Nature of seasonal variation in development of acute tolerance to morphine.

Morphine inhibits contractions of coaxially stimulated guinea pig ileum. Acute tolerance to this effect occurs on continuous perfusion with morphine for 1.5 h. This is associated with an increase in the sensitivity of the tissue to acetylcholine. Acute tolerance does not always develop in spite of identical treatment, but shows a distinct seasonal incidence. It is significantly higher in the summer (May--Nov.) than winter (Dec.--April). This seasonal variation in development of tolerance does not appear to be related to changes in diet, environmental light or temperature, or to the sensitivity of the ileum to morphine. In the winter, the acetylcholine release from stimulated ilea is lower than in the summer. In addition to inhibiting acetylcholine release, morphine also has a non-specific blocking effect in the winter. This postjunctional effect could prevent the development of supersensitivity to acetylcholine during continuous morphine treatment so that acute tolerance cannot occur.


Modulation of heroin self-administration by neurohypophyseal principles.

Neuropeptides related to hypothalomic-neurohypophyseal hormones affect intravenous heroin self-administration behavior in rats. Desglycinamide9, arginine8-vasopressin and pressinamide reduced, while oxytocin and its C-terminal tripeptide, prolyl-leucyl-glycinamide facilitated this behavior. The effectiveness of the vasopressin analogue appeared to be of a long term nature. The data indicate a modulating effect of these principles on the reinforcing efficacy of heroin.


Fenfluramine long-term administration and brain serotonin.

Long-term administration of fenfluarmine induced a decrease of brain 5-HT to the same extent as did an acute dose. 48 h after drug withdrawal, the brain serotonin level returned to the control value. The present study provides evidence to suggest that a degenerative lesion of 5-HT neurons is not involved in fenfluramine activity.


Behavioral suppressant effects of clonidine in strains of normotensive and hypertensive rats.

The behavioral effects of orally administered clonidine were investigated in Long--Evans (LE), Sprague--Dawley (SD) or Kyoto Wistar (KW) rats assumed to be normotensive and in NIH spontaneously hypertensive (SH) rats. Although clonidine (0.05-1 mg/kg) resulted in the same qualitative effect, i.e., depression of motor  activity, the dose of clonidine required to depress motor activity to 50% of control levels (ED50) tended to vary according to strain. An analysis of variance of the dose response curves for the four strains of rats indicated a significant strain effect. When the effects of clonidine on food-reinforced operant responding were investigated it was observed that SD and SH rats differed with regard to rate and temporal pattering of IRT greater than 20 sec responding. Although oral administration of clonidine (0.006-0.1 mg/kg) produced similar percentage decreases from control in SH and SD rats, and analysis of the temporal patterning of responding indicated differences in responsiveness to the behavioral effects of clonidine. These studies demonstrate strain-related differences in responsiveness to the behavioral suppressant effects of clonidine. Marked differences between genetically hypertensive rats and rats assumed to be normotensive were not evident.


Effects of 5HT uptake inhibitors on the pressor response to 5HT in the pithed rat. The significance of the 5HT blocking property.

A study was made of the effects of several serotonin (5HT) uptake inhibitors on 5HT-induced pressor responses in pithed rats, 5HT uptake into rat brain synaptosomes and 5HT-induced contractions of rat ileum in vitro. All drugs except desimipramine were potent uptake inhibitors (IC50 less than 10(-7) M), Femoxetine, chlorimipramine, imipramine and desimipramine all inhibited 5HY-induced contractions of the rat ileum in vitro and the pressor response to 5HT in vivo. FG 7051, FG 7052 and dexchlorpheniramine were weak 5HT antagonists on the rat ileum but potentiated the pressor responses to 5HT; the most potent uptake inhibitor, FG 7051, was the strongest potentiator. These results suggest that uptake inhibition is important for this potentiation. It is concluded that 5HT uptake inhibitors with potent 5HT receptor blocking properties antagonize the pressor response to 5HT and mask the potentiation due to uptake inhibition.


Effects of chronic bretylium treatment on the sympathetic neuron and the smooth musculature of the rat.

The effects of chronic i.p. injection of high doses of bretylium on sympathetic nerves on the smooth musculature of the vas deferens of adult and newborn rats were examined using fluorescence histochemistry, light and electron microscopy and organ bath physiological techniques. Bretylium treatment caused mitochondrial swelling, loss of cristae and the formation of electron-dense inclusions in the mitochondria of sympathetic neurons. However, neuron degeneration was not observed and fluorescent histochemical appearance of adrenergic neurons was normal. A small transient supersensitivity of the isolated vas deferens of bretylium-treated rats to noradrenaline, but not to acetylcholine, occurred. There was, however, considerable increase in the maximal contractile response to both noradrenaline and acetylcholine. In high calcium concentrations acetylcholine-induced contractions of vasa deferentia from bretylium-treated rats were significantly greater than control; there was no difference in magnitude of noradrenaline-induced contractions.


Behavioral interactions between naloxone and dopamine agonists.

A fixed-interval schedule of food presentation was used to study the effects of apomorphine, ET-495 and clonidine and interactions between these drugs and naloxone in the rat. The rate of responding under this schedule was decreased by low doses of apomorphine (0.03--0.3 mg/kg), ET-495 (0.3-1.0 mg/kg) and clonidine (0.03--0.3 mg/kg). Naloxone, at a dose (3 mg/kg) which did not itself alter responding, potentiated the rate decreasing effects of apomorphine and ET-495 but did not alter the effects of clonidine. It is suggested that the rate decreasing effects of low doses of apomorphine and ET-495 may be related to presynaptic inhibition of dopamine neurons and that under certain circumstances naloxone may also inhibit dopaminergic activity.


Intragastric titration of acid in the perfused rat stomach preparation following parenteral and intraluminal stimulation.

The anaesthetised rat stomach preparation was adapted to assay intraluminally administered stimulants and inhibitors of acid secretion by continuously recirculating the perfusate (15 ml of 5% glucose) and measuring acid by the pH-stat technique. The responses obtained were linear. Continuous artificial neutralisation of the stomach to pH 5.5 as well as variation of the pH between 6.5 and 4.0 did not significantly alter the sensitivity of the preparation to intravenously administered human gastrin-heptadecapeptide I (HG I). Basal acid secretion however significantly declined following stepwise lowering of the intragastric pH between 6.5 and 4.0. The threshold values for responses to i.v. HG I were below 16 ng. 6 doses could be given per rat without tachyphylaxis. Acetylcholine, 1.3, 2.5, 5.2 and 10.4 micron g/ml in the perfusate, induced a dose-dependent linear (r=0.902) acid secretion. Metiamide 1.66 mg/ml in the perfusate, produced a parallel shift to the right of the HG I dose--response curve producing an agonist dose ratio of 3.66. The data suggest that intragastrically applied stimulants and inhibitors of acid secretion can be studied precisely in this relatively simple preparation.


The neurotoxicity of 5,7-dihydroxytryptamine in the mouse atrium: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea and by ethanol.

1-Phenyl-3-(2-thiazolyl)-2-thiourea (200 mg/kg, 1 h) protected the adrenergic nerve plexus in the mouse atrium against the destructive action of i.v. 5,7-dihydroxytryptamine. Protection was also observed with ethanol (4 g/kg, 1 h) and with nialamide (50 mg/kg, 2 h).


Depression of hepatic drug-metabolizing enzyme activity by B. pertussis vaccination.

In vitro measurements are described on N-demethylation of aminopyrine and ethylmorphine, the hydroxylation of aniline as well as the level and activity of the electron transport system in hepatic microsomal fractions from pertussis vaccinated mice. Results indicate that pertussis vaccination of mice markedly decreases the level and activity of the hepatic drug-metabolizing system.


Action of some natural polypeptides on the longitudinal muscle of the guinea pig ileum.

The structure--activity relationship of some natural tachykinins was investigated in the longitudinal muscle of the guinea pig ileum. The order of potency was eledoisin greater than uperolein greater than substance P greater than phyllomedusin greater than physalaemin. This ratio of activity is different from that observed in other experimental conditions, and in different in vivo or in vitro preparations; it is suggested that the N-terminal part of the molecule of the tachykinins plays a role in determining the degree of potency of these compounds.


Inotropic effects of 1-alpha-acetylmethadol (LAAM).

Inotropic effects of 1-alpha-acetylmethadol, 1-alpha-acetylnormethadol and 1-alpha-acetyldinormethadol were studied uilizing isolated left atria of guinea pigs. All three agents produced a biphasic response. Lower concentrations produced a slight, but significant increase in contractile force (p less than 0.05) and higher concentrations decreased contractile force (p less than 0.05). Significant drug interactions also were observe. The parent compound, 1-alpha-acetylmethadol, decrease the maximum positive inotropic response obtained with ouabain as well as that obtained with norepinephrine.


Erythropoietic precursors in murine blood.

Murine blood was examined for circulating erythropoietic precursors. Blood mononuclear cells harvested using a slight modification of the Ficoll-Hypaque technique were cultured using the methylcellulose clonal cell culture technique. Only erythropoietic burst forming units (BFU-E) were present in the blood. Erythropoietin dose response studies revealed a progressive increment in the number of erythropoietic bursts up to a concentration of 4 U/ml of sheep plasma erythropoietin. A linear correlation existed between the numbers of nucleated cells plated and the erythropoietic bursts for both normal mice and mice with phenylhydrazine-induced (PHZ) anemia. No individual erythrocytic colonies were detected in cultures from blood taken before or after PHZ injections. These results suggest that erythrocytic colony-forming units (CFU-E) do not participate in the migration of erythropoietic precursors in mice.


Mobilization of hematopoietic stem cells (CFU-C) into the peripheral blood of man by endotoxin.

Pseudomonas endotoxin was administered to three normal subjects in order to assess possible effects on stem cell circulation. Increased numbers of granulopoietic stem cells (CFU-C) transiently appeared in the peripheral blood, reaching a maximum after the time of maximal leukopenia. There was a mean 4-fold increase in CFU-C per ml of blood following endotoxin. A high proportion of these CFU-C did not require an added source of colony-stimulating activity for growth in agar.


Effects of chronic hypoxia on platelet production in mice.

Platelet production, platelet count, and RBC count were measured in mice after enclosure in silicone-rubber membrane cages. Results indicate that enclosing C3h mice in hypoxia chambers for 2 weeks caused increased RBC count and decreased platelet production leading to thrombocytopenia. Splenectomized C3H mice placed in hypoxia chambers also showed decreased platelet count and platelet production when compared to splenectomized ambient air control mice. Injection of rabbit anti-mouse-platelet serum (RAMPS) caused an immediate thrombocytopenia with rebound-thrombocytosis 5 days later in normal mice and mice transfused with RBC. However, mice exposed to hypoxia and given RAMPS injections exhibited marked inhibition of platelet production. Although indirect, these findings suggest that hypoxia-induced erythrocythemia causes thrombocytopenia by stem cell competition between the erythroid and megakaryocytic cell lines.


Reduced extrarenal erythropoietin production in rats treated with isoproterenol.

Erythropoietin production was studied in 30-day-old and adult rats previously injected with pharmacological doses of isoproterenol. The animals were stimulated either by hypobaric hypoxia or by a combination of hypoxia and acute anemia. The erythropoietic activity of the plasma was measured by 59Fe incorporation in total circulating red blood cells of mice made polycythemic by chronic hypoxia. The results were converted to units of erythropoietin (IRP). A significant reduction of erythropoietin production was observed only in young rats. Our interpretation of the findings is that isoproterenol induced the differentiation of the salivary glands in the young animals hence reducing hormone production at the extrarenal (submandibular) level.


Family research study at Eagleville Hospital and Rehabilitation Center.

The Eagleville Hospital and Rehabilitation Center Family Study Program is described, presenting an overview of the Family Research Study and the problem areas inherent in coordinating research with a new treatment program; an analysis of the sample of drug abusers, their families, and their course in family treatment is discussed. The Community School Program is included as a demonstration of the potential for effective primary prevention. Areas of promise for future development are reviewed as they provide direction for further clinical and research work with the family and drug abuse.


The addict as savior: heroin, death, and the family.

The high mortality rate among drug addicts is seen as a suicidal phenomenon with a family basis. The death wish, or instruction for the addict to die, is often quite clearly expressed by the family. He is placed in the role of savior and martyr. His death is seen as a noble, cleansing sacrifice in which he is often a willing participant.


The logical levels of complementary, symmetrical, and parallel interaction classes in family dyads.

It was postulated that the parallel interaction class is a higher logical order than complementary and symmetrical interaction, which appear to be of the same logical type. Father-mother, father-child, and mother-child dyads of 48 families were categorized into complementary, symmetrical, and parallel classes using the Relationship Styles Inventory. Each of the dyads in these three categories was then randomly assigned to one of two experimental conditions in which they jointly resolved a moral dilemma. In one condition, the dyads were asked to follow complementary rules, while in the second condition they were instructed to follow symmetrical rules. Results indicated that parallel dyads adjusted to both the complementary and symmetrical conditions, whereas symmetrical and complementary dyads did not successfully accomodate rules outside their own class. The implications in terms of therapeutic intervention and further research are discussed.


Family therapy training: program and outcome.

A family therapy training program has been conducted for staff of mental health agencies located throughout Pennsylvania. This paper is a report on the content and results of the four-year-old training program. Three hundred practitioners have been trained in family therapy. The program has also led to the development of a core group of 64 family therapy trainers. There has been an associated delivery of more family-oriented mental health services throughout the Commonwealth.


Divorced parents in family therapy in a residential treatment setting.

Divorced parents are required to participate together in the family therapy of their child placed in a residential treatment center. Different sources of resistance and treatment techniques are identified and discussed through a theoretical analysis and case study material. The therapy of these fractured families contributed to an elimination of recidivism and, according to followup reports, to significant and sustained improvement in the children's functioning in school, home, and community activities.


Introducing novice therapists to "go-between" techniques of family therapy.

The training of family therapists requires that learning objectives and expectations be specified in empirical terms so that the trainer and trainee can achieve clear goals, identify areas of progress, and meet the special needs of the trainee. This paper articulates the competencies, objectives, and criteria for evaluation used during a time-limited training program for therapists involved in family therapy research conducted at Centennial School of Lehigh University.


[Study of 1,5-benzodiazepines. II. Synthesis of 2,4-di-(N-alkyl,N-phenyl)amino-3H-1,5-benzodiazepine].

Following the procedure we described for synthesizing analogous compounds in Note I (7), reaction of N,N-dialkyl or (N-alkyl,N-phenyl)ethoxycarbonylacetamides with 4-chloro-1,2-phenylendiamine, in the presence of phosphorus oxychloride, afforded 2,3-dihydro-2-oxo-4-dialkyl (N-alkyl,N-phenyl)amino-chloro-1H-1,5-benzodiazepines. When a large amount of phosphorus oxychloride was employed in the reaction, the formation of 2,4-di-(N-alkyl,N-phenyl)amino-3H-1,5-benzodiazepines was achieved, starting from suitable o-phenylendiamines and (N-alkyl,N-phenyl)ethoxycarbonylacetamides. Pharmacological tests were carried out on some compounds described in the present paper and on others reported in the preceding Note (7); in this connection 4-amino-1,5-benzodiazepine derivatives showed weak CNS depressing activity in addition, in some cases, to clear, although moderate, anticonvulsant activity, whereas 2,4-diamino-1,5-benzodiazepine derivatives were practically without effect.


[Synthesis and pharmacological study of various 2-(alkylaminoalkyl)mercapto-5-aryl-1,3,4-oxadiazoles].

Work was continued on the pharmacological study of the 1,3,4-oxadiazole nucleus using aroylhydrazines already used for the synthesis of anti-MAO compounds. S-alkylaminoalkyl derivatives of some 2-mercapto-5-aryl-1,3,4-oxadiazoles were prepared bearing in the 5-position a 3,4,5-trimethoxyphenyl, a 3,5-dimethoxy-4-ethoxyphenyl or a 3,4-dihydroxymethylenephenyl radical. When subjected to pharmacological investigation the compounds showed clear hypotensive activity partially antagonized by atropine and antispastic activity on smooth muscle.


[Research on heterocyclic compounds. VI. Imidazo(1,2-b)pyridazine derivatives].

The preparation of a group of imidazo[1,2-b]pyridazin-2-carboxylic and -2-acetic acids is reported. The ethyl esters of these acids were prepared by reaction of some 3-aminopyridazines with ethyl bromopyruvate or 4-bromoacetoacetate. The acids were obtained by hydrolysis of the corresponding esters, and their anti-inflammatory activity was tested.


[Selectivity of beta-adrenergic compounds. IV. Studies on 1-(4'-methylphenyl)-2-isopropylaminopropanol].

The beta-adrenergic activity of 1-(4'-methylphenyl)-2-isopropylaminopropanol (H 35/25) was studied on isolated preparations (guinea pig atria, guinea pig and calf tracheal muscle, mouse cecum). H 35/25 shows variations in both affinity and intrinsic activity at the various levels tested. The discussion shows that this cannot be used as a means of characterizing beta-adrenergic receptors.


[Research on nitrogen heterocyclic compounds. XI. - New synthesis of 3H-benz(e)indole and its derivatives].

Glutaconic esters bearing a 2-naphthylamino moiety and a carbethoxy group at the 4-position underwent thermal decomposition to give 1-carbethoxy-3H-benz[e]indole derivatives. Alkaline hydrolysis of 1-carbethoxy-3H-benz[e]indoles gave the corresponding 3H-benz[e]indoles by loss of the carboxylic group. By this method were synthesized the known 3H-benz[e5indole and the 7-methoxy-3H-benz[e]indole. Glutaconic esters used in this procedure were prepared by condensation of ethyl propiolate with the appropriate 2-naphthylaminomalonate ethyl ester in the presence of a catalytic amount of sodium ethylate.


Isolation and identification of two hydroxylated metabolites of phenazopyridine in rat urine.

Together with the metabolites arised from the reductive cleavage of the azo linkage, two hydroxylated metabolites of phenazopyridine (2,6-diamino-3-[(4-hydroxyphenyl)azo]pyridine and and 2,6-diamino-3-[(2-hydroxyphenyl)azo]pyridine) were identified in rat urine, after the administration of 50 mg/kg of the drug. The structures of these metabolites were elucidated, after TLC separation, by means of I.R., N.M.R. and mass spectrometry. The presence of two hydroxylated metabolites of the intact drug support evidence that phenazopyridine is also subjected in vivo to oxidative metabolism.


[Lidoflazine derivatives with cycloaliphatic residues of coronary dilator activity].

The preparation of some derivatives of lidoflazine bearing a phenylcyclohexane residue in place of the m.xylene is described. Study of the coronary dilating activity on the isolated heart showed that this activity is markedly increased by the modification. Acute toxicity in rats is also strongly increased.


Distribution of serotonin and synthesizing enzymes in discrete areas of the brain.

With the use of sensitive radio-enzymatic microtechniques, serotonin and its synthesizing enzymes, tryptophan hydroxylase and L-amino acid decarboxylase, can be quantitatively detected in discrete regions of the rat brain. A microdissecting technique allows us to study their localization in specific brain areas and nuclei. Serotonin and its related enzymes are concentrated in the raphe nuclei. Relatively high serotonin concentrations are also present in areas and nuclei of the hypothalamus, limbic system, and brain stem, as well as in the circumventricular organs and the pituitary gland. The localization of its synthesizing enzymes in the same regions suggests that the formation of serotonin actually takes place in these areas. Catecholamines are also present in the raphe nuclei of the rat. Changes in catecholamine metabolism result in changes in serotonin levels in specific brain areas. These results suggest that serotonin may be involved in the regulation of a number of autonomic functions, and in neuroendocrine control mechanisms. The neuroanatomical and biochemical relations between the catecholaminergic and serotonergic system in the brain support the hypothesis of a physiological interaction of these two systems in specific, localized brain structures.


Adenosine deaminase deficiency and immunodeficiencies.

Severe Combined Immunodeficiency (SCID) is a fatal disorder of infancy in which patients exhibit profound defects of both cellular and humoral immune function. Approximately 50% of patients with the autosomal recessive form of SCID have a genetically determined deficiency of the purine salvage enzyme adenosine deaminase (ADA). Prenatal diagnosis of SCID-ADA deficiency has been successful and detection of heterozygous carriers has been shown to be feasible. A mutation at the structural locus for ADA has been found in several cases but clinical heterogeneity indicates that genetic heterogeneity at the molecular level is to be expected. In vitro model studies and clinical course suggest that the pathophysiology may involve primarily an inhibition of T-cell maturation with lesser effects on B-cell maturation as well as "self-destruction" of differentiated cells following antigen stimulation. The culprit may be adenosine itself or one of its metabolites such as ATP or cAMP, which are elevated in these patients. Bone marrow transplantation remains the recommended mode of therapy but red cell transfusion may offer an alternative when bone marrow transplantation is not feasible. The finding that deficiency of  the next enzyme in the purine salvage pathway, nucleoside phosphorylase, is also associated with an immune deficiency disorder suggests that integrity of the purine salvage pathway may be crucial for normal differentiation and function of immunocompetent cells in man.


The use of clomiphene citrate.

Two hundred and fifty-five women received clomiphene citrate during a 10-year period. Fifty-six were treated diagnostically and one hundred and ninty-nine therapeutically for infertility. It is concluded that clomiphene may aid in confirming the diagnosis and establishing a prognosis in patients with primary or secondary amenorrhea. The success of clomiphene therapy in patients with anovulatory infertility is related to the etiologic factor responsible for the anovulation, but results can be improved by adjustment of the therapeutic regimen used. In the present series, 48% of the patients who ovulated became pregnant, and 25.3% of the pregnancies were miscarried. Those patients who ovulated spontaneously and became pregnant after having discontinued clomiphene therapy showed only a 10% abortion rate. A review of the results indicates that both the ovulation rate and the pregnancy rate can be improved if adjustments are made in therapy to ensure normal follicular maturation and corpus luteum function.


An evaluation of etiologic factors and therapy in 665 infertile couples.

Six hundred and sixty-five unselected infertile couples were investigated and treated in a private clinic during a 15-year span. Male infertility factors were involved in 28%, ovulatory disturbances in 31.5%, tubal factors in 16.3%, and undiscovered factors in 17.6% (117 couples). In 50 couples (7.5%) fertility-reducing factors were found in both partners, with a 14% pregnancy rate, compared with a 54.3% pregnancy rate when only a female factor was involved. The chances of successful treatment of females decline steadily with age, correlating with the fact that the longer the exposure time before the start of treatment, the less the chance of pregnancy. Investigation following 1 year of exposure should be advised. Pregnancy rates were 50% in ovulatory disturbances and 30% with tubal factors. Predictably, a progressive increase in the pregnancy rate was noted during the span of this study.


Amenorrhea following the use of oral contraceptives.

Clinical aspects and the incidence of the various underlying etiologic factors were studied in 86 patients with post-oral contraceptive amenorrhea. Patients were divided into two groups according to the presence or absence of detectable galactorrhea. Group I was composed of 55 amenorrheic patients without detectable galactorrhea and group II included 31 patients with amenorrhea associated with galactorrhea. Both groups were comparable for age, gravidity, duration of intake of oral contraceptives, and duration of amenorrhea. The incidence of previous oligomenorrhea and late menarche was high in both groups. The most striking difference between the two groups was in the incidence of pituitary prolactin-secreting tumor--32% among patients with galactorrhea and less than 2% among patients without galactorrhea. Identification of galactorrhea and accurate diagnosis of its causes are mandatory for successful management of postpill amenorrhea.


Comparison of ethinylestradiol and mestranol in sequential-type oral contraceptives in their effects on blood glucose and serum insulin in oral glucose tolerance tests.

Forty 3-hour oral glucose tolerance tests (OGTTs) were performed in 10 assumedly healthy female volunteers 19 to 30 years old, each serving four times as her own control. Each subject was taking a sequential type oral contraceptive containing either 50 microgram of ethinylestradiol or 80 microgram of mestranol alternatingly in four consecutive treatment cycles. The OGTTs were performed on the 6th day of each cycle, during pure estrogen medication. Blood glucose and serum insulin values did not differ significantly under either estrogen as tested by the t-test for paired observations. Our results do not support the findings of others that mestranol has a more pronounced or even exclusively adverse effect on glucose tolerance as compared with ethinylestradiol.


Serum immunoglobulin levels in vasectomized men: preliminary report.

Seventy-five men undergoing vasectomy were tested by radial immunodiffusion assay prevasectomy and at 6 weeks and 3, 6, and 12 months postvasectomy for possible changes in serum immunoglobulin (Ig) levels. No significant changes occurred when the results were analyzed on a group basis per time period. However, when each individual's prevasectomy Ig level was considered as his norm, significant changes appeared to occur in serum IgG levels at 6 weeks, 6 months, and 12 months postvasectomy; in serum IgM levels at 6 weeks; but not, to date, in serum IgA levels. Seasonal, environmental, and infectious factors do not seem to be associated with the changes found. No significant seminal Ig changes have been demonstrated. Consideration of these findings and implications for possible immunopathology are briefly discussed.


Administration of prostaglandin F2alpha for the recovery of fertilized eggs from the vaginas of rabbits.

Nonsurgical recovery of fertilized eggs from the vaginas of prostaglandin F2alpha (PGF2alpha)-treated rabbits was attempted. Eighty-two eggs were collected by the vaginal washing method, and the earliest egg was recovered 20 hours after mating. Twenty eggs recovered vaginally 24 to 107 hours after mating were transferred to six synchronized, pseudopregnant rabbits to test the viability of the eggs; four newborns, two fetuses, and one implantation site were obtained. These results indicate that some viable eggs are discharged into the vaginas of rabbits treated with PGF2alpha.


Hormone-mediated oviductal influence on mouse embryo development.

This study presents evidence that estradiol, mediated through oviduct fluid, may adversely affect the development of early embryos. Two-cell mouse embryos were cultured in Whitten-Biggers medium with or without 0.2 to 20 microgram/ml of estradiol or progesterone or in mouse oviduct fluid from donors treated with estradiol or estradiol and progesterone. Embryos cultured in fluid from estrogen-dominated donors were significantly less able to develop to morula (65%) or blastocyst (14%) than were those cultured in either Whitten-Biggers medium (91% and 41%) or progesterone-dominated fluid (87% and 36%). Transfer of cultured morulae and blastocysts to uteri of pseudopregnant recipients resulted in 2/3, 4/6, and 0/7 recipients' becoming pregnant for control, progesterone-dominated, and estrogen-dominated, respectively. When estradiol or progesterone was added directly to the control medium, no inhibitory effects were observed at levels higher than those found physiologically in plasma. Protein concentration and osmolalities for representative samples of oviduct fluid were 5.2 mg/ml and 329 mOsM for estrogen-dominated fluid and 1.6 mg/ml and 339 mOsM for progesterone-dominated fluid.


Can bilharziasis of the seminal vesicles be a cause of obstructive infertility?

In patients with bilharzial seminal vesiculitis, it has been proved by the fructose test, seminal vesiculography, and casting that the vesicular and ampullary canals as well as the ejaculatory ducts are patient. Thus bilharziasis plays no role in the production of obstructive infertility in males.


Once-daily treatment for mixed anxiety/depressive states: a comparison of slow release amitriptyline and fluphenazine with nortriptyline.

Patients suffering from mixed anxiety/depressive states referred to a psychiatric out-patient clinic completed a four course of either a once-daily table of 30 mg nortriptyline with 1-5 mag fluphenazine, or a sustained release capsule of 50 mg amitriptyline once daily, on a double-blind basis. Depression improved satisfactorily on either treatment, but there was a greater reduction of anxiety on fluphenazine/nortriptyline, Drowsiness, however, occurred more frequently among the patients on amitriptyline, suggesting the sedative properties of this drug did not substitute adequately for a specific anxiolytic effect. Dry mouth was also noticeably more frequent with amitriptyline. As might be expected on pharmacokinetic and phsyological grounds, the results suggest that the sustained release characteristics of the amitriptyline preparation lead to a maximization of side-effects during the day without conferring any therapeutic advantage.


Sustained action tetracycline preparation--tetrabid-organon blood level study.

A comparison of the plasma levels of tetracycline obtained whilst taking standard therapeutic doses of Tetrabid-Organon was made in twelve healthy volunteers. Two standard production batches were used in the study which was conducted under double-blind conditions. Sampling 12 hours and 8 hours after dosing showed no significant differences in plasma levels, with each batch. Even at these lowest levels satisfactory concentrations were rapidly obtained following initial administration, and were maintained when the drug was given at 12-hourly intervals. No side-effects of the drug were noted.


A clinical assessment of locabiotal in the treatment of infections of the nose and throat.

One hundred and twenty patients suffering from diseases of the nose and throat were admitted to an open clinical trial of the aerosol inhaler Locabiotal which contains the antibiotic fusafungine. The patient population was derived from three sources--out-patients, patients subjected to surgery and emergencies. The aerosol was administered five times daily to the throat or into the nose. The aerosol was highly effective in controlling infection and in relieving the various symptoms of the diseases treated. Variation in particle size was considered to be an advantage in penetrating various parts of the upper respiratory tract. Thirty-three patients experienced minor side-effects. These were thought to be misuse of the inhaler, or possible allergy to the antibiotic. This form of medication is recommended for a variety of diseases of the nose and throat.


Fentiazac as a therapeutic aid in the treatment of tuberculosis.

The authors point out the clinical usefulness and optimal tolerability of Fentiazac in patients suffering from tuberculosis and whose condition requires therapeutic intervention with non-steroid anti-inflammatory drugs.


Development of cortical spreading depression and of its transition to the caudate nucleus in rats.

The development of Leão's spreading depression (SD) of electroencephalographic activity was studied in young rats by recording the accompanying slow potential changes (SPC). The propagation rate of cortical SD increased from 1.65 mm/min on Day 15 to 2.6 mm/min on Day 20; the increase of SPC amplitude and the decrease of SPC duration were less evident over the same period. The SD elicited in the caudate nucleus by microinjections of KCl did not spread to neocortex in 20- and 30-day-old rats and transition occurred in only 5% of KCl applications in 40-day-old rats. Application of a pyrrolopyrimidine derivative (BW 57-271; 5 mg/kg) increased the cortico-caudate SD transition of 100% in rats aged 20 days or older and increased the SPC amplitude in both structures. The development of SD parameters can be ascribed to dendritic growth and to the decrease of extracellular space; the cortico-caudate propagation block can be ascribed to morphological immaturity of the transitional zone.


Development of locomotion toward home nesting material in neonatal rats.

Neonatal rats were individually placed in a narrow choice zone between home and fresh nesting materials. At Day 2 postpartum the pups made significantly more home-choosing responses (vs responses for fresh nesting material). At a mean of 5.6 days (range, 4 to 9 days) the pups reached a criterion of 2 consecutive days of responses all for home nesting material. The number of head contacts increased abruptly upon reaching the criterion. In a 2nd experiment we observed that the pups which were repeatedly tested performed no better than those which were tested for the 1st or the 2nd time. Thus, (a) home-seeking responses appear to emerge substantially earlier than previously reported by other investigators, (b) head-contact responses appear to be related to successful home-chossing, and (c) some maturational rather than experiential factors are important for the development of both head-contact and home-choosing responses.


Effect of handling on maternal behavior following return of pups to the nest.

Handling rat pups during the 1st week after birth altered adult behavior in the open-field, whereas simply spearating the pups from their mothers during the same period produced differences in body weight at weaning. Observations of mother-infant interaction following pup treatment yielded different patterns of maternal behavior. Moreover, pups receiving early treatment were more active as adults in a novel environment and had a greater body weight at weaning. The quality of maternal care and the immediate effects of infantile stimulation on the mother-infant relation should be considered in specifying a mediating mechanism for the effects of early experience.


The effect of criterion level on the acquisition and retention of a 1-way avoidance response in young and old rats.

Young (23-25 days old) and adult (80-84 days old) rats (n = 8, per group) were trained on an active-avoidance task to a criterion of 0, 5, or 15 consecutive correct trials and then tested for retention 30 days later. In original training, both age groups acquired the response in about the same number of trials when the criterion was set at 5/5 but young subjects required significantly more trials than older subjects to learn the response under the 15/15 criterion. In retraining, both age groups performed equally well when original training was to the 15/15 criterion although adults retained significantly better than weanlings when original training was 5/5 correct responses.


Position discrimination in the salamander, Ambystoma tigrinum.

Twenty larval tiger salamanders (Ambystoma tigrinum) were collected from a playa lake in West Texas and maintained in the laboratory for 7 days prior to the beginning of position training. Ten subjects in the larval state were trained on a position problem in a T-maze for 5 trials per day to a criterion of 80% correct responses, using a self-correction procedure. Following metamorphosis to the adult stage, these subjects were tested for retention. The remaining 10 subjects were allowed to metamorphose prior to training on the position problem. The results indicate reliably faster learning in the adult (terrestrial) subjects, and reliable retention of the response following metamorphosis. These results, taken in conjunction with informal observation of the behavior of the subjects in the experimental environment, suggest that the performance of the adult subjects was a result of their better perceptual apparatus.


Effects of parental environment on the prevalence of convulsive seizures in Onychomys torridus.

Male and female southern grasshopper mice (Onychomys torridus) were reared in 1 of 3 different parental environments: (a) with the natural male and female parents; (b) with the female parent only; or (c) with foster parents of a closely related species, Peromyscus leucopus. All mice were weaned at 25 days of age, then observed individually in an open field arena at 10-day intervals from 30 to 100 days of age. Twenty-seven of 59 subjects (45.8%) that were reared by the natural parents exhibited convulsive seizures during at least 1 of the 8 tests in the open field arena. The prevalence of convulsive seizures increased significantly in subjects that received altered parental care: 27 of 41 subjects (65.9%) reared by the female parent only or by Peromyscus foster parents seized during at least 1 of the 8 tests in the open field. Subjects from the 3 treatment groups did not differ in the mean number of seizures observed during the 8 open field tests. These results demonstrate a significant influence of the preweaning parental environment on the prevalence of convulsive seizures on Onychomys torridus.


Ontogenetic changes in pup-elicited maternal pituitary-adrenal activity: pup age and stage of lactation effects.

Ontogenetic changes in pup-elicited maternal corticosterone responsiveness were investigated. Patterns of maternal corticosterone change were found to depend on pup treatment: shocked pups elicited larger corticosterone elevations than pups that had been handled. In addition both the age of the stimulus pups and the state of lactation when the mother was tested affected the pattern and magnitude of maternal pituitary-adrenal activity.


Alleviation of separation distress in 3 breeds of young dogs.

Twenty-four puppies (8 each of Shetland sheepdogs, Telomians, and beagles) served as subjects in this experiment which was designed to examine the effectiveness of 12 stimulus conditions (food, toys, canine contact, and human contact) on alleviation of separation-induced distress vocalization. Testing consisted of a prestimulus trial, stimulus trial, and post-stimulus trial each session 3 times a week from 4 to 8 weeks after birth. Overall results showed human contact to be the most effective, followed by canine contact, toys, and food. Breed differences were significant in only 2 of the stimulus conditions. In the typical case of effective treatment, the vocalization rate declined from the prestimulus trial to a low point in the stimulus trial and then increased again in the post-stimulus trial.


The effect of insulin on vascular reactivity to norepinephrine.

The effect of insulin on the vasoconstrictor response to norepinephrine of the resistance bed of the isolated perfused rat tail has been studied. Insulin produced a significant attenuation of this response in concentrations of both 120 mU./ml. and 150 micronU./ml. It is suggested that this effect may be relevant to the hypotensive action of insulin observed in diabetics.


Short-term effect of insulin and 5(3-piridyl) tetrazole on serum triglycerides in insulin-dependent diabetic patients.

A group of insulin-dependent diabetic patients was studied in order to determine the possible short-term regulatory effect of insulin and that of an antilipolytic drug on serum triglycerides. Subcutaneous crystalline insulin (one third of the usual morning dose of intermediate long-acting insulin, NPH) and an oral dose of 5(3-piridyl) tetrazole, 800 mg., were administered. During the three-hour period of the study, the amount of both substances was sufficient to suppress free fatty acids and to produce a progressive lowering of serum triglycerides without significant changes in serum cholesterol. However, although the level of blood sugar was normalized with insulin, it did not change with the administration of 5(3-piridyl) tetrazole. The rate of fall of plasma free fatty acids and serum triglycerides was similar in both substances and positively correlated with its basal concentration.


Acute renal failure following intravenous use of radiographic contrast dyes in patients with diabetes mellitus.

Acute renal failure following roentgenologic procedures employing intravenous administration of contrast media was observed in seven diabetic patients over an 18-month period. All had long-standing diabetes mellitus complicated by retinopathy and cardiovascular disease; six had mild impairment in renal function before x-ray studies. The renal failure occurred within 48 hours of the procedure and was of the oliguric type in six of the patients. Renal function returned toward the prestudy levels within four weeks. None of the patients required dialysis. Combined analysis of our data and those of 31 cases reported in the literature suggest that certain factors in diabetic patients make them prone to develop dye-induced acute renal failure: These include old age; long duration of diabetes; preëxisting impaired renal function; the presence of diabetic complications such as retinopathy, neuropathy, and cardiovascular disease; and dehydration. All diabetic patients should be monitored closely after a radio-contrast study to detect the development of acute renal failure so that appropriate management can be instituted early in the course of the disease.


Normalization of glycemia in diabetics during meals with insulin and glucagon delivery by the artificial pancreas.

An extracorporeal "closed-loop" system has been employed to maintain glycemia in the normal range during consumption of meals in nine insulin-treated diabetics. This artificial pancreas system incorporated continuous blood glucose monitoring (0.05 ml. per minute, delay time 90 seconds), a computer programed to respond to glycemia, and a hormone delivery system. Intravenous insulin delivery rates were determined by control parameters responsive to both glucose concentration and its rate of change. Because insulin-dependent diabetics often defend themselves poorly against hypoglycemia (in some cases due to inadequate glucagon responses), the instrument was also programed for exogenous glucagon delivery. A priori selection of ideal parameters for insulin and glucagon delivery for each individual is not yet possible. Consequently, when the parameters were used for the first time on each subject, they were varied over a reasonable range. This approach resulted in a corresponding variety of glycemic responses, the average of which characterized a set of initial parameters that is generally applicable. Appropriate control parameters are presented that successfully prevented hypoglycemia. Glucagon delivery directly related to glycemia appeared sufficient for this purpose, thus obviating the need for dextrose administration. This system provides a technique for complete normalization of blood glucose concentration in the types of diabetics tested, during both fed and interprandial periods. It has yielded insights essential to the development of more sophisticated future devices.


Diabetic vascular changes in children.

The microvascular complications of diabetes are demonstrated in the eye at a very early stage with the use of retinal fluorescein angiography. One hundred and fifty-four children who have had diabetes mellitus for durations varying from one month to 18 years had their retinal vasculature evaluated with fluorescein angiography. Seventy-five per cent of the children examined had vascular abnormalities, including 20 children who had diabetes for one year or less. Twenty-five per cent of the children showed no vascular abnormalities. This included one child who had diabetes for 12 years. The severity of the vascular abnormalities increased with the duration of diabetes. Vascular abnormalities did not appear related to diabetic management or control. The possibility of two types of diabetics, one with the other without associated vascular abnormalities, is suggested.


Alteration of bile acid metabolism and vitamin-B12-absorption in diabetics on biguanides.

Since vitamin B12malabsorption has been described in diabetics on biguanides and inhibition of bile acid absorption found in rat ileum the effect of treatment with different biguanides (phenformin, buformin, metformin) on bile acid metabolism and vitamin B12 absorption was assessed in maturity onset diabetics. Biguanides did not alter faecal weight or faecal fat excretion, but they decreased faecal bile acid excretion. All biguanides tested increased deconjugation of glycocholic acid, as determined by a simple breath test technique. Vitamin B12 malabsorption was most prominent in patients on metformin. Discontinuation of biguanide treatment, or administration of antibiotics, normalized or improved the increased deconjugation of bile acids and the Schilling test. Decreased faecal bile acid excretion, positive 14C-glycocholate breath tests, pathological Schilling tests and the reversal of pathological tests by antibiotic treatment suggest that small intestinal bacterial overgrowth, leading to binding of the intrinsic-factor-vitamin B12-complex to bacteria, is responsible for the previously observed pathological Schilling tests in diabetics on biguanides. Bile acid malabsorption, possibly responsible for the cholesterol-lowering effect of biguanides, does not occur in diabetics on biguanides. Whether qualitative changes in small intestinal bile acid composition might affect cholesterol metabolism remains to be determined.


Relationship between heterogeneity of insulin responses and insulin resistance in normal subjects and patients with chemical diabetes.

Plasma insulin responses and insulin resistance were determined in 75 subjects, defined as having a normal, borderline abnormal, or abnormal oral glucose tolerance test (OGTT). Although considerable heterogeneity of insulin response existed, most patients with abnormal OGTT's had insulin responses greater than normal; none had insulin responses less than normal. The degree of insulin resistance also varied, but most patients with abnormal OGTT's were also abnormally insulin resistant A significant correlation (r=0.64, p+/-0.001) existed between insulin response and the degree of insulin resistance. However, when both variables were taken into consideration, the entire population could be divided into two groups. One group was characterized by both normal insulin responsiveness and sensitivity, the other by increased insulin response, associated with greater insulin resistance. Most patients with abnormal OGTT's fell into the latter group, but some had glucose intolerance without either an exaggerated insulin response or insulin resistance. These results suggest that true heterogeneity exists in patients with abnormal OGTT's.


Glomerular size and structure in diabetes mellitus. III. Early enlargement of the capillary surface.

The present electron microscopic study shows that the kidney hyperfunction in early diabetes can be due to a significant morphological change: an increased glomerular filtration surface. Applying standard stereological methods, the area of the peripheral wall of the glomerular capillaries was measured in biopsy specimens obtained from 7 patients with early diabetes and 7 controls.--An 80% enlargement of the capillary wall (the surface of the peripheral basement membrane) was found in the diabetics (2p=0.0096). Also the total area of the interface between the tuft and the urinary space was increased by 70% (2p=0.029). Since the thickness of the peripheral basement membrane is known to be unchanged in patients with early diabetes the finding of an increased area of the membrane implies that an increased quantity of basement membrane material is present in these patients. The significance of this phenomenon for the understanding of the metabolism of the basement membrane is discussed, and a working hypothesis is advanced for the pathogenesis of the diabetic microangiopathy.


A study of insulin binding sites in the chicken tissues.

Specific binding of chicken and porcine insulin was demonstrated in isolated chicken hepatocytes, chicken liver plasma membranes and chicken erythrocytes. In the liver, the binding reaction was characterized by a sensitivity and an apparent affinity which were similar to those observed in rat liver and, in contrast, by a decreased number of binding sites. In chicken liver, there were about 5 times fewer binding sites per mg of membrane protein or per unit of cell surface area than in rat liver. In chicken erythrocytes, the number of insulin binding sites per cell was even lower than in chicken hepatocytes. This decreased insulin binding was not accounted for by a faster insulin degradation in chicken tissues. Glucagon binding sites also appeared to be less numerous in chicken than in rat liver, at least at low glucagon concentration; however, the decrease in maximal binding capacity in chicken liver involved insulin and not glucagon binding. That chicken cells are equipped with insulin receptors which are less numerous than in mammalian cells may explain, partly at least, the physiological state of insulin resistance observed in the chicken.


Differences in cardiovascular morbidity and mortality between previously known and newly diagnosed adult diabetics.

498 diabetics were discovered in a survey of ischaemic heart disease in 10,059 men aged 40 years and over in Israel. -The diabetics were divided into previously known and newly diagnosed. -During a 5 year follow-up period, the incidence rates of fatal and non-fatal myocardial infarction and the incidence of intermittent claudication were considerably greater in both groups of diabetics than in non-diabetics. The frequency of hypertension and left ventricular hypertrophy was about the same in both groups, and in non-diabetics. -However, the pattern of increased morbidity for angina pectoris and the increased rate of sudden death is seen only in the previously diagnosed diabetics. Different pathological mechanisms might be responsible for angina pectoris and sudden death, as compared to myocardial infarction and these might be related in diabetics to the duration and severity of the disease.


Immediate effect of lesion of the ventromedial hypothalamic area upon glucose-induced insulin secretion in anaesthetized rats.

Insulin secretion, measured in vivo following an intravneous load of glucose to anaesthetized rats, was markedly increased ten minutes after bilateral electrolytic lesions of the ventromedial hypothalamic (VMH) area when compared to both sham-operated and unoperated controls. The successful lesioning of the VMH area was assessed by the subsequent occurrence of hyperphagia, as estimated by the increase in body weight. It is concluded that the ventromedial hypothalamic area exerts an inhibitory influence upon the secretory activity of the B-cells. Furthermore, the rapid disappearance of such inhibitory influence following lesions of the VMH suggests that this area of the brain may be of importance in the minute to minute regulation of insulin secretion. The precise anatomical location of the hypothalamic "nucleus" (or "nuclei") involved, as well as the neural or humoral nature of its inhibitory effect upon the endocrine pancreas remain to be elucidated.


B1-3,5-diiodotyrosine insulin: a valid tracer for insulin.

Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.


B-cell function and blood glucose control in insulin dependent diabetics within the first month of insulin treatment.

Seventeen insulin dependent diabetics were studied after two to four weeks of insulin treatment in a situation approximating to their normal daily life. Some endogenous insulin secretion, assessed by plasma C-peptide determinations, was present in all. Plasma C-peptide concentration was positively correlated with the blood glucose concentration and increased after breakfast, lunch and dinner (p less than 0.01); both peak values and relative increases were lower than those observed in normal subjects (p less than 0.01). The highest insulin secretory capacity was found in subjects with the least unstable blood glucose concentration (r=0.57, p less than 0.03), and these patients required the smallest insulin doses (r=0.54, P less than 0.04). These findings demonstrate the metabolic importance of a preserved B-cell function.


The mechanism of insulin secretion after oral glucose administration V. Portal venous IRI concentration in dogs after ingestion of glucose.

Concentrations of immunoreactive insulin activity and of blood glucose were measured in portal and peripheral venous blood in six conscious dogs after oral administration of 1.0 g/kg glucose. Portal venous samples were obtained either by chronic catheterization or by direct puncture of the portal vein through a London-cannula. Portal venous IRI was already significantly increased 5 min after the onset of the stimulus. Peripheral venous IRI pattern reflected this early increase, but the peripheral venous blood glucose level was unchanged. The results indicate that the early peripheral venous IRI increase reflects a pancreatic insulin secretory reflex.


Evaluation of exogenous insulin homoeostasis by the artificial pancreas in insulin-dependent diabetes.

With the artificial pancreas used by the authors, insulin was delivered through a venous infusion and the rate of delivery was adjusted according to data provided by a continuous blood glucose monitor. After different trials we selected control algorithms integrating two parameters: instantaneous blood glucose concentration and increasing or decreasing patterns of blood glucose. A constant basal insulin infusion rate was added and improved the control of glycaemic excursions. Different parameters concerning exogenous insulin homoeostasis were determined. The delay to reach an insulin effect was 18+/-2 min and was shortened by a priming-dose at the beginning of the infusion. The insulin effect remained for 28+/-2 min after the infusion had been stopped, but differences were noted in the morning (21+/-2 min), in the afternoon (32+/-2 min) and during the night (25+/-3 min). Insulin needs were evaluated during meals. Related to the amount of carbohydrates, the doses fell from 0.53 units/hr/g of carbohydrate for breakfast to 0.15 for dinner. From these data, it appears that the efficiency of exogenous insulin exhibits a circadian rhythm.


[Myocardial infarction in the young: evolution and clinico-coronarographic correlation (author's transl)].

Fifty patients who suffered from an acute myocardial infarction at age 40 or below and underwent coronary arteriography, were studied from 8 to 184 months after the infarction (mean follow-up 56 months). Hyperlipidaemia (60%) and cigarette-smoking (82%) were the most common risk factors, while hypertension and diabetes mellitus were found in 10% of all patients. Thirty-seven patients had two or more risk factors. Preinfarction angina was present in 7 subjects. Death rate was 14% within five years and was related to the severity of symptoms. Out of the patients with normal coronary arteriogram (6 patients) or with a single vessel disease 21 were free of angina and 30 did not suffer a reinfarction. Out of 17 patients with two or more coronary vessel disease, angina was present in 14 and reinfarction was seen in 5.


[Left atrial rhythm. Electrocardiographic study (author's transl)].

The electrocardiograms of 15 left atrial rhythm and sinusal rhythm patients are studied. The spontaneous occurrence of LAR and the possibility of return to SR by vagal stimulation manoeuvers are reported. The electrocardiographic modifications of the ectopic rhythm are shown and compared either with those of the coronary sinus rhythm or junctional A-V rhythm, or with those of the tracings recorded during atrial pacing. The intermittent occurrence of the LAR in the studied cases is theoretically ascribed to the awakening of an ectopic focus, localized in the left atrium, acting as a new pace-maker because of its excited activity or abnormal depression of the sinus.


[A contribution to ergometric tests in the definition of gravity of mitral stenosis. The importance of the behavior of the left ventricular function, not always correlation to hemodynamic alterations above the valve (author's transl)].

An attempt to evaluate the severity of the valvulopathy was performed in 50 patients with pure mitral stenosis, 36 females and 14 males, by a haemodynamic study and by an exercise test. In 76% of the cases, electrocardiographic "ischemic" abnormalities were observed during the exercise test; after the exclusion of patients over 45, and patients with atrial fibrillation and/or digitalis treatment, a high frequency (63,15%) of electrocardiographic ischemic changes with effort is still observed. No correlations between the result of the exercise test either with pulmonary pressure values, or with other haemodynamic data (cardiac index and pulmonary vascular resistances) were demonstrated. The electrocardiographic abnormalities induced by exercise in these patients are discussed; the authors conclude that this behaviour under effort is significant for the importance of the impairment of the left ventricle function in mitral stenosis.


[The surgery of atrial septal defect in adults (author's transl)].

33 cases of A.S.D. whose age ranged between 30 and 50 years are presented. Surgical indications, post-operative complications and arrhythmias are described. Atrial fibrillation due to pulmonary hypertension in the post-operative period is particularly emphasized. The authors point out that surgical indication for A.S.D. in adults is closely related to the hemodynamic of pulmonary circulation.


[Infectious endocarditis in patients with intracardiac prosthesis (author's transl)].

Infectious endocarditis involving intracardiac prosthesis continues to be a common and dangerous complication of cardiac surgery, but the incidence and severity of the disease are probably underestimated in this country. 14 cases of prosthetic endocarditis observed in a 5 years period are reported in this paper. 7 were early cases and 7 late cases. Etiology, clinical course, and pathological lesions, were similar in the two groups, while mortality was higher in the first group (100%) than in the second (85%). Delay in the diagnosis, negative blood cultures in a third of all cases, and doubts in indications for surgery, were the main reasons for a higher mortality than usual. Only one patient was reoperated on, unsuccessfully, but no patient who had not improved after two weeks of correct antibiotic treatment, survived; such cases, especially if diagnosis has been late and/or blood cultures negative, should be reoperated on without delay. The greatest efforts should be made in the prevention of the disease and, in particular, pre-operative and late post-operative prophylaxis should become more rigid and systematic.


[External recording of His bundle electrical activity (author's transl)].

A noninvasive method to record His' potentials in man is described. In several patients who needed intracardiac recording, a bipolar lead was placed across the chest, directed as conveniently as possible for the recording of His bundle electrical activity. A signal filtered (70-300 Hz) and amplified (X 100.000), was processed by a multichannel analyzer for averaging. The temporal regime of the averager was determined by a trigger which established a fiducial point on the ECG. For this purpose a QRS detector fed to a normal peripheral bipolar lead was used. The temporal stability of the system was continually checked in order to reject the recordings over the limits of +/- 1 msec. The computer program was chosen in order to select a window (usually 200 msec) which occurred up to 150 msec prior and 50 msec after the trigger signal. The sampling rate was 5 KHz for 1024 samples and the sweep counts were fixed from 128 to 512. At the same time, the D1, D2 and D3 were recorded in the other three channels of the analyzer for a more accurate measurement of the HV interval. Then an example comparing the external and interval recording was presented. Finally several external recordings were measured and the exact reproducibility of the G wave was confirmed. In conclusion we can say that the G wave is significant and suggests the electrical activity of the bundle of His.


Effect of atropine on food-stimulated gastrin release after truncal vagotomy in man.

Studies have been performed on man after truncal vagotomy to ascertain the effect of 1.2 mg of atropine sulfate on basal and postprandial immunoreactive gastrin. Atropine had no effect on basal gastrin, but it caused a significant increase in both the peak postprandial gastrin (135 to 240 pg per ml without the 139 to 308 pg per ml with atropine) and the integrated gastrin response (10.2 and 15.5 ng-min per ml over 2 hr respectively). This indicates that vagal integrity is not essential for the enhancement of the gastrin response by atropine and implies a direct effect on the antral gastrin cell.


Participation of the jejunum and ileum in postprandial gastric secretion in man.

The role of the small intestine in postprandial gastric secretory function was determined in 6 normal volunteers by diverting chyme at the ligament of Treitz and comparing the results with those obtained in the same individuals when chyme was exposed to the entire small intestine. Because diversion of chyme caused a lesser gastric secretory response, it is concluded that the small intestine contributes appreciably to the magnitude of gastric secretory responses to meals.


Effect of dietary fiber on complications of gastric surgery: prevention of postprandial hypoglycemia by pectin.

The dumping syndrome is a very troublesome problem to some patients after gastric surgery. Gel-forming carbohydrates have recently been used to modify glucose absorption. The addition of 14.5 g of pectin to a 50-g oral glucose load prevented the occurrence of hypoglycemic symptoms and maintained the blood glucose levels above control values by 64% at 90 min (P less than 0.002) and 46% at 120 min (P less than 0.01) in postgastric surgery patients whose 120-min values after 50 g of glucose alone had fallen below 50 mg per 100 ml (2.8 mmoles per liter). Breath H2 production, used as an index of bacterial fermentation of glucose, was abolished or reduced by pectin in all 5 cases in which this had previously occurred. A trial of 10 g of pectin per day prevented recurrent postprandial hypoglycemic attacks in the most severely affected individual. Pectin and perhaps other unabsorbable polysaccharides are likely to prove useful in the treatment of abnormal carbohydrate absorption after gastric surgery.


Oral cholecystography after alcoholic pancreatitis.

Retrospective and prospective studies were done to evaluate the efficacy of oral cholecystography (OCG) performed before hospital discharge on alcoholic patients with acute pancreatitis. In the retrospective study, OCG adequately opacified the gallbladder in 21 of 26 patients (81%). Of the 5 patients with inadequate opacification, 1 was jaundiced at the time of OCG; the other 4 had OCG before resumption of solid food. In the prospective study, OCG done in nonjaundiced patients shortly after resumption of food yielded adequate opacification in 19 of 21 patients (90%) without gallstones. We conclude that in nonjaundiced alcoholic patients with acute pancreatitis not caused by gallstones, OCG performed after resumption of a solid diet and before hospital discharge is usually successful in opacifying the gallbladder.


Stimulation of pancreatic secretion of water and electrolytes by furosemide.

The effect of furosemide on secretin-stimulated pancreatic secretion was examined in 12 normal subjects using a perfusion method to quantitate pancreatic output. During continuous secretin infusion (0.9 U per kg per hr), secretory volume rose to a steady state level of 32.5 +/- 10.2 ml per min. When a bolus injection of furosemide (20 mg) was given during continuous secretin infusion, mean secretory volume increased further to a maximum value of 110 +/- 14.7 ml per min. Similarly, the outputs of bicarbonate, sodium, and chloride increased significantly after furosemide, compared to values obtained with secretin infusion alone. Total bilirubin output fell after furosemide, suggesting that the effect of furosemide on secretory volume and electrolyte output was not due to a stimulatory effect on bile flow. Furosemide also had no effect on duodenal water transport. These observations demonstrate that furosemide stimulates pancreatic secretion of water and electrolytes, possibly via inhibition of pancreatic ductal absorption of sodium.


Benign pneumoperitoneum after fiberoptic colonoscopy. A prospective study of 100 patients.

A prospective study of 100 consecutive unselected patients undergoing both diagnostic and therapeutic firoptic colonoscopy was undertaken. Our incidence of colonic perforation is 1%, which is similar to the incidence reported in the literature. This study suggests that even when immediate postcolonoscopic supine and erect abdominal radiographs as well as pre- and postcolonoscopic total blood counts and enzyme levels to supplement clinical impressions are obtained, the incidence of perforation of the colon after fiberoptic colonoscopy is low and not any higher than that reported in the literature. Pneumoperitoneum may occur after fiberoptic colonoscopy with minimal or no clinical evidence suggesting perforation. Perforation in some patients may be treated conservatively without the need of emergency laparotomy.


Reassessment of the Widal test in the diagnosis of typhoid.

The Widal test was done in 100 nontyphoidal febrile pients, 53 patients with proven typhoid, and in 61 patients with immunological disturbances in an are where typhoid is endemic. Salmonella typhi H or O agglutinin titers of 1:160 or more were seen in only 1% of nontyphoidal fevers. Using these criteria, the Widal test was of diagnostic value in 50 of 53 (94.3%) of patients with typhoid. The Widal test was positive in 85.7% of patients even in the first week of the illness, possibly owing to the hyperimmune state of the patients. A false-positive test was found in 11.5% of patients with major immunological disturbances in whom the Widal test must therefore be interpreted with caution.


Symptomatic diffuse esophageal spasm. Manometric follow-up and response to cholinergic stimulation and cholinesterase inhibition.

Uniform criteria for defining symptomatic diffuse esophageal spasm (SDES) are lacking. Records of patients undergoing esophageal motility studies over a 3-year period were reviewed. Those patients who fulfilled a predefined set of arbitrary criteria for SDES returned for repeat motility study. Manometric abnormalities seen on initial examination remained unchanged on follow-up evaluation. In addition, response in SDES to two pharmacological agents--a cholinergic agonist and cholinesterase inhibitor--was evaluated and compared to that seen in normal subjects and in subjects with heartburn. Patients with SDES responded similarly to both agents, and their responses were significantly greater than those seen in controls or in subjects with heartburn. The results suggest that SDES is a relatively homogenous entity, with respect to both maintaining stability of manometric abnormalities and response to two different pharmacological agents. The future evaluation of similarly defined patients may lead to ascertaining more clearly the underlying pathophysiology of this "syndrome".


Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). I. Chemical analysis and biological properties of PEG 400.

A new approach to the measurement of intestinal permeability in man has been developed, using low molecular weight polyethylene glycol (PEG 400) as probe molecules. PEG 400 (range of molecular weight 232 to 594) is a mixture of water-soluble molecules of different sizes which can be extracted readily from biological fluids and analyzed by gas-liquid chromatography. PEG 400 is nontoxic, not degraded by intestinal bacteria, not metabolized after absorption, and rapidly excreted in urine. The different-sized molecular components cross the intestinal epithelium at different rates, allowing characterization of the passive permeability properties of the mucosa.


Measurements of intestinal permeability using low molecular weight polyethylene glycols (PEG 400). II. Application to normal and abnormal permeability states in man and animals.

A new approach to the measurement of intestinal permeability using low molecular weight polyethylene glycols (PEG 400) has been applied to the study of normal and abnormal permeability states in man and animals. Successful assessments of gastric, jejunal, ileal, and colonic permeability suggest that the technique has application to any area of the gastrointestinal tract. The method has shown that bile acids alter mucosal permeability in the stomach and colon and that celiac sprue is associated with decreased intestinal permeability. These examples illustrate the potential of the technique for studying the function of diseases intestine in man.


Effect of histamine H2 antagonism by metiamide on the response of the canine gastric mucosa to acid and bile salt.

Prevention of acute gastric erosions with histamine H2-receptor blocking agents suggests that these drugs may improve the ability of the gastric mucosa to maintain electrical, ionic, and protein concentration gradients. In 5 awake mongrel dogs, transmural potential difference, ion fluxes, and protein loss were measured across Heidenhain pouches topically exposed to isotonic solutions containing either 80 mM HCl or 80 mM HCl plus 20 mM sodium taurocholate (BS). The dogs received an intravenous infusion of either saline (as a control) or the H2 antagonist metiamide, 10 mumoles per kg-hr. Metiamide increased the H+ clearance rate found after acid test solution exposure but had no significant effect on potential difference or ion fluxes. H2 antagonism decreased the protein loss but not the increase in cation permeability due to BS. Net H+ loss actually increased, which, along with a decrease in Cl- gain, suggests inhibition of acid secretion by metiamide in BS-exposed gastric mucosa. These effects of metiamide point to histamine as a likely mediator of the gastric mucosal damage due to BS.


Exocrine pancreatic insufficiency syndrome in CBA/J mice. III. Pathological and genetic analysis.

A clinical and histopathological description of exocrine pancreatic insufficiency syndrome in CBA/J mice is presented. Amelioration of clinical symptoms by pancreatic enzyme replacement therapy is described, as are breeding experiments designed to test the hypothesis that the etiology of this syndrome is a recessive mutation. Our failure to propagate the expected numbers of animals with the syndrome by genetic means leads us to the conclusion that it is not transmitted as an autosomal recessive mutation. Our finding of focal histological lesions of the exocrine pancreas in large numbers of clinically normal CBA/J mice suggests that the CBA/J genetic background is some way predisposes this strain to the spontaneous necrosis and atrophy of exocrine cells that is pathognomonic of this disease.


Modulation of colonic motility by peripheral neural inputs to neurons of the inferior mesenteric ganglion.

Colonic motility is known to be regulated, in part, by postganglionic sympathetic neurons whose cell bodies are located in the inferior mesenteric ganglion (IMG). Several studies have demonstrated that the neural activity of postganglionic neurons located in the IMG results from the synaptic integration of neural input received not only from the central nervous system via the inferior splanchnic nerves but also from sensory receptors located in the periphery and received via the lumbar colonic, intermesenteric, and hypogastric nerves. To investigate some of the interactions among colonic motility, peripheral neural input to the IMG, and postganglionic neural activity, intracellular recordings were made from single neurons located in the IMG of in vitro IMG-colon preparations obtained from guinea pigs. Recordings of colonic intraluminal pressures were simultaneously obtained with these neurophysiological recordings. Gross afferent input to the IMG from colonic mechanoreceptors was found to be nonadapting, to the correlated with physiological levels of intraluminal pressure, and to vary with propulsive motor activity. Both peripheral and central preganglionic inputs to the IMG reduced or abolished colonic motiligy, but with varying degrees of effectiveness. It is concluded that the firing patterns of sympathetic postganglionic neurons affecting motility of the terminal colon result primarily from the synaptic integration of inputs from preganglionic fibers of both central and peripheral origin.


Percutaneous transhepatic catheterization of the portal vein for the study of portal hemodynamics and shunts. A preliminary report.

A technique for catheterizing the portal vein transhepatically, based on our method for percutaneous transhepatic cholangiography, is described. Using this technique, quantitation of the intrahepatic shunt and extrahepatic shunt from the splenoportal axis is possible. It involves injection of 99mTc-macroaggregated albumin into the splenic vein at the splenic hilum and 131I-macroaggregated albumin into the portal trunk, followed by differential counting over predetermined areas of the liver and lungs. Catheterization was successful in 20 of 30 patients in whom it was attempted. The intrahepatic shunt indices varied from 1.0 to 78.4% and the extrahepatic shunt indices ranged from 0 to 49.9%. These values appeared to correlate closely with the size of collaterals opacified by portography.


Radioimmunoassay of bile acids: development, validation, and preliminary application of an assay for conjugates of chenodeoxycholic acid.

A rapid, sensitive, precise radioimmunoassay for conjugates of chenodeoxycholic (chenic) acid has been developed and validated. Immunogen was prepared with chenylglycine couples to bovine serum albumin, emulsified in Freund's complete adjuvant, and injected intracutaneously in rabbits. Antibodies of moderate titer (used at 1:7500 final dilution) were obtained. Tracer of high specific activity was prepared by reductive tritiation of delta11-chenylglycine. The binding step required 1 hr at room temperature; separation of bound tracer was achieved by addition of ammonium sulfate. The limit of sensitivity of the assay was about 20 nmoles per liter, and the lower limit of the working range was 0.4 mumole per liter. The assay was validated by measuring levels in samples of fasting state serum to which known amounts of chenylglycine had been added; the assay was also validated by means of gas-liquid chromatography on sera from jaundiced patients. The median fasting state serum level in 56 Caucasians and blacks was 0.9 mumole per liter (upper limit of normal (95% confidence) being 2.3), which is in the same range as that reported by others using gas-liquid chromatography. A 5- to 10-fold increase in levels of chenyl conjugates was observed 1 hr after the ingestion of a liquid meal in healthy persons.


Increased sulfation and decreased 7alpha-hydroxylation of deoxycholic acid in ethinyl estradiol-induced cholestasis in rats.

Deoxycholic acid conjugation, transport capacity, and metabolism were compared in control and ethinyl estradiol-treated rats. Control rats were found to have a lower capacity to transport deoxycholic acid than taurodeoxycholic acid, and both were decreased by ethinyl estradiol treatment. During [24-14C]sodium deoxycholate infusion, [14C]biliary bile acid secretion increased, but bile flow did not change significantly in either control or ethinyl estradiol-treated rats. Ethinyl estradiol-treated animals excreted significantly less 14C as taurocholic acid than did control animals, consistent with an impairment of 7alpha-hydroxylation of taurodeoxycholic acid. Ethinyl estradiol treatment did not impair conjugation of deoxycholic acid, but did result in an increase in sulfation of taurodeoxycholic acid from 1.5% in controls to nearly 4.0% (P less than 0.01). These results are consistent with the hypothesis that the rat has a poorer tolerance for deoxycholic acid than do certain other species. Furthermore, the rat converts deoxycholic acid, a poor choleretic, to taurocholic acid, a good choleretic. When this conversion is impaired with ethinyl estradiol treatment, sulfation may be an important alternate pathway for excretion of this potentially harmful bile acid.


Studies of idiopathic intestinal pseudoobstruction. I. Hereditary hollow visceral myopathy: clinical and pathological studies.

A 15-year-old girl with idiopathic intestinal pseudoobstruction is reported. She presented with a long term history of low grade obstructive symptoms, diarrhea, and poor nutrition culminating in an acute obstructive attack leading to exploratory laparotomy. At surgery, the small bowel and colon were dilated, with no mechanical obstruction found. Further evaluation revealed her to have a diffuse disorder of gastrointestinal smooth muscle function involving esophagus, small bowel, and colon. Because medical management failed to control symptom, a gastrojejunostomy was done to bypass a megaduodenum. A third laparotomy was necessary 2 months later because of intractable obstructive symptoms. At this last laparotomy, the afferent loop was taken down and a duodenoplasty and duodenojejunostomy were performed, resulting in clinical improvement. Light and electron microscopic study of the excised small intestine showed marked thinning and degeneraton of the smooth muscle, with replacement by fibrous tissue. The myenteric plexus was normal. This case demonstrates that a degenerative disease of smooth muscle may be one cause of idiopathic intestinal pseudoobstruction.


Studies of idiopathic intestinal pseudoobstruction. II. Hereditary hollow visceral myopathy: family studies.

Twelve relatives of a 15-year-old girl with idiopathic intestinal pseudoobstruction were studied with esophageal manometry or cine-esophagography to determine whether the disease was genetically transmitted. Four maternal relatives, including the patient's mother, 13-year-old brother, one aunt, and one of that aunt's children had mild dysphagia and esophageal motor dysfunction. In addition, the patient's mother and 13-year-old brother had a flaccid bladder and bilateral ureteral reflux, respectively. The brother had abnormal bladder smooth muscle by light microscopy. We conclude that idiopathic intestinal pseudoobstruction in this family is secondary to a generalized disease of smooth muscle which is transmitted as a dominant trait of variable expressivity, manifested in some family members as a mild disorder of esophageal smooth muscle dysfunction, at times accompanied by bladder dysfunction. We suggest that this form of idiopathic intestinal pseudoobstruction be called "hereditary hollow visceral myopathy." Esophageal manometry may prove useful as a tool for studying the inheritance of this disorder.


Downhill varices: report of a case 29 years after resection of a substernal thyroid gland.

A case of varices of the entire esophagus in a patient who had undergone resection of a substernal thyroid gland 29 years previously is reported. Dilated esophageal veins, varices, may serve as collateral channels between the portal and systemic systems. When the superior vena cava is obstructed, blood from the upper extremities and head is returned to the heart via downhill varices. Obstruction of the superior vena cava proximal to the azygos vein results in varices of the upper esophagus. Obstruction distal to the asygos vein, as in this patient, results in varices of the entire esophagus. Portacaval shunt has no place in the management of these patients. Downhill varices should be considered in any patient with superior vena caval obstruction from any cause.


Hepatic veno-occlusive disease due to pyrrolizidine (Senecio) poisoning in Arizona.

An infant with documented hepatic veno-occlusive disease due to ingestion of pyrrolizidine alkaloids is presented. The alkaloids were ingested in the form of an herbal tea commonly used as a folk remedy among the Mexican-American population. Among these people, this herb is known as gordolobo yerba. The patient presented with acute hepatocellular disease and portal hypertension which progressed over 2 months to extensive hepatic fibrosis. Other potential causes of hepatic venous occlusion were absent.


Specific diagnosis of foodborne disease.

To control foodborne disease effectively and to treat patients and their contacts appropriately, it is important to determine the etiology of a foodborne disease outbreak. The majority of such outbreaks reported to the Center for Disease Control are of undetermined etiology, usually for lack of appropriate laboratory tests. In this paper, the commonly reported foodborne diseases are differentiated clinically by their median incubation period, predominant symptomatology, and median durations of illness, and epidemiologically by their vehicles of transmission, geographic locations, and seasonal predilections. Laboratory tests are recommended with which to confirm the initial clinical and epidemiological impression.


Effects of calcium and magnesium ions upon fat absorption by sacs of everted hamster intestine.

Sacs of everted hamster jejunum were incubated with fatty acid and monoglyceride in bile salt solutions either with or without added salts of calcium and magnesium. At very low concentrations of Ca2+ and Mg2+, the intestine produced very few chylomicrons. However, at physiological concentrations of the ions, the gut-preparation released numerous chylomicron-like particles into the serosal fluid.


Thyroxine-evoked decrease of jejunal lactase activity in adult rats.

Daily administration of L-thyroxine (20 micrograms or 200 micrograms/100 g body weight) to adult male rats decreased jejunal lactase activity by 35% after 2-, 3-, 4- and 10 days. Four days of injections of D-thyroxine (200 micrograms/100 g body weight/day) produced a similar decrease of lactase activity. Sucrase activity was uninfluenced except for a 30% increase after daily injections of L-thyroxine (200 micrograms/100 g body weight) for 10 days. Acid beta-galactosidase activity was unaffected by either D- or L-thyroxine.


Histamine-sensitive adenylate cyclase of human gastric mucosa.

The adenylate cyclase system of human fundic gastric mucosa was found to respond to histamine, prostaglandin E 2 and the non-hormonal activators NaF and 5'-guanylyl-imidodiphosphate (GMP(PNP)). Half maximal stimulation of enzyme activity was observed at a histamine concentration of 50 micrometer. Maximal stimulation (about 25%) occurred at a histamine concentration of 1 mM. The stimulatory effect of histamine was competitively inhibited by cimetidine. The stimulatory effect of prostaglandin E 2 was found to be dose-dependent over a concentration range from 0.1 micrometer to 1 mM exerting maximal effects at 0.3 mM. NaF and GMP(PNP) by inducing an about 3.5-fold increase of enzyme activity were more potent in stimulating the human enzyme system than histamine and prostaglandin E 2. Maximal stimulatory doses of prostaglandin E 2 and histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. This implies that histamine acts on an individual adenylate cyclase system. Our results are suggestive for the existence of an adenylate cyclase system in human gastric mucosa coupled to histamine H 2-receptor sites.


An inhibitory innervation at the gastroduodenal junction in anesthetized dogs.

Our aim was to investigate the existence of an inhibitory innervation at the gastroduodenal junction (GDJ) in the whole animal. Motility induced by vagal stimulation was monitored with strain force transducers on the gastric antrum, pylorus and duodenum. The experiments were carried out in two phases: the control phase following vagotomy (TV), and the treated phase where atropine sulfate (1 mg/Kg) was injected intravenously (TV+A). After TV, antral, pyloric and duodenal contractile activity was significantly increased (P less than 0.01) during the period of vagal stimulation. After (TV+A), spontaneous activity in the antrum and duodenum was abolished and vagal stimulation did not increase motility in these organs. Spontaneous pyloric activity present after atropine administration was inhibited by stimulation, and a concomitant relaxation of the pylorus was also demonstrated. Following the termination of the stimulus, a significant increase in contractions was noted on the pylorus. These experiments demonstrate the existence of an atropine-resistant inhibitory innervation at the GDJ in the anesthetized dog.


[Programmed labor: methods, results, guidelines (author's transl)].

The programming of labor (setting the best possbile time under optimal conditions) was carried out in the University Women's Hospital, Freiburg i. Br. between 1970 and 1975 in 1121 cases. No perinatal mortality was reported. The secondary frequency of cesarean section for this primarily uncomplicated labor was 3.21% (general hospital statistics for this time period: 6.29%). The most important factors for the strict standardized method of induction is the observation of the pelvic score (desired: greater than 6) and a moderate dose of oxytocin or prostaglandin based on the essential amniotomy. In a statistical comparison of three groups of patients (n = 786): programmed labor (n = 427), induction via the same type of method where transference was suspected (n = 158), and uncomplicated spontaneous labor (n=183), the results with induced labor were better than those with spontaneous labor. In addition for the fact that the course of labor could be preplanned and the period of labor shortened intrauterine and partal complications occurred less frequently with programmed labor than with spontaneous labor. Placental complications and the tendency toward postpartum atony must be discussed. Minor complications decreased as the weight, length and gestation period of the newborn increased. Individual palpation until the physiological maturity for birth is reached would, therefore, seem to be required. Observe the conditions and increase antepartal controls. Only by setting the exact time for labor with modern methods of supervision is it theoretically possible to eliminate the danger of active management. The organizational problem involved with a general programming of labor poses the major problem at present.


[Atypical forms of the Mayer-Rokitansky-Küster-syndrom (author's transl)].

The internal genitalia in extraordinary forms of müllerian duct malformations were studied in ten patients wit the so called Mayer-Rokitansky-Küster syndrome. Additional abnormalities of the kidneys and the urinary tract were observed in seven cases. Unilateral malformations of the genitalia were not necessarily combined with homolateral malformations of the kidneys and the urinary tract.--Another pathogenetic mechanism seems therefore to exist. There are some clues, that a faulty gonadal differentiation might be responsible, thus inducing regression of the müllerian ducts, as normally seen in male individuals.


[Two-dimensional echography with a real-time scanner in extrauterine pregnancy (author's transl)].

Fifty-nine cases of ectopic pregnancies in the region of the adnexa and 2 cases with intracervical localization were described with the help of picutres acquired via the so-called "rapid intensity modulated ultrasonography". The findings were based on 16,000 examinations. Problems involved with interpretations were presented. The possiblities and limitations of the methods were discussed in light of the available literature.


[Development of perinatal mortality rate in a central hospital (author's transl)].

Perinatal mortality rate is an important parameter of the obstetrical efficacy. The analysis of case reports of 10 590 newborn infants results in the fact, that perinatal mortality could be decreased from 27,15% to 20,11%. Special interest is directed to subpartual mortality, being the proportion of entire mortality reflecting the quality of intrapartal supervision. Critical and precise single case analysis of subpartual deaths was performed in order to detect failures of the supervision system with consequential amelioration of perinatal care. Methods of intensive obstetrical care, introduced since 1973 such as ultrasonic diagnostic, screening for placental insufficiency, amniotic fluid diagnostics tocolysis, cardiotocography and micro-blood analysis, resulted in a significant raise of quality. Unselected perinatal mortality could be decreased by approximately 25%.


[Parametrial aspiration cytology (author's transl)].

Cytologic reports of fine needle aspiration from the parametrial region are compared with the clinical course of 48 patients with and without recurrence after therapy of gynaecologic cancer. Parametrial aspiration cytology is a reliable as histology done by Van Silverman biopsy. The frequency of complications and insufficient material is low. Anaesthesia is not necessary. The procedure is simple. Aspiration cytology seems to be a progress in detecting recurrence of cancer in the parametrial soft tissue region.


[Needle biopsies of areas suspicious of recurrence in patients with gynaecological tumors (author's transl)].

With the biopsy needle of Franzén, 403 needle biopsies were carried out in 263 patients with gynaecological malignant tumors. In 152 cases the results of the aspiration cytology were compared with microscopic examinations or with the clinical course for at least 6 months. In 88 cases with probable recurrence the needle biospy showed a positive or suspicious result in 73 cases. A positive needle biopsy result was confirmation of recurrent tumor whereas a negative result did not rule out a recurrence. Aspiration cytology is a valuable ancillary method in the diagnosis of the recurrence of gynaecological tumors.


[The diagnosis and treatment of mixed anaerobic vaginal dischargs (authors' transl)].

In about 5% of 3355 patients the microscopic examination of the vaginal discharge in normal saline showed a characteristic fast moving rod. More than 80% of these patients  complained of a discharge with a foul smell during the menstrual period. Bactriology showed an anaerob gram negative rod which was difficult to grow and is as yet unclassified. Following treatment with one gram of Mimorazol every 12 hours for 3 doses, 71,5% of the patients were cured and showed a normal vaginal flora without further treatment. In around 24,13% of the patients the gram negative rod disappeared but a persistent mixed flora required further treatment. In 4.3% of the patients a recurrence occurred. An attempt was made to prevent recurrent infection prior to the follow-up examination by prohibition of sexual intercourse with an untreated partner, bathing in public swimming pools, and the use of sponges or wash cloths. In the course of the investigation the suspicion of contamination from the water of public pools became apparent. The diagnosis, treatment and transmission and the pathogenecity of the fast moving negative rod is discussed.


The effect of descriptive anger expression, insult, and no feedback on interpersonal aggression, hostility, and empathy motivation.

In a test of the hypothesis that descriptive anger expression elicits less subsequent aggression and greater empathy than does aggressive insult, 60 male undergraduates were instructed to set varying levels of shock for an opponent during a series of competitive trials before and after hearing one of four types of taped comment. Results indicated that descriptive anger expression led to a significant decrease in aggression, while no feedback (opponent said nothing) led to an increase in aggression. Insult and no anger feedback resulted in little change in aggressive behavior. In contrast, descriptive anger expression, insult, and no anger feedback produced more residual hostility than did no feedback. Descriptive anger expression Ss appeared to be more motivated by empathy in setting shocks, as compared to the other three groups. Empathy was found to be generally associated with lower shock settings initially and with reductions in shock settings following the opponent's comments. Empathy, however, was not related to Ss' hostility ratings. The results tend to support the clinical utility of descriptive anger expression in improving interpersonal relations.


Who is responsible for elderly patients on orthopedic wards?

A retrospective survey of the geriatrician's role on the orthopedic ward showed that his or her main aim should be to advise the orthopedic team of the advantages of long-term planning for every elderly patient admitted. From the moment of the initial assessment, it is important to emphasize the need for a more detailed medical, social, and psychiatric history; to alter the management of incontinence; and to point out the differences in the nursing and rehabilitation requirements of elderly patients. Once this is achieved, the geriatrician should revert to the role of the clinical adviser in medical diseases affecting the elderly.


Understanding and diagnosing senile dementia.

Dementia is one of the most common syndromes afflicting the aged, and it should be ranked as a major cause of death. Senile dementia and Alzheimer's disease should now be viewed as one and the same. Familiarity with the cardinal signs of dementia enables the physician to differentiate it from various "functional" disorders. Before making a diagnosis of senile dementia, it is important to exclude all forms of treatable disease, including toxic, metabolic, infectious, neoplastic, and traumatic disorders. Most older patients with dementia will be found to have Alzheimer's disease, for which no definitive treatment is available.


Evidence for a transmissible factor in Crohn's disease.

The injection of rabbits' ileum with homogenates of both normal and Crohn's affected human bowel tissue gave Crohn's-like changes in 11 of 27 animals after six months, but 12 months after injection the rabbit bowel had reverted to normal. The addition of ampicillin to the homogenates prevented the appearance of these Crohn's-like changes in 12 out of 12 rabbits. These results are interpreted as providing evidence for a transmissible factor present in both normal and Crohn's affected bowel in the aetiology of Crohn's disease.