Steroid receptor levels and histology of endometriosis and adenomyosis.

Steroid receptors in endometriosis and adenomyosis were investigated to clarify their clinical significance. The receptor levels were determined by Scatchard plot analysis (4 degrees C, by dextran-coated charcoal). In the cytosols of both tissues, the 17 beta-estradiol-estrogen receptor (ER) complex demonstrated a dissociation constant (Kd) of 4.5 x 10(-10) M; the Kd of the progesterone-progesterone receptor (PR) complex was 1.5 x 10(-9) M; and the Kd of the dihydrotestosterone-androgen receptor (AR) complex was 4.0 x 10(-10) M. Seven cases of ovarian endometriosis were studied. The ER and PR levels in endometriosis seemed to be lower than those in the corresponding normal endometrium. AR was also present. There was a suggestion that most endometriosis is least responsive to progestogens. Ten cases of adenomyosis were studied. Histologic dating revealed a delay in the most aberrant endometrial tissue in adenomyosis, as compared with dating of corresponding normal endometrial tissue. ER and AR were detected in all cases. PR was not detected in some cases and, when detected, the content seemed to be lower, possibly suggesting the delayed dating.


HLA antigen studies in women with recurrent gestational disorders.

The frequencies of HLA antigens were determined in an experimental group of women with recurrent gestational disorders mainly expressed as spontaneous abortions of unknown etiology. The estimated antigen frequencies in this group were compared with the antigen frequencies in 158 unrelated persons (79 couples with no record of secondary infertility). A significantly higher frequency of antigen HLA-A9 was found in the experimental group as compared with the controls (corrected P = 0.0015). A greater degree of HLA compatibility was found between each woman from this group and her husband, considering 45 couples, as compared with 79 control couples. These results indicate that gene(s) close to the HLA region may have an influence on the reproductive performance in humans.


Changing profiles in vasectomy subjects in the past decade.

Two groups of vasectomy patients were reviewed: 376 men operated upon between 1968 and 1971 and 608 between 1974 and 1978. Average age, length of marriage, and number of living children prior to vasectomy were greater in the first group (P less than 0.01). The results are compatible with the idea that couples are planning smaller families and turning increasingly to vasectomy as a reliable permanent birth control method immediately following the completion of their families.


Serum gonadotropins and testosterone in infertile patients with varicocele.

Serum concentrations of gonadotropins and testosterone in 25 infertile men with varicocele were compared with those in control men and men with idiopathic oligo-azoospermia. No significant difference was found in values of serum follicle-stimulating hormone (FSH) (14.9 +/- 13.6 mIU/ml), luteinizing hormone (LH) (24.9 +/- 19.1 mIU/ml), and testosterone (5.0 +/- 2.1 ng/ml) when the group with varicocele was compared with either the control group (FSH, 7.0 +/- 3.2 mIU/ml; LH, 23.6 +/- 16.0 mIU/ml; testosterone, 5.3 +/- 1.8 ng/ml) or the group with idiopathic oligo-azoospermia (FSH, 23.0 +/- 22.69 mIU/ml; LH, 36.7 +/- 24.1 mIU/ml; testosterone, 5.31 +/- 2.3 ng/ml). However, compared with the control group, there was a significant elevation of serum FSH levels in patients with varicocele whose testicular biopsy score counts were between 1 and 4. The importance of preoperative determination of the serum FSH level is discussed.


The Laurence-Moon-Bardet-Biedl syndrome: unresponsiveness to the action of testosterone, a possible mechanism.

The pathogenesis of hypogonadism and hypogenitalism was investigated in a male patient with the complete form of the Laurence-Moon-Bardet-Biedl syndrome. Synthetic gonadotropin-releasing hormone induced an increase in serum luteinizing hormone levels from 16.5 mIU/ml to 19.3 mIU/ml and in follicle-stimulating hormone levels from 18.5 mIU/ml to 25.9 mIU/ml. Serum testosterone levels were normal and did not rise after stimulation with human chorionic gonadotropin. The administration of thyrotropin-releasing hormone resulted in an increase in serum thyrotropin levels from 9.0 microU/ml to 12.0 microU/ml. Serum testoterone/estradiol-binding globulin, adrenocorticotropic hormone, and T3 resin uptake were normal. Serum cortisol showed a normal diurnal variation. The sex chromatin test was negative and the karyotupe revealed a 46,XY chromosome pattern. On biopsy, the left testis lacked germinal cells and the right testis showed spermatogenic arrest. Signs of hypogonadism and hypogenitalism persisted after 11 months of testosterone treatment. In this patient the target-organ unresponsiveness resulted in hypogenitalism and hypogonadism.


Electrophysiology of the rabbit oviduct following tubal microsurgery.

The ability of tuboplastic microsurgery to restore electrical continuity across an anastomosis site was investigated in the rabbit. Three to six weeks following transection and end-to-end anastomosis of the tubal ampulla or isthmus, the pattern of electrical activity adjacent to and across the anastomosis site was examined. Recordings were made in vitro using arrays of closely spaced suction electrodes 68 to 72 hours after an ovulating dose of human chorionic gonadotropin. The pattern of electrical activity across anastomosis sites was not significantly different from corresponding portions of unoperated control oviducts. Microsurgical anastomosis restored electrical continuity between anastomosed segments in both the ampulla and isthmus.


Studies of the immunologically specific retention of antigen-activated lymphoid cells in antigen-containing lymph nodes.

Mouse spleen lymphocytes proliferating under the influence of SRBC, or educated thymocytes were labelled in vivo or in vitro with 3H-thymidine and transferred intravenously to syngeneic recipients, which had received a subcutaneous injection of the same, or a non-cross-reacting, antigen (SRBC, rat or chicken RBC, DNP-proteins) into the right front footpads. The left footpads had been injected with a control (non-cross-reacting) antigen. The right (ipsilateral) and left (contralateral) regional lymph nodes were compared on the basis of their radioactivity and radioautography. SRBC-containing lymph nodes retained specifically both viable primed spleen cells and educated thymocytes. Treatment of donor spleen cells with anti-T serum and complement prevented specific retention. Administration of anti-SRBC serum to the recipients had a similar effect. Retention occurred during 6 days after administration of the antigen to the recipients and was mediated by radioresistant host lymph node cells. It declined profoundly when host macrophages were blocked with charcoal particles. The data obtained suggest a major role of the direct contact between T cell receptors and macrophage-bound antigen in the specific lymphocyte retention.


[A quantitative analysis of urinary 17-KS by GC-MS (author's transl)].

A quantitative analysis of seven components of 17-KS in human urine was successfully carried out by GCMS. The sample including deuterated 17-KS was introduced into TMS derivatives by BSTFA in pyridine. The derived TMS derivatives were analysed using the GC-MS system equipped with the column of 0.5% NPGS Chromosorb W AW DMCS, and the temperature was programmed from 180 degrees C to 240 degrees C at 3 degrees C/min. increment. Seven components were well separated, and each fraction was analysed by MS spectrum. Normal human urine was analysed by this method, the result of which is summarized in Table 3.


The incidence of divorce within cohorts of American marriages contracted since the Civil War.

The proportion of marriages that end in divorce can be estimated from vital registration or from census data. The former source suggests considerably higher levels of divorce than does the latter. A new series, combinig the two sources, is presented for annual marriage cohorts back to 1867. Actual experience to 1970 is traced and a projection beyond that point is made for cohorts with incomplete divorce histories. The cohort divorce series moves steadily upwards and shows much less variability than an equivalent series of period divorce rates. Factors related to high divorce within a cohort are armed service mobilization and high unemployment rates in the year of marriage, and slow national economic growth between pre- and post-marital periods.


Seasonal migration and seasonal variation in fecundability: effects on birth rates and birth intervals.

Seasonal patterns in conception rates have been documented in several recent studies. In this paper, a mathematical model of the reproductive process is developed through which the impact of such variation in conception rates is assessed. It is found that the effect on fertility can be quite substantial, but that the birth rate when seasonal variation is occurring is approximated well by the birth rate calculated when conception rates are constant at their mean. These results indicate that further documentation of seasonality in conception rates and exploration of the causes of these patterns and their change is an important area for demographic research.


Bias in graduated life table functions.

Survival proportions and expectations of life estimated directly from observed crude mortality rates are usually unbiased. Estimates of survival proportions and expectations of life obtained from graduated mortality rates at individual ages tend to be positively biased, although the actual bias is small for reasonably large experiences.


A close look at the demography of Afghanistan.

The first survey designed to allow estimates of the demographic characteristics of Afghanistan's sedentary population was conducted during the period 1972-1974. Our analysis of these data, based on recently developed techniques for handling imcomplete or inaccurate data, suggests that this population lives under conditions that are extreme when judged by modern standards.  Marriage is early, especially for females, and universal. Marital fertility conforms to a pattern of natural fertility and total fertility is high. The birth rate is among the highest in the world today, and the expectation of life at birth is among the very lowest. Mortality is lower in urban areas than in rural areas, whereas total fertility is approximately the same in both. Our estimates of fertility and mortality imply stable populations which match closely the observed age distributions for both the rural and urban areas.


The two generation urbanite hypothesis revisited.

It is generally accepted that socioeconomic differentials in fertility are minimal among urban couples with nonfarm origins -- two generation urbanites. In this paper, we replicate Duncan's (1965) analysis to see if the two generation urbanite hypothesis holds for more recent cohorts of American women. In four cohorts of women, drawn from three recent fertility surveys, we find no support for the two generation urbanite hypothesis. It appears that the links between farm background, socioeconomic status and fertility were different for the low fertility cohorts of women born in the early 1900's and the more recent cohorts of women who experienced the baby boom.


Models of illegitmacy: United States, 1969.

Three theoretical perspectives on illegitimacy, the anomic, the subgroup, and the demographic, are reviewed and compared. A composite causal model is then developed and estimated using areal data derived from the 1970 U.S. Census. While theoretical nonspecificity disallowed a definitive test, all three perspectives yielded valuable insight into the complex mechanisms underlying illegitimacy rates. Results indicate that variation in illegitimacy rates is systematically related to variation in social structure and that integration of the three positions should prove useful to further research.


The changing U.S. labor force and occupational differentiation by sex.

The degree of occupational differentiation by sex in the U.S. labor force is examined utilizing various measures and occupational classifications over the period 1900-1970. A consideration of comparable occupations over time indicates that while occupational differentiation by sex is still substantial, an irregular, measurable decline in that differentiation has occurred during this century. Existing labor force structure seems relatively unimportant in explaining this ongoing change. Apparently more significant are social and historical factors as they have influenced specific occupations in certain decades.


Sex differences in patterns of career mobility.

Using the 1970 Census data, this paper examines differences by sex in patterns of intragenerational occupational mobility over a five year period (1965-1970) for two cohorts of white, U.S. men and women. The observed mobility patterns are separated into that part due to structural factors (i.e., the different distributions over occupational origins and destinations by sex) and that due to sex-related individual and group characteristics. Most of the observed differences in mobility patterns are found to be the result of occupational sex segregation.


RNA and protein synthesis of dyskeratotic cells in morbus Darier. An autoradiographic study.

RNA and protein synthesis of dyskeratotic cells in Darier's disease was studied by autoradiography after in vitro incubation with 3H-uridine, 3H-leucine and 3H-histidine. These three isotopes were incorporated in cells constituting the basis and wall of the lacuna, while they did not accumulate in isolated acantholytic and dyskeratotic cells in the lacuna, corps ronds and grains.


[Phototoxicity of Bergamot oil. Comparison between humans and guinea pigs].

Phototoxicity of bergamot oil in solar simulating radiation (SSR greater than or equal to 290 nm) and in long ultraviolet radiation (LUV greater than or equal to 320 nm) has been compared by studying photoaugmentation of erythema in the guinea pig after 24 h and pigmentary photoaugmentation in man on the 8th day. The results show that a close relationship exists between guinea pig and human responses, with both radiations used, and that man seems to be slightly more sensitive to phototoxic effects of bergamot oil than the guinea pig. This difference of sensitivity necessarily implies the participation of UVA (320--400 nm) in the phototoxic reaction of bergamot oil with solar radiation. This UVA participation is particularly obvious in the guinea pig; in man, the results are less clear and a certain synergy of UVB rays (290--320 nm) may be involved in the phototoxic UVA-induced reaction of bergamot oil. Despite these slight differences, the erythematous reaction in the guinea pig appears to be a remarkable experimental model to show out potential phototoxic reactions of products containing psoralens in man.


Generalized cutaneous calcinosis and mixed connective tissue disease.

A 49-year-old female patient with a history of fever episodes, muscular weakness, Raynaud's phenomenon, cardiac insufficiency and increasing cutaneous calcinosis over a period of 4 years is reported. Based upon clinical as well as histological and immunological findings, the disease is diagnosed as mixed connective tissue disease with generalized cutaneous calcinosis in an extent yet unpublished, to our knowledge, in this 'overlap syndrome'. The pathogenesis of cutaneous calcinosis is discussed with particular reference to the phenomenon of calciphylaxis, and some therapeutic implications are considered.


Granulomatous inflammation of the vulva and penis--a genital counterpart to cheilitis granulomatosa.

3 patients are described, in whom chronic swelling of the external genitals occurred after recurrent infections. The histological findings were identical to those seen in cheilitis granulomatosa, the dermal component of Melkersson-Rosenthal syndrome. The authors suppose that the disease of the 3 patients is a genital counterpart to cheilitis granulomatosa, and the name vulvitis or posthitis granulomatosa is suggested.


[Vasculitis racemosa hemoplegica].

The secondary symptomatic forms of livedo reticularis can follow cerebrovascular incidents with consecutive hemiplegia; this is rarely known. A further patient is described who developed an asymmetrical livedo reticularis on the hemiplegic half of the body. The reason of the hemiplegia was an intracerebral hemorrhage.


Actinic keratoses treated with a combination of topical 5-fluorouracil and dinitrochlorobenzene.

A comparative study of topical 5-fluorouracil (5FU) alone and 5FU with dinitrochlorobenzene (DNCB) therapy in the treatment of actinic keratoses of the upper limbs is described. 5 out of 10 patients had better results with a combination of the two medications, while there was no difference in the results in 4 of the patients. Complications in the form of contact dermatitis to DNCB was experienced in 5 patients. Therapy of actinic keratoses of the upper limbs is recommended for a 6- to 8-week period with 5FU alone because of the difficulties associated with DNCB usage.


Managing chronic skin conditions with two differing topical corticosteroids.

A study to demonstrate methods of using topical preparations to control chronic skin conditions is described. 25 patients with atopic eczema or psoriasis were followed for an average of 10 months. Both self-assessment using a diary card and clinical assessment were used to evaluate the treatment. The study shows that, when used correctly, topical corticosteroids can provide an effective means of controlling these intractable conditions without producing the side-effects associated with their misuse.


The size and number of intramembrane particles in cells of the photosynthetic bacterium Rhodopseudomonas capsulata studied by freeze-fracture electron microscopy.

By freeze-fracture electron microscopy, particles have been observed on the protoplasmic leaflet (PF face) of cytoplasmic and intracytoplasmic membranes of the photosynthetic bacterium Rhodopseudomonas capsulata. The particles are present under all culture conditions of chemotrophically and phototrophically grown cells. However, the number of particles per microM2 increased significantly when the formation of the photosynthetic apparatus in the membrane is induced. Intracytoplasmic membranes, where the bulk of photosynthetic activity is localized, always have a higher density of particles than cytoplasmic membranes. Under all conditions particles with a diameter of 9.5 nm dominate. The frequency of particles with diameters greater or smaller than 9.5 nm changed with culture conditions. A comparison of biochemical and electron microscopic data have lead us to the conclusion that the particles, formed under conditions which allow the synthesis of the photosynthetic apparatus, are composed of photochemical reaction centers and antenna light-harvesting bacteriochlorophyll I (B 875)-protein complexes. The total molecular weight of these particles is calculated to be 500,000.


Coumarin-induced disturbances of morphological development and cell wall formation in Trichophyton mentagrophytes.

When Trichophyton mentagrophytes thalli are placed on a medium containing 300 microgram/ml of coumarin, their growth rate is drastically reduced and the newly formed mycelium consists of curled and branched hyphae showing subapical bulges and swollen tips. Under the electron microscope, the most relevant abnormalities concern the cell walls which are often thickened by aberrantly shaped zones that are usually smeared unevenly over the surface of the "primary" wall instead of being deposited in discrete ridges. An ultracytochemical analysis suggests that the irregular thickenings are formed of chitin. Arguments suitable to explain the phenomena observed are discussed.


Visualization of the interphase chromosomes of Ornithogalum virens and Muntiacus muntjak.

A technique for visualizing "interphase chromosomes" was applied to nuclei of the angio-spermous plant, Ornithogalum virens (2 n = 6), and the male mammal, Muntiacus munjak (2 n = 7), in an attempt to correlate the numbers of "chromosomes" visible during interphase with the respective diploid chromosome numbers. The alterations in chromosome structure observed during G1, S, and G2 periods were comparable to those previously reported in Allium cepa and Chinese hamster (CHO line) cells [33], but for technical reasons it was only possible to make accurate counts of interphase chromosomes in the G1 nuclei of O. virens. In addition, from our observations of interphase chromosomes that were pulse-labelled with tritiated thymidine and a parallel study of premature chromosome condensation (PCC) using pulse-labelled M.muntjak cells, we conclude that, although chromatin decondensation may be required for DNA synthesis, extreme chromatin decondensation can occur in the absence of DNA synthesis. Generally a morphological description of alterations in chromatin during interphase only roughly parallels the G1, S, and G2 phases defined by autoradiography following incorporation of tritiated thymidine. We suggest that both methods are valid through different ways of describing interphase.


[The fine structure of myotendinous and myo-epithelial junctions in the guinea pig tongue (author's transl)].

The insertion of muscle fibers in the subepithelial connective tissue layer of the guinea pig tongue was studied light and electron microscopically. Fibers of the tractus verticalis approach the epithelium penetrating the lamina propria, both the reticular and papillar layer. Terminating muscle fibers split up and form branching finger-like cytoplasmic processes. The myotendinous junctions of such terminal processes fine structurally correspond to myotendinous junctions generally observed in skeletal or smooth muscles. The entire brush-like formation, however, is more far-reaching and highly differentiated. Filament bundles (spine-like profiles) originate from the plasmalemma and extend to the lamina densa of the basal lamina, especially in those regions where actin filaments are attached to the plasmalemma. Microfibrils (10 to 12 nm diameter) reach the lamina densa of the basal lamina. They form bundles which are continuous with fibrotubular strands of elaunin fibers and elastic fiber microfibrils. Furthermore, microfibrils are interwoven with collagen fibrils.


Diabetes mellitus and pregnancy--management and results at Rikshospitalet, Oslo, 1970-1977.

During the years 1970-1977, 234 pregnant diabetics were treated in Oslo. A regimen of close metabolic and obstetric control was used. The total perinatal mortality was 4.3%, and 3.1% in 160 patients followed from before week 28. In 74% of patients mean blood glucose (determined 4 times daily) during the last 5-6 weeks of pregnancy was below 6 mmol/1 and in only one patient above 8 mmol/1. There was a low incidence of ketoacidosis (5 patients), pyelonephritis (3 patients), and severe preeclampsia (1 patient), although mild to moderate preeclampsia occurred in 28 patients. Preeclampsia was not associated with foetal loss. Macrosomia was rare. Respiratory distress occurred in 33 infants, in most cases light to moderate. Two foetal deaths were associated with respiratory distress. Progression of retinopathy was frequent, and appearance of or progression of proliferative changes occurred in 15 patients with retinopathy before pregnancy. Loss of visual acuity was rare, and reading vision was not lost by any patients. Induced vaginal delivery has been used in half the deliveries during the last years, whereas Caesarean section was preferred during the first years. Mean duration of pregnancy at delivery has been 260 days, 256 days during the first four years, and 262 days during the last four.


Use of a glucose controlled insulin infusion system (artificial beta cell) to control diabetes during surgery.

An artificial beta cell has been used to achieve and maintain a preset plasma glucose concentration in five diabetic patients undergoing surgery. These subjects were compared to control groups of normal subjects receiving either saline or glucose, and diabetics receiving glucose intraoperatively. Hyperglycaemia during surgery was seen in normals (mean plasma glucose +/- SEM: 185 +/- 16 mg/dl) and, to a greater degree, diabetics (247 +/- 36 mg/dl) receiving glucose. Insulin and C-peptide levels did not increase during 2 hours of operation in any of the control groups, suggesting beta cell suppression during surgery. As C-peptide levels declined similarly in normal subjects whether they received saline or glucose, the hyperglycaemia seems to be due to an inability to use exogenous glucose. This is confirmed by a correlation of maximal plasma glucose to glucose infusion rate (r = 0.78, p less than 0.01). The artificial beta cell was able to achieve the same plasma glucose after 2 hours of operation (128 +/- 21 mg/dl) as normal subjects receiving saline (110 +/- 7 mg/dl). The artificial beta cell proved to be a safe, convenient and effective way of monitoring and controlling the hyperglycaemia seen in diabetic patients undergoing surgery.


Effect of physical training on glucose tolerance and on glucose metabolism of skeletal muscle in anaesthetized normal rats.

The effect of physical training on glucose tolerance in vivo and skeletal muscle glucose metabolism in vitro was investigated in normal rats. Treadmill running for 10 days up to 240 min/day led to a decrease of basal and glucose-stimulated plasma insulin levels without major alterations of the IV glucose tolerance (1 g/kg body weight). Swim training of two weeks' duration, i.e. exercise up to 2 X 75 min/day, which did not induce significant changes in body composition, skeletal muscle glycogen levels or citrate synthase activity, resulted in a significant improvement of IV glucose tolerance and substantial reductions of basal and glucose-stimulated plasma insulin levels. Associated with this apparent improvement of insulin sensitivity in vivo, significant increases of the insulin-stimulated glucose uptake (+ 55%) and lactate oxidation + 78%) in vitro were found on perfusion of the isolated hindquarter of swim-trained animals. It is suggested that mild physical training can improve glucose tolerance and insulin sensitivity in normal rats, at least in part, due to an increase of insulin sensitivity of skeletal muscle glucose metabolism.


Control of blood glucose levels in the streptozotocin diabetic rat using a long-acting heat-treated insulin.

Diurnal plasma glucose levels have been studied two hourly in streptozotocin diabetic rats during insulin treatment. Protamine Zinc Insulin induced a very steep fall in plasma glucose level from 359 +/- 100 (SD) mg/100 ml to 91 +/- 49 mg/100 ml within two hours. Plasma glucose was then low (13-60 mg/100 ml) until after 18 hours when an equally steep rise in glucose concentration ocurred. Six other insulin preparations and several insulin treatment regimens were tested with the aim of normalising the 24 hour plasma glucose profile of streptozotocin diabetic rats. One preparation, a non-commercial, very long acting Ultralente NOVO (Mc, ox pH 5.5) yielded a diurnal plasma glucose profile reasonably close to normal when it was administered once a day and when the dose was based on daily blood glucose measurements. Mean plasma glucose was 122 +/- 55 mg/100 ml with a nadir of 55 +/- 15 and a maximal of 187 +/- 99 mg/100 ml.


Early insulin release following suckling in neonatal lambs and rabbits.

Developmental changes in the plasma insulin response to milk ingestion have been determined in neonatal lambs fed by bottle and in naturally suckled infant rabbits. In lambs at 4 days of age and older plasma insulin increased within 5 min of suckling and declined again before increasing to a second peak 60 to 120 min after the feed. The early insulin peak was not associated with any change in plasma glucose and was absent in lambs at 1 day of age. When the early insulin peak was absent the increase in plasma glucose following the meal was greater. The early, apparently reflex, release of insulin also occurred in some 'sham-fed' lambs. Atropine administration before feeding abolished the early peak in insulin. A marked early peak of insulin release, not accompanied by any consistent change in plasma glucose, was also observed in naturally-suckled infant rabbits at 1, 5, 10 and 15 days after birth.


Hospital admission rates of diabetic children.

In 1973 a children's diabetic clinic was established in Oxford. An analysis has been made of the effects this has had on the pattern of emergency admissions classified as severe hyperglycaemia (A), moderate hyperglycaemia (B) and hypoglycaemia (C). A comparison of the admission rate per "diabetic year" over the four years before and the three years after the children's clinic was established showed a significant decrease in admission rate for all hyperglycaemic admissions (p less than 0.05). This decrease was shown to be mainly due to a reduction in admissions with severe hyperglycaemia (A) (p less than 0.01), there being no significant change in admission rate for moderate hyperglycaemia (B). There was no significant change in admission rate for hypoglycaemia (C).


The effect of oral galactose on GIP and insulin secretion in man.

The insulinotropic effect of 50 g galactose given orally to 5 normal volunteers on two occasions--once with and once without a period of hyperglycaemia produced by an intravenous glucose infusion--was studied. Oral galactose caused a rise in plasma GIP from fasting levels of 260 +/- 50 ng/l (mean +/- S.E.M.) to a maximum of 900 +/- 65 ng/l 30 min after ingestion, but in the presence of induced hyperglycaemia the GIP response was significantly diminished and delayed (maximum plasma GIP levels 595 +/- 110 ng/l at 45 min, p less than 0.05). The insulin response to galactose was greatly enhanced by IV glucose (mean area under plasma insulin curve with galactose alone 236.5 +/- 66.0, with galactose + IV glucose 451.9 +/- 81.6, p less than 0.025). The mean rise in plasma galactose was significantly lower in the presence of IV glucose (mean peak level 1.97 +/- 0.28 mmol/l with galactose alone, 0.69 +/- 0.16 mmol/l galactose + IV glucose, p less than 0.025). Oral galactose caused the release of GIP, which is powerfully insulinotropic in the presence of moderate hyperglycaemia. The lower plasma GIP and galactose levels observed following oral galactose in the presence of IV glucose may be accounted for either by postulating that insulin inhibits the absorption of oral galactose, or that insulin exerts a negative feed-back control on GIP release and accelerates galactose disposition in the body.


Metformin in management of pregnant insulin-independent diabetics.

Sixty pregnant "maturity-onset" (insulin-independent), established and gestational, diabetics were treated with Metformin in the second and third trimester after dietary treatment had failed. The incidence of Metformin failure was 53.8% in the established diabetics and 28.6% in the "gestational" diabetics. The 27 Metformin failures were transferred to other therapy, leaving for further analysis 33 patients who received Metformin up till delivery. Two neonatal deaths occurred in this group (1 congenital abnormality and 1 preterm infant) giving a perinatal mortality of 61/1000. This compares with a perinatal mortality of 103/1000 in the Metformin failure group and 105/1000 in a group of insulin-dependent diabetics treated during the same period. Apart from a high incidence of neonatal jaundice requiring phototherapy the infant morbidity in the Metformin group was low. The mothers of 3 infants with congenital abnormalities had received Metformin only during the last trimester of their pregnancy.


Characterisation of somatostatin release from the pancreas: the role of calcium and acetylcholine.

The effect of calcium on somatostatin secretion was investigated in the isolated, perfused canine pancreas preparation and compared with those of acetylcholine, glucose, isoproterenol and arginine. Calcium (5 mmol/l) stimulated somatostatin release in a typical biphasic response pattern being about 5 times as potent as acetylcholine (1 mumol/l), arginine (5 mmol/l), and isoproterenol (2 ng/ml) while the release of insulin and glucagon in response to calcium and the other secretagogues were of the same magnitude. Somatostatin release increased progressively when perfusate calcium was increased step-wise from 0 through 1.25 and 2.5 to 5.0 mmol/l. Calcium stimulated the secretion of somatostatin in the absence of glucose. The stimulatory effect of calcium was, however, modulated by the glucose concentration being about twice as large at 200 mg/100 ml as at 25 mg/100 ml glucose in the perfusion medium.


Effect of oleic acid on insulin secretion by the isolated perfused rat pancreas.

The isolated perfused rat pancreas was utilized to investigate the effect of oleic acid on insulin secretion. In the absence of glucose, a continuous infusion of oleic acid (1500 micromol/l) induced a biphasic insulin release. This effect was reduced at low extracellular calcium concentration. In the presence of oleic acid 1500 micromol/l, the insulin response to 10 mmol/l arginine occurred earlier, the total amount of insulin released in response to the amino acid being unchanged. Such an effect was not obtained when oleic acid in the medium was 750 micromol/l, but it was observed in the presence of oleic acid 1500 micromol/l when the concentration of albumin in the perfusate was increased from 2 g/100 ml to 4 g/100 ml. The insulin response to a continuous infusion of glucose (4.4 mmol/l and 16.7 mmol/l) was potentiated by the presence of oleic acid 1500 micromol/l in the perfusate. No modification of the biphasic pattern of insulin response to glucose 16.7 mmol/l was observed. These results demonstrate that high concentrations of oleic acid stimulate insulin release from the isolated perfused rat pancreas and modulate the insulin response to arginine or glucose.


Achalasia, diffuse esophageal spasm, and related motility disorders.

From 1972 to 1977, the authors observed 156 patients with primary esophageal motility disorders which caused such a severe degree of dysphagia that treatment by pneumatic dilatation was deemed necessary. Before dilatation, 24% of the patients presented with motility disorders that did not fit well into the two classical disease entities, diffuse esophageal spasm and achalasia (absence of peristalsis with presence of lower esophageal sphincter (LES) relaxations or presence of peristalsis with absence of LES relaxations). After treatment with pneumatic dilatation, these "intermediate" forms constituted 45% of the motor disorders. This was due mainly to the reappearance, on manometric tracings, of peristaltic contractions and of LES relaxations. Radiologic and manometric observations suggest that in many patients, this "return of peristalsis" may be an apparent change in pressure pattern rather than a real change in motility. In 6 of the 156 patients, a deterioration of the esophageal motility disorder was observed, which was characterized by the loss of peristalsis and of LES relaxations over a period of a few months or years. The frequent occurrence of intermediate types of motility disorders and the transition from diffuse spasm to achalasia suggest that achalasia and diffuse esophageal spasm are part of a spectrum of related motor disorders.


Effect of metoclopramide on guinea pig stomach: critical dependence on intrinsic stores of acetylcholine.

This study is concerned with an investigation of the hypothesis that metoclopramide enhances the contractile activity of the guinea pig antrum by increasing acetylcholine release from the postganglionic cholinergic nerve ending. Longitudinal muscle strips were stimulated repetitively (200 microseconds pulses, 20 Hz, supra maximal current) for 2 hr in the presence of hemicholinium-3 (200 micron). Pretreatment in this manner produced a mean reduction of 50% in the acetylcholine content, when compared with that in repetitively stimulated control strips not incubated with hemicholinium-3. In the hemicholinium-3-treated strips the normal excitatory response to metoclopramide (60 micrometer) was prevented. Only a small reduction in response to metoclopramide was detected in strips which were incubated with hemicholinium-3 but not stimulated repetitively, and in which there was no significant change in acetylcholine content. The stimulant effect of metoclopramide depends, therefore, upon maintenance of intrinsic stores of acetylcholine.


Cimetidine is an antiandrogen in the rat.

Cimetidine has been associated with gynecomastia as a side effect. Because other antiandrogens have been linked to the development of breast enlargement in men, the suggestion by earlier workers that cimetidine possessed antiandrogenic properties prompted us to study the endocrine effects of cimetidine in rats. Cimetidine directly antagonized the effects of exogenously administered testosterone on androgen target tissues. Ventral prostate and seminal vesicle weights were less in cimetidine-treated castrate adult male rats androgenized with testosterone-filled subcutaneous silastic capsules than in vehicle-injected controls. Cimetidine possessed no intrinsic androgen-like bioactivity in prepubertal male rats when given in doses of 50 mg/kg/day for 1 wk. Cimetidine competitively inhibited DHT binding to its cytoplasmic receptor and decreased specific nuclear uptake of [3H]dihydrotestosterone in rat ventral prostate slices. No effects on plasma gonadotropin or testosterone concentrations were observed. We conclude that cimetidine is a nonsteroidal-antiandrogen and that this property may contribute to the production of gynecomastia in cimetidine-treated men.


Pancreatic polypeptide. Metabolism and effect on pancreatic secretion in dogs.

In dogs with gastric and pancreatic fistulas, porcine pancreatic polypeptide (PP) was infused intravenously in doses of 50, 100, 200, 400, and 800 pmol kg-1 hr-1 in the basal state and in doses of 100, 200, and 400 pmol kg-1 hr-1 during stimulation with submaximal doses of secretin (125 ng kg-1 hr-1) plus caerulein (50 ng kg-1 hr-1). Plasma concentrations of PP were measured by radioimmunoassay, and pancreatic bicarbonate and protein outputs were monitored. The half-time for disappearance of PP was 5.5 +/- 1.0 min, the metabolic clearance rate was 25.6 +/- 1.0 ml kg-1, and the volume of distribution was 209 +/- 42 ml kg-1. Basal pancreatic flow and protein output were significantly inhibited by the lowest dose of PP tested, 50 pmol kg-1 hr-1. The lowest dose of PP significantly inhibiting stimulated pancreatic secretion was 100 pmol kg-1 hr-1 for bicarbonate output and 200 pmol kg-1 hr-1 for protein output. The mean +/- SE peak increment in PP concentration in response to a meal of meat, 210 +/- 39 pM, was greater than the mean peak increment with the 400 pmol kg-1 hr-1 dose of exogenous PP, 175 +/- 19 PM. We conclude that exogenous doses of PP that produce smaller increments in PP concentration than those seen after feeding inhibit pancreatic bicarbonate and protein secretion stimulated by secretin and caerulein. This suggests that the amount of PP released by a meal is sufficient to inhibit pancreatic secretion.


The hemostatic defect of chronic liver disease. Kinetic studies using 75Se-selenomethionine.

With the use of cohort labeling with 75Se-selenomethionine, simultaneous platelet, fibrinogen, and plasminogen survival studies were carried out in 8 patients with chronic alcoholic liver disease and in 5 normal subjects. Clinical features, liver function tests, coagulation and fibrinolytic system activities, and platelet function were also assessed. On the basis of platelet survival, the patients could be divided into two groups. Three patients had shortened platelet survival; they were all thrombocytopenic and had greater prolongation of the prothrombin time (PT) and activated partial thromboplastin time (PTT) than the other 5 patients. However, platelet turnover was decreased in all the patients, and there was no difference between the two groups with regard to fibrinogen or plasminogen survival nor in the in vitro evidence of disseminated intravascular coagulation (DIC). Fibrinogen survival was increased in 5 of the 8 patients. Plasminogen survival was normal in 6 patients and prolonged in 2 patients with very low plasminogen levels. The absence of increased fibrinogen turnover in the patients studied indicates that the abnormalities in coagulation tests were not due to consumption coagulopathy. The authors' studies suggest that, at least for patients with chronic stable alcoholic liver disease, the concept that the coagulopathy of liver disease is due to increased utilization of clotting factors should be revised with caution.


Microstructure of gallstones.

Electron microprobe analysis, x-ray diffraction, and infrared spectroscopy have been used to investigate the nature and arrangement of materials present in gallstones. Calcium phosphate and carbonate deposits present centrally in many stones were mixed with a pigmented phase containing copper and protein. In several stones, the central calcium deposits were surrounded by discrete adjacent layers of calcium bilirubinate and cholesterol. The calcium bilirubinate layer was distinguished from other pigmented layers by its higher protein content and increased iron/copper ratio. This sequence of calcium salt and cholesterol deposition occurred in the outer layers of some stones. The phase relationships shown by the present study are consistent with a biphasic mechanism of stone growth in which calcium salts and lipid were alternately deposited. Calcium salt precipitation has been inferred to initiate the sequence as calcium salts were found at the stone centers. The layer sequence has been discussed in terms of some possible effects of damage to the gallbladder wall caused by the calcium salt deposits.


Bilary lipid metabolism in obesity. Effects of bile acid feeding before and during weight reduction.

Obese subjects are prone to supersaturated bile, which is maintained or increased during weight loss. In this report, two related studies were carried out on  obese subjects to investigate effects of bile acid feeding on biliary lipid metabolism before and during weight reduction. In one study, chenodeoxycholic acid (CDCA), 750 mg/day, was given to 12 obese subjects during weight maintenance (1st mo) and during weight reduction (2nd mo). In the second study, effects of two bile acid preparations, CDCA and Bilron (containing mostly cholic acid and deoxycholic acid), randomly administered, were compared in another 12 obese subjects undergoing weight reduction. The results show that obese subjects had large pools of bile acids during weight maintenance which decreased on caloric restriction (1,000 kcal/day). CDCA increased pool size only modestly during weight maintenance, from 3,536 +/- 1,267 (SD) mg to 4,735 +/- 1,434 mg. Both CDCA and Bilron markedly reexpanded the contracted pool of bile acids in obese subjects on weight reduction. However, significantly reduced saturation of bile occurred only in those on CDCA and weight reductions, whereas supersaturation was unaltered when weight was maintained constant in these patients, or when Bilron was given. No significant side effects were noted during bile acid feeding for any of the subjects. Thus, CDCA given to obese subjects on weight reduction will reduce bile saturation and could protect against gallstones.


Effect of acute alterations in small bowel transit time upon the biliary excretion rate of bile acids.

The rate of biliary bile acid excretion is a product of bile acid pool size and enterohepatic cycling frequency. Cycling frequency, in turn, is determined by the time necessary for bile acid to travel from the ampulla of Vater to its small bowel absorptive site, from its absorptive site to the liver, and from the liver to the duodenum. In 10 subjects receiving constant intraduodenal infusion of an isocaloric formula containing the nonabsorbable markers polyethylene glycol and beta-sitosterol, the authors altered small intestinal transit time and measured the effect upon biliary bile acid excretion rate. Sorbitol (15% formula) shortened transit time by 38% and increased hourly bile acid excretion rate by 31%. Atropine (0.04 mg i.m. q 2 hr) increased transit time by 38% and decreased hourly bile acid excretion rate by 38%. Biliary excretion rates of cholesterol and of bilirubin, substances excreted in bile but not subject to enterohepatic circulation, did not change with changes in transit time. This suggests that sorbitol and atropine were not acting upon the biliary limb of the enterohepatic circulation but rather on the intestinal limb. The authors conclude that small bowel transit time is a major determinant of enterohepatic cycling frequency.


Prevention by menadione of the hepatotoxic effects in chickens fed rapeseed meal. Observations on coagulation factors and cytochrome P-450.

Rapeseed meal, the residue after oil extraction, is an animal feed of great commercial interest. Some genetic strains of rapeseed yield a meal which when fed in high concentration produces hemorrhagic lesions in the liver of chickens. These lesions are reduced in incidence by the simultaneous feeding of menadione. This hepatotoxicity is accompanied by elevated levels of cytochrome P-450, delta-aminolevulinic acid synthetase, and the clotting factors V and X. The hemorrhagic lesions were associated with hepatic necrosis, and menadione was protective by mechanisms other than its effect on blood coagulation.


Analysis of the albino-locus region of the mouse. I. Origin and viability.

Numerous specific-locus experiments designed to test the mutagenic effect of external radiation have yielded, in over 3,600,000 animals observed, altogether 119 presumed mutations involving the c locus. Of these, 55 were viable and albino (cav), 13 were viable and of various intermediate pigment types (cxv), four were subvital (cas and cxs), seven were neonatally lethal albinos (cal), 28 prenatally lethal albinos (cal); 12 died untested. All of the prenatally lethal and at least one of the neonatally lethal c-locus mutations (cal classes) are probably deficiencies that we have analyzed extensively in other experiments. Since absence of the locus mimics albino in phenotype, the intermediates (cxv and cxs groups) probably resulted from intragenic changes. The class of viable albino mutants (cav) might include, in addition to intragenic changes, some extremely small deficiencies. --The effects on viability of c-locus lethals (cal's) in heterozygous condition are not drastic enough to be perceived in stocks of mixed genetic background except in the case of the two longest known deficiencies and a few others. --Analysis of the relation between radiation treatment and type of c-locus mutants obtained shows that the relative frequency of viable mutations, for each germ-cell type, is greater for low-LET than for neutron irradiation; however, the difference for any individual cell type is not significant. The majority (66.7%) of mutations derived from X- or gamma-ray irradiated spermatogonia are viable, and the proportion of "intermediates" among these viables is similar to that among presumed spontaneous c-locus mutations. No significant dose-rate effect on the proportion of lethals could be demonstrated within the set of mutants induced by low-LET irradiation of spermatogonia. Although sets from other germ-cell stages are too small for statistical tests, the results for oocytes are similar, as far as they go. Furthermore, most of the c-locus mutations induced in spermatogonia, even by high-dose-rate X-ray or gamma irradiation, are of a type most likely to result from single-tract events (62% cxv, cxs, and cav; plus 16% presumed deficiencies not involving the closest marker). These results support the view that most of the reduction in mutation frequency at low dose rates is not due to a change in relative proportion of two-track and one-track ionizing events.


Analysis of the albino-locus region of the mouse. II. Mosaic mutants.

Among 119 mutations involving the c locus that were recovered in the course of mouse specific-locus experiments with external radiations, 16 were found in mosaic, or fractional, mutants. The number of additional c-locus fractionals that could have occurred in these experiments and, for a variety of reasons, might not have been clearly identified, probably does not exceed the present number.-There was no evidence for radiation induction of the fractionals, and even those occurring in the irradiated groups may thus be assumed to be of spontaneous origin. Since only two mutations in the control groups were found in whole-body mutants, it appears that the bulk of spontaneous c-locus mutations are fractionals.-None of the mutations recovered in fractional mutants was homozygous lethal; 25% were viable intermediate alleles, and the remainder were albino-like mutants, all viable except for one subvital and one not tested.-Genetic tests of the fractionals indicated no major selection against the new mutations, either gametically or in the progeny.-For the group of fractionals as a whole, about one-half of the germinal tissue carried the mutation, indicating that the fractionals came from an overall blastomere population that was one-half mutant. Such a population could result from mutation in one strand of the gamete DNA, in a daughter chromosome derived from pronuclear DNA synthesis of the zygote, or in one of the first two blastomeres prior to replication. Since the mouse embryo does not stem from all of the cleavage products of the zygote, the frequency of fractionals observed underestimates the frequency of mutational events that result in two types of blastomeres.


X-ray stage sensitivity of mouse oocytes and its bearing on dose-response curves.

A detailed cytogenetic study of maturing mouse oocyte radiosensitivity was performed. Oocytes were collected at various intervals ranging from 1.5 days to 28.5 days after irradiation with 50, 100, 200, and 300 R of acute X-rays. The observed sensitivity to chromatid aberration induction varied greatly over this time span. Sensitivity was lowest at the shortest time interval before ovulation and gradually increased up to 9.5 days; it then remained constant until insufficient numbers of oocytes could be collected. The data were analyzed in three ways. First, the data from all time intervals at each dose were pooled; second the data from the least sensitive time intervals, at each dose, were pooled, and third, the data from the period of uniform sensitivity, at each dose, were pooled. Dose-response regression analyses were done on these pooled data and the best fits obtained were to the models Y = a + bD + cD2 and Y = a + cD2 for both deletions and interchanges. This result is interpreted as indicating that the aberrations result from a predominantly two-track process. The cytogenetic data were compared to specific-locus mutation induction data in comparable oocyte stages, and qualitative similarity in dose-response characteristics were observed. This similarity is interpreted to mean that both events result from the same mechanism, and that the large dose-rate effect, observed for both events, is a reflection of the two-track component in the dose-response curves.


Localization of Streptomyces stanfordii endonuclease I (SstI) cleavage sites on genomes of human adenovirus types two and five.

The SstI restriction endonuclease cleaves adenovirus 2 and 5 (Ad2 and Ad5) DNAs into 15 and 16 fragments, respectively. Cleavage sites were positioned with respect to several other cuts made by seven restriction endonucleases. There are relatively few SstI sites in the middle portion and in the right side of the genome, while several are located within the 16.5--20% region which contains "leader sequences".


A new site-specific endonuclease from Streptomyces lavendulae (SlaI).

A new restriction-like endonuclease, SlaI, was found and partially purified from Streptomyces lavendulae ATCC8664. This endonuclease cleaved bacteriophage lambda DNA at only one site, and cytosine-substituted bacteriophage T4 DNA at 16 sites. The recognition sequence was determined by using SlaI fragments of cytosine-substituted bacteriophage T4 DNA. The hexanucleotide recognized by SlaI endonuclease was (Formula: see text), with the sites of cleavage as indicated by the arrows. Therefore, SlaI endonuclease was an isoschizomer of XhoI endonuclease.


Change with age of anisotropic properties of collagen bundles.

Form birefringence curves and linear dichroic properties of aging rat tendons are different from those of adult controls. The steepness of the form birefringence curves and the increased retardations found in aging tendons are ascribed to an increase in collagen aggregation accompanied by loss of tissue water. Based on increase of retardations due to intrinsic birefringence, a rise in crystallinity levels is suggested for the collagen bundles of aging tendons. The inversion of the dichroism signs and the change in the d11 (collagen fibers oriented parallel) and d1 (collagen fibers oriented perpendicular) spectral absorption profiles, mainly at the adsorption peaks for sections stained with toluidine blue solutions at pH 4.0 and 5.0, indicate modificiations at the acid glycosaminoglycan molecular orientation level with advancing age.


Obesity as an aetiological factor in the development of osteoarthrosis.

A quantitative survey was carried out on the subcutaneous and abdominal adipose tissue of two inbred strains of mouse; STR/ORT is a strain in which the knee joints of the males have a very high incidence of osteoarthrosis, whereas the incidence of the disease in the females is much lower; the CBA/ORT mice represent a normal laboratory strain which rarely suffers from osteoarthrosis. In terms of the weight of readily removable subcutaneous and abdominal adipose tissue, the male STR/ORT mice were slightly leaner than the male CBA/ORT mice, the female STR/ORT mice were obese when compared with their CBA/ORT counterparts. Thus, in these mice, there was no positive correlation between obesity and osteoarthrosis. This evidence confirms previous mouse studies and is contrary to the commonly held view that in humans obesity predisposes to osteoarthrosis.


Pharmacokinetics of salicylates in elderly.

In order to study changes in the pharmacokinetics of salicylates in old people, we used two groups of inpatients without hepatic or renal impairment: the first comprised 15 patients more than 65 years old, mean age 77 years; the second, 7 patients of mean age 21 years. Each patient was given 1 g of acetylsalicylic acid orally in the morning while fasting. Blood samples were subsequently taken after 30, 60 and 90 min and 2, 3, 4, 6, 8, 10, and 24 h. Fluorimetric assay results were analyzed kinetically with a mathematical model corresponding to a single diffusion compartment model. The results showed only a slight increase in the absorption half-time in old subjects, and a marked increase in elimination half-time (3.71 and 2.38 h in old and young subjects, respectively; t = 2.33: p less than 0.05) and in the volume of distribution (5.51 and 3.83 liters respectively; t = 3.20: p less than 0.1). On the other hand, bioavailability varied little, as did metabolic clearance. This study confirms that intestinal absorption of this drug is not much impaired in old people, while hepatic and/or renal elimination functions are changed. This finding agrees with results found for aminopyrine, antipyrine, and digoxin.


Effect of short-term cold stress on the respiratory metabolism of brain tissue homogenates of male garden lizards of two different age-groups.

The endogenous oxygen uptake and the uptake with added substrate of whole-brain and mid-brain homogenates were significantly lower in older lizards as compared to younger. Both whole brain and mid-brain showed responses to cold stress for different lengths of time but the decline in oxygen uptake was more pronounced in the younger age-group. Respiratory rate and response to cold stress were more marked in the mid-brain than in the whole brain. Basing on earlier reports on mammals and on the present findings, it is suggested that the decline in physiological adaptation in older animals may be a general feature in vertebrates.


Mortality in geriatric surgery. With special reference to the type of surgery, anaesthesia, complicating dieeases, and prophylaxis of thrombosis.

The post-operative mortality of 17,199 patients of whom approximately 20% were aged 70 years or more was studied. The primary mortality of patients aged 70 or more in major operations was 9.2%. In emergency operations, the mortality was 36.8%, in elective surgery 7.8%. Pulmonary embolism was the cause of death in 33%, cardiac collapse in 11%, and the primary illness in 9%. The mortality of patients with mental diseases was 45%, of diabetics 26%, and of cardiac patients 17%. 39% of cardiac patients died of pulmonary embolism. 26% of all deaths occurred during the first 3 post-operative days, and 35% between the 4th and 7th post-operative day. In operations lasting more than 2 h, the mortality was 36%, in those lasting less than 2 h, 7.5%. Macrodex (dextran 70) infusions during high-risk operations decreased the incidence of lethal pulmonary embolism.


Assessment of chemical tests for faecal occult bleeding and correlation of results with presence or absence of anaemia.

Stools from 88 consecutive patients in acute geriatric wards were tested for occult blood by four common commercial methods. The Peroheme and Haemostix tests were found too sensitive for general use, the Okokit and Haemoccult tests being preferable. Positive tests were correlated with anaemia in 27 patients, iron deficiency in 26, iron deficiency anaemia in 15, non-anaemia in 52, non-iron deficiency in 43 and with absence of both in 27. Such testing has been considered unnecessary in anaemic patients without gastrointestinal symptoms.


Age-dependent enzymatic poly (A) metabolism in quail oviduct.

The poly(A) metabolism in oviducts from adult and senescent quails has been studied. The incorporation studies by double-labelling of mRNA with [3H]adenosine and [3H]uridine revealed, that after inhibition of transcription by actinomycin D, the incorporation ratio adenosine/uridine increases drastically in adult animals compared with the ratio determined for mRNA from senescent animals. This finding is a hint that in senescent animals the poly(A) stretch of mRNA is shorter than in adult animals. This assumption is supported by the finding that the activity of the extractable poly(A) exoribonuclease is higher in senescent than in adult animals. The activity of poly(A) exoribonuclease is even enhanced after stimulation of senescent animals with progesterone. The activity of the other catabolic enzyme studied, the poly (A) endoribonuclease, as well as the activity of anabolic poly(A) enzyme, the poly(A) polymerase, are almost identical in oviducts from adult and senescent animals. The properties of the catabolic poly(A) enzymes and of the anabolic poly(A) polymerase seem to be identical.


Influence of age and spironolactone on lysosomal enzyme activities, DNA and protein content of the rat liver after partial hepatectomy.

Measurements of DNA and protein content and determinations of lysosomal enzyme activities (beta-glucuronidase, beta-acetylglucosaminidase, cathepsin D) were performed in the rat liver following partial hepatectomy and spironolactone administration. The rats (SIV) were divided into three age-groups: 6 weeks old, 10 months old and 18 months old. 60 h after the administration of spironolactone (2 x 10 mg Aldactone/100 g body weight/day orally via gastric tube for 3 days) partial hepatectomy was performed. The removed two thirds of the liver and the regenerating liver (24 h after partial hepatectomy) were prepared for the biochemical examinations at 4 degrees C. The measurements of the enzyme activities were performed in liver homogenates. The results indicate that the administration of spironolactone cause (1) a weight increase in the normal as well as in the regenerating liver, especially in the older animals; (2) an increase of the protein content of the normal liver in the oldest age-group; (3) a decrease in the DNA content of the normal and regenerating liver of old rats, and (4) an age-dependent increase of decrease of the three lyososomal enzymes beta-glucuronidase, beta-acetylglucosamidase and cathepsin D.


Release of motilin by oral and intravenous nutrients in man.

Motilin is a hormonal peptide found in the duodenum and jejunum which potently influences gastrointestinal tract motility. Its role in human physiology is not yet established. After a standard hospital lunch the plasma concentration of motilin showed a small, transient, but significant rise in 28 healthy subjects. Individual food components either stimulated (oral fat) or suppressed release (oral glucose). Plasma motilin levels were, in addition, altered to an equal extent by intravenous nutrients, with glucose and amino acids suppressing release, and intravenous fat causing a significant rise in plasma concentration. These results demonstrate a consistent response to food stimuli, whether oral or intravenous. The release mechanism appears to be complicated and after a balanced meal, containing food components which both stimulate and suppress release, there is only a small net change.


Intestinal absorption under the influence of vasopressin: studies in unanaesthetised rats.

Experiments were carried out in different segments of the intestine of unanaesthetised rats to assess the effect of vasopressin on intestinal absorptive processes. The following data were observed. (1) Within a physiological range of doses (Aziz, 1969), ADH diminished the net sodium absorption mainly by reducing the unidirectional sodium influx, whereas the behaviour of the efflux was not uniform. (2) The unidirectional volume fluxes showed the same behaviour as did the sodium fluxes. (3) ADH produced an oral-aboral gradient (jejunum greater than ileum greater than colon). (4) ADH did not significantly change the transfer of actively transported sugars; it did influence, however, passively transported substances. (5) During the intravenous application of ADH, a substance was secreted into the perfusion solution which diminished the absorption of volume and electrolytes. (6) Cyclic AMP acted on intestinal absorption in the same way as did ADH. In view of these results two mutually independent transport pathways for sodium and water are supposed, one of which is influenced by ADH or cAMP. Based on a two membrane model, an ADH mechanism is discussed: the permeability of the luminal membrane system is enhanced in the presence of vasopressin.


Amino acid and peptide absorption after proximal small intestinal resection in the rat.

In experimental animals with massive proximal intestinal resection, in vivo ileal absorption of an amino acid mixture containing L-leucine and glycine as well as two different dipeptides, L-leucyl-glycine and glycyl-L-leucine, were compared. Both amino acid and dipeptide absorption were markedly enhanced in the ileal segments. However, the absorption rates from the two perfused dipeptides differed. L-leucine absorption from L-leucyl-glycine was much greater than from glycyl-L-leucine. Brush border amino-peptidase activities after resection were also increased but dissociation between absorption and hydrolytic activity occurred. This study indicates that certain dipeptides are handled differently by adapting ileal segments. Furthermore, the changes observed probably reflect mucosal cellular hyperplasia occurring in association with intestinal adaptation.


Absorption of antigens after oral immunisation and the simultaneous induction of specific systemic tolerance.

Antigenic proteins may be absorbed intact. We report here results from in vivo experiments in mice showing that the prior feeding of protein antigen may reduce the subsequent absorption of that antigen without altering its elimination from the circulation. This may be a function of local immunity. We have also shown that the same feeding regime can paradoxically induce a state of systemic tolerance and suggest that the two phenomena contribute to the safe handling of these antigens.


Variability of gluten intolerance in treated childhood coeliac disease.

Fifty children consecutively attending a clinic for coeliac disease co-operated in a trial; 10 found to have flat mucosa were excluded. Forty children of mean age 9.8 years, whose duodenal or jejunal mucosa had returned to normal or near normal appearance after a mean of 5.8 years on gluten-free diets, were put back on normal diets. In 37, mucosal occurred in a mean of 16.9 months (four to 74 months). Four of the 37 had serial biopsies, in which mucosal enzymes (particularly lactase) fell and interepithelial lymphocyte counts rose before the mucosal morphology was regarded as definitely 'coeliac'. Three children had normal mucosal appearance after 58 to 73 months on normal diets, one of whom showed temporary mucosal abnormalities, another having occasionally low enzymes, in both suggesting underlying gluten sensitivity. Lactase suppression and raised IEL counts appear to be sensitive indicators of gluten intolerance. In our experience, a diagnosis of coeliac disease based on severe mucosal damage and a satisfactory response to a gluten-free but milk-containing diet implies a very strong likelihood of permanent or prolonged gluten intolerance, but with a striking variability in its expression.


Serum bilirubin: a prognostic factor in primary biliary cirrhosis.

We followed up 55 patients with proven primary biliary cirrhosis for several years or until death. A graph of the level of serum bilirubin versus time that was constructed for each patient shows an initial period of variable length in which the serum bilirubin level remained constant. This was followed by a period of rapid rise in serum bilirubin which culminated in the patient's death. Whenever two successive serum bilirubin values taken six months apart exceeded 34 mumol/l (2.0 mg/dl) the patient had entered a late phase of disease and lived an average of 49 months. Ninety-five per cent confidence limits on survival time were 32-74 months. If two successive six month bilirubin values exceeded 102 mumol/l (6.0 mg/dl), calculated survival time was 25 months, and if two successive six month bilirubin values exceeded 170 mumol/l (10.0 mg/dl), survival time was 17 months. Fifteen of the 41 living patients had two consecutive serum bilirubin levels greater than 34 mumol/l (2.0 mg/dl). However, the slope of the rising bilirubin in the living patients is only 35 mumol/l/yr (1.5 mg/dl/yr) compared with 42 mumol/l/yr (2.5 mg/dl/yr) in the dead patients. This means that patients with this disease not may be living considerably longer.


Rectal biopsy in patients presenting to an infectious disease unit with diarrhoeal disease.

The role of sigmoidoscopy and rectal biopsy was investigated in patients referred to an infectious diseases unit with diarrhoea. Seventy-four patients were studied. Nine patients (12%) had inflammatory bowel disease, either ulcerative colitis or Crohn's disease. Thirty-six patients (48%) had infective diarrhoea. A wide variety of conditions accounted for the diarrhoea in the remaining patients. Sigmoidoscopy was abnormal in 25 patients and rectal biopsy in 56. The abnormalities in rectal mucosal histology were classified into six grades. Some patients with infective diarrhoea showed rather characteristic histological changes which may be of diagnostic value. Eight showed features which suggested a diagnosis of inflammatory bowel disease. However, repeat rectal biopsy in the convalescent period showed a striking improvement in the patients with infective diarrhoea. In contrast, the histological changes persisted in the patients with inflammatory bowel disease. Repeat rectal biopsy may be essential before making a firm diagnosis of inflammatory bowel disease in some patients who present with diarrhoea and apparently typical histological changes.


Rectal IgE cells in inflammatory bowel disease.

Immunoglobulin-contained cells in the rectal mucosa of patients suffering from non-specific inflammatory bowel disease (IBD) were counted and compared with those in a control population. While the numbers of IgA, IgM, and IgG-containing cells in both ulcerative colitis and Crohn's disease did not differ from normal, both disease groups exhibited a marked increase in IgE-staining cells. This increase in IgE-cells did not correlate with severity, duration, or treatment of disease and it did not prove possible, using these immunological studies, to differentiate between Crohn's disease and ulcerative colitis.


Gynaecomastia associated with cimetidine.

Gynaecomastia has occurred unilaterally or bilaterally in five out of 25 male duodenal ulcer patients after more than four months treatment with cimetidine 1.6 g daily. All elected to continue treatment to 12 months and their breast enlargement regressed rapidly and disappeared after stopping treatment. During treatment all patients were found to have normal concentrations of plasma testosterone and oestradiol, and serum prolactin was normal in the two patients measured. Excision biopsy of the subareolar tissue in one patient revealed histology typical of the florid stage of gynaecomastia. Blockade of androgen-responsive receptors receptors in the target organ appears to be the most likely mechanism involved.


Hypobetalipoproteinaemia--a variant of the Bassen-Kornzweig syndrome.

A patient is reported with hypobetalipoproteinaemia and clinical features resembling the Bassen-Kornzweig syndrome (abetalipoproteinaemia) more completely than previously described. This supports a link between hypobetalipoproteinaemia and abetalipoproteinaemia and it is suggested that the Bassen-Kornzweig syndrome has a wide spectrum with serum betalipoprotein ranging from absent to normal. It is likely that there are different genetic entities with similar end results.


Peutz-Jeghers syndrome associated with gastrointestinal carcinoma. Report of two cases in a family.

Patients with the Peutz-Jeghers syndrome carry a slight, though definite, increased risk of gastrointestinal carcinoma. The malignant potentiality of Peutz-Jeghers hamartomatous polyps, generally considered benign, is supported by this report. Two cases of metastasising gastrointestinal carcinoma associated with the Peutz-Jeghers syndrome are described in a 56 year old female and her 29 year old son. Both mother and son died from duodenal and gastric carcinomas respectively, which developed in hamartomatous polyps with extensive metastases. Both cases also showed dysplastic areas within hamartomatous polyps. These features indicate that hamartomatous polyps may, in some cases, be the precursors of digestive tract carcinomas.


Pure pancreatic juice studies in normal subjects and patients with chronic pancreatitis.

Pure pancreatic juice was obtained from within the pancreatic duct in 54 patients after endoscopic cannulation of the papilla of Vater. In all 20 normal subjects there was a brisk response to intravenous injections of GIH secretin in small dosage (1 and 4 CU). Peak bicarbonate concentrations occurred after a 4 CU stimulus, whereas volumes, and bicarbonate and protein outputs were greatest after 70 CU. Total protein and amylase concentrations were highest in the first specimens collected from each patient, and fell rapidly after stimulation. Plateau levels for all indices were achieved 10-20 minutes after starting infusions of secretin and pancreozymin. When normal patients and those with chronic pancreatitis were compared, there was considerable overlap in all indices (volume, bicarbonate and total protein concentrations) after bolus injections of secretin. Most patients with chronic pancreatitis achieved a peak bicarbonate concentration in excess of 100 mmol/l. The median concentrations were not significantly different from normal after any dose of secretin when pooled 10 minute samples were analysed. However there were significant differences in peak bicarbonate concentrations (after 1 and 4 CU, but not after 70 CU), when one minute samples were compared. There were also statistically significant differences in the median 10 minute responses for volume after 1 and 70 CU, for bicarbonate output after 1, 4, and 70 CU, and for protein output after 70 CU. The results of juice studies in patients believed to have early chronic pancreatitis did not differ significantly from those in normal subjects or those with chronic pancreatitis. Endoscopic duct cannulation cannot guarantee complete recovery of pancreatic secretions, and measurements of volume and output may be inaccurate. When standard biochemical indices are used, the diagnostic role of pure juice studies is limited; further research may reveal more specific disease markers.


Impaired pancreatic polypeptide release in chronic pancreatitis with steatorrhoea.

Pancreatic polypeptide (PP) is a newly discovered hormonal peptide localised in a distinct endocrine cell type in the pancreas. PP circulates in plasma and in normal subjects levels rise substantially on the ingestion of food (mean rise 138 pmol/l). In 10 patients with chronic pancreatitis with exocrine deficiency the PP response to a test breakfast was greatly reduced (mean rise 20 pmol/l, P less than 0.001). PP response to the meal was normal in 10 patients with active coeliac disease and 12 patients with acute tropical sprue with steatorrhoea.


[Clinical experiences with lumboscopic kidney biopsy].

Lumboscopic renal biopsy is a new, quite convincing technique to gain renal tissue for histopathological and immunological examinations, which Sommerkamp introduced in 1974. A small flank incision (approx. 2 cm) is necessary to introduce a lumboscope into the retroperitoneal space. The lower pole of the kidney can be reached through the capsula adiposa and biopsy may be performed under view. The histopathological results and the postbioptic course in 55 patients show the advantages of this method against open surgical and percutaneous biopsy.


[Ultrasonic diagnosis and sinus diseases].

By employing ultrasound in the routine diagnosis of sinus diseases, the margin of error in the accuracy of diagnosis can be reduced by 10% compared to that using clinical records and x-rays, provided however, that the investigator has sufficient experience in operating the ultrasonic equipment. The inclusion of ultrasonic diagnostics has proven itself particularly valuable in the diagnosis if both discharges and tumors in children and for progress control of patients having had conservative treatment or operations.


[Long lasting psychotropic effects after long-term treatment with a hemoderivative].

Up to now there has been scarcely any publication of precise tests on the duration (lasting effect) of psychotropical effects which have appeared in brain activity after conclusion of a longterm therapy with vasoactive or metabolical substances. In 32 patients with symptoms of arteriosclerosis (average 72 years) a six weeks trial treatment was carried out with the haemoderivat Actihaemyl (6 weeks twice weekly 10 ml i.v.) according to the double blind method and checking the results with variance analysis. In the following mental areas positive effects have been proved: memory functions, creative behaviour, general psychophysical behaviour and in emotional, social and clinical behaviour. 12 weeks after conclusion of the therapy it was observed, that with the same test method there was a wide maintenance of the improvements in the psychical performance and this exceeded in many areas the status as observed immediately after conclusion of the therapy. The reason for this longterm effect of the haemoderivat which was under test is discussed.


[The antipyretic effect of Lonarid N in children].

Lonarid N was used in 78 children suffering from different febrile diseases. It was available in suppositories for infants and children. Body temperature dropped to subfebrile values in 78.5% of all doses. In 8.6% a lowering effect was distinct but incomplete, in 12.9% no satisfying effect occurred. After one hour average lowering of 1.5 to 1.9 degrees C was seen in nearly half of the cases, after three hours normal temperatures were found in all cases responding to Lonarid N at all. Lonarid N is acting promptly and normal body temperature is reached as expected. No complications of therapy were seen.


[A new geriatric battery test].

Both the clinical and the experimental field of geriatrics are in need of an instrument to test the cognitive abilities of people aged 60 and above. By means of a pre-test of the new geriatric test-battery, those abilities, which generally decrease with age, are tested first in order to obtain a testability rating for a particular patient. The geriatric test-battery, which is based on a theory of a 4 dimensional intelligence clearly delineating the differential development of specific cognitive abilities into old age, allows a precise, differentiated assessment of the cognitive abilities of the elderly. Considering the particular characteristics of the old person, the geriatric test-battery was given a new form which minimizes the feeling of being threatened by the test and at the same time maximizes motivation. The geriatric test-battery is pleasant for both the patient and the tester, it is simple to administer, can easily be given to physically impaired or bedridden patients, and is not time consuming.


[Diagnosis of hypertension in childhood].

A significant increase in arterial blood pressure is considerably less common in childhood (as compared with adults), and, to a larger degree, is high-grade. The mild forms more frequently reverse spontaneously, and severe cases are more often asymptomatic. It is of a secondary nature in a much larger percentage (preponderantly of renal, but also of vascular, adrenal or other demonstrable etiology), i.e., susceptible to causal therapy. The growing interest within pediatrics in problems of primary (essential) hypertension with regard to epidemiology, etiology, pathogenetics and prognosis (!), lends additional importance to the particular difficulties involved in reliable blood pressure measurement and control, and additionally, the question of a useful definition of the criteria for pathological blood pressure increases, which is relatively uncertain in children (moreover, the normal values are highly age-dependent). The symptomatology of arterial hypertension shows certain age-specific characteristics. In the secondary forms, the underlying disease is ofter far advanced at the moment of manifestation and, even more so, of completion of the diagnosis. Certain risk factors (obviously also relevant for the later years of life) related to primary hypertension, the incidence of which is still quite controversial, can already be detected in childhood (familial and hereditary factors).


[Cervix cerclage surgery. A way for reducing prematurity].

Indications and results of 202 cerclage-operations are reported. There are prophylactic as well as therapeutic indications for a cerclage-operation. Regarding the results it is obvious that prophylactic cerclage has better prepossessions for a normally terminated delivery. Therapeutic cerclages show best results when performed within the 15th to 27th week of pregnancy. A cerclage performed after the 32nd week of pregnancy shows no statistically significant reduction of early delivery but only a postponing of the delivery-date into a phase of better survival chance for the child. A reduction of the early delivery rate is regarded to  be effective by prophylactic as well as therapeutic cerclages up to the 27th week of pregnancy.


[Continuous lumbar peridural anesthesia in obstetrics].

Review of 1000 continuous peridural anesthesias during labor and delivery. Reasons and conditions for the application of this analgetic procedure in our delivery rooms are discussed. The duration of labor and delivery is reduced by this method. The rate of vacuum extraction and forceps delivery is slightly increased. The rate of cesarean section is independent of this procedure. No adverse effects on the fetus were found. We obtained complete analgesia in 93 per cent of the cases. Severe complications were not observed.


[Dynamic measurement of blood pressure in human nailfold capillaries].

Dynamic blood pressure was measured in 33 human finger nailfold capillaries after direct cannulation with glass micropipettes by means of a resistance servonulling pressure measuring method. ECG, finger pulsations and respiratory thorax excursions were monitored simultaneously. All recordings exhibited pulsatile oscillations related to the cardiac rhythm. These oscillations resembled the wave forms of arterial pulsations with steep upstroke and dicrotic notch when the pressure amplitudes were above 10 mmHg. There was no apparent dependence on respiration. In 12 instances pressure fluctuations with frequencies ranging from 0.2 down to 0.07 Hz were observed in both the arteriolar and venular limb. Blood pressure in human skin capillaries is pulsatile and subject to remarkable fluctuations in the arteriolar as well as in the venular limb, systolic pressure values ranging from 14 to 71 mmHg and from 11 to 52 mmHg respectively.


[Regeneration of the gastric and intestinal mucosas].

The physiological cell renewal of gastrointestinal mucosa is regulated in man as in animal through certain mechanisms with measurable kinetic data. Pathologic mucosal alterations, metabolic disorders, pharmacological agents etc. clearly affect the regenerative processes of the gastrointestinal epithelium. Gastrin and pentagastrin stimulate the growth not only of the parietal cells, but also of the superficial epithelium of the gastric mucosa, whereas secretin does not change cell growth. Glucocorticoid steroids inhibit epithelial regeneration in all parts of the gastrointestinal tract. 5-fluorouracil has a similar effect but acts at a different site in the regeneration cycle. Epithelial cell proliferation of the gastric and intestinal mucosa is likewise inhibited in an uremic condition. In inflammatory changes in the human gastric mucosa epithelial cell hyperproliferation relative to the severity of gastritis and anomalous proliferation within regions of dysplasia can be demonstrated. Foveolary hyperplasia in Ménétrier's disease occurs on the basis of excessive hyperproliferation with displacement of regeneration zones.


[Adaptation of statistics to medicine].

In respect of the useful way of questioning and the properties of medical data rank tests and rank scores tests fit better than the so-called standard tests. Yet, rank tests in their wide variety are so far too poor for our medical purposes. Therefore some urgently needed methods for data analysis have been developed.


[Management of gastrointestinal diseases using a motility-regulating preparation. Results of a field study using bromopride (Viaben) conducted by 530 general practitioners on 4182 patients].

Abnormalities of oesophago-gastro-intestinal motoricity play an important etiologic role in various affections of stomach, intestine, oesophagus and associated complaints. The new monosubstance bromopride produces a selective action restoring the basal motility of stomach, pylorus, duodenum and of the lower oesophageal sphincter to normal. The effect and tolerance of Viaben (bromopride) were examined in an open field study on 4182 subjects. The drug was given in average doses of one capsule three times a day. The results were assessed as very good in 37.9% of cases, and as good in 47.9%. No change was seen in 12.2%, while only 2.0% were aggravated. 64.7% of all patients benefited within the first fortnight. Nausea, vomiting and intolerance to drugs even disappeared in the first days of treatment. Individuals exhibiting a nervous, irritative stomach also had a rapid response to the drug. Pain, which is a fairly common complaint, passed off quickly. Side effects were seen in 6.8% of cases. However, the question whether they were due to the treatment, is not easily answered in an open study. The most common side effect was tiredness (3.7%), which was reported to be mild in some cases. The dyskinesia observed in subjects treated with other ortho-substituted benzamides was only seen in 0.4% of all patients.


[Hyperbilirubinemias; diagnostic and therapeutic aspects].

In the newborn functional disturbances of bilirubin metabolism may be threatening for the life of affected infants. Apart from states with massive overproduction of bilirubin caused by hemolytic crisis functional hyperbilirubinemias in adults represent preponderant hereditary disorders (Gilbert's syndrome, Dubin-Johnson-syndrome, Rotor-syndrome), full compatible with normal life span. Affected subjects are considered as normal persons and should be advised to live a normal life, avoiding however all well-known exogenous factors which may exacerbate the disease. The important clinical and characteristic diagnostic criteria of the mentioned disorders of bilirubin matabolism as well as the possibilities of their symptomatic therapy are discussed.


[The Reiter syndrome. 2. Diagnosis, therapy, prognosis].

The incomplete form, the so-called Reiter-trias (three-fold Reiter's syndrome) and the form supplemented by skin- and mucous-membrane-lesions are presented. Iritis, conjunctivitis, urethritis as well as visceral complications are being discussed referring to their appearance and frequency. Of essential importance seems to be a specific analysis which will bring to light the often fleeting (eyes, urogenital-region) or willingly concealed (urethritis) symptoms. A differential diagnosis, recommendations for therapy and a prognostic outlook are concluding this short demonstration of Reiter's syndrome.


[TSH-screening program for congenital hypothyroidism. Experiences with early thyrotropin (TSH) screening].

14,919 newborn infants were screened for congenital hypothyroidism within the last 5 years using a sensitive TSH method. 10 infants with congenital hypothyroidism were discovered thus presenting a frequency of 1:4500. Four of these infants showed abnormally high TSH levels and normal thyroxine levels. The determination of TSH in cord blood--or combined with the screening program for phenylketonuria--in eluate of dried filter paper specimens is the most sensitive test for primary hypothyroidism without false negative results and a low false positive recall rate of 0.16%. After initiation of therapy with thyroxine the TSH level falls unless therapy is delayed for longer. In the latter case TSH levels may remain elevated for several months despite therapy with thyroxine. We would suggest to start therapy with triiodothyronine for up to 14 days prior to initiation of the usual thyroxine therapy.


[Congenital hypothyroidism].

The clinical picture of congenital hypothyroidism in the newborn period as well as in infancy is presented. Those signs and symptoms are particularly emphasized which in spite of being clearly present in the newborn are frequently not registered and mostly not correctly interpreted. This is meant to aid in earlier clinical diagnosis of congenital hypothyroidism. Furthermore, guidelines for diagnostic work-up, therapy and follow-up are presented. For an optimal mental and neurological prognosis early treatment is of paramount importance.


[Diet therapy in chronic kidney failure].

The dose of proteins of high biological value and eventually the use of selective diet with protein mixture of highest value such as the potato-egg diet, the dose of essential aminoacids as part of the so-called Sweden-diet and finally the application of ketoanaloges of essential aminoacids, all these measures make possible a removal of all uraemic symptoms as well as a long lasting rehabilitation inspite of a strongly restricted renal detoxication.


[Chlamydia infections of the urogenital system].

During the last years Chlamydiae have been increasingly recognized as an important cause of urogenital infections. This paper is concerned with the classification, microbiology, cultivation and clinical findings of Chlamydiae, especially Chlamydia trachomatis, as causative agents of genital tract diseases.


[Complications following mediastinoscopy. Prevention and therapy].

Mediastinoscopy, being practised since 20 years, is a research method giving a high degree of information and during this time has become indispensable in diagnosis of diseases of the chest. The close neighbourhood of vital organs, small and easily vulnerable blood vessels and nerval tissues of functional importance first seemed to burden this method of investigation with an incalculate risk. But subtle operative technique with its instruments by Carlens and others let the number of complications remain remarkably small even in great collective statistics. The number of lethal complications ranged below 0.2%, more severe ones about 1%. But in these latter ones one almost always succeeds in achieving a restitutio ad integrum bei performance of consequent after-treatment. The more frequent mediastinoscopic investigations are performed in regions of marked pathologic changes, the higher is the number of described complications. But it must be considered that in many cases the more perilous and functionally straining thoracotomy can be avoided using mediastinoscopy. Complications occurring most frequently are described and possibilities of therapy are discussed.


[Prognosis and therapy of peripheral facial nerve paralysis. Electrodiagnostic ways of evaluation].

The function of the facial nerve can be examined by four electrodiagnostic methods. In the nerve excitability test and electroneurography with determination of the distal latency the facial nerve is stimulated over the stylomastoid foramen. Chronaximetry and electromyography are performed in the muscles. Whereas chronaximetry renders an impression of the severity of neural lesion, electromyography can also determine the onset of reinnervation activity. Early prognosis within 6 days of onset can be determined only by nerve excitability test and electroneurography, preferred by us, which assesses the muscle potential. If the potential amplitude decreases more than 35% within two days and the muscle potential disappears between the fourth and sixth day, total degeneration of the nerve with poor prognosis is indicated. Such data can be gathered by at least two electrodiagnostic investigations preferably on the third day after onset and one to three days later. The cosmetic disfigurement through peripheral facial nerve palsy poses immediately the question of prognosis and of the therapeutic possibilities. Usually, this question can be answered by clinical examination alone. As soon as paralysis of facial muscles exists, prognostical statements can be made by electrodiagnostical methods alone. Because of the possiblility of operative treatment it is necessary to assess the infavorable courses early.


[Nystagmus as a diagnostic criterium in neurology].

The most frequent seen nystagmus is jerk nustagmus. It is a versional eye movement comprising a quick and a slow phase. For diagnostic reasons it is very important to know the connections involved in vestibulo-oculomotor control. Besides peripheral, labyrinthine disturbances the observation of nystagmus is a very good tool in the topodiagnosis of the brain stem and mesencephalon. By ENG recordings, which normally should be used only after clinical examinations according to Frenzel and Jung, we can find much more better and reliable results in clinical topodiagnosis. Further tests of vestibulo-oculomotor function (rotation, optokinetic tests e.g.) offer the possibility of a discriminating topodiagnosis of the brain stem. This means an efficient use in clinical neurology. Following these considerations examples of single cases including ENG recordings are given.


[Measurement and evaluation of industrial noise].

Different methods for measurement and assessment of industrial noise are discussed. It is shown, that momentary the best approach to stress caused by noise is the "Trakt-Maximalpegel-Verfahren" with a cycle time of 5 s. For more exact description of acoustic recording of sound level and harmonic analyzis are indispensable.


[Reduced blood supply of the vestibular centers. Clinical and experimental studies].

To explain the origin of the narrow nystagmus writing (petite écriture) selected patients with hypoxemia were examinated using the pendular rotating test and ENG. Blood gas analysis was used to determine pO2 reduction. The decreased oxygen saturation was corresponding to the decreased amplitude of nystagmus. In a second experiment with alert rabbits the inspired gas mixture was altered to obtain hypoxia (8% O2+ 92% N2, controlled with blood gas analysis). A significant reduction from the normal nystagmus reaction was observed. This reduction in the amplitude (about 50%) is immediately reversible by giving oxygen. These experiments were repeated with each animal several times, the results being reproductible. There is a significant decrease  in amplitude of nystagmus through the influence of hypoxia.


[Pathophysiology and therapy of perinatal asphyxia in a mature newborn].

Based on modern knowledge about the pathophysiology of perinatal asphyxia a new concept of therapy is discussed. Besides cardiopulmonary resuscitation for the initial shock reaction the therapy of secondary complications according to the multi-system-reaction is emphasized. After the description of the correlation of partial asphyxia and the development of neurological defect syndromes in animal models the necessity of a "cerebral resuscitation" is mentioned.


[The biliary excretion of azlocillin].

The excretion of azlocillin into the human biliary tract was investigated in 8 patients with a T-tube in the common bile duct after intravenous injection of 2 g. Samples of serum and common duct bile were assayed from 15 min to 12 hours after injection. Biliary tract levels generally run parallel to serum levels but were about 15 times higher than those. Peak levels in T-tube bile averaged 1137 mg/l 60 to 90 min after administration. 12 hours after administration there were still mean concentrations of 13 mg/l to be found. It is concluded that azlocillin concentrations in bile exceed for a long time the minimum inhibitory concentrations for gram-negative and gram-positive causative organisms (above all E. coli, enterococci, Klebsiella spp., Proteus spp., staphylococci) of biliary tract-infections.


Effect of metaproterenol on ketone body metabolism of the forearm in healthy and diabetic subjects.

Muscular ketone body metabolism was studied by the registration of arterial-deepvenous concentration differences of glycerol, beta-hydroxybutyrate and acetoacetate, and of muscular blood flow in 53 healthy volunteers and 23 juvenile diabetics. In six subjects of each group substrate metabolism was also investigated during the intrabrachial arterial infusion of metaproterenol (0.4 microgram/min). Identical rates of muscular glycerol release and ketone's fractional extraction were obtained in healthy and diabetic subjects during the basal period. A significant correlation between muscular ketone extraction and arterial ketone concentration was calculated in both groups. During the infusion of metaproterenol the diabetics, unlike the controls, revealed enhanced muscular glycerol output and reduced fractional extraction of beta-hydroxybutyrate. These findings are in line with the present view that the impairment of muscular ketone body utilisation in diabetic ketoacidosis may at least partly be due to enhanced muscular lipolysis.


On the effect of insulin on glucose-6-phosphate dehydrogenase and fatty acid synthetase activity in mouse liver.

Regulation of glucose-6-phosphate dehydrogenase and fatty acid synthetase activity in mouse liver is examined in diabetic and normal mice. Up to a 4-fold increase of both enzymes can be observed in streptozotocin diabetic mice when transferred to a fatless, inducing diet. Administration of insulin does not increase enzyme activity at several doses and under a variety of conditions. This is a strong indication that insulin is not a necessary component of the induction system.


The use of perfused rat intestine to characterise the glucagon-like immunoreactivity released into serosal secretions following stimulation by glucose.

Isolated perfused intestine of rat was used to demonstrate the glucose-stimulated release of glucagon-like immunoreactivity (GLI) into serosal secretions. The released GLI was characterised using immunoaffinity chromatography on columns of immobilised antibodies specific for the N (residues 1 to 18) and for the C (residues 19-29) terminal portions of glucagon followed by gel-filtration. The immunoreactivity was present in a variety of molecular species. These include a large GLI which has a molecular weight about 12000 and binds to antibodies specific for the N-terminal portion of glucagon and two polypeptide fractions with molecular weight closer to that of glucagon. While one fraction of the small GLI boun both to antibodies specific for the C-terminal and N-terminal portions of glucagon the other bound only to the former antibodies. The relevance of these findings to the origins of circulating GLI and the possible precursor relationship between large and other forms of GLI is discussed.


Serum T4, T3 and reverse T3 during treatment with propranolol in hyperthyroidism, L-T4 treated myxedema and in normal man.

Serum concentrations of T4, T3 and reverse T3 were studied in two hyperthyroid groups (n = 13 and 11), in a group of normals (n = 9) and in a group of L-T4 substituted patients (n = 7) with severe pretreatment hypothyroidism. Serum T4 did not change except in one of the hyperthyroid groups change to in which a slight decrease was found. In all groups a significant fall in serum T3 and a significant rise in serum reverse T3 were found. An expected increase in serum TSH in the normal and in the L-T4 substituted groups could not be demonstrated.