Studies on the mechanism of somatostatin action on insulin release in man. II. Comparison of the effects of somatostatin on insulin release induced by glucose, glucagon and tolbutamide.

Somatostatin in as small a dose as 70 mug given over a period of 90 min to seven healthy subjects inhibited insulin release induced by glucose (500 mg/kg as a bolus + 20 mg/kg/min). This inhibition seemed to be of competitive nature since the effect was nearly overcome when the glucose dose was raised considerably. Somatostatin in nine subjects also inhibited insulin release induced by glucagon and tolbutamide, and this inhibition was of the same order of magnitude as that of glucose induced insulin release. Since all these insulinogogues enhance of the accumulation of cyclic AMP in the beta-cells, it is suggested that the edenylate cyclase-cylic AMP system might be involved in the action of somatostatin. Somatostatin did not seem to interfere with the glycogenolytic effect of glucagon on the liver.


Studies on the mechanism of somatostatin action on insulin release. III. Effect of somatostatin on arginine induced release of insulin and glucagon in man and perfused rat pancreas.

In man, 3 mug per kg per 90 min of linear somatostatin significantly inhibited basal as well as arginine induced insulin and glucagon release. One mug per kg per 90 min of somatostatin significantly inhibited basal insulin release but not basal glucagon release or arginine induced insulin and glucagon release. In the perfused rat pancreas, as little as one ng per ml of perfusate of somatostatin significantly inhibited argine induced insulin but not glucagon release, while 10 ng per ml of somatostatin by more than 50 per cent reduced the effect of arginine on insulin and glucagon release. Thus, linear somatostatin seemed to be a slightly more potent inhibitor of insulin than of glucagon release in man and in the perfused rat pancreas.


Multicomponent gas chromatographic analysis of urinary steroids excreted by an infant with a defect in aldosterone biosynthesis.

The urinary steroids excreted by an infant with a salt-wasting syndrome due to a suspected defect in the 18-oxidation of corticosterone have been analysed by gas chromatography-mass spectrometry. The excretion of tetrahydroaldosterone was low (3.5 mug/24 h) whilst the excretion of 3alpha,11beta,21-trihydroxy-5alpha-pregnan-20-one (allo-tetrahydrocorticosterone) and other corticosterone metabolites was high (total about 2 mg/24 h). The excretion of cortisol metabolites was apparently normal for age (total about 2 mg/24 h) but 3alpha,11beta,17alpha,21-tetrahydroxy-5alpha-pregnan-20-one (allo-tetrahydrocortisol) rather than tetrahydrocortisone, was the major component of the group. The excretion of an 18-hydroxycorticosterone metabolite 3alpha,18,21-trihydroxy-5beta-pregnane-11,20-dione (18-hydroxytetrahydroCompound A) was higher than normal for infants of this age (between 50 and 200 mug/24 h), suggesting that the defect was in 18-hydroxysteroid dehydrogenase rather than 1,-hydroxylase. In addition, 18-hydroxytetrahydrocorticosterone, another metabolite of 18-hydroxycorticosterone was tentatively identified and it was found that the rate of excretion of this compound was of similar magnitude to 18-hydroxytetrahydroCompound A. The salt balance of the infant has been sucessfully controlled by salt administration (77 mEq./24 h) and treatment with Fludrocortisone (0.5 mg/day).


Effect of metyrapone on cortisol binding capacity in plasma.

Metyrapone was added in vivo to six different samples of normal plasma (0.1 mg/ml plasma) and administered orally (30 mg/kg) to 5 adrenalectomized patients. An increased ratio free, non protein-bound cortisol: total cortisol in plasma was demonstrated after metyrapone in all six in vitro studies and in 4 of the 5 adrenalectomized patients. These findings may explain the accelerating effect of metyrapone on cortisol metabolism.


Decarboxylation of ornithine and adenosymethionine in rat ovary during pregnancy.

The activities of L-ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.50) fluctuate markedly in rat ovary during the normal oestrous cycle. Ovarian ornithine and adenosylmethionine decarboxylases also showed profound changes during pregnancy of the rat. Both enzyme activities were remarkably low in the ovary through the first 11 days of pregnancy, but sharply increased at the time the placenta is formed in the rat. The enzyme activities remained elevated almost until term. It appears that the stimulated of polyamine synthesis in rat ovary, as reflected by the enhanced decarboxylation of ornithine and adenosylmethionine, is associated with the growth of the ovarian tissue rather than the secretory function of the corpus luteum during pregnancy.


Relationship between oestrogen, prostaglandin F2alpha and histamine in delayed implantation in the mouse.

Treatment of pregnant mice ovariectomized on day 3 (23.00-2330 h) with progesterone (1 mg/day/mouse, from day 4 through 11 post coitum (p.c.)) and oestrogen (single injection of 0.05 mug on day 8 p.c.) induced implantation in all the animals. Implantation was inhibited in animals following three subcutaneous injections of indomethacin given on the morning and afternoon of day 8 and the morning of day 9 p.c. A single injection of histamine on day 8 p.c. partially compensated the effect of indomethacin. A complete reversal of the antifertility effect of indomethacin was achieved following intraperitoneal administration of histamine (2 mug at noon of day 8 p.c.) and PGF2alpha (20 mug on the morning and afternoon of day 8 p.c.). This study suggests that in the mouse uterus indomethacin impairs the physiological changes which are required for the decidual cell formation and implantation. It is likely that an injection of oestradiol in the progesterone treated ovariectomized mice triggers the release of PGF2alpha and histamine and that these compounds are involved in the chain of events leading to implantation of blastocysts.


The ontogenesis of human foetal hormones. II. Luteinizing hormone (LH) and follicle stimulating hormone (FSH).

The content and concentrations of immunoreactive LH (LER-960) and FSH (LER-869) were determined in 79 human foetal pituitary glands from 68 days of gestation to term, and in the pituitary glands of 3 anencephalic infants, 10 infants and children 2 weeks to 7 years of age, and 4 adults. In addition, the concentration of immunoreactive serum LH, FSH, LH-HCG, and HCG was determined in 48 foetuses and 6 anencephalic infants. The mean content of LH in the pituitary glands of the female foetuses increased sharply from 88.2 +/- 44.2 ng at 10 to 14 weeks to 4983.8 +/- 1128.4 ng at 25 to 29 weeks of gestation. In the male foetuses, the mean content of pituitary LH rose from levels of 21.0 +/- 11.6 ng to peak levels of 114.5 +/- 57.1 ng at 20 to 24 weeks of gestation. The concentration of LH in the pituitary glands of the children was comparable to that of foetuses at mid-gestation. The mean content of FSH in pituitary glands of female foetuses rose from 7.4 +/- 5.2 ng at 10 to 14 weeks to 4788.6 +/- 1460.7 ng at 25 to 29 weeks of gestation. In the male foetuses the pituitary content rose from 1.8 +/- 0.7 ng at 10 to 14 weeks to 14.5 +/- 69.1 ng at 25 to 29 weeks of gestation. The differences in pituitary content of LH and FSH between the male and female foetuses were highly significant from 15 to 29 weeks of gestation. The correlation of the incremental changes in the pituitary content of LH and FSH with gestational age was significant (P less than 0.02). Immunoreactive serum FSH was detected as early as 84 days of gestation at a concentration of 11.0 ng/ml (LER-869). Serum FSH rose to peak levels (18.2 +/- 3.6 ng/ml) at 20 to 25 weeks in a range comparable to that of castrate adults. A decrease was noted by 30 to 34 weeks to levels of 1.7 +/- 0.05 ng/ml, comparable to that in cord samples at term (1.8 +/- 0.2 ng/ml). A significant negative correlation with gestational age was shown after the mid-gestational period (P less than 0.01). Immunoreactive LH, measured by a specific LH assay, was unaffected by levels of HCG present in the foetus. Immunoreactive LH was present in high concentrations by 99 days of gestation (21.5 ng/ml LER-960). Peak levels were attained by 100 to 180 days of gestation with a decrease at them to less than 1.0 ng/ml. A significant negative correlation was noted between serum LH and gestational age. Serum HCG quantified in a betaHCG radioimmunoassay decreased from the relatively high levels in foetuses at 90 to 120 days gestational age to term. The mean concentration in umbilical cord sera was 268.5 +/- 161 mIU/ml in contrast to 5400 +/- 200 mIU/ml in maternal plasma at term. ...


Lymphocyte transformation, leucocyte migration, specific IgE, IgG and IgM before, during, and after penicillin treatment without adverse reaction. A follow-up study.

This in vitro follow-up study of the penicillin-induced immune  response by a well-tolerated regimen was conducted with an association of four tests: lymphocyte transformation test; leucocyte migration test; passive anaphylaxis on monkey lung tissue; and passive hemagglutination. It showed (1) that previously sensitized subjects (including IgE) tolerated the treatment by pencillin. (2) That the treatment induced either a transient positive conversion of previously negative tests or a negative conversion of previously positive tests. These in vitro findings are in accordance with previously established concepts based upon cutaneous tests and must be taken into consideration when interpretating in vitro diagnosis of penicillin allergy.


Rapid extraction of grass pollen allergens and separation of their active fractions.

The immediate effects of nasal provocation tests with dry grass pollen, correlated with recent botanical evidence of almost instant release of allergens from the pollen wall, suggested that prolonged extraction of pollens was unnecessary and perhaps undesirable. It has now been shown that all the active allergens from undefatted dry grass pollens of the 12 major British species are extracted completely in 15 min. Gel chromatography of such rapid extracts has shown clear-cut separation of active from inactive material, as confirmed by skin and nasal provocation testing. It is probable that active fractions thus obtained contain the only pollen allergens of importance to clinical allergy. Further purification may produce specific allergens useful for the accurate standardisation of vaccines.


D. pteronyssinus-tyrosine adsorbate: biological and clinical properties.

Adsorption of D. pteronyssinus on tyrosine gives a depot formulation with retained immunogenicity. Preliminary clinical evaluation of this material showed improvement in the majority of allergic subjects after receipt of the initial six doses, improvement being continued during subsequent maintenance therapy.


[Frequency and correlative relation of diagnostic criteria in animal dander allergy].

355 out-patients with signs of bronchial asthma were studied with special reference to animal dander sensitization. Case histories allowed the clinical diagnosis of an allergy to animal dander in 75 patients (21.1%). Skin testing is a useful means, as large reactions appear in most cases of animal dander allergy (60.7% are greater than or equal to + + + -reactions). Skin reactions, however, often are "false positive" or "false negative". Therefore, bronchial provocation tests are necessary if the case history is doubtful and/or the skin reaction is less than a + + + -reaction. There is a positive correlation between skin reaction and bronchial provocation test. No negative inhalation tests were seen when the skin reaction was greater than + + +. However, a positive inhalation test can be correlated with a negative or weakly positive skin test. The probability of common structural properties of different mammalian dander allergens is discussed. Avoidance of exposure to the animal is recommended as the therapy of choice.


Precipitating antibodies against Micropolyspora phaeni in sera from mushroom workers.

A new method for determining precipitating antibodies in allergic alveolitis is presented. The principle used is immunoelectrophoresis, either as a counterelectrophoresis or as a crossed immunoelectrophoresis with intermediate gel. Twenty-two mushroom workers without anamnestic signs of allergic alveolitis and 15 control persons were investigated. Twelve mushroom workers (55%) had precipitating antibodies as determined by crossed immunoelectrophoresis, and nine of these persons had antibodies demonstrated with counterelectrophoresis. Thus, the sensitivity seems greater in the crossed immunoelectrophoresis, but we find that the simpler counterelectrophoresis is an excellent screening procedure in patients suspected of allergic alveolitis. In the controls only one person had precipitating antibodies, though the antigen tested for Micropolyspora phaeni exists ubiquitously. It seems probable from this study that the antigenic load is important, although it is remarkable that no mushroom worker with precipitating antibodies against M. phaeni had ever experienced symptoms compatible with allergic alveolitis.


Prick- and radioallergsorbent tests (RAST) to Alcalase in a population not exposed to enzyme detergents.

A total of 301 persons in a population unexposed to enzyme detergents (Rumania) were prick-tested with Alcalase, and RASTs were performed on their sera. The material consisted of three groups, one atopic, the second non atopic, and the third healthy. In the first two groups the percentage of positive prick-test reactions amounted to 6 and 5% respectively. Only one positive RAST was found (second group). In the third group no positive prick-tests were found and no positive RASTs. The majority of the positive prick-tests were considered non specific, and no correlation was found between results of prick-tests and RASTs in this material of non exposed individuals.


A new technique for measurements of the urethra pressure profile.

A new standardized technique for continuous recording of the urethral pressure profile simultaneously with intravesical pressure has been developed. The pressures were recorded using two micr-transducers enclosed in a thin Dacron catheter. The catheter moved with a constant speed through the urethra with the aid of a specially designed instrument. This instrument is described. Twenty-five healthy women were examined. The patients were divided into two groups: (A) 10 postmenopausal women, and (B) 15 fertile women. The results of the recordings showed that the functional length and the absolute length of the urethra could be reproduced with an error of less than 1 mm. The maximal pressure amplitude was significantly less in group A.


Nuclear size classes in the follicular epithelium of lymphoid thyroiditis.

Nuclear size classes of the type originally described by Jacobj were studied in the follicular epithelium of biopsy smears from lymphoid thyroiditis. Thus, a great number of large nuclei in size classes distinct from the bulk of fairly identically sized nuclei could be clearly distinguished. By cytophotometric measurement of Feulgen-DNA, these large nuclei were found to correspond closely to nuclei in separate DNA-content-classes and they were therefore called HDC-nuclei (High DNA-quantity Class nuclei). Such nuclei proved to be more common in lymphoid thyroiditis than in normal thyroids and non-toxic goitres without lymphoid thyroiditis. Among lymphoid goitres, the percentage of HDC-nuclei was positively correlated with the age of the patients. In the present paper, the relationship between Askanazy cells and HDC-nuclei is also discussed.


A comparison of two glucocorticoid regimens for acceleration of fetal lung maturation in premature labor.

This study compares fetal corticoid response from conventional dose (12.0 mg) intramuscular betamethasone to large dose (1,000 mg) intravenous cortisol administered to women in premature labor for acceleration of fetal lung maturity. To compare these two regimens, 14 women selected at random were treated in groups of seven with either cortisol or betamethasone. Peripheral levels of unconjugated estriol were measured by specific radioimmunoassay prior to the cortisol dose and at 1, 4, 8, and 12 hours following the dose. The rate of corticoid delivery to the fetal hypothalamic-adrenal axis was estimated by the per cent suppression of unconjugated estriol at each post-treatment interval. Least-squares regression lines fitted (P less than 0.01) for each regimen were compared for time saved (delta t) when cortisol was used. Mean delta t (1, 4, 8, and 12 hours) was 9.0 +/- 0.2 S.E.M. hours. It is concluded that: (1) Intravenous cortisol delivers a fetal corticoid effect that is significantly more rapid in onset and more profound in magnitude than does intramuscular betamethasone and that (2) the cortisol regimen is probably better suited to the acceleration of fetal lung maturation in premature labor when time is short and rapid action is essential.


The inhibition of pulmonary maturation in the fetal rabbit by maternal treatment with phenobarbital.

Phenobarbital was administered to pregnant rabbits, 7 to 10 days before the delivery of their fetuses at 27 to 30 days of gestation. There were no differences in body weight or wet or dry lung weights between control animals and phenobarbital-treated pups at similar gestational ages. The phospholipid content (PLC) of the alevolar wash was lower in the phenobarbital-treated group, but there was no difference in the lung tissue PLC between the treated and control groups. Phenobarbital-treated pups had higher opening pressures and fewer lamellar bodies than the control animals. These data suggest that phenobarbital may have an inhibitory effect on surfactant production and/or release.


The relationship between premature rupture of the membranes and the respiratory distress syndrome.

The records of 212 patients of 36 weeks' gestational age or less were reviewed to study the relationship between premature rupture of the membranes (PRM) and the development of the respiratory distress syndrome (RDS). PRM greater than 16 hours resulted in a statistically significant decrease of RDS in neonates of 32 weeks' gestational age  or less but not in the group from 32 to 36 weeks' gestational age. However, survival was significantly improved with PRM greater than 16 hours in the latter group but not in the former. A possible explanation for this observation is offered. Black patients had a higher over-all infant mortality rate than white patients, and, although the incidence of RDS is similar in both races, it may be a more lethal condition in black patients. There was no significant difference noted between female and male infants. Sepsis was responsible for only seven deaths in this series, and three of those cases could not be etiologically related to prolonged PRM.


Total throidectomy in the management of Graves' disease. A review of 282 cases.

Antithyroid drugs, radioactive iodine, and surgery, either alone or in various combination, are used in the management of Graves' disease. If surgery is selected as the treatment of choice for Graves' disease than nothing less than total thyroidectomy should be performed.


The effect of various forms of milk on gastric-acid secretion. Studies in patients with duodenal ulcer and normal subjects.

Milk is commonly recommended as therapy for patients with peptic ulcer. The purpose of this study was to examine the effect of various forms of milk and 0.15 M NaCl (control) on gastric-acid secretion in five patients with duodenal ulcer during a period of remission and in five normal subjects. A significant (P less than 0.05) increase in acid secretion in both groups was produced by 240 ml of whole, low-fat, and nonfat milk. The acid secretory responses to milk were equivalent to approximately 20% to 35% of maximal betazole - or pentagastrin-stimulated acid output. Gastric-acid secretion produced a significant (P less than 0.05) increase in acid secretion in the patients with duodenal ulcer but not in the normal subjects. Because milk contains both protein and calcium, and each are stimulants of gastric-acid secretion, there is reason to question its frequent ingestion by patients with peptic ulcer.


Penetration, permeation, and resorption of 8-methoxypsoralen. Comperative in vitro and in vivo studies after topical application of four standard preparations.

The penetration, permeation, and resorption of radioactively labelled 8-Methoxypsoralen was investigated in human skin. Siultaneously, the effects to time and ointment carrier on the penetration kinetics were ascertained. The carriers tested were: vaseline, aqueous wool-wax alcohol ointment, aqueous hydrophilic ointment and polyethylene glycol ointment. The absolute concentrations of 8-Methoxypsoralen were estimated in the horny layer, epidermis and dermis. With the most advantageous carrier, aqueous wool-wax alcohol ointment, 4-6X10(-5) M and 10(-5) M were attained in the epidermis and dermis, respectively. Moreover, it was shown that the substance penetrates rapidly (10 min) into the epidermis and dermis and the high concentrations reached constant over a period of 16 h. Only with a formulation of aqueous wool-wax alcohols is any accumulation at all achieved in the deeper areas of the horny layer. A uniform decrease in drug concentration with increasing depth of the horny layer is found with the other 3 vehicles, whereby slight variations in concentrations pertain from carrier to carrier. 4 h after local application, 8-Methoxypsoralen can be detected in the urine. Regardless of the ointment base employed, 8-Methoxypsoralen is no longer detectable in the urine 40 h after application. In comparison to the oral therapy, the same magnitude of percutaneous resorption into the central compartment is to be derived from the data, if half the body surface is treated locally.


Osteoporosis of the slender smoker. Vertebral compression fractures and loss of metacarpal cortex in relation to postmenopausal cigarette smoking and lack of obesity.

A group of thirty-eight women under age 70 who sustained vertebral compression fractures during minor trauma included more postmenopausal smokers than a group of 34 similar women with fractures resulting from major trauma and more than a group of 572 other women. Advanced idiopathic osteoporosis occurring before age 65 was found rarely among nonsmokers. The percent cortical area at the second metacarpal midpoint was measured in 103 white women aged 40 to 49 years, and 208 white women aged 60 to 69 years. In the younger group, no quantitative differences were demonstrated between bones of the obese and the nonobese or between smokers and nonsmokers. In contrast, among the older group, postmenopausal smokers exhibited much more bone loss than did nonsmokers (P less than .001), and nonobese women demonstrated much more bone loss than did obese women, this difference being most striking among smokers.


A phase I study of cytembena.

Twenty-two patients were given progressively increasing doses of Cytembena to determine toxicity patterns and to establish a dosage which produces definite but clinically tolerable toxicity when the drug is given by intravenous injections in a 5-day intensive course. Toxicity consisted primarily of nausea, vomiting, arm pain, and transiently decreased renal function. At higher doses, an "autonomic-storm" phenomenon was observed consisting of hypertension, tachycardia, tachypnea, hyperperistalsis, frequent explosive defecation, facial flushing and paresthesias, and chest pain with accompanying ischemic EKG changes. There was no evidence of mucocutaneous, hepatic, or hematologic toxic effects. Toxicity was dose-related, first being recognized at a daily dose of 300 mg/m2 and becoming clinically intolerable at a daily dose of 475 mg/m2. No permanent damage was observed in any of the organ systems monitored. An acceptable treatment regimen for most patients is 400 mg/m2/day for 5 days. Patient discomfort can be reduced by dividing each day's dose into two intravenous injections given at an interval of at least 6 hours. Coronary artery disease and impaired renal function should be contraindications to Cytembena therapy, and caution should be employed in the patients with significant impairment of liver function. Two of 22 patients, both with far-advanced carcinoma and previous chemotherapy failures, showed a favorable objective response to Cytembena therapy. Phase II studies to assess the magnitude of the drug's antineoplastic activity seem warranted.


Lymphosarcoma. A comparison of extended to conservative chemotherapy.

Sixty-three patients with Stage III and IV lymphocytic lymphoma were randomized for induction treatment between a single course of nitrogen mustard and a 14-day course of prednisone (conservative therapy) or sequential rotation of BCNU, nitrogen mustard and cytoxan with intermittent vincristine and prednisone for 6 months (extended therapy). Maintenance therapy by an oral alkylating agent (cytoxan or chlorambucil) with or without prednisone was given. Complete remission occurred in 75% of the conservative and 77% of the extended therapy group. The median duration of remission was similar, and greater than 27 months in both groups, and there was no difference in survival. At 1 year 80% of patients with no prior chemotherapy were in remission vs. 47% of patients with prior chemotherapy (p less than .01). No significant advantage for extended chemotherapy was found. The addition of vincristine was not helpful in induction and prednisone during maintenance did not improve the duration of remission or survival.


Paraplegia following intrathecal methotrexate: report of a case and review of the literature.

A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity.


Oral cancer in 57,518 industrial workers of Gujarat, India: a prevalence and followup study.

In Gujarat, India, 57,518 industrial workers over 35 years old were examined for oral lesions. At a two-year interval, 43,654 workers were re-examined. Biopsies were taken from 13,223 lesions. In the initial examination, 29 oral cancers were diagnosed, representing a prevalence rate of 50/100,000. After two years, 22 new oral cancers were diagnosed, representing an incidence rate of 25/100,000 per year. Over 90% were squamous carcinomas, with the majority of lesions occurring in the oropharynx and tongue. All patients who developed squamous carcinomas had tobacco habits, while 85% of the entire study population had oral habits in some form. Their most common habits were smoking tobacco alone or in combination with chewing "pan"/"supari." Of the carcinomas that developed during  a two-year interval, 62% appeared in previously normal appearing mucosa. Leukoplakia was the only oral lesion that proved to be precancerous, with a transformation rate of 0.13% in a two-year interval.


Enhancement of the antitumor activity of arabinofuranosyladenine of 2'-deoxycoformycin.

The 6C3HED lymphosarcoma, a tumor cell line very sensitive to 9-beta-D-arabinofuranosyladenine (ara-A), and 6C3HED/ara-A, a line resistant to ara-A, were studied. Both were responsive to 9-beta-D-arabinofuranosylcytosine (ara-C). Two lines of cells. L1210 and L1210/ara-C, are both resistant to ara-A and have very high levels of the deaminase that inactivates ara-A. When an effective inhibitor of the deaminase, 2'-deoxycoformycin, was combined with ara-A in the treatment of mice bearing L1210 or L1210/ara-C tumors, both became responsive to ara-A. Studies are reported on the extent of effects of 2'-deoxycoformycin at several dose levels and the duration of its effect in tumor cells and normal tissues. Single doses produce essentially complete inhibition of the deaminase, and little recovery was seen before 24 hr. However, DNA synthesis in normal tissues recovered more quickly. It is suggested that ara-A and ara-C, the former as a new derivative (9-beta-D-arabinofuranosyladenine 5'-phosphate) and possibly combined with 2'-deoxycoformycin, be regarded as potentially alternative drugs for the treatment of neoplasms.


Interactions with the absorption of tetracyclines.

All tetracycline derivatives are bacteriostatics and their concentration in serum should not fall during the therapy below the generally accepted minimum therapeutic concentration of 0.5 to 1.5 mug/ml. Tetracyclines have a high affinity to form chelates with polyvalent metallic cations such as Fe+++, Fe++, Al+++, Mg++ and Ca++. Many of these tetracycline-metal complexes are either insoluble or otherwise poorly absorbable from the gastro-intestinal tract. Milk and other dairy products, antacids containing polyvalent cations, as well as various iron salts ingested simultaneously with tetracycline derivatives, might interfere with their absorption by 50 to 90% or even more. The severity of interaction depends both on the nature of the tetracycline derivative and of the cation, on the doses used, on pharmaceutical factors, and on time schedules in dosing. An interval of 3 hours between the ingestion of tetracyclines and cations prevents the interaction. The pharmacokinetic interactions in absorption of tetracyclines likely to be clinically significant in cases where the infecting pathogens are moderately resistant to tetracyclines and relatively high serum concentrations are needed for proper bacteriostasis.


Transient hypothyroidism after delivery in autoimmune thyroiditis.

The spontaneous occurrence of, and recovery from primary hypothyroidism were observed after delivery in 6 women with autoimmune thyroiditis. Diffuse goiter was noticed 1-3 months after delivery. The blood thyroid hormone level was found to be lowest at 3-6 months post-partum, with a thyroxine iodine value of 1.0 +/- 0.6 mug/dl (mean +/- SD) (normal 3.0-7.2), triiodithyronine value of 77 +/- 11 ng/dl (normal 90-190) and T3 resin sponge uptake of 21 +/- 2.8% (normal 24-37). During this period the serum level of thyrotropin was increased to 307 +/- 235 muU/ml (normal less than 8) and 131I thyroid uptake in 24 hours was more than 60%. Then 6-9 months after delivery, the enlarged thyroid gland decreased in size, and the values in thyroid function tests returned to the normal range without any treatment. Anti-thyroglobulin antibodies were positive in 3 cases. Anti-thyroid microsomal antibodies were positive in all cases with titers of 1:10(4)-4:10(9), and titers were highest during the period of hypothyroidism and decreased thereafter. We suggest that these transient changes might be induced by pregnancy and delivery during the course of autoimmune thyroiditis.


Human thyroid adenyl cyclase-stimulating activity in immunoglobulin G of patients with Graves' disease.

We have studied the characteristics of the stimulation of adenyl cyclase (AC) activity in human thyroid plasma membranes by thyroid-stimulating hormone (TSH) and by immunoglobulin G (IgG) from the sera of patients with Graves' disease. AC activity was measured as adenosine 3',5'-cyclic monophosphate (cAMP) generated by membranes in a 10 minute incubation. IgG from two patients with Graves' disease possessed particularly potent human thyroid AC-stimulating activity; the dose-response curves with these IgGs were essentially parallel to those obtained with TSH. As little as 30 mug of the IgG of one patient with Graves' disease or 8 muU of TSH caused significant AC stimulation. A Lineweaver-Burk plot of the data suggested similarity in the site of action of both TSH and human thyroid adenyl cyclase stimulator (HTACS) in Graves' IgG. Submaximal doses of HTACS and TSH had additive effects on AC stimulation, but a large dose of a Graves' IgG with potent AC stimulating activity did not enhance AC stimulation by a maximal dose of TSH. The effect of HTACS on AC was slower in onset and longer in duration than an equipotent dose of TSH. HTACS was detectable in IgGs of 9 of 15 untreated hyperthyroid Graves' disease patients; its concentration, however, did not correlate significantly with tests of thyroid function, nor with long-acting thyroid stimulator (LATS) activity. In another 11 treated patients with Graves' disease, selected for the presence of LATS, HTACS and LATS were significantly correlated. We observed no inhibition of LATS activity in a Graves' IgG chosen for such testing because of its high titer of HTACS and no detectable LATS. However, an inhibitor of HTACS was detected in 2 of 4 IgGs; one of these two IgGs also inhibited AC stimulation by TSH. 1) Some Graves' disease IgGs contain a human thyroid AC stimulator (HTACS), probably different from LATS. 2) HTACS may act via a common pathway with TSH; it differs from TSH, however, in having a slower onset and a greater effect during more prolonged incubation with plasma membranes. 3) There is also an inhibitor of HTACS activity in some Graves' disease IgGs.


Separation and partial characterization of surface-active fractions from mouse and rat lung homogenates. Identification of a possible marker system for pulmonary surfactant.

The purpose of this study was to identify a "marker system" for pulmonary surfactant. A density gradient centrifugation procedure was developed to concentrate the surface-active material in mouse and rat lung homogenates. These fractions contained morphologic variants of surfactant such as lamellar bodies and tubular myelin. Lipid and protein analyses were consistent with other techniques indicating that these preparations were surface active. A comparison of the nonspecific esterases in these and other surfact-active preparations (i.e., pulmonary lavage fluid and isolated type II cells) allowed the identification of certain surfactant-associated esterases which are distinguishable electrophoretically and cytochemically from the other pulmonary esterases and which, therefore, may be used as "markers" for surfactant. Possible uses for these enzyme markers in studies of (a) the sites of synthesis and routes of clearance of surfactant and (b) the assessment of variations in surface activity due to either diseases such as the respiratory distress syndrome or to experimental manipulation are discussed.


Hypertension screening of 1 million Americans. Community Hypertension Evaluation Clinic (CHEC) program, 1973 through 1975.

During 1973 through 1975, more than 1 million persons were screened in the nationwide Community Hypertension Evaluation Clinic (CHEC) program at 1,171 sites. While those screened were not from defined populations, findings paralleled those of recent surveys of US population samples. First, CHEC confirmed the scope of the problem of elevated blood pressure in the United States. Of those screened, 247 of 1,000 had a diastolic reading of 90 mm Hg or higher; 116 of 1,000 had a reading of 95 mm Hg or greater. Prevalence of elevated blood pressure rose with age up to age 50 years, was higher in blacks than in whites, and was higher in men than in women. Second, CHEC data confirmed the challenge of undetected, untreated, and uncontrolled hypertension. Previously undetected hypertension was present in 27.7% of hypertensive people, detected but untreated in 10.7%, and treated but uncontrolled in 16.7%--totaling 55.1%.


Heavy-particle therapy in acromegaly and Cushing disease.

A total of 349 patients with pituitary tumors, including acromegaly, Cushing disease, Nelson syndrome, prolactin-secreting adenoma, and chromophobe adenoma, have been treated with heavy-particle radiation during the past 17 years. The incidence of side effects has been low. Only 30 patients, 8.6%, have died, most of preexisting cardiovascular complications. Heavy particle therapy provides a form of treatment with no mortality and extremely low morbidity, and its use in treating pituitary disorders has resulted in dramatic improvement in the signs and symptoms of patients with acromegaly and Cushing disease.


Training in advanced cardiac life support.

The nationally recognized training and certification program in Advanced Cardiac Life Support consists of lecture material and a new concept in training and testing for the practical skills of Advanced Cardiac Life Support. The course content follows closely the concepts of advanced life support as explained in the standards on cardiopulmonary resuscitation and emergency cardiac care.


Awareness of pediatric hypertension. Measuring blood pressure.

Surveys of patients at three pediatric teaching hospitals showed a low percentage of blood pressure recordings by the examining physician in the walk-in or emergency clinics. The frequency of blood pressure measurement was higher among inpatients, especially on medical services. A recommendation for obtaining blood pressure measurements is made on three bases: 1. many patients use these ambulatory services as their major source of care, 2. many conditions for which care is sought and many therapeutic agents are associated with hypertension, and 3. unless measurements of blood pressure become customary during training, it is likely that blood pressure recording may not be included as part of routine physical examinations.


Trace elements in sickle cell disease.

Trace elements in 84 adult patients (38 men and 46 women) with sickle cell disease (SCD) were reflected in clinical and biochemical data. Height was retarded in six men and five women. Eighty percent of the SCD patients in this sample were below the 50th percentile from the normal mean for weight. Twenty-eight men showed a lack of facial and body hair, and five additional subjects showed only scanty facial hair. Whereas zinc in plasma, red blood cells, and hair was decreased, the excretion of zinc in urine was increased in SCD patients as compared to the controls. We believe that one of the mechanisms accounting for zinc deficiency in SCD may be hyperzincuria and that growth retardation and hypogonadism in men so commonly seen in SCD may be related to zinc deficiency.


Nitroprusside therapy. Treatment of hypertensive patients with recurrent resting chest pain, ST-segment elevation, and ventricular arrhythmias.

Five hypertensive patients with acute myocardial infarction and persistent postinfarction hypertension who experienced severe and recurrent resting chest pain, ST elevations, and severe ventricular arrhythmias refractory to conventional treatment with bed rest, sedation, oxygen inhalation, nitrates, and antiarrhythmic agents received sodium nitroprusside by continuous intravenous infusion, titrated to reduce systolic blood pressure to 100 to 110 mm Hg. Treatment resulted in noticeable improvement in symptoms, reduction in ST elevations, and abolition of ventricular arrhythmias in all five patients. In four patients, cessation of nitroprusside infusion after 48 hours resulted in prompt recurrence of hypertension, chest pain, ST-segment elevations, and ventricular arrhythmias. These were all rapidly reversed following reinstitution of the nitroprusside therapy for seven to eight days, strongly suggesting a cause-and-effect relationship. Nitroprusside infusion in these patients suggests a potentially important use for such therapy in this clinical setting.


Cholecystostomy hazard in acute cholangitis.

Four patients with acute cholangitis were seen, all of whom died following cholecystostomy or cholecystoduodenostomy. The diagnosis of cholangitis is frequently missed in elderly patients with jaundice and sepsis. Cholecystostomy, in the face of cholangitis without documentation of patency of the cystic duct, is uniformly fatal. Diagnosis of cholangitis should be confirmed and immediately followed by adequate common duct drainage. Finally, immediate reoperation, rather than antibiotic manipulation, is advised to establish common duct drainage in those patients who do not respond to cholecystostomy within 24 hours.


Clinical spectrum of pseudomembranous colitis.

Five cases of pseudomembranous colitis (PMC) provided the opportunity for observation of clinical, endoscopic, and histologic features, and evaluation of potential modes of therapy. Although PMC may occur postoperatively or concomitantly with staphylococcal infection, if most frequently occurs following the administration of a variety of antibiotics. Patients with this disorder often have chronic, debilitating diseases. The clinical course may vary from a self-limited diarrheal illness to a fatal process. Onset with abdominal pain, diarrhea, and fever is characteristic. Barium enema contrast findings are nonspecific. Proctoscopy usually permits an accurate diagnosis. In the typical case, multiple elevated nodules formed by cream-colored plaques of pseudomembrane are scattered about the inflamed mucosa. Biopsy of these nodular lesions will confirm the diagnosis. Therapy must be individualized.


Secundum atrial septal defect. Nonoperative closure during cardiac catheterization.

A 17-year-old girl had clinical and cardiac catheterization findings compatible with a secundum atrial septal defect. During cardiac catheterization, the atrial septal defect was sized and closed using a transvenous umbrella technique.


Rheumatoid arthritis with rheumatoid heart disease and granulomatous aortitis.

Aortic insufficiency and aortitis are frequent complications of ankylosing spondylitis but are considered rare in rheumatoid arthritis. A 49-year-old woman with severe rheumatoid arthritis had the cardiovascular changes common to both diseases. At autopsy, the heart and aorta showed granulomatous ane fibrinous pericarditis and epicarditis, "core" granulomas in the aortic valve cusps and mitral valve leaflets, and coronary arteritis. These are considered to be classical changes of rheumatoid carditis. In addition, there were mesoaortitis with obliterative endarteritis of the vasa vasorum and fibrosis of the aortic cusps with separation of the commissures. These are considered to be changes of ankylosing spondylitis. This case, therefore, represents a mixed form of cardiovascular involvement within the spectrum of the rheumatoid diseases.


Early debridement in pit viper bites.

From my observations of snakebite over the last 22 years and the studies I have done, several things are important: (1) Pit viper envenomation is a surgical emergency as is any disease in which gangrene of human tissue occurs. (2) Severe pit viper envenomation causes complex problems similar to those seen in Gram-negative septicemia, and they require complex methods of treatment. (3) Early surgical inspection of the snakebite wound is as essential as early appendectomy in appendicitis. Its results are as gratifying. (4) Present knowledge of anesthesia, coagulation problems, infections and antibiotics, blood gas changes, electrolytes and fluid therapy, and other advances in the surgical field allow the physician to treat severe pit viper envenomation by scientific means rather than by hocus-pocus. (5) Crippling from pit viper envenomation is caused by too little treatment, too much first aid, or both.


Tubulointerstitial and glomerular nephritis associated with rifampin. Report of a case.

In a patient with tuberculosis and acute renal failure related to administration of therapeutic rifampin, treatment was discontinued for five weeks. It was reinstituted three weeks later. Unlike other patients previously described, the expected adverse renal reaction occurred only gradually and without symptoms, although tubular and glomerular disease developed. Also unique was a striking deposition of immunoglobulin about the tubules. This finding, in association with interstitial nephritis and tubular glycosuria, is similar to an experimental autologous renal disease mediated by antibody to tubular basement membrane.


Splenectomy or radiation and splenectomy for hypersplenism in lymphosarcoma.

This is a retrospective study of 14 patients with lymphosarcoma with hypersplenism. Eight patients received radiation to the spleen followed by splenectomy for recurrence of hypersplenism. Six patients underwent primary splenectomy for hypersplenism. Radiation decreases the size of the spleen but recurrence of hypersplenism is seen in an average of 8 mo. Splenectomy in these cases improves the hematological picture. Average postsplenectomy survival is 27.6 mo. Splenectomy alone in hypersplenism also improves the hematological picture. Postsplenectomy survival in this group is 13 mo. One case of primary lymphosarcoma of the spleen is reported.


Solitary peripheral pulmonary artery aneurysms. Pathogenesis and surgical treatment.

The case of a solitary peripheral pulmonary artery aneurysm in a patient with congenital heart disease and secondary pulmonary hypertension is presented. The aneurysm appeared following an episode of bacterial endocarditis and was probably mycotic in origin. Resection was prompted by a recent increase in size. A successful aneurysmectomy was performed. Lobectomy was the procedure employed in seven other reported cases treated surgically. A brief review of the literature emphasizes the necessity for resection whenever the diagnosis is made to prevent a fatal outcome due to rupture. A classification of pulmonary artery aneurysms based on their etiology is proposed, together with a possible explanation for the pathogenesis of peripheral aneurysms of nonspecific etiology.


Hashimoto's thyroiditis and breast cancer.

The question of a possible association between Hashimoto's thyroiditis and breast cancer was evaluated in (1) an autopsy series and (2) a follow-up of a cohort of patients with Hashimoto's thyroiditis at the Mayo Clinic. In the autopsy study, 174 subjects with histologic diagnosis of Hashimoto's thyroiditis were matched with a control group. There was no significant difference in the frequency of a history of breast cancer in the two groups. In the cohort of Olmsted County residents with a clinical or histologic diagnosis of Hashimoto's thyroiditis for whom there was a substantial period of follow-up, no excess frequency of breast cancer was note. These results contrast with those of a recent study reporting that Japanese women with Hashimoto's thyroiditis were a high risk group for breast cancer.


The common infectious diseases in Australia. A report from the australian general practitioner morbidity and prescribing survey.

A study of the common infectious diseases occurring in Australia during 1969 to 1973 showing the total patient-doctor contact for these diseases, the contact rate per episode and the estimated annual new cases seen is presented. In addition, the frequency by age-group and comments made on annual variations, sex differences (where applicable) and the treatment ordered by a large panel of general practitioners are shown.


Eye disorders: Using ultrasound in ophthalmologiç diagnosis.

Ultrasonography (echography) is a valuable diagnostic modality in ophthalmology. Its use in the detection and differentiation of intraocular and orbital diseases is expanding. B-scan provides cross-sectional display of diseased tissues and is valuable in detecting unsuspected disease. Quantitative A-scan is capable of demonstrating the internal texture of lesions, and this capacity coupled with the physician's familiarity with the histologic appearance of certain intraocular lesions often can lead to an accurate tissue diagnosis or can identify a group of possible diagnoses.


Coronary arteries in children up to the age of ten years II. Intimal thickening and its role in atherosclerotic involvement.

The frequency, histologic feature and topographic distribution of the first foci of intimal thickening were investigated in the coronary arteries of 40 fetuses, 40 neonates and 90 children up to the age of ten years. Particular hemodynamic and mechanical stresses seem to be involved in the precocious development of these isolated foci of intimal thickening which appeared in the early fetal life as well as in their progressive extension and fusion which give rise to diffuse thickened intima. After birth the stressed areas with thickened intima might evolve toward fibrosis and the "protected" ones toward degenerative and necrotic processes. These processes were detected in approximately 8% of the 5-10 year-old children and appeared before the development of fatty streaks or other forms of lipid accumulation.


Coronary heart disease and its risk factors in a group of 5,000 middle aged men in urban environment.

The results obtained at entry in the subjects included in a pilot study (Institute of Internal Medicine, Bucharest) for the detection and prevention of coronary heart disease and hypertension, are presented. These data are the prevalences of the risk factors of coronary heart disease (high serum cholesterol, hypertension, smoking, overweight, diabetes, nonspecific minor ECG signs, family history), as well as the prevalences of the various forms of coronary heart disease. The study of the frequency distribution of biologic parameters likely to become risk factors showed that in middle aged subjects the upper limit of the normal should be lowered from the 95th percentile to the 76th one.


Long-term study of the risk factors in atherosclerosis.

A study of the risk factors in atherosclerosis carried out in 595 subjects over a period of 10 years showed an increased prevalence of arterial hypertension, of high serum cholesterol values and of overweight in 1970 as compared to 1960. This rise was significant for all the parameters studied and was particularly evident in serum cholesterol values and overweight, beginning with the 21 to 30 age decade. The frequency of subjects with risk factors increased with age. During the period of study there occurred certain changes within the population such as an increase in the total consumption of calories and in the lipid contents of the food, as well as of the cultural level of the population. The authors show that the increase in the number of subjects with risk factors and the natural history of the various diseases or disturbances depend on the changes of living conditions and of environment.


[An investigation into the presence of staphylococci in farm milk (author's transl)].

Two hundred bulk milk samples drawn from milk collected in cans, which came from cows at stable at 40 farms in the Food Inspection District Utrecht, were examined for Staphylococcus aureus, by means of Baird-Parker's medium. Cultures obtained were phage typed with international, bovine, and additional Dutch phage series. About 60% of the isolated strains were found to be of human origin and about 20% of bovine origin. Isolated strains appeared to be farm specific. Approximately 70% of the farms supplied bulk milk containing 0.08-1.3X10(4) coagulase and DNAse positive staphylococci/ml. The conclusion is inescapable that this type of bulk milk still represents a latent hazard for human health.


Serum fibrinogen-fibrin related antigen and protamine sulfate test in patients with septic abortion and acute renal failure.

Decreased platelet count and platelet adhesiveness as well as increased values of the protamine sulfate test were found in 26 patients with septic abortion (9 of them anuric). Serum fibrinogen-fibrin related antigen (FR-antigen) values, detected in 13 patients (7 of them anuric) were greatly increased although euglobulin lysis time was rather prolonged (more than 400 min). Less increased FR-antigen values were noted in 15 cirrhotic patients with enhanced fibrinolytic activity in the circulating blood (euglobulin lysis time less than 120 min). These findings suggest that an important increase of FR-antigen in serum is likely to indicate a local fibrinolytic response to an initial coagulation event. Since platelet count and adhesiveness as well as FR-antigen and protamine sulfate test were similarly changed in patients with septic abortion who developed acute renal failure and in those who did not, it seems that the above mentioned parameters are not predictive for the evolution of thrombotic deposits and for possible renal complications following an episode of disseminated intravascular coagulation.


Absorption studies in patients with parasitic infestation of the small intestine, before and after treatment.

Forty adult patients having intestinal infestation with giardia or with parasitic associations, such as giardia-strongiloides, giardia-taenia solium, were subjected to morphological explorations, iron and vitamin B12 absorption tests, steatorrhea assay and serological tests, before treatment as well as six months and one year after eradication of the infection. On admittance, jejunal morphological lesions were noted only in 15 cases especially in associated infestation, iron depletion in six patients, vitamin B12 malabsorption in five patients and steatorrhea only in two cases. After the lapse of six months and one year, respectively, all the tests ranged within normal values, and the jejunal morphological aspect improved significantly indicating the pathogenetic role of intestinal parasites in the development of selective malabsorption.


Congenital dyserythropoietic anemia type II. Radioautographic, ultrastructural and cytogenetical study in two familial cases.

The case of two sisters is reported in whom morphological (multinucleated erythroblasts in the bone marrow) and serological (positive Ham test, negative sucrose and water-sugar tests) characteristics of a congenital dyserythropoietic anemia type II were found. Radioautographic, cytogenetic and electron microscope studies confirmed the presence of an inefficient erythropoiesis and of a membrane defect, common in this disease. The finding of a nil LAP score has never been reported so far.


New devices: the McDermott spirometer.

The assessment of a new bellows spirometer against a water spirograph showed: slight alinearity, minimal overestimation of FVC (1.7%) and underestimation of FEV 1-0 (2.9%) as well as of the ratio FEV 1-0/FVC (4.8%). The main advantages of the instrument are: lightness, easy operation, ruggedness and low cost; it seems mainly indicated for use in large scale field surveys.


Serum pseudocholinesterase activity during experimental fattening.

The exact role of serum pseudocholinesterase (PSCE) is not known. Its main role probably consists in the degradation of butyril-choline, an intermediate of lipid metabolism. Decreased values have been described in liver cirrhosis as an index of diminished proteosynthetic function. An increased activity of this enzyme was reported in obesity, diabetes mellitus, nephrosis, hyperthyroidism and in hyperlipemic subjects without obesity. A significant correlation was found between serum cholesterol, triglycerides and PSCE, as an expression of lipid metabolism. In view of assessing the possible change of this enzyme during fattening, the authors investigated PSCE activity during fattening in pigs (the same breed). The results indicate a statistically significant increase of PSCE during fattening, from 30.4 +/- 1.7 to 43.6 +/- 1.7 (p less than 0.001). These results together with those reported in a previous paper concerning blood lipids and cholesterol, show a positive correlation between these parameters and PSCE during fattening in pigs, which might be due to an adaptative increase of the hepatic synthesis of this enzyme in response to the increased lipid metabolism.


[Biomechanic examination of prenatal lung maturity. Testing of amniotic fluid specimens and lung homogenates on Wilhelmy's scale].

In all traditional methods of determining fetal lung maturity the content of phospholipids in the amniotic fluid is used as parameter. The function of the other parts of the surfactant is not taken into account. The dynamic surface tension measurements using the Wilhelmy balance simulate the interplay of the whole biological system. We have tested 76 specimens of amniotic fluid and 17 lung extracts from 25 weeks' gestation onwards using the biomechanical procedure. In addition, the L/S ratio in the amniotic fluid was determined. There was a correspondence between the values of the amniotic fluid and the lung measured in the same week of pregnancy. The results of the surface tension measurements show a good correlation with the standard method. The following are the advantages of the Wilhelmy balance: results show a small range of dispersion, procedure can be easily learned and carried out quickly and simply.


[Experiences with a new antiphlogistic and analgetic drug ("Eumotol") in orthopaedic and accident surgery patients (author's transl)].

The Bumadizon-Ca ("Eumotol") which does not contain any hormones or steroid bodies was applicated in 130 orthopaedic and accident surgical patients as an antiphologistic an analgesic drug. In over 90 percent of these cases we could state a good antiphologistic and following analgesic effect. Even when applicated for longer terms there were no allergic, toxic or some what disturbing secondary effects. The compatibility of this drug proved generally to be good. In five cases only with gastritis and peptic ulcer we had to stop the application."Eumotol" is strictly forbidden to be applicated in patients with hypersensitivity against pyrzol bodies and in cases of leukopenia. When a decreased function of kidneys and liver is evident the drug should be only given under certain precantionary measures.


[Sensory and chemical changes of dried foods under the influence of extreme storage conditions. 1. Method of sensory evaluation (author's transl)].

This paper described a method for the evaluation of sensory changes in the quality of dried foods, which have been stored under extreme conditions. The applied method is based on the 5 point DLG-scale, the structure of this scale has been adapted to the requirements of a methematical-statistical evaluation. In addition standard samples are provided as reference during the test.


[Sensory and chemical changes of dried foods under the influence of extreme storage conditions. 2. Sensory changes (author's transl)].

The sensory quality of dried infant foods is decreasing steadily during the storage under extreme conditions. Odor and taste are influenced to a higher degree than colour and consistency. A package with a high permeability for oxygen and water vapor has an unfavourable effect on the storability. The composition of the investigated products has no influence on the sensory estimation, but a significant influence on the storage behavior.


The effect of cyproterone acetate on the adrenal of the male hamster.

Administration for different doses of cyproterone acetate (CPA) to male hamsters for 5 weeks slows down the growth of the adrenals and the increase in body weight. This effect is still present 4 weeks after cessation of CPA treatment, though some recovery can be seen. Histological and histometrical evaluations confirm an atrophy of the adrenal, particularly in the zona fasciculata and in higher doses also in the zona reticularis. After operative castration it is the zona reticularis which shows the most marked atrophic changes. It is therefore concluded, that CPA possesses besides its anti-androgenic properties an inhibiting corticoid-like effect on the adreno-pituitary feed-back mechanism.


Specific binding sites for L-triiodothyronine in rat liver and kidney cytosol.

Binding of 125I-labelled triiodothyronine (T3) to rat liver and kidney cytosol was examined. In both organs a very similar binding protein was detected. The apparent equilibrium association constants amounted to 4.8 X 10(7) M-1 for the liver protein and to 1.8 X 10(7) M-1 for the kidney protein. In the two organs a high capacity for T3 binding was observed: maximal binding capacities of respectively 4.3 and 33.2 pmol per mg total cytosol protein. Displacement studies using thyroid hormone analogues showed that the binding exhibited similar specificity.


A familial syndrome of progressive cone dystrophy, degenerative liver disease, endocrine dysfunction and hearing defect. I. Ophthalmological findings.

Seven patients, 6 females and one male, with progressive cone dystrophy are reported. One patient developed amaurosis in one eye and fere amaurosis in the other. The least affected patient (13 years of age) had fairly good central cone vision, but a rod response only outside the central area. Attenuated retinal vessels, disc pallor and general atrophic appearance without pigmentation were typical findings. Six of the patients originated from 2 sibships. Increasing impairment of vision during pregnancy was seen in two patients. Pathological glucose tolerance, diabetes, liver disease, endocrinological disturbances, and hearing defects were recorded. Thus, this cone dystrophy appears to be part of a disease affecting several organs. The familial occurrence suggests that this disorder is inherited.


Electrophysiological and anatomical effects of cetylpyridinium chloride on the rabbit cornea.

The effects of cetylpyridinium chloride on the trans-corneal potential difference and the surface anatomy of the cornea have been examined. Concentrations of cetylpyridinium chloride from 0.21 mM to 2 mM were used for either 1 or 2 minute exposure times on the in vitro and in vivo cornea for the electrophysiology studies. The potential difference of the in vitro cornea showed a concentration and exposure-time dependent decrease, the in vivo cornea shows a qualitatively similar behaviour although quantitatively less. The fall in potential difference is preceeded by a hyperpolarization. The scanning electromicroscopy reveals a loss of microvilli and microplicae as well as surface pitting, with some exposure of cells underlying the superficial epithelium. These changes occur in a dose-dependent manner. The effect of cetylpyridinium chloride on the cornea is to enhance the permeability of the superficial cells by destroying the cell membranes and causing lysis of the cells.


Diagnostic value of the water-drinking test in early detection of simple glaucoma.

A series of 64 patients (119 eyes) subjected 10 years previously to water provocative tests on a suspicion of simple glaucoma were followed up. At that time the intraocular tension exceeded 20 mmHg, but there were no optic disc changes and no visual field defects. The follow-up examination comprised ophthalmoscopy, visual acuity, gonioscopy, intraocular tension, and perimetry. Setting a rise of 8 mmHg as the lower limit, the water provocative test ten years previously had been positive in 31 eyes. Nine of these developed glaucomatous visual field defects despite treatment (29 per cent). The test had been negative in 88 eyes. Of these, 21 (24 per cent) developed glaucomatous visual field defects. The water-drinking test was negative in 70 per cent of the eyes which subsequently developed visual field defects and negative in 75 per cent of those in which no defects developed. Thus the test was neither of diagnostic nor of prognostic value. All the eyes with a positive test which later developed visual field defects had been treated, whereas 57 per cent of the eyes with a negative test which subsequently developed visual field defects had received no treatment. This indicated that a negative water-drinking test gave a false security. It is shown that an alteration of the lower limit of a tension rise does not render the water provocative test any more useful.


A portable hemianopsia tester.

A pocket-size static perimeter provided with four test lights, one for each quadrant of the visual field, has been constructed and applied to 190 visual fields in 97 patients. The main advantage of the instrument is its ability to disclose hemianopic defects in bedridden and certain sick patients unable to co-operate with other methods, including the confromtation test. This was performed in 12 fields in 7 patients.


Lens thickness and angle-closure glaucoma. A comparative oculometric study in South African Negroes and Danes.

A group of Negro patients without ocular disease ("normal" group), a group of Negroes with angle closure glaucoma and a normal Danish population are compared in terms of anterior chamber depth, less thickness, vitreous body length and axial length of the globe. It is noted that the normal black population has a significantly thinner lens than the black population with angle closure glaucoma and the normal Danish population. The latter groups have a lens thickness which is similar. This finding is discussed in relation to the lower incidence of acute closure attacks in the black population. Attacks of angle closure in this populatin are generally of the chronic type.


Demonstration of the hemiopic border in the normal person.

The hemiopic border is the vertical line in the visual field separating the two halves which represent each cerebral hemisphere. This border, which becomes clinically manifest in the hemiopias, may be demonstrated in the normal person either (1) by covering an eye with the palm of the hand while facing the sun with the eyes closed, or (2) by fixing a near point and observing the background while the two eyes are dissociated by red and green glasses, or (3) by two-object perimetry, in which an inhibition may be observed along the vertical median through the fixation point.


Blood circulating changes in the eye and limbs with relation to pregnancy and female sex hormones.

Alterations in corneal indentation pulse (CIP) amplitudes and pulse volume recordings (PVR) on the limbs were demonstrated in pregnant women, indicating that significant changes occur in the peripheral blood circulation during pregnancy. The PVR measured at week 30-36 of gestation demonstrated a significant increase when recorded on the forearm and index finger. In the eye an increase in CIP amplitudes was found early in pregnancy. From week 20 on, however, a steady decrease occurred, until the CIP amplitudes at term averaged about 1/3 of the values from normal, non-pregnant women. Similar changes, although less pronounced, were demonstrated in the ocular blood circulation during oral contraceptive treatment and, to some extent, during menstruation. Intake of gestagens and diaethyl-stilboestrol did not alter the CIP amplitudes.


Visual functions after perinatal macular haemorrhage.

Perinatal macular haemorrhage has been suggested as being a cause of amblyopia and strabismus. 39 of 48 children with macular haemorrhage after birth were examined at the age of 5 years. The study comprised visual acuity with E-test types and cycloplegic refraction. Binocular function was evaluated by cover test, and 4d-prism test. Fixation was studied by an ophthalmoscope with a central dark star. Sensory function was estimated by Schober test and Worth 4-dot-test. The observations gave no support to the existence of organic amblyopia or strabismus following perinatal macular haemmorrhage.


Orbital phlebography. Technique and clinical applications.

The technique for orbital phlebography is described and the phlebographic anatomy of the orbit and the skull base presented. The possibilities and limitations of phlebography in the diagnosis of different intraorbital and ophthalmoneurological disorders is discussed and illustrated out of personal experiences from 200 cases.


Traumatic hyphaema treated with the antifibrinolytic drug tranexamic acid.

During the year 1975 (Jan. 1st-Dec. 31st) 72 patients, consecutively admitted to the eye department of Arhus Kommunehospital with traumatic hyphaema, were treated with the antifibrinolytic drug tranexamic acid. Secondary haemorrhage occurred in one case. This incidence of secondary haemorrhage (1.4%) seems to be the lowest on record. A group of patients from the period 1965-1968, treated identically with the exception of the tranexamic acid, were selected for comparison. This group of 135 patients included 9 cases (6.7%) with a secondary haemorrhage. The difference between these two groups is statistically significant (P less than 0.05).


Greater bile acid excretion with soy bean than with cow milk in infants.

The excretion of fecal sterols and bile acids was measured in five infants from the 1st week of life to 2 or 3 months of age as the composition of their diet was changed from cow milk to soy bean milk. Bile acid excretion, adjusted for body weight, was initially lower during the 1st than during the 3rd week, when it reached adult values. The average excretion of bile acids was 6.8 mg/kg per day with soy bean milk and 3.6 mg/kg per day with cow milk. Net sterol excretion (total sterol output minus cholesterol intake) was also twice as high with soy bean milk and probably reflected enhancement of cholesterol re-excretion as well as of synthesis since the cholesterol content of soy beans is nil. However, net sterol excretion remained higher with soy bean than with cow milk even when egg yolk cholesterol was added to the soy bean milk. It is concluded that the substitution of soy bean milk for cow milk, which lowered the plasma cholesterol in all infants (even in the presence of dietary cholesterol) leads to an increase in bile acids and probably also in cholesterol excretion in young infants.


Oral treatment of acrodermatitis enteropathica with zinc sulfate.

In a 7-year-old boy with acrodermatitis enteropathica, oral administration of zinc sulfate brought about complete relief of symptoms and signs, with clearing of the skin lesions, arrest of diarrhea, and growth of new hair. Considering the dramatic results obtained, we believe that oral treatment with zinc sulfate is an innocuous, inexpensive, and very effective medication for acrodermatitis enteropathica, which can replace the previously used and toxic diiodohydroxyquin-like drugs.


Erythropoietin production in the rat: additive role of kidney and liver.

Erythropoietin (Ep) levels were evaluated in serum of neonate, weanling, or adult rats subjected to 1) sham operation, nephrectomy, and/or subtotal hepatectomy and 2) a standard bout of hypoxia (0.45 atm air/6 h, starting 1 h after the operation). Ep activity was quantitated by means of strictly controlled assays in exhypoxic polycythemic mice. The sum of Ep titers in the serum of nephrectomized or hepatectomized rats was compared to Ep levels in sham-operated animals of corresponding age levels, with the exception of 1-wk-old rats: it is relevance that no significant difference is apparent between these Ep production curves. Thus, evidence is presented indicating for the first time that Ep derives from two functionally distinct and additive sources, i.e., the kidney and the liver. Liver Ep, although prevalent in neonatal animals, is obscured in the weanling adult rat by both gradual initiation of massive renal Ep production and progressive decrease of hepatic Ep activity.


Keratoconus associated with retrolental fibroplasia.

Three adult male patients with keratoconus associated with severe bilateral retrolental fibroplasia were studied. Two of these presented with acute corneal hydrops. The association may be of some interest in determining the etiology of keratoconus.


Autoimmune factors associated with anaemia in acute Haemobartonella and Eperythrozoon infections of rodents.

Eperythrozoon coccoides and Haemobartonella muris produced in mice and rats respectively, essentially the same disease, characterized by anaemia, splenomegaly and in severe cases, haemoglobinuria with death. In both infections anaemia was associated with phagocytosis of erythrocytes by monocytes of the spleen, and with the presence of cold-active haema-glutinin for trypsinized red cells (CAH). An antigen similar to the serum antigen (SA) associated with acute malaria and babesiosis was also found in the blood of the anaemic animals. One or two days later antibody to SA (ABSA) was detected and for several days thereafter, both SA and ABSA could be detected in plasma samples. Anaemia crisis with haemoglobinuria was better correlated with the appearance of ABSA than  with the presence of CAH. It is suggested that CAH, and complexes of SA and ABSA could have acted as anaemia factors and were in part causal in the sequestration or haemolysis of erythrocytes during acute infection.


Massive colchicine overdose: a report on the toxicity.

A case of an overdose of colchicine for suicidal purposes is presented. The main complications observed involved the hematopoietic, the gastrointestinal, the respiratory and the central nervous system. Heinz bodies were noticed in the red blood cells, a finding which had not been previously documented in patients with colchicine overdose. Despite intensive management the patient died on the thirteenth hospital day of central nervous system complications.


Effect of long term use of oral contraceptives on glucose tolerance.

The effect of long term use of oral contraceptives on glucose tolerance was studied in 133 women. Oral contraceptives were taken for a period between 3 and 12 years. 25 women without any hormone treatment served as a control group. The intravenous glucose tolerance test (IVGTT) has indicated no pathological decrease of glucose tolerance, measured by k. The glucose tolerance test was performed on all subjects (0.33 Gm. of glucose per kg bodyweight). In one subject we diagnosticated a clinical diabetes. Two patients had a subclinical diabetes. After 10 years of treatment a significant decline was noted in k, also in women with family history of diabetes or a past obstetrics history. Several doubtfully pathological k-values were recorded in women more than 40 years of age. No significant relation could be established between parity and the developement of an abnormal glucose metabolism, while taking the drugs. The effect upon glucose tolerance is not related to the type of oral contraceptive. The evidence is not sufficient to warrant the elimination of oral contraceptives. In is suggested that at least in diabetes suspects, repeated controls of glucose tolerance be carried out during long term cyclic use of oral contraceptives.


[Regionally different activity of enzymes within placentones of human term-placentas. Histochemical and biochemical investigations (author's transl)].

After a short summarizing review earlier histological and first histochemical investigations on the functional morphology of placentones results of histochemical and biochemical studies about thirteen enzymes are presented. Histochemical and biochemical investigations demonstrate that the placental villi situated in the centers of the circulation-units show enzyme-patterns which only differ quantitatively not qualitatively from those of the villi situated in the periphery. Specific acitivity is found to be weaker in the central villi. The results confirm our former histological investigations which gave evidence that the villi situated in the centers of placentones were relatively immature compared to those of the periphereal areas. The centers of the placentones therefore are to be considered for regions of regeneration and growth whilst in the periphery placental metabolism and maternofetal exchange takes place.


[Children's development after placental dysfunction (author's transl)].

Katamnestic neurological and electroencephalographic studies were performed on a group of 6 to 11 year old children who had been born in the years of 1960 to 1966 with the signs of placental dysfunction. Of a total of 288 children (2,8% of the deliveries at the department of obstetrics & gynecology of the Cologne university) 177 were  analized katamnestically and 152 uncerwent a clinical examination. For comparison a group of 384 children were studied who had been born in the same years spontaneously from vertex presentation after a maximum duration of labour of 16 hours. At the time of delivery these children were mature and eutrophic. 133 children of this group were studied katamnestically and 114 underwent clinical examination. The katamnestic studies showed that the group with symptoms of placental dysfunction differed in their development from the control group: these children learned later to sit, to walk, to speak, to dress without help, and to control urination. No differences were found in the ability to write and to read or in their results at school. However a larger percentage of the control group was found to attend a higher educational institution. No differences were found in the incidence of disease or behavioral abnormalities. Sleeping problems and lact concentration were more often observed in the group of children with symptoms of placental dysfunction. The general clinical examination showed no differences between the two groups. The applied different tests to examine grow movements were performed less perfect in a higher percentage by the children born with signs of placental dysfunction. Even greater differences were found in testing the voluntery skilled movements. The electroencephalogram of children of both groups showed a normal basic activity, a distinct blocking effect and a significant activation upon  hyperventilation. An abnormal and pathological EEG was however significantly more often found in children born with symptoms of placental dysfunction. The results of the examination of the individual children and the combination of these results in the groups of symptoms showed that children with signs of placental dysfunction demonstrated a significantly higher incidence of symptoms. It was furthermore obvious that these symptoms were not singular but part of a complex disturbance which was manifested in the obstetrical characteristics as well as in the katamnesis and in the clinical examination. Thus, these studies have demonstrated a higher rate of morbidity in children with placental dysfunction in addition to the known high perinatal mortality. This points the necessity of an early prepartual diagnosis in particular in pregnancies with predisposition, in order to reduce not only the perinatal mortality but also to avoid the described complications in children born after placental dysfunction.


Helical structure of human native collagen.

A "fibroleiomyoma" of the lung obtained from a 40-year-old man as a surgical specimen was studied with both the light and the electron microscope. The unusual collagen in this tumor displayed a filamentous helical structure. The filaments measured 50 Angstroms across. Most of the fibrils did not show periodicity. Some, however, showed periodicity of about 700 A. Those with periodicity were smaller in diameter than the fibrils without periodicity. These observations suggest a helical structure of native collagen and may also represent weak cross-linking of tropocollagen in this tumor. This is the first report of collagen showing a helical filamentous structure from human material.


Central pontine myelinolysis and medullary myelinolysis.

Central pontine myelinolysis (CPM) is a rare, acute, and uniformly fatal demyelinative process that involves the pons almost exclusively. Three cases diagnosed at autopsy illustrate the characteristic clinical course and pathologic features of CPM. A unique extrapontine location of a similar process is noted in the medulla of a 6-year-old girl. The term "medullary myelinolysis" is a descriptive designation for demyelination that occurs predominantly in this area. The clinical and pathologic features of CPM are reviewed in detail, together with a brief review of theories of metabolic, nutritional, vascular, and endogenous and exogenous toxic factors that act either singly or in concert in the cause and pathogenesis of CPM.


Ultrastructural evidence of myofibroblasts in circumscribed fibromatosis.

The myofibroblast, which exhibits ultrastructural features of both smooth muscle cells and fibroblasts, is the predominant cell type in the granulation tissue of healing wounds. Similar cells were identified in an ultrastructural study of a case of circumscribed fibromatosis. Myofibroblasts have been described in several apparently unrelated conditions, suggesting that the acquisition of smooth muscle-like features is one of a limited number of ways in which fibroblasts may react to abnormal stimuli.


Granular cell tumors of the heart.

In a study of granular cell tumors arising in the hearts of three patients, no evidence was found, either histologically or ultrastructurally, to support the hypothesis that these tumors are derived from striated muscle or cardiac muscle. The anatomic location of the tumors in all three cases suggests that granular cell tumors are derived from Schwann cells or from the same precursor cell as the Schwann cell.


Severe combined immunodeficiency with thymic mast cell hyperplasia.

The autopsy finding on an infant with severe combined immunodeficiency was marked thymic mast cell hyperplasia. The clinical immune status showed a deficit in T (thymus derived) lymphocytes and low immunoglobulin levels. The autopsy showed the histologic pattern designated thymic alymphoplasia and a marked lack of development of the reticuloendothelial organs. The mast cell hyperplasia may be the result of an antigenic stimulus early in embryonic life and/or the result of mast cell differentiation at the expense of normal thymic lymphoid development caused by a genetic defect.


[Gynecological aspects of retroperitoneal diseases (author's transl)].

Current literature was reviewed for gynecological aspects of retroperitoneal diseases. Taking into account the original histological findings retroperitoneal diseases were divided into the following groups from a gynecological point of view: 1. Malignant and benign primary retroperitoneal tumors 2. retroperitoneal organs 3. malignant and benign tumors of retroperitoneal organs 4. retroperitoneal gynecological structures 5. retroperitoneal metastases 6. other retroperitoneal diseases.


A spindle cell varient of thymic carcinoid tumor. A clinical, histologic, and fine structural study with emphasis on its distinction from spindle cell thymoma.

We describe the clinical, histologic, and fine structural features of two thymic carcinoid tumors that had a major spindle cell component, and present the reason for classifying our two cases as variants of thymic carcinoid tumors. These tumors pursued an aggressive clinical course, demonstrated histologic features such as vascular invasion and mitotic activity, ultrastructurally contained numerous dense-core granules, and lacked prominent tonofilaments and well-formed desmosomes. Radiotherapy, even for apparently encapsulated cases, may be indicated for this aggressive mediastinal neoplasm, which can be clearly separated from the thymoma by clinical, histologic, and fine structural criteria.


Goblet cell carcinoid of the appendix. An ultrastructural and histochemical study.

In a patient with a goblet cell carcinoid tumor of the appendix, light and electron microscopical studies demonstrated mucinous material and enterochromaffin granules within the same cell. Transitions between cells containing primarily mucin and cells containing numerous argentaffin granules were observed. Fluorescence studies demonstrated that the tumor cells contain biogenic amines.


Isoproterenol, endotoxin shock, and the generalized shwartzman reaction.

Adult hybrid albino rabbits were divided into seven groups. Three groups were given two respective intravenous doses of 10 mug, 25 mug, or 100 mug of endotoxin at an interval of 24 hours. Three other groups were given endotoxin as above, and, in addition, were given 0.5 mg of isoproterenol hydrochloride (Isuprel) by subcutaneous injections at eight-hour intervals beginning at the time of the first injection of endotoxin. A single group was given isoproterenol only. The animals were observed for clinical signs of shock beginning at the time of the first injection of endotoxin. The mortality during the course of the experiment was noted. At the time of death, the animals were studied grossly, and sections were taken for light microscopy. Results showed no meaningful enhancement of endotoxin toxicity as manifested by shock, generalized Shwartzman reaction, or mortality.


Experimental meningococcal septicemia. Effect of heparin therapy.

The pathogenesis of experimental meningococcal septicemia and the efficacy of heparin sodium therapy were evaluated by inoculating rabbits intraperitoneally with type B meningococci in mucin. Half the rabbits died, and the respiratory distress and circulatory failure that occurred during the terminal phase of the disease were associated with diffuse pulmonary capillary and venular thrombosis and with renal glomerular fibrin deposition. Platelet and leukocyte counts and plasma fibrinogen levels decreased in all rabbits, and prothrombin and partial thromboplastin times were prolonged. Pretreatment with heparin sodium diminished intravascular fibrin deposition but failed to prevent the pulmonary microthrombi and did not either reduce the mortality or improve the survival time. We conclude that death in meningococcal septicemia is due to widespread thrombosis of the pulmonary microcirculation. The disease is complicated by diffuse intravascular coagulation, which can be controlled with heparin sodium but which is not immediately life-threatening.


Gastrointestinal effects of acute ferrous sulfate poisoning in rats.

Ferrous sulfate administered intragastrically to rats produced two types of intestinal lesions: corrosive injury to the stomach and upper part of the small intestine, and ileal infarcts associated with venous thrombosis in some animals given fatal doses. Iron was deposited at the interface of viable and necrotic mucosa and in blood vessels of all layers. By means of electron microscopy the iron deposits were located in the basement membrane of the vessels. Fatal doses were always associated with intestinal injury, although the time of death suggests that death was caused by absorption of iron rather than by the local injury.


Rectal suction biopsy in the diagnosis of Hirschsprung disease in infants.

Our experience with 47 rectal suction biopsies performed in infants up to six months of age indicates that this is a simple and effective method for the exclusion of Hirschsprung disease. It requires the recognition of immature ganglion cells in neural units as equivalent to mature ganglion cells. Absence of these immature neural units in an adequate sample is highly suggestive of Hirschsprung disease.


Fine structure of pancreas in cortisone-treated guinea pigs and rabbits.

Twenty-eight male rabbits and 28 male guinea pigs received daily intramuscular injections of cortisone acetate for four to 31 days (rabbits, 5 mg/kg; guinea pigs, 10 mg/animal). Moderate hyperglycemia ensued. Insulin concentrations of the pancreatic tissue varied but were higher in cortisone-treated animals than in untreated controls. In rabbits, degranulation of beta cells, hyperplasia of islets, and proliferation of ductular structures were the major light microscopic findings. Ultrastructural studies suggested that beta cell neogenesis took place mainly within pre-existing islets but probably also within ductular structures. Mixed (acinar-islet) cells were not identified. In guinea pigs, ductular proliferation was not noted, and beta cell neogenesis appeared to take place exclusively within preexisting islets and islet cell nests. In both species, cells of several types contained glycogen deposits.


Congenital complete tracheal rings. Report of a case.

An unusual congenital tracheal anomaly is described. Complete (closed) tracheal rings, occupying the entire length of the trachea, have seldom been reported. Most affected patients succumb to respiratory infections in early infancy. Diagnosis of this anomaly is difficult during life, but radiographic and endoscopic examinations may be revealing. There is no known definitive treatment, although the airway may be managed long enough for body growth to relieve the obstruction. This rare anomaly should be considered in those cases of intermittent respiratory obstruction that are not associated with other more common causes of stridor.


The hydrophobic adsorption of charged molecules to bilayer membranes: a test of the applicability of the stern equation.

To describe the hydrophobic adsorption of charged molecules to bilayer membranes, one must recognize that the adsorption produces a change in the electrostatic potential at the surface of the membrane. The surface potential produced by the adsorption of the charged molecules can be described most simply by the Gouy equation from the theory of the diffuse double layer. This potential will tend to lower the concentration of the adsorbing ions in the aqueous phase immediately adjacent to the membrane, a phenomenon which can be described by the Boltzmann relation. The number of adsorbed ions is, in turn, a function of the aqueous concentration of these ions at the membrane solution interface and can be described, in the simplest case, by a Langmuir adsorption isotherm. If the ions are regarded as point charges, the combination of the Gouy, Boltzmann, and Langmuir relations may be considered a simplified Stern equation. To test experimentally the applicability of this equation, one should measure both the charge density and surface potential as a function of the concentration of adsorbing molecules in the bulk aqueous phases. Direct, accurate measurements of one of these parameters, the number of moles of 2, 6-toluidinylnaphthalenesulfonate ions bound to vesicles formed from phosphatidylcholine, are available in the literature (Huang, C., and Charlton, J.P. (1972), Biochemistry 11, 735). We estimated the change in the surface potential in two independent ways; by means of conductance measurements with "probe" molecules on planar black lipid membranes and by means of electrophoresis measurements on multilaminar unsonicated vesicles. The two estimates agreed with one another and all of the data could be adequately described by the Stern equation, assuming, at 25 degrees C, a dissociation constant of 2 X 10(-4) M and a maximum number of binding sites of 1/70 A2.


Uptake of 36Cl-toxaphene in mosquito fish, Gambusia affinis.

The toxicity syndrome of toxaphene to G. affinis was divided into 5 stages, and the residue level at each stage was determined. By the time fish were exhibiting the first toxicity response (stage 2), 90.3% of the mean fatal residue level had been sorbed. Regression analysis indicated that sorption of toxaphene is a linear function with respect to time. Excretion was not observed following an 8 hour exposure to 2ppm toxaphene. Metabolic alteration of toxaphene during the experiments appeared to be minimal. Differences in individual mortality appeared to be due to differences in uptake rather than differences in ability to tolerate particular body loads of toxaphene.


Education at school about sexually transmitted diseases.

Although sex education in West German schools started officically in 1968, a survey of 700 children aged 14 to 15 years showed that they understood more about birth control than about sexually transmitted disease (STD). This contrasts with the rising incidence of gonorrhoea and falling birth rate. There is a general lack of published information of STD and it is proposed that an international body like the IUVDT should be formed to promote the spread of information.


The situation in Eastern Europe.

The administrative structure for the management of patients with sexually transmitted disease is described. The association of dermatology and venerology had psychological advantages for patients attending a combined clinic, but because it was considered that the future development of venereology might suffer an Institute of Venereology has been founded in Poland. The functions of this Institute are described and the organization of undergraduate and postgraduate medical training is outlined.


The situation in Scandinavia.

The history of legislation controlling the treatment of venereal infections and undergraduate and postgraduate training in venereology is outlined. Arrangements for research into these infections and the advantages of centralized facilities for serum antibody tests are described. Syphilis, gonorrhoea, chancroid, and lymphogranuloma venereum are notifiable. One present problem is the difficulty of collecting information on non-gonococcal urethritis. There is a high incidence of infection in Greenland and further research should be undertaken there.


Role of the medical auxiliary in the control of sexually transmitted disease in a developing country.

Venereal diseases are becoming a major health problem in many developing countries where the greater part of primary medical care is undertaken by medical auxiliaries. Under these circumstances, the medical auxiliary has an important role to play in the control of these diseases but he can only do this with adequate training, support, and supervision from the professional doctors and specialists. In this paper, the role of the medical auxiliary is outlined and a case is also made for a specially-trained cadre for venereal disease work in busy urban clinics in developing countries.


Venereal disease among immigrant workers in Vienna.

Official physical examinations of migrant workers upon immigration are required before work permits are issued. The screening of 74,983 applicants during 1972 to 1974 revealed sera reactive to serological tests for syphilis in 0-8 per cent. (range 0-5 to 1-1 per cent.) of all persons concerned and fifteen cases of early syphilis. The incidence of recent infections among immigrants is lower than that reported among the inhabitants of Vienna. General statistics on the spread of venereal diseases among immigrant workers are not available after they start work. Some evidence is provided by those who had to be traced for compulsory examination because they had defaulted from treatment or follow-up, because they were suspected of clandestine prostitution, or because they were reported to be sources of infection. 257 (60-6 per cent.) of 414 individuals who were wanted for reasons of syphilis control could be located and eighteen (7 per cent.) of those who were examined had early infectious lesions.


Reappraisal of the problem of British mariners and sexually transmitted infection.

A detailed appraisal of the British seafarer and his way of life is described and the prevailing management of sexually transmitted disease in the seafarer is outlined. It is shown that the available statistics on the incidence of sexually transmitted disease among seafarers are inadequate. Management at sea and ashore remains generally unsatisfactory. Suggestions are made to improve the management of venereal disease in foreign ports and a simple method is described of managing sexually transmitted disease at sea with trimethoprim/sulphamethoxazole.


Exchange of contact information between East Germany and other countries about persons infected with VD or at risk of infection.

26 per cent. of all contacts exchanged in both directions between East Germany and Poland in 1973, concerned people infected with STD. This high rate of efficiency obtained by the present methods of contact tracing justifies further cooperative epidemiological work in the field of STD, especially in view of the increasing industrial and economic cooperation and tourism between the two countries which is expected in the future.


VD education in developing countries. A comparison with developed countries.

No new method of control of the sexually transmitted diseases is imminent. Reliance has to be placed on existing methods including health education. Health education has a double role, being a primary method in its own right, and--of equal or greater importance--being involved in the enforcement of all of the other tried methods. A comparison is made of the situation in countries with a developed or an underdeveloped venereal disease control service, in respect of organization, statistical reporting, the various agencies treating venereal disease, clinic and diagnostic facilities, personnel concerned in venereal disease management, and other aspects. The vicious circle inherent in developing countries is outlined. A lack of awareness of the extent of the problem and the presence of other serious competing diseases lead to a low budget, thence to poor diagnostic and treatment facilities, and to few cases being seen in the official clinics and hospitals. Thus relatively small numbers of cases are reported and there is consequently a continuing lack of awareness of the problem. A method of cutting through such a circle is suggested, and the importance of health education activities during this period is emphasized.


Education of physicians in the sexually transmitted diseases in the United Kingdom.

Undergraduate and postgraduate training in sexually transmitted diseases and genitourinary medicine in the UK is described. The course for overseas postgraduate students is briefly described. It is noted that once funds are available it has been agreed to establish a professorial chair of venereology at the Middlesex Hospital Medical School. This will be a major advance and is the most desirable goal to aim at in the encouragement of education in STD for the next few years.


Laboratory-associated infections: summary and analysis of 3921 cases.

Instances of overt laboratory-associated infection recorded in published reports and additional cases disclosed by questionnaires and personal communications have been tabulated. Of a total of 3921 cases, 2465 occurred in the United States and 164 were fatal. Only 64% of the cases were reported in the literature. Analysis of the available information revealed that only 18% of the infections were due to known accidents; 42% were caused by bacteria; 27% by viruses; 15% by rickettsiae; 9% by fungi; 3% by chlamydiae; and 3% by parasites. It may be significant that fewer infections have been recorded in the past decade than in any of the four preceding decades. Possible reasons for this apparent decrease are discussed.