonization reached its maximum intensity. Semiquantitative rectal swab cultures were found to be correlated with counts of colony-forming units of strain RDEC-1 per gram of ileum, cecum, and colon and their contents and were used to chart the course of colonization of the rabbit gut. The actual number of colony-forming units per gram was dependent on the stage of colonization and ranged from 4.0 X 10(3) to 2.4 X 20(6) in the ileum to 3.1 X 10(5) to 3.6 X 10(7) in the cecum. The number of colony-forming units per gram was not affected by the presence of diarrhea. E. coli RDEC-1 colonizes the ileum, cecum, and colon of rabbits heavily for a relatively long period of time.


Comparison of peritoneal macrophages from germfree and conventional mice.

Morphology, lysosomal enzyme activities, and phagocytosis via immunological receptors were tested in peritoneal macrophages from germfree and conventional mice. Nonstimulated macrophages from germfree mice showed less spreading and were more easily detached when seeded on glass than conventional macrophages. The activities of the lysosomal acid phosphatase and cathepsin D were similar in the two cell groups, whereas beta-glucuronidase showed higher activity in macrophages from germfree mice. F(c) receptor-mediated phagocytosis of opsonized sheep erythrocytes was equally effective in germfree and conventional macrophages, and both cell types attached but did not internalize erythrocytes via the C(3)b receptor. Intraperitoneal injections of mineral oil caused a significantly higher influx of macrophages in conventional mice than in germfree mice, whereas the influx of polymorphonuclear cells was enhanced in both animals. Stimulation in vivo with oil or Escherichia coli endotoxin increased cell size, spreading ability, membrane ruffling, and lysosomal enzyme activities in macrophages from both conventional and germfree mice. The Fc-mediated phagocytosis was not influenced by stimulation, whereas the capacity to internalize via C(3)b receptor was triggered in macrophages from conventional mice, but not in corresponding cells from germfree mice. Similar results were obtained after stimulation with endotoxin in vitro. Culture in fetal calf serum for 72 h caused intracellular rises in all three enzyme activities tested in macrophages from conventional mice, whereas only the activity of acid phosphatase was increased in macrophages from germfree mice. Stimulation with zymosan in vitro caused selective release of lysosomal enzyme activity in macrophages from both animal groups. We conclude that peritoneal macrophages from germfree mice share several properties with cells from conventional mice, however, unstimulated beta-glucuronidase activity was increased, whereas spreading on glass, chemotactic response, in vitro induction of lysosomal enzymes, and the capacity to internalize via the C(3)b receptor after stimulation were reduced or absent.


Localization of the third component of complement on the cell wall of encapsulated Staphylococcus aureus M: implications for the mechanism of resistance to phagocytosis.

Encapsulated Staphylococcus aureus strains are more virulent than unencapsulated staphylococci, and this phenomenon has been associated with decreased opsonization of encapsulated bacteria by normal human serum. Peptidoglycan, a major cell wall component of S. aureus, has been shown to promote opsonization of this bacterial species by certain components of the serum complement system. However, when the processes of complement activation and opsonization of encapsulated staphylococci have been studied, it has been found that encapsulated bacteria activate complement efficiently and C3 is bacteria associated, yet these organisms are not efficiently phagocytized by human polymorphonuclear leukocytes. In this study, the hypothesis was tested that opsonically active molecules are not on the true external surface of encapsulated organisms but rather are cell wall associated and thus "hidden" from human polymorphonuclear leukocytes. By using immunoelectronmicroscopy, C3 was found to be localized on the cell wall of an encapsulated S. aureus strain after incubation of the organism in normal human serum. When shrinkage of the capsule was prevented by treatment with anticapsular antibody, the C3 was again shown to be cell wall associated and located beneath the bacterial capsule. These results suggest that encapsulated S. aureus may resist phagocytosis because opsonically active C3 molecules are not exposed at the true external surface of the bacterium.


Bactericidal effect of oleic acid on group A streptococci: mechanism of action.

In contrast to Staphylococcus aureus and coagulase-negative staphylococci, group A streptococci are infrequently present on normal human skin, except in certain populations with endemic impetigo. This has been attributed to differences in susceptibility to the bactericidal effect of skin surface lipids, particularly unsaturated fatty acids. When an M type 6 strain group A streptococcus was exposed to 500 mug of oleic acid per ml, viable counts decreased by 4 logs in 5 min. The rank order of killing was 35 > 20 > 4 degrees C. Oleic acid did not kill a strain of S. aureus, a strain of coagulase-negative staphylococcus, or a strain of Escherichia coli, but bound rapidly to these bacteria as well as to the group A streptococcus. The loss of [(3)H]uridine from labeled oleic acid-treated group A streptococcal cells was greater than 100 times that of controls. There was no loss of [(3)H]-thymidine from group A streptococci or of [(3)H]uridine or [(3)H]thymidine from identically exposed coagulase-negative staphylococci. When [(3)H]uridine was added to group A streptococci during mid-log-phase growth, cessation of uptake occurred within 5 min of addition of 50 mug of oleic acid per ml. Electron microscopic changes seen within 5 min included condensation of the nucleoid and distortion of the streptococcal surface by numerous clumps and blebs. Coagulase-negative staphylococci, S. aureus, and E. coli similarly exposed showed no comparable electron microscopic changes. We propose that oleic acid kills group A streptococci by altering the integrity of the cell membrane with resulting loss of ribonucleic acid but not deoxyribonucleic acid.


Antibody-induced capping of the intracellular stage of Trypanosoma cruzi.

Intracellular-stage Trypanosoma cruzi were isolated from infected mice. The effect of specific human antibodies on the membrane surface antigens was studied in vitro, using the immunofluorescent technique. The immune serum induced the aggregation of surface antigens, forming polar caps on the amastigotes.


Quantitation of the third component of human complement attached to the surface of opsonized bacteria: opsonin-deficient sera and phagocytosis-resistant strains.

The role of the third component of human complement (C3) in the opsonization of bacteria in nonimmune human sera was evaluated. The amount of C3 that becomes attached to the surface of bacteria upon incubation in serum was measured in a quantitative fluorescent immunoassay using fluorescein-conjugated monospecific antiserum to human C3. The intensity of the fluorescence from opsonized bacteria was found to be directly proportional to the absolute amount of C3 fixed, and this enabled the detection of as few as 300 molecules of bound C3 per bacterium. In normal serum the rate of C3 fixation was closely correlated with an increase in opsonization of the bacteria for human PMNs. Both C3 fixation and opsonization were maximal after 15 min of incubation. C3 fixation was also observed, albeit at a significantly slower rate, in human serum with a nonfunctional classical pathway but an intact alternative complement pathway and in serum deficient in immunoglobulins. Again, the kinetics of C3 fixation correlated with bacterial opsonization. Using a total of 21 strains of several bacterial species, including Staphylococcus aureus and Escherichia coli, encapsulation of bacteria was found to interfere with the process of C3 fixation in normal human serum, rendering these organisms resistant to subsequent phagocytosis by human polymorphonuclear leukocytes.


Attachment of Escherichia coli to urinary sediment epithelial cells from urinary tract infection-prone and healthy children.

Escherichia coli isolated from patients with recurrent urinary tract infections were tested for ability to attach to human urinary sediment epithelial cells in vitro. Higher mean capacity to bind bacteria was found for epithelial cells of the patient from whom the E. coli strain had been isolated than for epithelial cells from subjects without a history of urinary tract infection. The two populations were age matched. No relation was found between the age of the cell donor (0 to 15 years) and the capacity for E. coli attachement.


Evaluation of the immune response directed against the Salmonella antigenic factors O4,5 and O9.

A pair of O4,5,12 and O9,12 his(+) sister transductants derived from a virulent Salmonella typhimurium parent were used as intraperitoneal and oral challenge strains to determine whether immunity directed against the O9 and O4,5 antigenic components could be detected after immunization with heat-killed vaccines containing one or the other of these antigenic components. Challenge with a mixture (ca. 1:1) of the two strains and culturing of livers and spleens at intervals indicated that the O4,5,12 strain multiplied to a greater extent than the O9,12 strain after both oral and intraperitoneal challenge of CF1 and C57BL/6J control mice. Immunization with O4,5,12 or O9,12 vaccine resulted in diminished bacterial counts from the livers and spleens for the homologous strain but had little effect on the heterologous strain. The diminution of the homologous strain was more evident after intraperitoneal challenge but was clearly demonstrable after oral challenge, particularly in the C57BL/6J mice. Of several live vaccines tested, an FOR S. typhimurium (O4,5,12) strain phenotypically smooth but avirulent seemed the most promising, suppressing the multiplication of both members of the challenge pair. After oral challenge suppression of the O4,5,12 strain was greater. These results indicate that the specific immune response directed against either the O4,5 (O-acetyl abequose) or the O9 (tyvelose) antigen is a measurable component of the overall response after both intraperitoneal and oral challenge.


Taxonomic relationship of vole agent to Rochalimaea quintana.

We investigated the recent claim that the vole agent, a rickettsia-like microorganism isolated from wild voles by Baker in 1946, is actually a strain of Rochalimaea quintana, the etiological agent of trench fever. The two organisms were compared on the basis of percent guanine-plus-cytosine content, genome size, deoxyribonucleic acid-deoxyribonucleic acid hybridization, polypeptide composition, and serological relationships. Although the two organisms do have identical or nearly identical deoxyribonucleic acid base ratios and show some serological cross-reactions, they differ substantially by all of the other criteria employed. They are clearly different, although possibly related, organisms. It remains to be determined whether they can be regarded as two species of the same genus. On the other hand, an Old World strain and a New World strain of R. quintana were indistinguishable from one another by the same criteria.


Binding of anti-tumor immunoglobulins and their daunomycin conjugates to the tumor and its metastase. In vitro and in vivo studies with Lewis lung carcinoma.

The present study was undertaken in order to evaluate the possibility of using anti-tumor antibodies as specific carriers of chemotherapeutic drugs to tumor metastases. Xenogeneic and syngeneic antisera were prepared against a metastasizing C57BL tumor, the Lewis lung carcinoma (3LL). The binding of absorbed xenogeneic and syngeneic anti-3LL sera or their Ig fractions to 3LL tumor cells was assayed by direct and indirect methods. Antisera prepared against tumor cells from a local growth reacted to a similar extent with those obtained from the lung metastases. Radioiodinated immunoglobulins from syngeneic antisera injected into mice bearing metastases localized preferentially in metastasis-bearing lungs as compared to several other organs tested. No such preferential uptake was observed either in mice bearing metastases injected with iodinated normal Ig or in normal mice injected with iodinated anti-3LL Ig. This relative accumulation in the metastasis-bearing lungs was observed 3-4 days after the inoculation, when the whole Ig fraction was used, whereas a specific antibody-enriched preparation localized as early as 24 h after injection. Daunomycin--anti-3LL-Ig conjugates were effective inhibitors of tumor cells from both local and the metastatic growths. They were more active than either the free drug or drug conjugates of normal Ig, in in vitro assays.


Malignant behaviour of three adenovirus-2-transformed brain cell lines and their methyl cellulose-selected sub-clones.

Three adenovirus-2-transformed rat embryo brain cell lines and their methylcellulose-selected sub-clones were examined for fibronectin expression, anchorage-independent growth, saturation density, T antigen expression and morphology. Tumorigenicity studies were carried out on newborn and ATS immunosuppressed syngeneic rats and congenitally athymic nude mice. With one exception the methylcellulose sub-clones contained significantly fewer fibronectin-positive cells than the parent lines; a number of sub-clones contained no fibronectin-positive cells. Methylcellulose selection did not always alter cell morphology, saturation density or anchorage-independent growth as compared with parent lines. However, the methylcellulose sub-clones were considerably more malignant than the parent cell lines as measured by invasion and metastasis in nude mice. No in vitro characteristic correlated with malignant behaviour.


[Chronic osteomyelitis: open excision and grafting after saucerization (author's transl)].

From January 1960 to January 1974, 180 cases of chronic osteomyelitis were treated by the same surgeon in the infection unit of Notre-Dame Hospital in Montreal. Of these cases, 71.4% were treated by saucerization, followed by secondary closure or by skin grafting. In ten cases (5.4%) the limb was amputated. However, in 39 cases two similar techniques of open excision and grafting were used. The infection was mostly traumatic in origin and a staphylococcus was cultured in 75% of cases. The organism was sensitive to cloxacillin and dicloxacillin in the majority of cases. Since 50% of these 39 cases were referred for amputation, the results were much betts. Two late recurrences were recently seen and treated, one 17 years and one 4 years after the initial treatment.


Dietary prevention of coronary heart disease: the Finnish Mental Hospital Study.

A controlled intervention trial, with the purpose of testing the hypothesis that the incidence of coronary heart disease (CHD) could be decreased by the use of serum-cholesterol-lowering (SCL) diet, was carried out in 2 mental hospitals near Helsinki in 1959--71. The subjects were hospitalized middle-aged men. One of the hospitals received the SCL diet, i.e. a diet low in saturated fats and cholesterol and relatively high in polyunsaturated fats, while the other served as the control with a normal hospital diet. Six years later the diets were reversed, and the trial was continued another 6 years. The use of the SCL diet was associated with markedly lowered serum-cholesterol values. The incidence of CHD, as measured by the appearance of certain electrocardiographic patterns and by the occurrence of coronary deaths, was in both hospitals during the SCL-diet periods about half that during the normal-diet periods. An examination of a number of potential confounding variables indicated that the changes in them were small and failed to account for the considerable reduction in the incidence of CHD. It is concluded that the use of the serum-cholesterol-lowering diet exerted a substantial preventive effect on CHD.


Clinical aspects of the treatment of obesity by drugs: a review.

The safety, short-term and long-term efficacy of appetite-suppressant drugs are reviewed. Seven drugs widely available on prescription under the UK national health service are discussed.


Effects of acetylenedicarboxylate: relationship between decreased carcass lipid and increased liver size and lean body weight.

Potassium acetylenedicarboxylate, when administered in the diet, reduced the body lipid content of normal mice, genetically obese (ob/ob) mice, and their lean (+/?) littermates, and mice made obese by treatment with goldthioglucose. Food intake was unchanged in the lean mice but decreased in the obese mice. Carcass lipid was decreased in genetically obese mice compared to pair-fed controls. Oxygen consumption per mouse was increased in normal mice. The reduction in carcass lipid was not produced in normal mice that were dosed orally or were fed on a diet containing 55 per cent sucrose. Nor was it produced in male castrated mice or streptozotocin-treated mice that were given daily injections of insulin. The reduction in body lipid weight in lean mice was correlated with an increase in liver weight. Liver weight was not increased in genetically obese mice, but there was an increase in lipid-free dry weight. Weight gain was increased in lean mice and decreased in the obese mice compared to ad lib-fed controls. A red colouration of the skin developed in situations where body lipid content was decreased; plasma histamine was increased in lean mice. It is proposed that increased histamine synthesis leads to increased protein turnover and decreased body lipid content.


Insulin resistance in obesity: a critical analysis at enzyme level. A review.

Based on the consideration that insulin does not act directly on metabolic processes but affects membrane carriers and key-enzymes that regulate metabolic pathways, determination of insulin responsiveness of the various key-enzymes is suggested as a very appropriate method for studying insulin resistance. Insulin resistance, as it occurs in obese or obese-diabetic humans and animals, is most often associated with hyperinsulinemia, and is characterized not only by increased activity of key-enzymes of pathways known to be stimulated by insulin (glycolysis, lipogenesis), with the possible exception of glycogen synthesis, but also by a trend towards increased activity of key-enzymes of 'catabolic pathways', normally depressed by insulin. In the adipose tissue there is a normal-to-enhanced basal lipolysis, which in man would result from the prevalence of the active over the inactive form of triacylglycerol lipase. In muscle, the increased amino-acid release that can be inferred from the elevated blood level of both alanine and branched-chain amino acids suggests an enhanced proteolysis. In liver, there is an elevation in the activity of the key gluconeogenic enzymes, which forms the basis of the augmented gluconeogenesis. In both muscle and liver, phosphorylase is also elevated with no change in glycogen synthase. Therefore, insulin resistance seems to consist of the failure of insulin to depress the key-enzymes of catabolic pathways. Possible resistance of glycogen synthetase, which might account for decreased glucose utilization in muscle, may be due to the opposing effects of the phosphorylation process on glycogen synthetase and phosphorylase, implying that activation of phosphorylase (which occurs in obesity) entails inhibition of the synthetase. The fact that insulin insensitivity concerns only the 'catabolic' but not most 'anabolic' pathways makes it unlikely that the unresponsiveness is due to a reduction in insulin receptors or increase in insulin degradation. Since resistance to insulin is shown by enzymes regulated by such different mechanisms as induction-repression (gluconeogenic enzymes), covalent modifications (lipase, phosphorylase), and changes in lysosome stability (lysosomal proteases responsible for proteolysis, a single basic mechanism for explaining insulin insensitivity cannot be envisaged at present.


Insulin secretion and peripheral insulin sensitivity in obese children. Evidence of deficient glucose-stimulated early insulin release despite hyperinsulinemia.

Insulin secretion and peripheral insulin sensitivity were studied in 19 grossly-obese girls and 17 age-matched non-obese girls by means of the intravenous glucose tolerance test (IVGTT) and the simulated early insulin response test (SERT) respectively. SERT measures the fall in fasting blood glucose after a short infusion of insulin, performed so as to simulate the early phase of insulin release to the acute stimulus of an intravenous glucose load (ERex). In the IVGTT, the obese girls showed significantly increased early insulin response (ERend) in comparison with the non-obese girls. The glucose disappearance rate (KG) was similar in the two groups, although four obese girls had borderline low values. In the SERT, the rise in plasma insulin caused a much smaller decrease in blood glucose in the obese girls, than in the reference girls over the whole range of insulin levels studied. The relationship between insulin sensitivity and insulin secretion of each subject was evaluated from the plot of the ERex/ERend ratio vs blood glucose decrement. This showed that the hyperinsulinemia of the obese girls did not match the degree of peripheral resistance.


Prolonged fever and anemia as the sole manifestations of a false aneurysm in a transplant patient.

A patient with a false aneurysm of the iliac artery following removal of a right allograft developed a prolonged fever and anemia of unknown origin. The patient's condition was initially misinterpreted largely because these symptoms were attributed to dialysis treatment. This case emphasizes fever and anemia as the sole manifestations of a false aneurysm appearing as a late complication of kidney transplantation.


Changes in average length of stay and average charges generated following institution of PSRO review.

A five-year review of accounting data at a university hospital shows that immediately following institution of concurrent PSRO admission and length of stay review of Medicare-Medicaid patients, there was a significant decrease in length of stay and a fall in average charges generated per patient against the inflationary trend. Similar changes did not occur for the non-Medicare-Medicaid patients who were not reviewed. The observed changes occurred even though the review procedure rarely resulted in the denial of services to patients, suggesting an indirect effect of review.


Physician participation in Medicaid: evidence from California.

The objective of this paper is to investigate physician participation in the Medicaid program. In particular, how sensitive is the physician's involvement with Medicaid to variations in Medicaid reimbursements? How important are fee levels in the private market? What is the impact of inflation on the costs of physicians' inputs, particularly if the Medicaid fee remains relatively constant? These questions are explored through an empirical analysis fo data from the California Medicaid program. Two aspects of physician participation form the focus of the study: 1) the percentage of physicians participating in Medicaid in a given county and 2) the average number of nonaged, Medicaid patients treated by each participating physician. Information on these variables and on Medicaid fees and private charges come from Medicare and Medicaid claims records for more than 3,000 physicians. The most significant result of the study is the reaffirmation of the importance of the amounts of both private charges and Medicaid payments in determining participation rates and average Medicaid case loads per participating physician. Both dependent variables are, as expected, inversely related to physicians' average billed revenue per patient and are positively related to average Medicaid payments per patient. In addition, it appears that the long-run impact of a change in billed revenue is significantly larger in absolute value than a corresponding change in the amount that Medicaid is willing to pay.


Developing criteria for quality of assessment: effect of the Delphi technique.

We examined the effect of the Delphi iteration procedure in developing explicit criteria for ambulatory care assessment. Practicing internists chose items they believed to be essential with regard to the care of certain specified conditions. The initial responses were tabulated and "fed-back" to the participants. The second round of criteria selection, with the first-round summary available, produced few and relatively minor changes in the items chosen by group consensus.


[The crying infant].

The different types of crying which can be observed in the healthy and in the sick infant are described. Recent findings on behavioral and electrophysiological research are reviewed which led to a better understanding of the characteristics and possible causes of the different crying behaviors as well as of the effectiveness of therapeutical interventions.