Neural mechanisms for entrainment and generation of mammalian circadian rhythms. The identification of a direct retinohypothalamic tract (RHT) terminating in the supra-chiasmatic nuclei (SCN) has focused attention on the role of these structures in the entrainment and generation of circadian rhythms in mammals. Light effects on circadian rhythms are mediated by both the RHT and portions of the classical visual system. The complex interactions of these systems are reflected both in their direct anatomical connections and in the functional changes in entrainment produced by interruption of either set of projections. Destruction of the RHT/SCN eliminated both normal entrainment and normal free-running circadian rhythms. No circadian rhythms has survived SCN ablation in rodents, but a variety of non-circadian cycles can be generated by lesioned animals. The complex behavioral patterns produced by SCN-lesioned hamsters suggest that circadian oscillators continue to function in these animals, but that their activity is no longer integrated into a single circadian framework. The available evidence indicates that the mammalian pacemaking system comprises a set of independent oscillators normally regulated by the SCN and by light information that is transmitted via several retinofugal pathways.


Photoentrainment, pharmacology, and phase shifts of the circadian rhythm in the rat pineal. Photoentrainment of circadian rhythms in mammals is mediated by the retinohypothalamic projection to the suprachiasmatic nucleus of the hypothalamus. It should therefore be possible to mimic or block the effects of light on the circadian pacemaker with appropriate pharmacological agents. Such agents and their effects should be useful in identifying the neurotransmitters involved in photoentrainment and their mechanisms of action on the circadian pacemaker. The effects of light on the circadian rhythm in rat pineal serotonin N-acetyltransferase activity are described. Carbachol, a cholinergic agonist, was found to mimic the effects of light on this rhythm, including the acute reduction of nocturnal activity and phase-shifting of the free-running rhythm. These results raise the possibility that acetylcholine is involved in the photoentrainment of mammalian circadian rhythms.


Nutritional factors affecting quantity and quality of carcass fat in chickens. Nonpathological fattening of a bird occurs when the amount of energy consumed exceeds its requirements for maintenance and growth. Dietary energy and protein levels, particularly the ratio of these two, are the main dietary factors affecting fatness. Consumption of diets low in protein results in excess energy intake and an increased hepatic lipogenesis. Excess protein has the opposite effect. It also increases the energy expenditure required to dispose of excess amino acids in the body. Severe deficiency of a specific amino acid does not increase fattening. The degree of fattening, particularly of the liver, induced by corticosterone injection is greater in birds fed diets containing a wide energy-to-protein ratio in comparison to a narrow ratio. The content of dietary fat per se does not affect carcass fat concentration although it alters the rate of liver fatty acid synthesis. The dietary fatty acid composition affects the composition of tissue fatty acids. Consumption of diets containing vegetable oils or high in protein increases the degree of unsaturation of tissue fat and thereby its susceptibility to oxidation. Dietary dl-alpha-tocopheryl acetate increases the stability of the lipids of adipose and muscle tissue of chicks with relatively saturated body fat, but the dietary effectiveness of this vitamin in improving the stability of tissues of birds having relatively unsaturated fat is limited.


Danazol treatment of endometriosis: long-term follow-up. Forty-nine women diagnosed as having pelvic endometriosis were treated with 800 mg of danazol/day for a mean duration of 6 months. The average length of the follow-up period was 78 months. Side effects were minimal, and regular ovulatory menses returned within 25 to 90 days (average 42 days). Forty-two (85.7% of these women had associated infertility. Recurrence of symptoms was reported in 33% but in no patient were the symptoms worse than before entering the study. Of 30 patients desirous of pregnancy, 20 were potentially fertile; of these, 10 conceived within 6 months of discontinuing therapy, for a conception rate of 50%. Nine of the remaining ten patients required additional therapeutic procedures (surgery and/or danazol), and four of these conceived within 12 months. These results compare favorably with those of other investigations, since most of our patients were referred to us after being subjected to a variety of regimens, both hormonal and surgical.


Accumulation of ethinylestradiol in blood and endometrium of women taking oral contraceptives: the sequential therapy. A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women under sequential oral contraceptive therapy (chlormadinone acetate, 2 mg, plus mestranol, 80 microgram) for 6 to 84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age the mean plasma EE-2 concentrations were similar during the first (989 +/- 94 pg/ml) and the second half of the cycle (1053 +/- 186 pg/ml) (P greater than 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 microgram/gm of wet tissue, respectively). On the other hand, five women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentrations was 0.9 +/- 0.6 microgram/gm of wet tissue (P less than 0.05). Although plasma follicle-stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential oral contraceptive therapy cannot be disclosed from this limited number of determinations.


Three siblings with premature gonadal failure. Of a brother and two sisters with infertility, one female sibling was found to be mosaic for Turner's syndrome. The brother and the other sister, of average intelligence, were phenotypically normal, with no dysmorphic features or ambiguous genitalia, but both showed hypergonadotropic hypogonadism. It is suggested that the basic defect in these two siblings is the same and is of genetic origin. As the parents were consanguineous, the defect is most likely due to an autosomal recessive gene.


The effect of copper in vivo on specific progesterone binding by human endometrial cytosol. Copper has been shown to interfere with specific progesterone binding by human endometrial and myometrial cytosol in vitro. These results suggested that one possible mode of action of the copper-bearing intrauterine devices (IUDs) is through interference with the action of progesterone at its target sites. A prospective study was carried out to determine whether the proposed mode of action of copper-bearing IUDs could be demonstrated in vivo. The results of this study revealed a significant difference in specific progesterone-binding capacity between proliferative and secretory endometria (P less than 0.001). However, when secretory endometria of the controlled subjects were compared with those of the copper-bearing IUD wearers, no significant difference was observed in the specific progesterone-binding capacity (P greater than 0.2). These data suggested that copper released from copper-bearing IUDs in vivo may not interfere with the binding of progesterone to its receptors in vitro. It is doubtful that the contraceptive effectiveness of copper-bearing IUDs could be due to the ability of copper to prevent progesterone from exerting its full effects on the endometrium.


Open-ended vasectomy, sperm granuloma, and postvasectomy orchialgia. The presence of a sperm granuloma at the vasectomy site prevents epididymal pressure build-up, perforation, and the formation of an epididymal sperm granuloma. It thus enhances reversibility of the vasectomy and lessens the likelihood of epididymal discomfort. In two prospective vasectomy series, a sperm granuloma was intentionally allowed to form by not sealing the testicular end of the vas. The sperm granuloma resulted in no instance of orchialgia, but created a greater risk of spontaneous recanalization. This latter problem could only be solved by more careful sealing of the upper end of the vas. In a separate series of nine patients vasectomized elsewhere and specifically referred to us for chronic and persistent postvasectomy orchialgia, seven had no sperm granuloma at the vasectomy site. Pain in these cases was localized in the epididymis and was relieved by vasovasotomy. Any technique of vasectomy carries a very small risk of orchialgia, whether due to the presence of a sperm granuloma at the vasectomy site or to increased epididymal pressure.


Clomiphene therapy in male infertility: a negative report. The enthusiastic acceptance of the use of clomiphene citrate in the treatment of the subfertile male prompts the issuance of this report. Fifty-four subfertile males were treated following recommended guidelines. In addition, testicular biopsy was performed in each patient. Analysis of the results, even excluding those with elevated follicle-stimulating hormone levels (which everyone concedes spells a poor prognosis), shows only a small percentage of improvement.


Male hyperprolactinemia:effects on fertility. Male hyperprolactinemia was detected in 4% (7 of 171) of infertile men. In seven patients with excessive serum prolactin concentrations, the clinical manifestations were infertility, hypogonadism, impotence, and galactorrhea and the etiologic factors were pituitary adenoma, hypothalamic dysfunction, drug use, and idiopathic. The testes and prostate were small or normal and the semen analysis revealed low semen volume, normal or low sperm count, and normal or impaired sperm motility. The testicular biopsy showed normally preserved seminiferous tubules with normal or decreased spermatogenesis and damaged or fibrotic seminiferous tubules among normal ones. Patients with hyperprolactinemia were investigated by sellar polytomography, visual field examinations, and hormone assays. Treatment with bromocriptine (Parlodel) gave satisfactory results in all patients. The use of bromocriptine with human menopausal gonadotropin and human chorionic gonadotropin was beneficial in treating hypogonadotropic hypogonadism with hyperprolactinemia.


Carbohydrate metabolism and the semen profile: glucose, insulin, and sperm studies. Twenty-seven men attending an infertility clinic received detailed studies of their ejaculate and carbohydrate metabolism. The latter was done using a 3-hour oral glucose tolerance test with a 100-gm glucose load and measuring both blood glucose and plasma insulin levels. There was no significant difference in either the blood glucose or the plasma insulin values between the men with normal sperm counts and those with abnormal sperm counts. These data suggest that mild subclinical states of carbohydrate abnormalities do not routinely alter male fertility.


The effect of steroids on the in vitro migration of washed human spermatozoa in modified Tyrode's solution or in fasting human blood serum. In modified Tyrode's solution, 17 beta-estradiol at concentrations between 0.1 microgram/ml and 320 nmoles/ml was effective in increasing human spermatozoal forward migration. 17 alpha-Estradiol, although structurally similar to 17 beta-estradiol, had no effect on human spermatozoal motility. DL-Norgestrel at concentrations between 0.1 migrogram/ml and 320 nmoles/ml inhibited spermatozoal motility. These stimulatory and inhibitory effects were not observed when fasting human blood serum was used as a penetration medium in place of the modified Tyrode's solution. Also, the motility of spermatozoa suspended in fasting human blood serum was better than that of spermatozoa suspended in modified Tyrode's solution or in seminal plasma. These observations indicated that there is a component(s) of fasting human blood serum which increases spermatozoal motility and can counteract the activation or inhibition of spermatozoal motility by 17 beta-estradiol or DL-norgestrel at the concentrations used here.


The effect of a single lethal x-irradiation exposure on the activity of lipoprotein lipase in the tissues of the rat. Wistar male rats, both fed and fasting for 16 h prior to irradiation, were exposed to a single lethal X-ray dose of 387 mC X kg-1 (1 500R). The activity of lipoprotein lipase in white adipose (epididymal) tissue and heart muscle and the concentration of serum triglycerides were determined at 1, 6, 24, 48, and 72 h after radiation exposure. In the early time periods, at 1 and 6 h after exposure, the activity of lipoprotein lipase was decreased in adipose tissue and increased in heart muscle of the irradiated fed rats; in fasting rats it was decreased in heart muscle at 1 h after exposure. The concentration of serum triglycerides was increased at 1 h and decreased at 6 h after exposure in fed rats. In these rats, alterations in serum triglycerides correlated with changes in lipoprotein lipase activity in adipose tissue. Alterations observed at the later time periods were more dependent on the time interval between radiation exposure and the analysis. Lipoprotein lipase activity increased with time after radiation exposure up to the maximal values at 72 h. Fasting prior to and after irradiation substantially modified the response of animals to radiation.


Syngeneic lines of chickens. VI. Immunoglobulin allotypes. In the course of study of alloantigenic immunoglobulin polymorphisms in 10 inbred chicken lines we detected 7 IgG allotypic specificities and 3 IgM allotypes. All birds in a given line possessed a unique combination of several IgG alloantigenic specificities (forming the phenogroup) which is presumably controlled by one allele at the locus designated a. We found five such phenogroups and five corresponding alleles (allele ac in three C lines, aI in three I lines,  aW in two W lines, aM in line M, and aF in line F) in inbred lines tested. Furthermore, it could be inferred that each IgM allotype is the marker of one allele at the locus D. The distribution of these alleles among inbred lines was determined (allele dC was present in lines C and F, allele dI in lines I and M, and allele dW in lines W). A 2.8% recombination between loci a and d that are linked was found. The study of linkage between immunoglobulin allotype loci and blood group loci A, E, B, C, D, and I revealed no deviation from independent assortment of thse loci.


[The incidence of antithyroid antibodies in relatives of patients with thyroid disorders (author's transl)]. In order to elucidate a predisposition for so-called autoimmune thyroid disorders such as Graves' disease, chronic thyroiditis and myxedema, the incidence of thyroid antibodies was studied in relatives of patients with thyroid disorders. The relatives studied were all limited within a two degree relationship of the patients. Serum antibodies to thyroglobulin and thyroid microsome were determined by susing the method of a hemagglutination test. The following results were obtained; 1) Thirty six of 103 relatives (35%) were found to have such antibodies, and sixteen (7.0%) of 230 hospital controls were positive. This difference was significant (P less than 0.001). 2) There was no difference in the incidence among relatives of patients with Graves' disease and those chronic thyroiditis. 3) With regard to age, the incidence in the more than 20 years old group was significantly greater than that in the under 19 years old group. 4) There was no difference in the incidence between male and female. These results suggested that the relatives of patients with so-called autoimmune thyroid disorders may have a predisposition for thyroid disorders.


[The vasopressor role of ADH in the maintenance of blood pressure in experimentally hypertensive rats (author's transl)]. In order to investigate the vasopressor role of ADH in the regulation of blood pressure, passive immunization experiments with an antibody to AVP were carried out in experimentally hypertensive rats. In hypertensive rats treated with deoxycorticosterone acetate (DOCA), spontaneously hypertensive rats (SHR) and spontaneously hypertensive stroke-prone rats (SHR-sp), the intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood pressure of 11 approximately 25mmHg, while in rats with two-kidney Goldblatt hypertension and normal rats, the blood pressure was not affected. This strongly suggests that ADH contributed to systemic vaso-constriction in DOCA hypertension and spontaneous hypertension in rats.


Effect of oleic and octanoic acids on glucose-induced insulin release in vitro. The isolated perfused rat pancreas was utilized to characterize the effect of 1.5 mM oleic acid and 1.5 mM octanoic acid on insulin release in response to glucose (4.4, 8.3, 11.1, 16.7 and 27.7 mM). Both oleic and octanoic acids potentiated glucose-induced insulin release without modification of the pattern of secretion. At 4.4 mM glucose, the potentiation of insulin release by fatty acids was clearcut for the first phase but not significant with respect to the total amount of insulin released during the stimulation period. Maximal potentiation was observed at 11.1 mM glucose both with oleic and octanoic acids. At all glucose concentrations, octanoic acid was more effective than oleic acid in the potentiation of the insulin secretion.


Mauriac syndrome: three cases with retinal angiofluorescein study. Three children with features of the Mauriac syndrome have been studied. Ocular complications, mainly characterized by increased capillary permeability have been demonstrated by fluorescein angiography. A decreased proximal tubular beta 2-microglobulin reabsorption has been found in one patient, and in another one, there was a slowed sensory nerve condition velocity. A liver biopsy, performed in one patient, has shown numerous fat filled cells and intralysosomal lipofuscin storage. No hormonal disturbance, which could explain the growth reardation, has been found. Bad metabolic control of diabetes could be responsible for all the anomalies of Mauriac syndrome.


Plasma fibrinogen in diabetes mellitus.

Plasma fibrinogen in diabetes mellitus. Plasma fibrinogen was measured in 285 diabetics (age range 15-85 years) and 209 controls (age range 23-74 years). Plasma fibrinogen concentration showed a positive skew distribution and an approximate normal distribution was obtained by log transformation. The mean log plasma fibrinogen in the diabetics was significantly increased (p less than 0.0001). Patients treated with a sulphonylurea (n = 81) had the highest mean log plasma fibrinogen concentration and this was significantly higher than in patients treated with insulin (n = 76; p less than 0.01), biguanides (n = 28; p less than 0.01) or sulphonyluera plus biguanides (n = 38; p less than 0.05). The biganide treated group had the lowest mean log plasma fibrinogen concentrations. No correlation was found between plasma fibrinogen and blood glucose, duration of diabetes or the presence of complications. Subjects with proliferative retinopathy (n = 38) had a similar mean plasma fibrinogen to those with background retinopathy (n = 55). Twenty-two maturity onset diabetics treated with a sulphonylurea and followed prospectively showed a significant increase in plasma fibrinogen after five months (p less than 0.0001), while a control diet treated group showed no alteration in plasma fibrinogen. It is concluded that plasma fibrinogen is significantly increased in diabetics and apart from age, the main factor related to the increase is treatment with sulphonylureas. It remains speculative whether this association has any correlation with long term cardiovascular morbidity.


Effect of calcitonin on insulin response to arginine in man. The aim of the present study was to evaluate the effect of calcitonin on insulin response to intravenous arginine in normal humans. For this purpose, eight normal subjects were submitted to an iv arginine tolerance test twice, under basal conditions and during the simultaneous infusion of calcitonin plus arginine. Calcitonin caused a clear inhibition of the insulin response to arginine (p less than 0.01) and also exaggerated the rise in plasma glucose seen with iv arginine (p less than 0.01). Theophylline (250 mg as iv bolus, followed by an iv infusion of 500 mg/h) failed to overcome the inhibitory effect of calcitonin on insulin secretion. It is hypothesized that calcitonin inhibits insulin secretion by changing calcium distribution in the pancreatic beta-cell.


Ketoprofen (Orudis) twice daily dosage in arthritis and tissue injuries: a general practice study. In a general practice study using ketoprofen (Orudis) in a twice-daily dosage regimen for the treatment of patients with articular and non-articular rheumatic conditions, data were collected on 2,644 patients, over one-third of whom had been previously treated with other anti-rheumatic preparations. More than 80% showed a clinical improvement and the overall incidence of side-effects was relatively low. Three patients suffered a haematemesis--the most serious side-effect encountered. It was concluded that 50 mg or 100 mg twice-daily therapy was equally as effective as the 50 mg thrice daily regimen previously recommended and that the tolerability of ketoprofen was not adversely affected by this concentration of the daily requirement.


Tolmetin and G-6-PD erythrocyte deficiency: research in vitro. In thirty-two patients, divided into four groups: normal, G-6-PD deficient, beta-thalaxemic heterozygote and carriers of both anomalies, the variations in erythrocyte GSH were studied after incubation with APH and a non-steroidal anti-inflammatory drug: tolmetin sodium. The results obtained show a considerable fall in GSH after incubation with APH above all in the G-6-PD deficient patients and in the carriers of both anomalies. On the other hand, after incubation with the drug under examination there were no significant variations in the erythrocyte GSH.


The effect on plasma potassium of a combined preparation of frusemide and slow-release potassium chloride (Diumide-K Continus tablets). An open trial was carried out on ten middle-aged and elderly patients in cardiac failure to assess the effect on plasma potassium levels of one or more tablets containing 40 mg frusemide and a controlled-release formulation containing 600 mg potassium chloride. Patients had previously been maintained on frusemide and potassium supplements given as separate tablets. No significant rise or fall was observed when treatment was changed to the combined tablet.


A retrospective evaluation of nifedipine therapy in Prinzmetal's angina. A retrosepctive evaluation has been made of blood pressure, pulse rate, and number of anginal attacks per day in twenty-one patients diagnosed as Prinzmetal's Angina and treated with the investigational drug nifedipine. The effect of combining nifedipine with short- and long-acting nitrates or with propranolol was also evaluated. In consideration of the statisically significant reduction in the number of anginal attacks per day, p less than 0.001, together with the non-significant mean changes in blood pressure and pulse rate as well as the compatibility with the other drugs, it is concluded that nifedipine is a very useful drug, in a dose range of 30--120 mg per day, for the treatment of Prinzmetal's Angina. Recorded side-effects were of minimal severity and in no case caused nifedipine therapy to be discontinued.


Comparison of multiple-dose regimens of netilmicin in patients with urinary tract infections. A clinical trial involving forty hospitalized patients with urinary tract infections was conducted to compare the effectiveness and tolerance of four dosage regimens of netilmicin: 1, 2, 3, and 4 mg/kg administered twice daily for 7 or 8 days. Each of the dosages was effective and the first three were equally well tolerated. At 4 mg/kg there was one case of renal dysfunction possibly related to netilmicin therapy. Serum concentrations of the drug measured 1 hour after injection were dose-related, as were those measured 1 hour before administration; no appreciable accumulation occurred with any of the regimens.


Beclomethasone dipropionate aerosol in the treatment of asthma in steroid-independent children. Sixty-eight steroid-independent children, whose asthma was poorly controlled by bronchodilators and other anti-asthmatic drugs, were treated for six weeks with 200 to 400 mcg per day of beclomethasone dipropionate aerosol. Symptoms of wheezing, blockage, and cough, reported by the children in a daily diary, improved in 80% of cases. Use of other anti-asthmatic medications, which the children were free to modify as they wished, decreased. Objective measurements of pulmonary function, VC, FEV1, and FEV%, evaluated by weekly spirometry, also improved in almost 80% of cases. The dosages used here had no effect on early morning plasma cortisol levels and none of the children developed signs of oral candidiasis.


Crotamiton cream and lotion in the treatment of infants and young children with scabies. Fifty hospitalized infants and small children in the age-group of 3 months to 2 years admitted with scabies were treated with 5 applications of either 10% crotamiton cream or lotion on consecutive days. In this trial, the second to be performed exclusively in infants and young children, an improvement in itching was observed in all patients within 3 days of starting the treatment and the examination on Day 7 showed absence of skin lesions in all patients. Crotamiton cream as well as lotion rendered a 100% cure rate. All patients, including those having secondary pyoderma and/or eczematization tolerated the treatment with crotamiton cream and lotion well and no adverse reactions, either due to the topical application or to the transcutaneous systemic absorption of crotamiton, were reported. Post-treatment laboratory investigations did not reveal any unwanted effect due to transcutaneous systemic absorption of crotamiton on the blood, kidneys or liver. Crotamiton is the only scabicide available today which displays not only antiprurtic but also marked antibacterial properties. It is especially indicated in the treatment of scabies in children as they are very prone to secondary bacterial infection following scratching. In view of its good efficacy and excellent tolerability the 5-application treatment schedule, with crotamiton cream applied to the whole body from the chin downward, can therefore be recommended as an optimum form of treatment for scabies in infants and young children.


An evaluation of Debrisan in chronic leg ulcers and pressure sores. Debrisan (Dextranomer) was subjected to a simple open assessment in the treatment of fifty-three chronic leg ulcers and thirty pressure sores in eight hospitals. It was found that 70% of leg ulcers and 76% of pressure sores improved, with a noticeable cleansing effect being evident in 79% and 83% respectively. No side-effects were recorded.


Three methods of application of econazole in the treatment of vaginal candidiasis. Pointing out the fact that there is a generalized increase in the incidence of vaginal candidiasis the authors describe a study involving a total of sixty-one patients to evaluate econazole in the treatment of the condition.


The control of liver regeneration by calcitonin, parathyroid hormone and 1 alpha,25-dihydroxycholecalciferol. Removal of the thyroid in normocalcemic rats with functional parathyroid transplants was found to reduce the hepatocyte DNA synthetic activity which normally follows partial hepatectomy. This proliferative incapacitation of hepatocytes appeared to be due specifically to a calcitonin deficiency since it was overcome by a single injection of pure synthetic salmon calcitonin shortly after partial hepatectomy. Salmon calcitonin and bovine parathyroid hormone were equally able to reverse the similar proliferative incapacitation of hepatocytes in hypocalcemic rats which had both their parathyroid and thyroid glands removed one day before partial hepatectomy. However, these two hormones (individually or together) could not reverse the proliferative incapacity resulting from a more prolonged (3-day) exposure to the hypocalcemic conditions in thyroparathyroidectomized rats, but the proliferative incapacity could be reversed by simultaneous treatment with the vitamin D3 metabolite, 1 alpha,25-dihydroxycholecalciferol. We suggest that extracellular calcium ions are the actual regulators of this hormonally-controlled hepatocyte proliferative development and that parathyroid hormone and the vitamin D3 metabolite affect proliferation indirectly by determining the extracellular calcium concentration, while calcitonin directly, or indirectly, sensitizes hepatocytes to the action of calcium.


Androgen-uterine interactions: an assessment of androgen interaction with the testosterone- and estrogen-receptor systems and stimulation of uterine growth and progesterone-receptor synthesis. This study investigates growth and the induction of progesterone-receptor synthesis in the immature (day 20--23) rat uterus after injection of different doses of 5 alpha-dihydrotestosterone (DHT) and testosterone (T) in long- and short acting injection vehicles. Moderate doses of T (300 microgram/day in saline for 3 days) elicit uterine growth (ca. 250% of control) that is abolished by concomitant injections of antiandrogen (1 mg flutamide/day or 8 mg DIMP/day) but is unaffected by injections of antiestrogens (60 microgram CI-628 or U11,100A/day). Uterine growth evoked by 17 beta-estradiol (3 microgram/day for 3 days) is, however, only antagonized with the antiestrogens but not antiandrogens. Experiments employing whole uteri in vitro indicate that the specific nuclear uptake of 10(-8) M [3H]T is markedly inhibited by the antiandrogens DIMP, flutamide, and the hydroxylated flutamide metabolite (LACT) [LACT greater than DIMP greater than FLUT] while the antiestrogens CI-628 and U11,100A are ineffective. In contrast, the specific nuclear uptake of 10(-8) M [3H]-estradiol is inhibited by only the antiestrogens and not antiandrogens. When very high (5 or 10 mg) doses of DHT Are administered in an oil-containing injection vehicle, nuclear translocation and cytoplasmic depletion of the estrogen receptor does occur and a uterotrophic response is elicited which is resistant to antagonism by antiandrogen. Likewise, the DHT-stimulated increase in progesterone-receptor content is not decreased by concomitant antiandrogen. Similar 5 or 10 mg doses of DHT, administered in a water-soluble dimethylsulfoxide vehicle, show little estrogen-receptor movement and the DHT-induced uterine growth and induction of progesterone-receptor synthesis is almost completely eliminated with antiandrogen. Regardless of the degree of uterine growth stimulation, however, the androgens are poor stimulators of uterine progesterone-receptor synthesis compared with estradiol. These results indicate that androgens may interact with both the androgen- and estrogen-receptor systems in the uterus in inducing uterine growth and that the nature of the cellular mechanism, i.e., whether the androgen- and/or estrogen-receptor system is involved, is dependent critically upon the in vivo dose of androgen and the mode of hormone administration.


In vitro biosynthesis of juvenile hormone by the larval corpora allata of Manduca sexta: quantificationby radioimmunoassay. An in vitro method has been developed for the investigation of the regulation of juvenile hormone biosynthesis by insect corpora allata. Glands were maintained in Marks medium 19AB and JH synthesis quantified by a modified radioimmunoassay for juvenile hormone I. The radioimmunoassay is specific for JH I and exhibits approximately 12.6% cross reactivity with JH II and no cross reactivity with JH III. The assay directly measures the JH present in culture medium and has a maximum sensitivity of 50 pg JH I equivalents. Corpora allata from day 5 last instar Manduca sexta larvae were used to define the kinetics parameters of the in vitro system, including a demonstration that small groups of right and left glands synthesize equivalent amounts of juvenile hormone. The juvenile hormones synthesized were identified as juvenile hormones I and II in a ratio of 1:4, respectively. Juvenile hormone III could not be excluded as a product of the corpora allata owing to the low cross reactivity of this homolog (1.7%) in the radioimmunoassay. Corpora allata from different developmental stages exhibited synthesis rates generally consistent with predicted activity based on in vivo hormone titers with the exception of day 5 of the last instar. The variation in gland activity relative to the control of juvenile hormone titer in vivo is discussed.


Prostaglandin synthesis by isolated rat renal glomeruli. The PGE2, PGF2 alpha and 6-keto-PGF1 alpha contents of the incubation medium of glomeruli isolated from rat kidney were measured at different times with or without addition of arachidonic acid. These prostaglandins accumulated progressively with time and reached equilibrium after 60--120 min incubation. Synthesis of the 3 prostaglandins was inhibited when indomethacin was added whereas it was markedly enhanced, mainly for PGE2, at increasing doses of arachidonic acid. Plateaus were reached above 5 micrograms/ml and concentrations corresponding to 50% of the maximum values were 2 micrograms/ml for PGE2 and PGF2 alpha, and 0.8 microgram/ml for 6-keto-PGF1 alpha. There were strictly linear relationships between PGE2 or PGF2 alpha productions and the concentration of glomerular protein. PGE2 and PGF2 alpha synthesis with or without arachidonic acid were maximum at 30--37 degrees C. PGE2 glomerular content was almost undetectable initially and increased with time. These data demonstrate that PGE2, PGF2 alpha and PGI2, in order of decreasing abundance, are synthesized by the glomerular cells and suggest that PGE2 and PGI2-sensitive glomerular adenylate cyclase activities and PGE2-sensitive renin synthesis may be stimulated by prostaglandins formed in the glomeruli themselves.


Search for progesterone receptors in testes from various animal species. Using [3H]R5020 as binding probe, we have looked for the presence of progesterone receptors in testis cytosol from a few vertebrate species ranging from the turtles to the humans. In addition, we have tested in the rat several experimental conditions potentially susceptible to induce progesterone receptors. With the exception of chicken, tfm patients and possibly the frogs, progesterone receptors could not be conclusively demonstrated in any of the other animal species tested nor could they be induced in the rat. Surprisingly, they were not present in Stanley-Grumbeck pseudohermaphrodite rats. In chicken testes, the levels of progesterone receptor were variable (3--45 fmol per mg prot.) in the adults and high (87 fmol per mg prot.) in one-day-old animals. The presence of progesterone receptor, a marker of estradiol action in many estrogen-target tissues, seems to be parallel to the capacity of chicken testes for sex reversal under the influence of estrogens. In human tfm, the presence of these receptors could also indicate that the gonads are estrogen-sensitive or that they were so during embryonic life although the nature of estrogenic action is not known.


Insulin production rate following glucose ingestion estimated by splanchnic C-peptide output in normal man. Insulin production rate has been estimated in healthy male volunteers (n = 16), and evaluated with respect to splanchnic glucose exchange. Insulin production rate was calculated from splanchnic immunoreactive C-peptide output. C-peptide secretion was estimated by the hepatic venous catheter technique both in the basal state and for 2 h following ingestion of various glucose loads (0, 12.5, 25, 50, 75, and 100 g). The results demonstrate a basal insulin production rate of 0.017 +/- 0.002 U/min (mean +/- SEM) or 2.04 U/2 h. Values rose in a dose dependent manner from 2.6 +/- 1.1 U/2 h after ingestion of 12.5 g of glucose to 10.8 +/- 1.1 U/2 h following a glucose load of 100 g. Insulin retention by the liver was estimated at 0.012 +/- 0.001 U/min in the basal state, and ranged from 47-85% (70 +/- 2%) of production following an oral glucose load. It was also demonstrated 1) that the relative splanchnic glucose output was inversely related to the amount of ingested glucose, and reached a minimum when glucose in excess of 50 g was ingested; and 2) that hepatic glucose retention was directly proportional to insulin production rate (r = 0.83; p less than 0.001; n = 15). It is suggested that the adaptive capacity of the splanchnic bed to retain glucose depending on the amount of ingested glucose guarantees that splanchnic glucose output fluctuates in healthy man only within a narrow range.


Variation in 125I-insulin absorption and blood glucose concentration. The absorption of monocomponent porcine 125I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125I-insulin dose. A significant correlation (p less than 0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.


Solubilization of insulin binding and degrading activity from guinea pig kidneys. Insulin binding and degrading activities were solubilized by a nonionic detergent. Triton X-100, from guinea pig kidney particulate fractions (100,000 x g pellet). The solubilized insulin binding activity appeared as a single peak on Sepharose 6B gel filtration with a Stokes radius of 73 A. The pI of the solubilized insulin binding activity determined by flat-bed isoelectric focusing was 5.6. On the other hand, the Stokes radius of the solubilized moelcule with insulin degrading activity was 54 A by the same column with a pI of 5.2. More than 98% of the insulin binding activity could be adsorbed to a column of concanavalin A-agarose, while about 94% of the insulin degrading activity could not be adsorbed to this column. These results strongly suggest that the macromolecule for the insulin binding activity is not identical to that for the insulin degrading activity.


The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle, and rabbit slow skeletal muscle. A protein-chemical analysis of muscle actin differentiation. Complete amino acid sequences for four mammalian muscle actins are reported: bovine skeletal muscle actin, bovine cardiac actin, the major component of bovine aorta actin, and rabbit slow skeletal muscle actin. The number of different actins in a higher mammal for which full amino acid sequences are now available is therefore increased from two to five. Screening of different smooth muscle tissues revealed in addition to the aorta type actin a second smooth muscle actin, which appears very similar if not identical to chicken gizzard actin. Since the sequence of chicken gizzard actin is known, six different actins are presently characterized in a higher mammal. The two smooth muscle actins--bovine aorta actin and chicken gizzard actin--differ by only three amino acid substitutions, all located in the amino-terminal end. In the rest of their sequences both smooth muscle actins share the same four amino acid substitutions, which distinguish them from skeletal muscle actin. Cardiac muscle actin differs from skeletal muscle actin by only four amino acid exchanges. No amino acid substitutions were found when actins from rabbit fast and slow skeletal muscle were compared. In addition we summarize the amino acid substitution patterns of the six different mammalian actins and discuss their tissue specificity. The results show a very close relationship between the four muscle actins in comparison to the nonmuscle actins. The amino substitution patterns indicate that skeletal muscle actin is the highest differentiated actin form, whereas smooth muscle actins show a noticeably cloer relation to nonmuscle actins. By these criteria cardiac muscle actin lies between skeletal muscle actin and smooth muscle actins.


The effect of vitamin A on cellular differentiation and mucous glycoprotein synthesis in long-term rat tracheal organ cultures. Rat tracheal explants maintained as organ cultures exhibited a normal mucocillary epithelium for at least 46 days in the presence of retinyl acetate. In the absence of vitamin A the explant epithelium became quiescent or underwent a metaplastic change to a keratinizing squamous epithelium. This process was accelerated if explants were derived from vitamin A-deficient animals. Autoradiographic examination showed that [3H]glucosamine label accumulated in various cell types in the explant, but especially in the epithelium. It was found that the explants secreted mucous glycoproteins into the medium and that the production and biochemical characteristics of a specific mucin fraction were dependent upon the vitamin A status of the explant.


Cross-reactivity to mammalian anti-H-Y antiserum in teleostean fish. Anti-H-Y antiserum, raised in highly inbred rats, is absorbed by gonadal cells of various species of fish. This cross-reactivity proved to be restricted to the male sex in the cyprinodont species Lebistes and Xiphophorus, known to have the XX/XY mechanism of sex determination. In members of the more primitive fish orders Isospondyli and Ostariophysi, cross-reactivity was shown to occur as well, but the amount of antiserum absorbed was very similar in both sexes. An antigen cross-reacting with mammalian anti-H-Y antiserum is assumed to exist in fish similar to that found in higher vertebrates. If this is true, this antigen may have been shared originally by both sexes. However, during evolution, its expression has become restricted to the heterogametic sex.


Cholesterol and bile acid metabolism in moderately advanced, stable cirrhosis of the liver. We have selected for this study a well-defined group of patients with moderately advanced but compensated alcoholic cirrhosis. They were well-nourished and had no ascites, varices, azotemia, or encephalopathy. Liver biopsy showed little or no necrosis and inflammation despite wide-spread fibrosis. Serum bilirubin, transaminase, alkaline phosphatase, albumin and globulins were essentially normal. Biochemical evidence for liver disease was restricted to modest elevation of BSP retention, gamma GTP, serum bile acid concentrations, and urinary bile acid excretion. Except for changes in the interrelationships among the three biliary lipids, they were generally spared the abnormalities of sterol metabolism described in other patients with more advanced, more active liver disease. Thus, striking abnormalities in the metabolism of cholesterol and bile acids probably require severe reductions in functioning hepatocellular mass, major portal-systemic shunting, high disease activity, or all three to become manifest.


Idiopathic familial cirrhosis and steatosis in adults. A family was studied in which three middle-aged siblings had unexplained cirrhosis and steatosis. Five of nine additional family members had abnormalities of liver function. Liver biopsy in those 5 revealed steatosis in 3, steatosis and fibrosis in 1, and increase in lipofuchsin pigment in another. Detailed investigation revealed no known metabolic defect, adverse environmental exposure, or alcohol abuse. We postulate that this family represents a unique type of idiopathic familial cirrhosis. The role of steatosis in the pathogenesis of cirrhosis in this family remains unsettled. The HLA haplotype A24, B18, DRW 4 X 7 was found in several family members, but the association of the disease with the HLA system remains to be established.


A single scan technique for estimating acid output. A single scan technique using 99mTc has been developed for the measurement of gastric acid output. After an overnight fast, pentagastrin (6 microgram/kg S.C.) was given 15 min before 99mTc (1 mCi i.v.), and a scan of the abdomen was performed 15 min later using a double-headed scanner. Accumulation of isotope within the stomach was then calculated from the scan and expressed as a percentage of the injected dose. Pentagastrin-stimulated intragastric activity correlated with acid output measured conventionally on a separate occasion (r = 0.87, P less than 0.0001). The test is rapidly performed with minimal inconvenience and discomfort to the patient, and the dose of irradiation used is small. The advantages of the method compared with intubation and gastric aspiration are discussed.


Ileal adenomas after colectomy in nine patients with adenomatous polyposis coli/Gardner's syndrome. Adenomas of the ileal mucosa are an uncommon finding in adenomatous polyposis coli/Gardner's syndrome. We report 9 patients who were found to have ileal adenomas 1 yr 11 mo to 25 yr 11 mo after colectomy. The ileal adenomas occurred proximal to an ileorectal anastomosis in 7 patients, both proximal to a cecoproctostomy and later proximal to an ileostomy in 1 patient, and in an ileostomy in 1 patient. The cases confirm that ileal mucosa is susceptible to adenoma formation in adenomatous polyposis coli/Gardner's syndrome and thus provide additional evidence that adenomas are not confined to the colon in these patients. In addition, the findings in the cases suggest that the ileal adenomas developed after colectomy. Thus, our cases suggest that the small intestine should be studied for the presence of adenomas after colectomy with either ileoproctostomy or ileostomy, as well as before resection. On the other hand, aggressive management does not seem warranted as carcinoma of the jejunum and ileum has been reported only rarely.


Traumatic constipation.

Traumatic constipation. In 4 patients, trauma to the lumbosacral area produced abnormalities similar to those seen after resection of the nervi erigentes. Mechanisms of the resulting constipation and fecal incontinence for liquid stools included a prolonged transit time through the entire colon, a low rectal pressure, spasticity of the anal canal, and abnormal anal reflexes. Previous trauma to the lower spine must be considered in the differential diagnosis of chronic constipation.


Alterations in serum and antral gastrin levels in genetically diabetic mice. Many gastrointestinal structural and functional properties are known to be altered in diabetes. In this study, we investigated whether serum and tissue gastrin levels are abnormally altered in a strain of genetically diabetic mice (C57BL/KSJ). Both serum and antral gastrin concentration were found to be significantly increased 3.4- and 2-fold above normal values in diabetic mice fed ad libitum. The increase in tissue gastrin concentration is most probably due to an increase in both cellular gastrin content and G-cell number, since the latter property is increased 130% in diabetic animals. Pair feeding studies demonstrated that diabetes associated hyperphagia is not a major factor in inducing these endocrine changes, since antral and serum gastrin are still significantly elevated above normal in diabetic animals fed a restricted diet. G-cell number, however, is not significantly increased above normal values in pair fed diabetic mice. The peak serum gastrin concentration after a meal and the duration of postprandial hypergastrinemia are also significantly increased above normal in diabetic animals. Gel filtration chromatography studies indicate that the antral nucosae of normal and diabetic mice have identical molecular forms of the hormone. It is therefore concluded that antral and serum gastrin concentration are increased in genetically diabetic mice due to both dietary alterations and other, as yet undefined, factors specific for the disease, and that the resultant hypergastrinemia may contribute to some of the gastrointestinal alterations seen in diabetes.


Fatal colonic explosion during colonoscopic polypectomy. A patient is described who sustained the first reported colonic explosion during colonoscopic polypectomy. Mannitol solution was used for bowel preparation, and the colon was completely clean. During snare removal of a cecal polyp using high-frequency current a loud explosion occurred. In spite of emergency surgery with transfusion of 45 units of blood, uncontrollable hemorrhage persisted from multiple bleeding points, and the patient died. This occurrence seems to us to justify the routine use of carbon dioxide insufflation during polypectomy and the avoidance of mannitol for bowel preparation.


Peutz-Jeghers syndrome with metastasizing carcinoma arising from a jejunal hamartoma. The association of Peutz-Jeghers (P-J) syndrome and gastrointestinal carcinoma is well documented, but an unequivocal histologic demonstration that malignancy may originate in a hamartomatous polyp has been very rarely given. A patient with the P-J syndome is described, in whom a definite intestinal adenocarcinoma with metastases to omentum and celiac lymph nodes was shown to originate in a jejunal hamartoma. Evidence that malignancy was derived from hamartomatous structures was given by the following observations: (a) Adenocarcinoma was intimately intricated with smooth muscle bands, and well-defined transitional zone of malignant cells could be observed in several glands of the degenerated P-J polyp; and (b) close to malignant areas, glands of this polyp exhibited a less-differentiated epithelium, but were still intermixed with nonstriated muscle bundles, which strongly suggest dedifferentiation of hamartomatous structures.


Progressive enlargement of an hepatic cell adenoma. Over a 5-mo period, an hepatic cell adenoma was noted to increase considerably in size, despite discontinuation of oral contraceptives. Progressive tumor enlargement was documented by hepatic angiography, computed tomographic scan (CT scan) of the liver and 99mTc liver scan. The repeat hepatic angiogram also revealed that the tumor had become more vascular. Multiple adenomas were in fact seen by all three techniques mentioned above. At surgery, seven hepatic cell adenomas were demonstrated, of which four were resected.


Reproductive isolation with little genetic divergence in sympatric populations of brown trout (Salmo trutta). Two reproductively isolated demes of brown trout coexist in a small Swedish mountain lake, Lake Bunnersjörna. We electrophoretically examined 102 specimens from that lake for 27 enzymes encoded by 54 loci. The two demes are fixed for different alleles at a lactate dehydrogenase locus (LDH-1); statistically significant allele frequency differences at five other loci further support the complete lack of gene flow between these demes. There are significant differences in growth rates between fish in the two demes, but no further morphological differentiation h-s been detected.--In light of these findings, the genetic distance between these populations is surprisingly small (Nei's I = 0.975). These demes represent one of the least genetically divergent, reproductively isolated sympatric pair of vertebrate populations that have been identified. The results are discussed from both an evolutionary and ecological perspective.


Genetic variability and divergence in grayling, Thymallus arcticus. In North America there are two disjunct forms of grayling, Montana and arctic, which have been separated for approximately 75,000 to 100,000 years. Electrophoretic analysis of thirty-six protein loci in these forms has revealed: (1) levels of gene duplication comparable to other salmonids, (2) a level of heterozygosity similar to other salmonids, (3) a fast and a slow evolving set of proteins, and (4) no obvious relationship between genetic variability and enzyme function. The genetic divergence between these populations may warrant subspecific designations for these two forms.


The use of restriction endonucleases to measure mitochondrial DNA sequence relatedness in natural populations. I. Population structure and evolution in the genus Peromyscus. In this study we introduce to natural population analysis a molecular technique that involves the use of restriction endonucleases to compare mitochondrial DNA (mtDNA) sequences. We have examined the fragment patterns produced by six restriction endonucleases acting upon mtDNA isolated from 23 samples of three species of the rodent Peromyscus. Our observations confirm the following conclusions derived from previous experiments with laboratory animals: (1) mtDNA within an individual homogeneous; (2) at least the majority of mtDNA present in an individual is inherited from the female parent. Our experiments demonstrate for the first time that there is detectable heterogeneity in mtDNA sequences within and among natural geographic populations of a species and that this heterogeneity can readily be used to estimate relatedness between individuals and populations. Individuals collected within a single locale show less than 0.5% sequence divergence, while those collected from conspecific populations separated by 50 ti 500 miles differ by approximately 1.5%. The mtDNAs of the closely related sibling species P. polionotus and P. maniculatus differ from each other by 13 to 17%; nonsibling species differ by more than 20%. Qualitative and quantitative approaches to analysis of digestion patterns are suggested. The results indicate that restriction analysis of mtNDA may become the most sensitive and powerful technique yet available for reconstructing evolutionary relationships among conspecific organisms.


The Munchausen spectrum: borderline character features. In this paper the author presents a continuum of disease simulation that ranges from hysteria to malingering, with a range of relative unawareness to awareness of producing such deception. Focus is on the particular group of patients who consciously and repeatedly simulate disease. The frequency and form of such disease mimicry vary within such a group. A continuum in terms of frequency ranges from occasional adventures to the simulation of disease as the center of a person's life. Two groups of patients designated as exhibiting Munchausen Syndrome are defined within this continuum: (a) those who work (mostly as nurses or in other medical professions) and (b) those called "hospital hobos" --the more prototypical Munchausen patient. The author takes a somewhat different approach to Munchausen Syndrome in that it is viewed as a subgroup of the borderline character. Further, the often found exhortation for psychiatric treatment of Munchausen patients is reexamined, and caution regarding such zeal and its potential negative effects is registered.


Psychological intervention in coronary heart disease: a review. Psychological intervention studies designed to reduce cardiac morbidity are reviewed. Preliminary findings suggest that various psychotherapeutic modalities may be effective. Such studies also provide an avenue through which the physical and psychological mechanisms involved in coronary heart disease and their interactions may be clarified. Implications for clinical interventions are also discussed.


The consultee-attended interview: an approach to liaison psychiatry. The consultee-attended (C-A) interview, a format in which the liaison psychiatrist interviews the patient in the consultees' presence, is described. The background, strategy, concepts and methods, obstacles and resistances, and countertransference difficulties of C-A interview are discussed. The C-A interview is an experiential teaching instrument with which to facilitate consultees' "participant-observation," a clinical posture that complements other approaches to the care of sick people.


Consultation-liaison psychiatry: past failures and new opportunities. Although the concept of liaison psychiatry is not new, progress in its development has been slow. Obstacles to its development are examined and new prospects discussed in light of combined economic, political, and social forces which provide the opportunity for an expanded scope of clinical, teaching, and research activities.


Into the breach: emergency psychiatry in the general hospital. In its position at the interface between the community and the general hospital, the emergency ward (EW) serves to reconcile the complex needs of the local population with the traditional organizational structure of the hospital. In recent years, the EW has been faced with the dilemma of managing increasing numbers of psychotic patients with chronic illness and psychosocial problems. In response to this impressive growth in the utilization of psychiatric emergency services, a variety of general hospitals have developed model programs of service delivery and methods for the evaluation of their effectiveness. This paper is an overview of utilization patterns, organization of services, and assessment of the evaluation and referral model. This issues facing general hospitals in the development of emergency care are clarified. The need for further research, program development, and clinical implementation is discussed.


Implementing a consultation-liaison service in a psychiatrically underserved area. Most multidisciplinary consultation-liaison services are developed in settings where there are both psychiatric residents and an adequate psychiatric liaison faculty. In this paper, the authors report some of the obstacles and attempts at overcoming them in the implementation of such services in an underserved area in which there is a scarcity of both residents in training and psychiatric liaison faculty. The process of collaboration between a primary-care-oriented medical school and a community general hospital is described, and roles of program participants are defined. Special attention is paid to funding problems.


The psychiatric liaison nurse in the general hospital: three models of practice. The creation and implementation of the role of the psychiatric liaison nurse in three general hospitals are described. The historical evolution and theoretical bases of the role are reviewed, as well as the specific reasons for creation of such a role in each of the three hospitals. Three typical patient consultations by liaison nurses illustrate the need for provision of such services within the general hospital. Similarities in the implementation of the role of liaison nurse in the three hospitals are discussed.


Psychological reaction to chronic skin disorders: a study of patients with vitiligo. Diseases that cause physical handicaps can seriously interfere with the life of a patient. Some disorders such as vitiligo cosmetically disfigure patients without producing any physical disabilities. The effects of such diseases as vitiligo on the life of a patient have not been widely investigated. The investigation reported here utilized a questionnaire survey to focus on emotional disturbances caused by vitiligo and on the factors that differentiated patients who cope well from those who cope poorly with this stress. The results indicate that the cosmetic disfigurement of a seemingly inconsequential skin disease also can seriously disrupt the lives of a large number of patients. Those who cope well with their disfigurement have higher self-esteem than a matched control group without the disorder. Those who cope poorly have significantly lower self-esteem, which suggests that response to disfiguring diseases is affected by basic ego strength. Younger patients and those individuals in the lower socioeconomic groups show especially poor adjustment. A number of suggestions for better patient care are offered.


Phobic symptoms in an elderly woman: a multidisciplinary case conference. A 67-year-old woman, previously self-sufficient, became housebound by phobic symptoms. During the patient's hospitalization for treatment of these disabling symptoms, a multidisciplinary case conference served to identify the underlying psychodynamic issues, which were related to separation anxiety. Treatment included helping the patient understand her relationships with her daughter and her own mother, and behavior modification to reduce the secondary gains of her symptoms. After treatment, the patient successfully returned to self-care.


Models for evaluating teaching in consultation-liaison psychiatry: I. An overview. In this paper two useful models are introduced for evaluation of teaching in consultation-liaison psychiatry: decision-oriented and conclusion-oriented research. These models, based on previous studies of educational evaluation, are defined here in terms of their purpose for liaison psychiatry. To clarify the models' usefulness, the methodologic requirements for each model are presented while the unique characteristics of the liaison environment are described in terms of their effect on conclusion-oriented evaluation.


Cancer and suicide.

Cancer and suicide. Issues of suicidal ideation, life-threatening behavior, and vulnerability in cancer patients are addressed. A review of pertinent literature is presented, including the areas of: suicide as a taboo topic; incidence of suicide in cancer patients; identifying patients' suicide potential; and suicide as coping behavior. Case examples are offered that illustrate psychiatric intervention with and psychodynamics of cancer patients demonstrating suicidal tendencies.


Body image and perfectionism of ballerinas: comparison and contrast with anorexia nervosa. The authors studied a group of young ballerinas through responses to a questionnaire and intensive interviews. The young women described a life characterized by complete dedication in which academics, social life, and pleasures were sacrificed and a program of intensive exercise and practice became their main activity. They tended to feel overweight in spite of being thin and continued to diet or to employ other means to become even thinner. Two heuristic conclusions were reached: (a) the goal of thinness was in part a flight from conflicts about adult sexuality that arose at puberty; and (b) repetitive practice was engaged in for its own sake, not for career advancement, in an attempt to lose themselves in a transcendental quest for perfection. A comparison was made between this group and girls of the same age with anorexia nervosa. Several similarities but many more differences were found. Findings are based on a very small sample and must be interpreted cautiously, but directions for further studies are implied.


The effects of a psychiatric liaison program on the utilization of psychiatric consultations: an evaluation by chart audit. The effects of a psychiatric liaison program were studied by a chart audit examination of psychiatric consultations on a medical service. A comparison of the full liaison ward with the other wards revealed significant differences in the use of emergency consultation and psychiatric follow-up treatment. The results indicated improved psychologic management of medical patients on wards with intense liaison involvement but no measurable change in attitude toward the psychiatrist. Evaluation methodology and implications of the results are discussed.


A questionnaire for the examination of psychiatric liaison-consultation programs. Liaison-consultation services have become an integral part of departments of psychiatry in medical schools and general hospitals. The evaluation of such services has focused most closely, thus far, on the efficacy of their educational programs. The author provides an extensive questionnaire which may be used for a global examination of the working structure of liaison-consultation services and recommends that liaison psychiatrists and personnel from the programs of other institutions be enlisted to participate in the process of evaluating programs.


A health care program for hospital staff. This paper illustrates the significance of one aspect of psychiatric consultation to questions of general hospital health care delivery. The contractual arrangements, implementation, and evaluation of a health care delivery program for nonprofessional hospital employees are presented. Changes in patients' perception of treatment were evaluated by random surveys of representative clinic and ward populations before and after this program was implemented. The program was evaluated by precourse-postcourse questionnaires completed anonymously by the hospital personnel group. The program was found to be successful in generating lists of major health care delivery problems and some possible solutions. The majority of personnel enjoyed and benefited from this program. A conceptual framework and implications of psychiatric consultation for problems of general health care delivery are discussed.


Psychotherapeutic intervention in acute medical situations. Psychotherapy in the extreme medical situation is an extension of the interviewing process. The interviewer must expeditiously and sometimes briefly assist the patient in elaborating his complaint, obtain information about the development of the complaint, and assess the patient's reactions to it. Past history, developmental patterns, reactions to previous illness and crises, the patient's present life situation, and past and present relationships may all be relevant and require evaluation. The interactive process requires that the therapist call upon specific knowledge as he engages with the patient, facilitates the expression of concern, appropriately reassures, instructs, and prepares, clarifies, and leads the patient to some insight about his altered state. Attention to the affective correlates of acute illness can enhance convalescence and the rehabilitative process.


Psychiatry's identity crisis: a critical rational remedy. Psychiatry has several partial identities reflecting its biologic, psychoanalytic, and social subspecialities. It has, however, no encompassing professional identity. This identity requires three features: (a) a common language and procedure for assessing psychopathology, (b) a common method for evaluation and use of knowledge from outside psychiatry, and (c) a common set of values regarding clinical and research activities. The authors discuss the clinical, biologic, and sociocultural psychiatric traditions to identify the roots and consequences of psychiatry's fragmented state. Psychiatry's identity problems cannot be solved by ignoring them or simply becoming more "medical." Rather, the authors propose a remedy--critical rationality--to help resolve the crisis. Critical rationality requires a discimplined approach to psychiatric knowledge that underscores the necessity of methodologic rigor, practicality, and mid-range theorizing (rationality); and the equal necessity for systematic self-criticism, reform, self-awareness, and attention to the ethical dimensions in teaching, practice, and research (critical).


Coping with illness by a concentration camp survivor. A 54-year-old concentration camp survivor was observed during her third medical hospitalization in the past 3 months. The meaning of her illness leads to a symbolic reexperience of her traumatic past. Typical features of the Survivor Syndrome are reviewed and compared with the patient's symptoms. Coping mechanisms and management are discussed.


Interdiscimplinary differences on a general hospital psychiatry unit. A questionnaire was distributed to staff members of a 28-bed general hospital psychiatry unit to determine and compare staff perceptions of the value of psychotherapies and the role of the disciplines in conducting treatments. Marked interdisciplinary differences were reported in attitudes toward the use of psychopharmacologic agents, the importance of diagnostic evaluation, the value of psychotherapy in the treatment program, the role of various disciplines in the program, and the therapeutic community approach. Clinical implications of the magnitude of interdisciplinary differences are discussed, and recommendations are made for resolving intergroup conflict.


Student attitude changes during "psychiatric medicine" clerkships. Whether psychiatrists can provide effective training of medical students in the psychosocial aspects of patient care should be questioned seriously in view of numerous reports showing that psychiatric education of student physicians had often been inadequate and unpopular. Consequently, objective evidence of psychiatry's ability to enhance knowledge, and especially to change attitudes, is needed in order to substantiate its claim to a significant role in the psychosocial training of doctors. A survey of 111 medical students who completed a "Psychiatric Medicine" clerkship reveals that they developed more favorable attitudes toward psychiatry and psychiatrists, as well as toward the treatability and likability of psychiatric patients. The meaning and implications of these findings are discussed.


A model for psychosocial phasing in cancer. The way in which patients cope with cancer throughout the course of treatment and illness can be demonstrated by correlating levels and types of vulnerability with different psychosocial phases. The concept of psychosocial phasing is a hypothesis, the aim of which is to integrate typical problems, concerns, and distress with clinical staging, treatment, and disease progression. Expectations differ at each phase. Accordingly, different problems may arise which clinicians can anticipate and relieve through appropriate interventions.


The current status of placebo in hospital practice. Despite a voluminous literature on the topic of placebo, there has been little documentation of either actual clinical practice of prescribing placebo or the attitudes that surround it. Through a questionnaire survey of all head nurses of clinical units in one health services area of Connecticut, data were obtained on current practices regarding placebo use in the natural hospital setting. Multiple reasons for placebo use in the natural hospital setting. Multiple reasons for placebo use were given, and it was noted that patients receiving placebo tended to be viewed in certain ways. The effectiveness of placebo in symptom relief was reported as nearly double that reported in the experimental literature. Methodologic issues of the study and of placebo investigation, in general, are discussed. Because common clinical problems appear to generate most instances of placebo use, several issues pertinent to medical education are raised. Some future directions for placebo research are proposed.


Models for evaluating teaching in consultation-liaison psychiatry: II. Decision-oriented research. The authors present a Program Audit Form (PAF), which can be used to evaluate liaison programs. Use of PAF illustrates the decision-oriented approach to evaluative research defined in Part I of this paper. The PAF includes three categories of information about the liaison program: (a) administrative arrangements, (b) program description, and (c) program feed-back. The information will provide the user with an overall picture of a Program's weaknesses and strengths, and a basis for making decisions about program change. The form is short and represents the minimal data program directors should have readily available without requiring technician time or research expense. Finally, it can be used to compare programs across institutions, because it includes descriptors of administrative arrangements.


Patient suicide: model for medical student teaching and mourning. The molding of the physician's role and identity takes place during crucial clinical years in medical training. This professional identity is influenced by experiences and models. The suicide of a medical student's patient provides a natural experiment for observing and working with important aspects of the developmental process of physicians in integrating the affective component of clinical work and learning. The facilitation of grief and mourning in a medical student and his five colleagues assigned to the same outpatient psychiatric rotation are important aspects of the clinical, educational, and professional developmental issues raised by the patient's death.


The psychiatrist's role in behavioral pediatrics training programs. Behavioral pediatric fellowships are available in 15 major medical institutions in the United States. In general, these programs focus on the psychologic, social, and biologic determinants of behavior and learning disabilities in children. Child psychiatry's participation in the formulative stages of these programs is considered vital. The authors caution psychiatry to avoid concentrating its energies upon these socially and developmentally inclined behavioral pediatricians to the detriment of all pediatric house staff.


Emergency use of intravenous haloperidol. Experience is reviewed with intravenous haloperidol in 20 cases in which the mental state was gravely impaired, prohibiting necessary investigation and treatment of physical disabilities. This use of haloperidol was efficacious and uncomplicated, although not specifically FDA approved.


Detection of cognitive deficits by a brief mental status examination: the Cognitive Capacity Screening Examination, a reappraisal and a review. Results of a brief mental status questionnaire, the Cognitive Capacity Screening Examination (CCSE), were compared with the clinical evaluations of 59 patients on a neurology service. In 71% of the cases, the CCSE scores correctly indicated a cognitive deficit (true-positive) or the absence of one (true-negative); false-negative results were observed in 15% and questionable negative results were found in 10%. Abnormal neurologic physical signs were present in 90% of all patients with cognitive deficits. In this population, although positive CCSE scores were reliable, negative scores were often misleading. Mild diffuse intellectual dysfunction (dementia) and some discrete intellectual deficits (aphasia and anosognosia) went undetected. Cognitive deficits associated with major cerebral disease were unappreciated in nine patients. Caution is recommended in interpreting negative CCSE scores. Abbreviated screening devices are only a preliminary approach to mental status evaluation; this test requires further refinement.


Alexithymia in somatizing patients.

Alexithymia in somatizing patients. Aexithymia is a clinical concept referring to the difficulty some people have in verbalizing their feeling states. It is prevalent in patients suffering from a variety of psychosomatic illnesses. The authors conduced a controlled study to investigate the presence of this trait among patients attending a psychosomatic clinic and those attending a traditional outpatient psychiatric clinic in a county general hospital. The results indicate that, in this lower socioeconomic population, alexithymia is equally present in both clinics. The discrepancy between these results and those previously reported are discussed, as are the ramifications of the findings.


Reactions of families to children with Duchenne muscular dystrophy. Twenty-five families were interviewed to examine their adjustments to having a child with Duchenne muscular dystrophy (DMD). Chronic emotional stress experienced by families of DMD children was found to be a significant problem in the overall management of the illness. Based on information obtained from the assessment of families' adaptation to their child's illness, recommendations are made concerning parent education, school placement, facilitation of marital harmony, informing the child about his illness, and sensitivity to the responses of other family members.


General psychiatry, primary care, and medical primacy. Nonmedical psychotherapists are able to present themselves to the public as psychiatrist-equivalents, except for prescribing drugs, because psychiatrists have neglected to emphasize the nature of medical responsibility, here called "medical primacy." Psychiatric identification with the psychoanalytic and public relations models is criticized. Three cases are presented to illustrate the functioning of the general psychiatrist as a primary care specialist. It is acknowledged that all psychiatrists may not be attracted to this role, which intersects certain transference and countertransference vectors.


[New series of thermostable phage T5 mutants carrying deletions in the region of the tRNA genes]. Six mutants of phage T5 have been selected by temperature inactivation in the presence of chelate-forming agents. Hybridization of DNA of the mutants with 4S RNA of phage T5+ has shown that all mutants have the deletions affecting tRNA genes. The size of the deletions and their location about the sites of DNA clevage with endonucleases EcoR1, Hind III, PstI and the nicks have been determined.


[Effect of mouse genotype on the hematopoietic stem cell count. II. The number of hematopietic stem cells in BALB/c and CC57BR strain mice differing by the level of endogenous colony formation]. The number of stem hematopoietic cells in the hematopoietic organs of mice of BALB/c and CC57BR strains and (CC57BRXBALB/c)F1 hybrids was studied by the method of exogenous colony-forming units. The assay of migration of stem cells from the bone marrow to the spleen was carried out. It was found that the spleen and the bone marrow of mice of the studied genotypes contain approximately the same relative number of hematopoietic stem cells. The number of stem cells which migrate from the bone marrow to the spleen is greater in the mice of BALB/c strain than in the CC57BR mice.


[Survival of the mutant clone. III. Catastrophic selection. The inadequacy of the selection coefficient for assessing clone fate]. Majorant estimations of the probabilities pr for the surviving of the clone of the dividing cells have been obtained in the catastrophic situation (monotonous diminishing of the clone almost to zero during the period of time from t=0 to t=T, T approximately 100 generation). At t=0 the clone consisted of 10(6) individuals. Average selection coefficient (s) was found to determine pr only roughly, that is the clone with s greater than --0.09 survives almost in all cases, whereas the clone with s greater than --0.13 becomes extinct practically always. Within this interval ps-inversion can be observed, i.e. preferential surviving of the clone with a worse s value. Results of three communications lead to the conclusion that the mutants with small selective advantage practically cannot be selected.


[Human chromosome polymorphism and disordered reproductive function. I. Routine chromosome variants]. Routine polymorphic variants of chromosomes of 58 married couples with reproductive failure (two or more spontaneous abortions, stillbirths and malformed children) and 48 control couples, having two or more normal children and no spontaneous abortions and stillbirths, were investigated by conventional staining technique. Extreme variants of chromosomes 1, 9, 16, 17, 13--15, 21--22 and Y were found in 17.2% of subjects with reproductive loss and in 15.6% of control individuals. No significant differences in frequencies of scored routine variants were noted between married couples with reproductive failure and couples with normal reproduction.


[Antimutagenic effect of alpha-tocopherol on the gene mutation frequency in Salmonella]. The work presents the data on the antimutagenic effect of alpha-tocopherol on the frequency of N-nitroso-N-methyl urea induced gene mutations in Salmonella in vitro and in vivo. In vitro tests have revealed the dependence of decreasing the rate of induced mutations both on combination of treatments with mutagen/antimutagen and on the dose of the mutagen. In vivo tests have demonstrated that the mutagenic effect of alpha-tocopherol depends on the duration of its action on organisms.


Fractionation and identification of spinach chloroplast transfer RNAs and mapping of their genes on the restriction map of chloroplast DNA. Spinach chloroplast 4S RNAs has been separated by two-dimensional polyacrylamide gel electrophoresis into about 35 species. After extraction from the gel, 27 of these RNA species were identified by aminoacylation as tRNAs specific for 16 amino acids. Individual tRNAs were labeled in vitro with 125I and hybridized to DNA fragments obtained by digestion of spinach chloroplast DNA with KpnI, PstI, SalI and XmaI restriction endonucleases. A minimum of 21 genes corresponding to tRNAs for 14 different amino acids have been localized on the restriction endonuclease cleavage site map of the DNA molecule. Of these, 15 genes corresponding to tRNAs for 12 amino acids are located in the larger of the two single-copy regions which separate the two inverted copies of the repeat region. Each copy of this repeat region contains a set of genes for the ribosomal RNAs and a gene for tRNA2Ile in the "spacer" sequence between the 16S and 23S ribosomal RNAs. The genes for tRNA1Ile, tRNA2Leu and tRNA3Leu also map in the repeat region, but outside the ribosomal DNA unit. At present, two more chloroplast tRNAs (for Pro and Lys) have been identified, but not mapped, while 4 unidentified 4S RNAs have been mapped in the large single-copy region of the DNA molecule. Evidence is presented that isoaccepting tRNA species can be transcripts from different loci.


Electron microscopic visualization of restriction sites on DNA molecules. DNA molecules were adsorbed to a polylysine-treated carbon film and digested directly on the film by restriction enzymes. After washing the film with 1 M NaCl, 0.4% Kodak Photo-Flo and 9% formamide, each cleavage site introduced was visualized as a gap under the electron microscope. By measuring the gapped positions on linear DNA molecules induced by other enzymes, a single EcoRI site on a lambda dv1 molecule and three HinHI sites on an fd1RF molecule were mapped at the positions expected from the cleavage maps, respectively. This electron-microscopic procedure may be useful for the construction of a cleavage map.


Reintroduction of gluten in adults and children with treated coeliac disease. Twenty-eight patients, thought to have coeliac disease and on gluten free diets, were put on a normal diet to confirm their diagnoses. Nineteen had been diagnosed in adult life (ACD) and nine in childhood (CCD). Patients were assessed on jejunal, morphological, and symptomatic parameters. Eighteen patients with ACD relapsed within seven weeks. Nine patients with CCD relapsed at variable times but five took longer than seven weeks, the longest period beint 10 months. Seven patients had no symptoms despite morphological deterioration during challenge and one patient, with ACD, did not relapse and was HLA B8 negative. This patient with ACD had subtotal villous atrophy on two jejunal biopsies and later showed morphological improvement on a gluten free diet. There was no correlation between the relapse time and time spent on a gluten free diet.


Effect of gastrin heptadecapeptide (G17) on oesophageal contractions in patients with diffuse oesophageal spasm. An intravenous bolus of pentagastrin significantly increased the amplitude and duration of oesophageal body contractions in seven patients with diffuse oesophageal spasm (DES) when compared with five normal subjects (P greater than 0.05). In order to determine whether this stimulation also occurred at physiological gastrin concentrations, the effect of an intravenous infusion of gastrin heptadecapeptide (G17), 25 pmol/kg-h, on oesophageal contractions was studied in DES patients. G17 had no significant effect on the amplitude and duration of oesophageal contractions compared with a saline control. This dose of G17 was near the D50 for gastric acid secretion and produced a rise in serum gastrin concentration comparable with a meal. G17 infusions at doses of 100 and 200 pmol/kg-h increased the amplitude and duration of oesophageal contractions, but the corresponding serum gastrin concentrations were higher than postprandial levels. Thus, endogenous fluctuations in serum gastrin heptadecapeptide, alone, are unlikely to alter oesophageal contractions in DES patients.


HLA and duodenal ulcer.

HLA and duodenal ulcer. One hundred and one white patients, consisting of 78 men and 23 women, with duodenal ulcer were HLA typed. An association was found between duodenal ulcer and HLA-B12.


Gastric acid secretion in uraemia and circulating levels of gastrin, somatostatin, and pancreatic polypeptide. Basal circulating levels of gastrin, somatostatin, and pancreatic polypeptide were measured in 30 chronic haemodialysis patients. Five patients had considerably raised serum gastrin (greater than 400 pmol/1) and also gastric achlorhydria while 75% of the patients who had normal (less than 55 pmol/1) or moderately increased (less than 400 pmol/1) serum gastrin had raised maximal acid outputs. Patients with serum gastrin greater than 400 pmol/1 had significantly lower plasma concentrations of somatostatin compared with both healthy individuals and uaremic patients with normal gastrin levels. Raised serum concentrations of pancreatic polypeptide were observed in the majority of the patients but no correlation was found between this peptide and gastric acid secretion or circulating levels of gastrin and somatostatin, respectively. Prolonged circulation time for gastrin and pancreatic polypeptide was demonstrated after food stimulation. Prolonged gastrin stimulation of the parietal cell mass may lead to work hypertrophy and gastric acid hypersecretion. Whether long-standing over-stimulation by gastrin also may induce atrophy of the cells remains to be studied.


Changes in enzyme activity in normal and histologically inflamed oesophageal epithelium. Oesophageal biopsies were obtained from 74 patinets undergoing upper gastrointestinal fibreoptic endoscopy. Thirteen patients with histological evidence of inflammation had a raised alkaline phosphatase activity (2.7 +/- 1.6 nmol/mg protein/min) compared with 49 normal controls (1.2 +/- 0.68  nmol/mg protein/min: P less than 0.001). The acid phosphatase level was lower (8.4+/- 4.0 vs. 5.8 +/- 2.2 nmol/mg protein/min: P less than 0.05) and the glucuronidase activity raised (0.44 +/- 0.17 vs 0.81 +/- 0.32 nmol/mg protein/min: P less than 0.001) and their ratio declined (24.0 +/- 1.9 nmol/mg protein/min: P less than 0.001) in patients with oesophagitis. This may be due to differential secretion of membrane coating granules, a form of lysosome found isophagitis--was assessed by point counting. The volume density rose from 10.9 +/- 4.25% in normal biopsies to 46.4+/-12.5% (P less than 0.001) in oesophagitis. These results show a consistent pattern that possibly indicates an intermediate stage between the clinically, histologically, and biochemically normal oesophagus and one that is inflamed on endoscopy.


Cell proliferation of pericryptal fibroblasts in the rat colon mucosa. The turnover of pericryptal fibroblasts in the rat colon mucosa was analysed after in vivo incorporation of tritiated thymidine. Thirty-six rats were serially killed one hour to 21 days after intraperitoneal injection of the radionuclide. At one hour, the labelling index of pericryptal fibroblasts was only 2.44%; labelled fibroblasts were slightly predominant along the lower two-thirds of the crypts. Within 24 hours, most underwent at least one cell division. No migration was observed and a significant proportion of labelled fibroblasts was still present after three weeks. It is concluded that those fibroblasts constitute a slowly renewing cell population. The data failed to confirm the hypothesis of an 'en bloc' migration of fibroblasts in synchrony with the epithelial cells.


In vitro electrical activity in canine colon. In vitro slow wave activity was studied in strips of right and left canine colon with silver/silver chloride electrodes. Using visual and computer analysis, slow wave frequency and coupling was assessed between different recording sites and the effect of a cholinergic agonist on coupling and frequency was determined. A regular slow wave was always found to be present. Frequency in the left colon was slightly higher than in the right with a slight decline noted with time. Spike activity was rarely seen in unstimulated specimens. Administration of a cholinergic agonist produced a decrease in frequency with no improvement in coupling. Coupling was usually better in a circular than in a longitudinal direction. It was concluded that if electrical activity is important in the control of colon contractions, it is more likely to be involved in the control of segmentation than in propagated contractions.


Eosinophils in the rectal mucosa. A simple method of predicting the outcome of ulcerative proctocolitis? One-hundred-and-thirteen rectal biopsies and 17 total colectomy specimens from 50 patients with ulcerative proctocolitis were examined. These patients had been followed for periods up to 220 months, mean 70 months. The histological changes were compared with the clinical features of the disease. Patients with relatively benign disease which responded to treatment had significantly raised eosinophil counts in the mucosa examined, compared with patients who had aggressive disease which failed to respond to medical treatment (P less than 0.001). Tissue eosinophilia in the rectal mucosa may provide a simple method for predicting the clinical course of patients with ulcerative proctocolitis.


Achalasia and diffuse oesophageal spasm in siblings. We report the occurrence of achalasia and diffuse oesophageal spasm in brother and sister. The familial occurrence of these unusual disorders is consistent with the possibility that they share a common aetiology and indicates the potential importance of genetic predisposition.


Absorption of factor VIII by aluminium hydroxide. The absorption of factor VIII from gel filtration fractions, concentrates and plasma by aluminium hydroxide has been studied. Significant quantities of factor VIII could be removed when the protein concentration was low; the percentage absorbed increased with decreasing initial protein concentration. Factor VIII R:Ag and VIII:C were removed in parallel, but absorption of a high purity concentrate resulted in selective absorption of the lower molecular weight forms of factor VIII. Elution of the absorbed proteins gave a poor yield of VIII R:Ag, with no detectable VIII:C. Absorption of plasma showed no detectable loss of VIII R:Ag, but an apparent decrease of VIII:C of about 10%.


Influence of a hypolipemic drug (procetofene) on platelet functions and lipid composition in type II B hyperlipoproteinemia. Platelet function was evaluated in platelet-rich plasma and in washed platelets in relation to their lipid composition, in 18 type II B hyperlipoproteinemic men treated with procetofene. The results were compared to those obtained in 15 young, healthy normolipemic controls and in 22 untreated male subjects with type II B hyperlipoproteinemia. In addition to completely normalizing platelet functions, procetofene was able to induce a 28-53% decrease in serum cholesterol and triglycerides. Solely, the aggregation to ADP (secondary), arachidonic acid and epinephrine was higher in the untreated hyperlipoproteinemic subjects. This increased susceptibility to aggregation does not appear to be related to the cholesterol or cholesterol-phospholipid content of platelets.


Warfarin treatment during pregnancy: a clinical note. The case history is presented of a woman aged 38 who received warfarin treatment because of a mitral valve replacement. During the first trimester of pregnancy, her prothrombin time was 20% of normal and kept at 40% until the 38th week of gestation. Then the patient received heparin until a few days after delivery of a normal child.


Deposition of human labeled platelets on damaged rabbit aorta before and after ingestion of acetylsalicylic acid. Human blood platelets were labeled with 51Cr and whole blood was reconstituted. The endothelium of rabbit abdominal aorta was removed with a balloon catheter and the inverted aorta was placed on a Plexiglas rod in a perfusion chamber. The reconstituted blood was perfused through the chamber of 10 min. Radioactivity of the aorta was measured and found to be mainly caused by the labeled platelets. The platelet deposition on the damaged aorta was measured before and after ingestion of 0.5 g acetylsalicylic acid twice a day for 1 week, and was found to be reduced after the use of this drug.


[Evaluation of the clinical efficacy and tolerance of vibramycin dry fill infusions]. In a study including a limited number of 33 patients with bacterial infections the use of doxycycline as a drip infusion of Vibramycin dry fill proved to have a good clinical effect. The bacteriological tests showed that 58% of the tetracycline-sensitive germs demonstrated before therapy had been eliminated and another 6% markedly reduced. Clinically very good or good results were achieved in 76% of the patients. Toleration was excellent in all cases.


[The obese child and its nutrition].

[The obese child and its nutrition]. Obesity in infancy is accompanied by an increase in number and size of adipose cells. These changes in adipose tissue are due to a false relation of nutrient intake to physical activity. Obesity is not caused by an increased nutrient intake alone, since our long-term investigations have shown obese children to take in 300 kcal per day more than normal children. Fat intake of obese children is slightly enhanced. An exact method for estimation of obesity is the measurement of triceps, subscapular and suprailiacal skinfold. With this method used in 12,000 children during the period 1970--1977 we could detect a frequency of obesity of 15% in children 3--6 years old and of 25% in children aged 6--14 years. Extreme obesity is recommended for treatment in a hospital. The moderate forms of obesity should be treated by the paediatrician with a reduction of calories, clear recommendations of the nutrient amount and education to regularity.


[Genetic and biochemical studies on familial neuroblastoma]. The diagnosis of bilateral neuroblastoma in the adrenal glands in a newborn led to the discovery of a family with clustering of tumors of neural crest origin. According to the two-mutation model of neuroblastoma development we searched for individuals with the first mutation, who are predisposed to neuroblastoma. Neither chromosomal analysis of the peripheral blood nor the examination of catecholamines nor of gm-phenotypes could mark the first step to neuroblastoma. However, it was possible to detect cystationinuria in familial neuroblastoma for the first time. Cystationinuria could be calssified as secondary to vitamin B6-deficiency. Since cystathioninuria and vitamin B6-deficiency were not only seen in blood-relations but also in relatives by marriage there was no fixed correlation to individuals with tumor or their relatives.


[Biological availability of digoxin from a combination drug]. In a randomized cross-over study with 14 voluntary test persons the absolute biological availability of digoxin in Card-Dusodril 1/8 and 1/4 respectively was investigated. 6 test persons received 4 drag. Card-Dusodril 1/8 (= 0.5 mg digoxin), 8 test persons 4 drag. Card-Dusodril 1/4 (= 1 mg digoxin) orally, in comparison to the corresponding group with intravenously applied digoxin as standard. Based on the cumulative digoxin excretion in the urine an absolute biological availability of Card-Dusodril 1/8 of 79%, of Card-Dusodril 1/4 of 76% could be demonstrated. With regard to an average resorption of oral digoxin preparations of approx. 70%, the present values, which correspond in direct comparison to those of acetyl digoxin, can be considered good. Maximum serum levels were achieved after 86 +/- 6.8 minutes which also indicates a quick resorption.


[Chest pain: differential diagnosis in general practice]. In patients with chest pain somatic pain (thoracic wall pain) has to be differentiated from visceral pain (organ pain). History and careful physical examination are diagnostic in most cases. Presented are rare and not well-known diseases like valvular aortic stenosis, idiopathic hypertrophic subaortic stenosis and the mitral valve prolapse syndrome. Not seldom they are masked by angina pectoris-like symptoms, although in general the coronary arteries are normal. In acute chest pain differential diagnostic considerations have to include lung embolism, acute pericarditis, spontaneous pneumothorax, acute dissecting aneurysm of the aorta and diseases of the gastrointestinal tract as well. Only after exclusion of any organic cause the diagnosis of "effort syndrome" may be made.


[Psychotic depression: therapy, prevention, side effects, patient information and prognosis]. Depressive syndromes are common disorders. They can be severely disabling and, too often, may lead to suicide. Pharmacological attempts to relieve depression have a long history. However, it was the development of monoaminooxidase inhibitors and tricyclic antidepressants which first provided truly effective antidepressants for medical use. Antidepressants, coupled with supportive therapy can usually accelerate improvement, diminish the intensity of symptoms and reduce the danger of suicide. The lithium salts lead to a better prognosis of many patients suffering from psychotic depression and promote social adjustment and occupational rehabilitation. Especially the tricyclic antidepressants are anything but ideal. They are slow-acting, have side effects, can cause fatal overdoses, and do not help every patient. In the course of an ideal antidepressant therapy a more immediate onset of drug action could decrease the risk of suicide and diminish the severe life disruptions that long illnesses can cause. Less toxic medications could also decrease their utilization for suicide attempts.