Role of growth hormone in the enhancement of the propylthiouracil-induced goitrogenesis by small doses of thyroxine. The potentiation of the propylthiouracil (PTU)-induced goitrogenesis after chronic administration of small doses of thyroid hormone has been attributed to the high circulating level of thyrotrophin (TSH) or to the re-instatement of insulin. In re-examining this problem radioimmunoassayable concentrations of TSH, thyroxine (T4), insulin, and growth hormone (GH) were observed in sera of rats at sequential intervals after surgical or chemical thyroidectomy and after thyroidectomy and replacement therapy with GH or T4. In addition, TSH, GH or a combination of both hormones were injected into hypophysectomized recipients in a further attempt to delineate the effect of either hormone on the thyroid. As expected, the rate of body growth was inversely proportional to the apparent severity of the hypothyroidism achieved in the several experimental groups. Goitrogenesis was enhanced after T4 treatment but evidently was not the exclusive result of increased blood levels of TSH or insulin. Evidence is presented that suggest the enhancement of goitrogenesis may be a growth phenomenon involving the additive or synergistic action of GH and TSH and possible of other hormones.


Organ culture of human somatotrophic pituitary adenomas: ultrastructure and growth hormone production. Ten somatotrophic adenomas removed from acromegalic patients and fragments of the non-tumoural surrounding pituitary were submitted to organ culture for periods of up to one month. Electron microscopic observation shows that these tumours retain their histological differentiation throughout the culture period. The cell morphology of the cultured tumours remains essentially unchanged and in particular the secretory granules keep their initial size (150 and 130 nm). However, the granules disappear gradually so that most of the cells look chromophobic by the 4th week of culture, and numerous lysosomes as well as autophagic figures appear at the same time. The hGH concentration in the culture medium has been measured of 4 adenomas. It is very high (10-fold greater than that from non-tumoural pituitary medium) during the first week (range 200-300 mug/ml). It still remains very high in the same experiments until the second week of culture in one experiment (200 mug/ml). After incubation of cultures with 3-H-leucine 3 H-hGH is obtained in the medium giving evidence of hormone synthesis by adenoma cells in culture. 3-H-hGH represents 40 percent of 3-H-proteins in the culture medium and gives the same elution pattern as standard hGH on Sephadex G 100 chromatography. A certain degree of correlation is observed between morphological and biological results: the greatest hGH production is obtained from explants which maintain the best histological appearance.


Binding of the 35-s of 35-s-propylthiouracil by follicular thyroglobulin in vivo and in vitro. Radioactivity was found bound to follicular thyroglobulin after administration of 35-S-propylthiouracil (PTU) to rats. Denaturation of the thyroglobulin using various procedures could not separate the 35-S from the protein; it was concluded that the 35-S is bound to thyroglobulin covalently. Fractionation of saline-soluble thyroid proteins was performed by ultracentrifugation on sucrose gradients. The PTU-sulphur/thyroglobulin (S/Tg) molar ratio was calculated in all fractions. One hour after the injection of PTU the S/Tg molar ratio was the same for 19S thyroglobulin from rats on stock diet and 18S thyroglobulin from rats on low iodine diet. Injection of KI to the animals before administration of 35-S-PTU significantly reduced the ratio. The highest S/Tg ratio 1.10 was noted at 19S thyroglobulin, 17 h after a single injection of PTU. Daily injection of PTU for six days increased the S/Tg ratio to 3.3. Inverse relationship between dose of PTU and S/Tg ratio was noted at one hour. In animals injected with large dose of 35-S-PTU and sacrificed several hours later the S/Tg was higher at the 12S subunits than at the 19S protein. The amount of PTU bound to 3-8S subunits was minimal. Sulphite liberated 64 percent of the 35-S bound to thyroglobulin which appeared as four compounds on thin layer chromatography plates. The main 35-S compound liberated by sulphite was sulphate.


Receptors mediating epinephrine effect on thyroid 131-i uptake and thyroxine synthesis in the rat. The adrenergic receptors mediating the inhibitory effect of epinephrine on the rat thyroid in vivo have been studied by the use of more specific alpha- and beta-adrenergic stimulators, and blocking agents. The effect of methoxamine was similar to that of epinephrine, while isoproterenol stimulated 131-I uptake slightly, and did not alter the ratio of monoiodotyrosine (MIT) to diiodotyrosine (DIT). However, like methoxamine, isoproterenol resulted in a decrease in thyroxine (T4) formation. Phentolamine could partially prevent epinephrine-induced decrease in 131-I uptake and T4 synthesis. The changes in the MIT/DIT ratio could be completely prevented by high doses of phentolamine. Propranolol enhanced the effects of epinephrine. It is concluded that the effect of epinephrine on the rat thyroid in vivo is predominantly alpha-adrenergic, but T4 synthesis may be decreased by stimulation of either receptor.


Reduction of circulating insulin levels during the infusion of different prostaglandins in the rat. The intravenous infusion of prostaglandin (PG) E1, E2, and A1 into normal rats at a dose of 2 mug/min significantly lowered plasma insulin levels with a tendency to recovery in the post infusion period. Whereas PGA1 infusion resulted in a moderate but significant hypoglycaemia, the administration of E-series PGs always produced a hyperglycaemic effect. The interference of PGE1 on insulin response to classical insulinogogues (glucagon, aminophylline, and tolbutamide) was also investigated. The results of these experiments demonstrate that PGE1 exerts an inhibitory action on insulin response to all insulin releasing agents investigated. As regards the haemodynamic effects of PGs, PGE1 and PGE2 lowered the arterial blood pressure by about 20 percent, while PGA1 was almost completely ineffective. On the other hand, the lowering effect of PGE1 on circulating insulin levels remained unchanged in rats treated with reserpine. These findings thus rule out a sympathetic over-activity secondary to the lowered arterial blood pressure as the mechanism of action of PGE1. A possible direct interference with the adrenergic receptor system of the pancreatic islets was also ruled out since the inhibitory effect of PGE1 was not overcome by phentolamine pre-treatment.


Steroid hormones and their binding in plasma of male patients with fatty liver, chronic hepatitis and liver cirrhosis. Oestrone (E1), oestradiol (E2), testosterone (T), androstenedione (A) and cortisol (F) as well as LH and the percentage of binding of E1, E2, T and F in plasma were measured and compared in normal young and old male subjects and in male patients with fatty liver, chronic hepatitis and cirrhosis of the liver. The alterations seen were most marked in the cirrhotic patients, but were partially also found in patients with fatty liver and in normal old subjects: a definite increase in E1, a smaller increase in E2, a decrease in T and a rise in LH. F remained unchanged. The ratios of E2/T and E1/T were higher in cirrhotic patients than in healthy young subjects. As the percentage of bound T in plasma rose, the oestrogen/androgen imbalance was greater in patients with liver disease and in old subjects than the ratio of total hormone plasma concentration indicates. The biological relevance of the extremely high E1 plasma concentrations in patients with cirrhosis of the liver is not known. It is suggested that the combination of elevated E1 and E2 and reduced T, which is strongly bound by increased sexual hormone binding globulin (SHBG) may be responsible for gynaecomastia and hypogonadism in chronic liver diseases. As similar alterations of steroid plasma concentrations and their binding to plasma proteins are found both in patients with liver disease and in old men, these changes may be caused by the same mechanism: namely an altered liver function.


The influence of short term submaximal work on the plasma concentrations of catecholamines, pancreatic glucagon and growth hormone in man. Studies were performed in 6 healthy, male volunteers to explore the effect of a work load on the blood concentrations of catecholamines in relation to pulse rate and blood pressure and the blood levels of pancreatic glucagon, insulin, growth hormone, glucose and glycerol. The work load consisted of 300 kpm/min for 5 min, followed by 600 kpm/min during the next 5 min and 900 kpm/min under a third 5 min period. The work load resulted in a marked increase in noradrenaline and adrenaline at 10 and 15 min of exercise. The pulse rate, the systolic pressure and the mean blood pressure were correlated to the blood levels of both adrenaline and noradrenaline. In spite of the rather marked activation of the sympathetic nervous system no increase occurred in glucagon as measured under exercise and up to 60 min after its completion. In 4 of the subjects the work load was followed by a prompt growth hormone response. The same 4 subjects also showed a marked increase in catecholamines. The 2 remaining subjects presented no change in growth hormone and their increase in catecholamines was relatively minor. Glycerol increased significantly during work and there was a positive correlation between the values recorded for glycerol and adrenaline. No significant changes occurred in blood sugar or insulin during work.


Combination contraceptive effects on monthly cycle of plasma aldosterone, renin activity and renin substrate. A post-ovulatory peak of fasting supine plasma aldosterone (PA) preceded or accompanied by an increase in plasma renin activity (PRA) was previously reported. These studies have now been extended in 4 additional normal menstruating women and 4 women taking oestrogen-progestogen oral contraceptive pills (OCP), all studied daily for an entire cycle. Distinct luteal phase increases in PRA were seen in the 4 normals, with 2 also demonstrating a rise in PA. Plasma renin substrate (PRS) was usually unvarying throughout the control cycles. The women taking OCP, on the other hand, all had PA and PRA peaks that were apparent by the fourth or fifth day of taking "the pill". All 4 of the treated women had elevated PRS levels but only one woman showed an increase which preceded the elevation of PRA and PA. Plasma cortisol levels were usually above the normal range in the women taking OCP. This study thus indicates that factors other than oestrogen-induced increased substrate production may be responsible for the PRA and PA rise during OCP treatment. Such factors might be the natri-uretic effects of oestrogens and progestogens or a direct effect on renin secretion by one of these steroids.


Aldosterone and corticosterone production in renal hypertensive rats. The development of hypertension, which had been elicited by clamping one renal artery in the presence of an untouched contralateral kidney, has been pursued in rats for up to six weeks after operation, and aldosterone and corticosterone production was studied at various intervals.


Effect of post-ovulatory administered oestrogens on corpus luteum function. The effect of orally given diethystilboestroldiphophate (DES) and 17alpha-ethinyl-oestradiol-3-methylether (EEM) on plasma progesterone levels was studied. Both compounds were administered for 5 days to 5 women in daily doses of 60 mg (DES) and 30 mg (EEM). The fully informed volunteers were found to have a normal menstrual cycle before the study. The mean corpus luteum phase (corpus luteum phase = days between LH surge and onset of menstruation) of all control cycles lasted 12.8 days. Daily plasma samples were collected for radioimmunoassay (RIA) of progesterone, immunoreactive oestrogens and LH. After a control cycle the first treatment was carried out with DES. The third and the fifth cycle were control cycles again. The EEM-treatment was done in the fourth cycle. Although the effect of the two compounds was different, a dependence of the age of the corpus luteum (CL) could be demonstrated for both. DES-treatment lowered plasma progesterone levels during administration. This effect was only demonstrable if the treatment was begun on the day of the LH-peak. The length of the CL-phase remained unaltered. EEM-treatment if started on the day of the LH surge, suppressed corpus luteum function in the late luteal phase. If the treatment was started later, the effect was less pronounced. The administration of both compounds did not shorten the time between ovulation and the next bleeding. After DES-treatment this interval was not altered. After EEM-treatment the subsequent bleeding was even delayed depending on slowly decreasing levels of plasma oestrogens.


Effects of prostaglandin f2a on ovarian blood flow and vascular resistance in the pseudopregnant rabbit. In the search for data supporting the hypothesis that the luteolytic effect of prostaglandins (PG) is initiated by a vascular mechanism, some haemodynamic parameters including ovarian blood flow and vascular resistance were measured in pseudopregnant anaesthetized rabbits before and after exogenous administration of PGF2a. The measurements were performed on days 5-10 of pseudopregnancy induced by 500 IU HCG iv.


The use of antiserum to rat prolactin to evaluate its role as luteotrophin in the hamster. Rabbit antisera to rat prolactin was found to cross-react with the hamster pituitary extract by double diffusion and quantitative precipitin techniques. Short term neutralization of prolactin by antiserum to rat prolactin either in early or late stages of gestation did not have any deleterious effects. Prolonged administration of rat prolactin antiserum resulted in an increase in the incidence of resorptions, but pregnancy was still maintained followed by normal parturition. This is in marked contrast to the abortive effects of an antiserum of ICSH. It was concluded that prolactin does not play a major role in maintaining pregnancy of the hamster.


Plasma dihydrotestosterone in normal adult males and its relation to testosterone. A radioimmunoassay for dihydrotestosterone (DHT) in plasma was developed using an antiserum raised against testosterone-3-oxime-bovine-serum-albumin. After extraction of 1 ml male plasma with diethylether, DHT was separated from testosterone (T) by thin-layer chromatography. A dextran-charcoal-suspension was used for the separation of bound and free ligand. The inter-assay variability was 10.4 percent (C.V.) and the detection limit 1.77 ng/100 ml. The accuracy of the method as determined by mass recoveries and the specificity were shown to be satisfactory. Normal values were obtained in 45 young to middle-aged (22-61 years) and 37 old (68-93 years) men. The median and the 95 percentiles were 20.5-51.9-76.3 (ng/100 ml) and 19.5-50.9-101.5 (ng/100 ml) respectively. While DHT did not change in old age T fell by 20.6 percent. DHT and T showed a significant correlation: rS = 0.426, P smaller than 0.01 (young men), rS = 0.752, P smaller than 0.001 (old men). After 3 daily im injections of 5000 IU human chorionic gonadotrophin (HCG), DHT increased 1.50 times (range: 1.15-2.09, n = 12), T 1.86 times (range: 1.20-2.91, n = 12). After 4 daily administrations of 40 mg fluoxymesterone DHT fell to 29.6 percent of the control level (range: 16.0-48.2 percent, n = 12). Blood samples were obtained from a 24 year old man every 15 min for 24 h. A close parallelism was observed between the concentrations of DHT and T in the plasma.


Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Plasma testosterone and androstenedione levels in men were measured after oral administration of free testosterone and testosterone undecanoate. Both androgens were determined by simultaneous, specific radioimmunoassays after separation and isolation by thin layer chromatography. While free unesterified testosterone had no effect on plasma androgen levels, a striking increase of both testosterone and androstenedione levels was noted after administration of testosterone undecanoate, which is otherwise only achieved by parenteral testosterone application. This effect of testosterone undecanoate is probably due to absorption via the lymph rather than via the portal vessels so that peripheral circulation is reached before metabolism in the liver. Testosterone undecanoate promises to be an effective medication for oral androgen replacement.


Endocrine testicular function in mink during the first year of life. The endocrine testicular function in mink (Mustela vison) was investigated during the first year of life encompassing puberty, the first mating season and the phase of regression thereafter. The mink, relatively easily accessible as a semi-domesticated animal, was chosen as an example of a mammalian seasonal breeder. In plasma samples from 7 to 17 animals collected on 10 occasions between July and April testosterone and delta4-androstenedione were determined by simultaneous radioimmunoassay. A steady increase of both androgens from November to early March, when the mating season occurs, and a rapid decline to pre-pubertal levels thereafter was observed. The ratio of testosterone to delta4-androstenedione was 1:1 from November to April. These findings parallel the known morphological transitions of the testes.


Relation between circulating levels of testosterone lh and fsh in intact and castrated, adult, male rats after testosterone administration. Serum levels of LH, FSH and testosterone were measured by radioimmunoassay in intact and castrated, adult, male rats after testosterone was administered subcutaneously for seven days in doses ranging from 25 to 200 mug per 100 g body weight per day. Such treatment increased circulating testosterone both in intact and castrated rats, but its effects on serum gonadotrophins were different in these animal groups. All doses of testosterone suppressed serum LH and FSH in the normal rat. In the castrates, treatment with the lowest dose of testosterone resulted in serum LH levels significantly above the high castrate levels, while serum FSH tended to drop. Administration of the highest doses of testosterone did not depress serum LH and FSH in the castrates to those of intact, normal animals, though serum testosterone in these castrates was much higher than in normal, male rats. It is concluded, that the sensitivity of the hypothalamic-pituitary system for daily, subcutaneous testosterone administration during seven days is not the same in the intact and castrated, adult, male rat and that testicular factors different from testosterone may play a role in regulating production and/or secretion of gonadotrophins by the hypophysis in male animals.


Effect of transplantation of the foetal testis to neonatal female rats on differentiation of the postpubertal secretory pattern of gonadotrophin. Rat foetal testes (day 19 or 20 pregnancy) were transplanted into the neck of 3-day-old female rats. When testicular grafts were left in the recipients until autopsy (at 90 days of age), anovulatory persistent oestrous syndrome developed in most of the recipient females. These changes were not influenced by the removal at 45 days of age of the testicular grafts. However, the incidence of anovulatory sterility was significantly reduced when the foetal testicular grafts had been removed 5 days after transplantation. Treatment of these recipient females with 40 IU HCG from the day of the transplantation to the day before the removal of the transplants markedly increased the incidence of anovulatory sterility in the recipient females. In histological examinations of the testicular grafts upon their removal, a significant stimulation of Leydig cell elements was noted in the groups of rats treated with HCG. It is highly probable that if sufficient levels of gonadotrophin (GTH) are present in the recipient females, testicular tissues from day 18-20 foetuses can secrete sufficient amounts of androgen for masculinizing GTH regulation.


Correlation of diameters of secretory granules in clinically non-functioning chromophobe adenomas of the pituitary with those of normal thyrotrophs. Diameters of secretory granules in thyrotrophs in gonadotrophs were measured in electron micrographs of operation specimens of 4 pituitary glands and of the secretory granules in operation specimens of 10 clinically non-functioning chromophobe adenomas. The mean diameter of the thyrotroph granules was 137 plus or minus 26 nm, of the gonadotrophs 204 plus or minus 38 nm, of 9 of the adenomas 141 plus or minus 20 nm and of the remaining adenoma 248 plus or minus 67 nm. The significance of the close correlation in granule size in most of the adenomas with that of thyrotrophin granules is discussed briefly.


Serum tsh and serum t3 levels during normal menstrual cycles and during cycles on oral contraceptives. Serum TSH and serum T3 levels were studied in 35 normally menstruating women and in 35 women on oral contraceptives in order to find out whether the levels of TSH and T3 were related to the menstrual cycle or changed by oral contraceptives. Serum TSH AND T3 were found to be unchanged throughout the normal menstrual cycles and during the cycles of oral contraceptives. The TSH level was higher in the women on oral contraceptives than in the normally menstruating women. This might be due to a direct thyroid inhibitory effect of oestrogen. As could be expected the levels of T3 and T4 were higher in women on oral contraceptives than in normally menstruating women.


Relation between thyroid function and serum levels of long-acting thyroid stimulator. Bioassays of long-acting thyroid stimulator (LATS) were performed in three groups of subjects: in normal controls, in thyrotoxic patients before and serially after 131-I treatment, and in patients with hypopituitarism. Of the untreated thyrotoxic patients, 27.7% had raised serum LATS levels initially. There was no correlation between the relapse rate after 131-I therapy and the initial or subsequent LATS titres: in particular, thyrotoxicosis sometimes recurred after an initially high LATS titre had fallen into the normal range. The distribution of the results of LATS assays in the hypopituitary patients was significantly different from that in the normal subjects; 4 out of 27 hypopituitary patients had LATS levels above the normal range, although they had no thyrotoxicosis. On the other hand, the majority of the patients with hypopituitarism, 19 out of 27, had LATS titres below the mean normal level, possibly due to deficiency of a substance we have termed pseudo LATS. These results raise doubts about a direct causative role for LATS in most cases of thyrotoxicosis.


Iodinated particles in the rat thyroid. II. Lysosomal characteristics. In a previous study (Simon et al. 1971) a procedure for the preparation and separation of iodinated particles was described in the rat. The present paper deals with further investigations on the nature of these particles. Acid phosphatase and iodine are conjointly sedimentable and display a latency that is unmasked on dilution in a hypo-osmotic medium and under acidification to pH 5.0. These properties together with the sensitivity to Triton X-100 are best accounted for by assuming that iodinated particles of the thyroid gland are lysosomes. Part of the particulate iodine is soluble in n-butanol (BEI fraction). The existence of this BEI fraction demonstrates that hydrolysis of thyroglobulin occurs within the particles which thus exhibit an acid protease activity. Both the sedimentable iodine pool and acid phosphatase are increased under TSH stimulation and decreased after thyroxine treatment. In addition, the general activity of the iodinated particles is dependent on the daily iodine intake as shown by the variation of their iodine pool, acid phosphatase activity and BEI fraction with the iodine diet. It is concluded that iodinated particles of the thyroid gland are secondary lysosomes which participate in iodine secretion under TSH control. By in vitro treatment with destabilizing media or after in vivo treatment with thyroxine, iodinated particles exhibit a parallel loss of iodine and acid phosphatase. After a short-term TSH treatment in vivo, their iodine pool is more increased than their acid phosphatase activity. It is concluded that, at least in the normal rat thyroid, iodinated particles are essentially secondary lysosomes; true colloid droplets actually accumulate only after sufficient TSH stimulation.


Acute suppressive effect of human growth hormone on basal insulin secretion in man. The acute effects of human growth hormone (GH) on the basal levels of glucose and insulin in blood were investigated in 11 healthy men. GH doses of 5, 10, 20, and 40 mug/kg body weight were given iv as a constant-rate infusion over 30 min, and resulted in peak hormone levels (30 min) of 20.5 plus or minus 1.0, 48.5 plus or minus 2.2, 108.2 plus or minus 4.5, and 229.2 plus or minus 14.6 ng/ml, respectively. There was a small (max 9.8 plus or minus 2.6%) but significant decrease in the blood glucose level, observed already at 15 min after the beginning of the GH infusion and persisting up to 90 min. The highest dose of GH induced the most marked changes, but there was otherwise no clear correlation between dose and effect. The basal plasma insulin levels showed a more marked (max 16.0 plus or minus 4.7%) decrease which was not correlated, in time or in magnitude, with the changes in blood glucose. In some subjects, in whom no significant decrease in blood glucose was observed, plasma insulin still demonstrated a similar fall (max 20.2 plus or minus 7.6%). Neither were these changes in plasma insulin correlated to the dose of GH within the range used in this study. The findings suggested that the early, insulin-like effect of GH on blood glucose is distinct from its effect on the pancreas. The latter is a suppressive one, consistent with earlier findings on glucose-induced insulin release.


Potentiation of insulin release by glucose in man. I. Quantitative analysis of the enhancement of glucose-induced insulin secretion by pretreatment with glucose in normal subjects. The effect of repeating a 60 min glucose infusion at a 40 to 70 min interval was investigated after an overnight fast in 14 healthy, non-obese subjects with normal glucose tolerance and normal insulin response to glucose administration. When a hyperglycaemic plateau of around 300 mg/100 ml was induced by the first glucose infusion, the insulin response to a second challenge was enhanced over the range of stimulations used. Both the early and late phase insulin responses were amplified, the enhancement being more marked with higher stimulatory levels of glucose. The blood glucose-insulin dose-response curve became steeper after pretreatment with glucose, the stimulatory threshold level not being altered. These findings suggest that the synergism between the glucose pretreatment, and the insulin releasing effect of glucose, is of multiplicative type, resulting in increase of the maximum effect of the glucose.


Potentiation of insulin release by glucose in man. II. Role of the insulin response, and enhancement of stimuli other than glucose. If two consecutive glucose infusions are administered with 40 min of rest between, the insulin response to the second challenge is markedly potentiated. When the insulin response to the first glucose infusion was suppressed by 65% with the aid of adrenaline, potentiation of the insulin response to the second infusion was not modified. This suggests that the generation of a state of enhancement in the islet does not necessitate that glucose exerts its insulin releasing action. It is postulated that islet glucose metabolism may be involved in producing the potentiation. Pretreatment of the subjects with a glucose infusion enhanced also the insulin responses to glucagon and to tolbutamide, given intravenously 50 min later. Thus, the potentiation generated by glucose is not restricted to the insulinogenic signal induced by glucose. The eventual role that the beta-cell adenylate cyclase may play in this respect is discussed.


Potentiation of insulin release by glucose in man. Glucose-induced potentiation of glucose-induced insulin release was quantitatively evaluated in 14 non-obese subjects with normal glucose tolerance but decreased insulin response, and in six non-obese patients with mild, adult-onset diabetes, by measuring the insulin responses to two consecutive glucose infusion tests, administered with 40 or 70 min interval. Enhancement of the second insulin response occurred in both groups. In low insulin responders, the dose-response relationship between blood glucose and plasma insulin was flatter and shifted to the right when compared to the control. Pretreatment with glucose increased strikingly the slope of this relationship, the responses now being within the normal range. The enhancement induced by glucose seems to be of multiplicative type. In mildly diabetic subjects, insulin response to glucose infusion was low and sluggish, only a minor initial response being observed. Pretreatment with glucose modified the profile of the insulin response, a clear-cut initial response of greater magnitude being obtained at least in some of the patients. The sensitivity of the islet to the potentiating action of glucose was higher in low insulin responders than in controls, the minimal glucose concentration needed to induce potentiations of the forthcoming response being much lower. The dose-response curve for the relationship between the blood glucose level of the preinfusion period and the percentual enhancement of the insulin response obtained at the second stimulation was, in low insulin response obtained at the second stimulation was, in low insulin responders, higher than and shifted to the left of the curve of the control subjects. In the group of diabetics, sensitivity for potentiation by glucose seemed not different from the controls.


The characterization of polar corticosteroids in the urine of the macaque monkey (macaca fascicularis) and the baboon (papio hamadryas). Computerised gas chromatography-mass spectrometry was employed in the identification of polar corticosteroid metabolites excreted in the urine from the macaque monkey (Macaca fascicularis) and the baboon (Papio hamadryas). The following steroids were identified in significant amounts in the urine from both species: 3alpha,17alpha,20alpha, 21-tetrahydroxy-5beta-pregnan-11-one; 3alpha,17alpha,20beta,21-tetrahydroxy-5beta-pregnan-11-one; 5beta-pregnane-3alpha,11beta,17alpha,20alpha,21-pentol; 5beta-pregnane-3alpha,11beta,17alpha,20beta-pentol; 5alpha-pregnane-3beta,11beta,17alpha,20beta,21-pentol. 11beta,17alpha,21-Trihydroxy-4-pregnene-3,20-dione (cortisol), 11beta,17alpha,20beta,21-tetrahydroxy-4-pregnen-3-one and 11beta,17alpha,20beta,21-tetrahydroxy-5xi-pregnan-3-one were identified in macaque monkey urine. Two steroids, 17alpha,20beta,21-trihydroxy-4-pregnane-3,11-dione and 17alpha,20alpha,21-trihydroxy-4-pregnene-3,11-dione were excreted as major C21 metabolites in the baboon but were not identified in the urine from the macaque monkey. 3beta-Hydroxy-5alpha-pregnane metabolites were identified in the urine from both species. All these steroids were excreted conjugated to glucuronic acid, evidenced by their recovery after hydrolysis with beta-glucuronidase enzyme. An efficient 20beta-reduction of corticosteroids in both species is apparent, and the excretion pattern of polar steroid metabolites in the two species was shown to be similar.


The lh-hcg receptor of human ovary at various stages of the menstrual cycle. Receptors specific for hCG were found in human corpora lutea and follicles. hCG and LH were found to bind at a similar receptor site. The dissociation constant for hCG ranged from 10-minus 10 to 10-minus 11 mol/1 in human corpora lutea. The number of binding sites for 125-I-hCG ranged from 10-minus 14 to 10-minus 15 moles/mg protein in human corpora lutea. The binding of 125-I-hCG to ovary was found to vary at different stages of the menstrual cycle. The binding of 125-I-hCG to human ovaries increased on days 13-15 of the cycle, then declined slightly, and increased again on days 22-23. Following day 23, there was a slow decline until day 27 when binding activity could no longer be measured. No binding could be measured by the corpus luteum after the onset of menstruation or in corpora albicans.


The concentration of prostaglandin f2alpha in maternal plasma, foetal plasma and amniotic fluid during pregnancy in women. The concentration of prostaglandin F2alpha has been determined in serial samples of peripheral venous plasma from women at defined times during labour, and studied in detail throughout two consecutive uterine contractions. In addition, the same compound has been measured in single samples of uterine venous plasma, cord venous plasma, and amniotic fluid in groups of patients during early and late pregnancy, labour and at delivery of the baby.


Implantation and maintenance of pregnancy in mated rhesus monkeys following bilateral oophorectomy or luteectomy with and without progesterone replacement. Six mated rhesus monkeys were bilaterally oophorectomized between the fourth and sixth day after ovulation, and received silastic implants containing crystalline progesterone subcutaneously. Five mated monkeys were subjected to luteectomy 5 or 6 days after ovulation. Three of these received progesterone implants subcutaneously. Pregnancy occurred in one oophorectomised monkey and in all three luteectomised monkeys treated with progesterone. It was evident from the steroid patterns observed in the pregnant monkeys that the ovarian tissue other than the corpus luteum contributes to part of the oestrogen seen around the time of implantation. The corpus luteum apears to be the main source of progesterone in the peripheral plasma during this period. Placental progesterone production in early pregnant rhesus monkeys starts at three weeks after ovulation and the placental production of progesterone precedes that of oestrogen.


Correlation between hcg (lh)-binding capacity, leydig cell number and secretory activity of rat testis throughout pubescence. Male rats varying in age from 10 to 110 days were examined for testosterone concentration of serum and testicular tissue and 125-I-HCG-binding capacity of testicular tissue. In addition, the Leydig cell number of testes was determined using two different staining methods. It could be demonstrated that specific 125-I-HCG-binding capacity of rat testis increased with age up to 60 days of life. This rise was accompanied by an increase in serum and testicular testosterone concentrations and can be explained by a concomitant increase in Leydig cell number up to this age. The calculated specific 125-HCG-binding capacity per Leydig cell does not change from day 30 to 110 of life. This finding is in contrast to the 125-I-HCG-binding capacity per Leydig cell at day 10 and 20, the former being 5-6 times higher than in the age groups of 30 to 110 days. The observation of high 125-I-HCG-binding capacity per Leydig cell at day 10 and 20 is discussed in the light of simultaneous elevated serum and testicular testosterone concentrations.


A radioimmunoassay for 5alpha-androst-16-en-3-one in porcine adipose tissue. A simple and reliable radioimmunoassay (RIA) for the estimation of 5alpha-androstenone (5alpha-androst-16-en-3-one) in porcine adipose tissue has been developed. Fatty tissue samples weighing 40-60 mg were used for assay. The bulk of fat was separated from the steroid by centrifugation in an ethylacetate-ethanol solution at about -70 degrees C. The sensitivity of the standard curve was found to be 25 pg (P smaller than 0.01) and the smallest amount of 5alpha-androstenone added to adipose tissue from castrated male pigs, that can be estimated by the method, is 0.09 mug/g. Analysis of the data from the accuracy study gave the regression line y equals 1.09 times + 2.7. The mean coefficients of variation for the inter- and intra-assay precision were 11.1 and 5.9%, respectively. In boars (n equals 9) a mean value of 2.09 mug/g adipose tissue was found (SD equals 2.56). In adipose tissue from 9 female pigs and 8 castrated male pigs the level of 5alpha-androstenone was found to be undetectable by the present method. In adipose tissue from one castrated male pig trace amounts of 5alpha-androstenone were found.


Mammary excretion of digoxin in goats.

Mammary excretion of digoxin in goats. The binding of digoxin to proteins in plasma and milk was about 20% lower after the addition of the drug to plasma and milk (in vitro) than its binding in plasma and milk from animals administered digoxin parenterally. The mammary excretion of digoxin was examined in the experiments on goats. The concentration of non-protein-bound digoxin in milk was slightly lower than the concentration of non-protein-bound in plasma suggesting a passive diffusion. The amount of digoxin excreted with the milk per day should be far below the dose usually recommended for a newborn child.


Tricyclic antidepressant agents. I. Comparison of the inhibition of the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices and crude synaptosome preparations of the midbrain-hypothalamus region of the rat brain. The simultaneous uptake of 3-H-l-noradrenaline (NA) and 14-C-5-hydroxytryptamine (5-HT) in slices from the midbrain-hypothalamus region of the rat brain was compared with the corresponding uptake in crude synaptosome preparations of the same brain region. In both preparations the uptake of the two amines was selective at the concentration used (1 times 10- minus 7 M or lower). The KM values for the amines (NA: 2 times 10- minus 7 M in synaptosomes and 5 times 10- minus 7 M in slices; 5-HT: 8 times 10- minus 8 M in synaptosomes and 6 times 10- minus 7 M in slices) and the inhibitory concentrations (IC50) of the antidepressant agents were lower in the synaptosome experiments than in the slices experiments. Moreover the order of the inhibitory activities differed between the two preparations. In the slices experiments the NA uptake was inhibited most markedly by desipramine followed by imipramine greater than chlorimipramine = nortriptyline greater than or equal to amitriptyline greater than or equal to chlordesipramine whereas in the synaptosome experiments the order was desipramine greater than nortriptyline greater than or equal to chlordesipramine greater than or equal to imipramine greater than amitriptyline greater than or equal to chlorimipramine. For the 5-HT uptake in slices the order of activity was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine = desipramine greater than or equal to nortriptyline whereas in the synaptosome preparations the order was: chlorimipramine greater than imipramine greater than or equal to amitriptyline greater than or equal to chlordesipramine greater than nortriptyline = desipramine. The role of protein binding and diffusion barriers in the causation of the difference in the results obtained with the two preparations is discussed.


Tricyclic antidepressant agents. II. Effect of oral administration on the uptake of 3-H-noradrenaline and 14-C-5-hydroxytryptamine in slices of the midbrain-hypothalamus region of the rat. The inhibition of the simultaneous uptake of 3-H-l-noradrenaline (NA) and 14-C-5-hydroxytryptamine (5-HT) in slices of the midbrain-hypothalamus region of the rat brain after oral administration of desipramine, imipramine, nortriptyline, amitriptyline, chlordesipramine and chlorimipramine was determined. All compounds were more active in inhibiting the NA uptake than the 5-HT uptake. This difference was very marked for desipramine, imipramine, nortriptyline and chlordesipramine. Chlorimipramine was almost as active on the 5-HT uptake (ED50 = 35 mg/kg orally) as on the NA uptake (ED50 = 20mg/kg orally) and amitriptyline had low activity on both uptake mechanisms (ED50 greater than 50 mg/kg orally). Desipramine and imipramine were the most active compounds on the NA uptake (ED50 = 8 mg/kg orally for both compounds) and the duration of the action was very long. The ED50 values for nortriptyline and chlordesipramine in inhibiting the NA uptake were about 20 mg/kg orally for both compounds. The inhibition of the 5-HT uptake was less than 50% at 50 mg/kg orally for all compounds except for imipramine (ED50 = 50 mg/kg orally) and for chlorimipramine. The role of the biotransformation for the inhibitory activities of imipramine, chlorimipramine and amitriptyline was investigated in animals pre-treated with SKF 525 A. The inhibitory potency of imipramine was increased by the same factor for both uptake mechanisms probably due to the large increase in the concentration of imipramine in the rat brain, which was demonstrated after the administration of 14-C-imipramine. The inhibitory activity of chlorimipramine was somewhat more increased for the5-HT uptake than for the NA uptake. The low activity of amitriptyline seems to be mainly due to poor resorption, since pretreatment of the animals with SKF 525 A only slightly increased the potency whereas intraperitoneal injection of amitriptyline had a rather marked effect on the NA uptake (ED50 = 11 mg/kg intraperitoneally).


Pharmacokinetics of cyclophosphamide in renal failure. The metabolism of cyclophosphamide was determined in five patients with severe renal insufficiency. After the intravenous injection of 14-C-cyclophosphamide the activities due to unchanged cyclophosphamide and metabolites were determined in samples from urine and serum for 2-3 days. Only 22% of the injected radioactivity could be recovered in the urine during the first 3 days as against the normal of some 65% The rate of biotransformation seemed normal and in agreement with these findings a very long term retention of metabolites could be demonstrated. The clinical implications of these results are discussed.


Effect of stress on the pharmacokinetics of sodium salicylate and quinidine sulphate in rats. Studies on the influence of foot shock stress on the absorption, distribution and overall serum elimination of sodium salicylate and guinidine sulphate were performed in rats. Foot shock stress was produced by grid floor electrical stimulation. The animals were stressed 1 hr before administration of the drugs and then throughout the experimental period. A significant induced stress was demonstrated by increased blood glucose levels and increased whole brain turnover of noradrenaline. Gastric emptying and intestinal transit as well as tissue levels of the drugs in the serum, heart, brain, liver, muscle and fat were determined. Results were obtained indicating that stress produced a significant increase in the gastro-intestinal absorption of quinidine sulphate while no change in the distribution pattern of overall elimination was noted. On the other hand, sodium salicylate did not show any marked change in the pharmacokinetic parameters during a stressful situation.


Effects of single doses and daily administration of pyrithioxine (pyritinolum,NFN, RINN) on the alcohol withdrawal syndrome in rats. Male Wistar rats were made physically dependent on ethanol by intragastric administration (4-10 g/kg/day) for 20 days. The dose of ethanol was adjusted to maintain the maximal level of intoxication compatible with adequate intake of a liquid diet. After withdrawal of ethanol a few animals developed spontaneous tonic-clonic convulsions. A marked increase in susceptibility to sound-induced convulsions and decrease in sensitivity to pain were observed in the rats after withdrawal, and their serum and red cell Mg++ contents were found to be significantly lower and red cell K+ content higher than in controls. Therapeutic amounts (0.01 g/kg/day) of pyrithioxine (pyritinolum NFN, rINN) (bis-3-hydroxy-4-hydroxymethyl-2-methylpyridyl-(5)-methyl)-disulphide dihydrochloride monohydrate) given with the ethanol for 20 days made the rats with withdrawal symptoms significantly more responsive to pain and slightly but insignificantly less susceptible to sound-induced withdrawal convulsions, but this pretreatment did not markedly prevent the deviations in electrolyte concentrations. Large amounts of the drug (0.2-0.3 g/kg/day), however, increased the number of spontaneous withdrawal convulsions. Acute administration of pyrithioxine (0.01 g/kg) after cessation of the intoxication period did not mitigate the withdrawal symptoms, and massive amounts (2 g/kg) killed the animals within a few hours. Voluntary alcohol consumption of Alko AA rats ( a high-consumer strain) was not altered by pyrithioxine. The results indicate that pyrithioxine may affect the symptoms of ethanol withdrawal in different ways, the effect depending on both dose level and time of administration. It is suggested that the reason for the slight beneficial effect of pyrithioxine on the withdrawal symptoms when taken regularly in combination with ethanol is the slight protection afforded against intoxication.


The effect of glycerol on the lacrate metabolism in the perfused tat liver. The effect of glycerol on the lactate metabolism was studied on the perfused rat liver. Addition of glycerol to the perfusion medium caused a significant output of lactate and uptake of pyruvate. The lactate/pyruvate- and beta-hydroxybutyrate/acetoacetate ratios rose indicating an effect of glycerol on the cytoplasmic and mitochondrial redox potentials which became more reduced. The output of lactate by the liver may be a result of the reduction in the redox level induced by the oxidation of glycerol.


The effects of cyclophosphamide and azathioprine on collagen in skin and granulation tissue in rats, and the effects of cyclophosphamide on collagen in human skin. Granulation tissue was produced in rats by subcutaneous implantation of cellulose sponges. The effect of daily intraperitoneal injections of cyclophosphamide or azathioprine on rat skin and granulation tissue was examined after 14 and 42 days. Skin biopsies from patients with glomerulonephritis were analyzed before and after 42 days of treatment with cyclophosphamide or placebo. In the rats, cytostatic treatment caused an increase in the dry weight of the skin, and azathioprine increased the dry weight and the protein content of the granulomas. The increase in the dry weight was accompanied by a decrease in water percentage. The alpha-amino nitrogen/OH-proline ratio in purified acid soluble collagen from skin and granulation tissue increased with the dose and duration of cytostatic treatment. No effect on the aldehyde content was observed. Cyclophosphamide caused a decrease in the alpha/beta ratio in acid soluble collagen from granulation tissue, but not in the collagen from the skin. Salt soluble collagen was increased in the skin after 14 days of cytostatic treatment, but remained unchanged in the granulation tissue. In human skin cyclophosphamide caused no statistically significant changes in the amount of salt soluble or total collagen. It is concluded, that daily treatment of rats with cyclophosphamide or azathioprine from 14 to 42 days seems to inhibit the catabolic processes in the skin and granulation tissue, to decrease the hydroxylation of proline in collagen, and to inhibit the intermolecular cross-linking in collagen.?222


Therapeutic effect of Leo 1031, an alkylating corticosteroid ester; in lymphoproliferative disorders. II. Lymphocytic lymphoma. Leo 1031, a chlorambucil ester of prednisolone, has been administered to 20 patients with generalized lymphocytic lymphoma (LL) fo various histologic types. The average daily dose was 40 mg orally; the treatment was given continuously for 1-17 months (mean 7). Complete remission was obtained in five patients and partial remission in ten. The best results were obtained in patients with a nodular type of LL. Significant leucopenia was induced in two patients; no thrombocytopenia has occurred in any patient. In two patients a cushingoid habitus developed after 8 and 4 months, respectively. Leo 1031 may be of value as the single drug in the treatment of some types of LL. A combination therapy will Leo 1031 and vincristine has been tried in 5 of these patients; in 2 as initial therapy and in 3 later in association with relapse. Further trials to assess the value of Leo 1031 as part of a combination schedule are desirable.


Ocular myasthenia gravis and Hashimoto's thyroiditis. Two patients had ocular myasthenia gravis coexistent with Hashimoto's thyroiditis. A 37-year-old woman presented with diplopia and displayed a head tremor and thyroid enlargement. Thyroid function tests showed an elevated thyroid stimulating hormone (TSH). A quantitative Tensilon test yeilded a "perverse" response and a needle biopsy indicated Hashimoto's disease. A 26-year-old woman presented with diplopia and subsequently developed blepharoptosis and thyroid enlargement. Examination revealed Cogan's eyelid twitch sign, a paradoxical quantitative Tensilon test, and laboratory studies revealed normal thyroid function tests. Treatment was directed at each disease entity separately. Ocular myasthenia gravis was managed with an anticholinesterase agent in combination with oral corticosteroids that provided additional control. Suppressive therapy with desiccated thyroid hormone reduced the size of the thyroid gland, diminished the signs and symptoms of hypothyroidism, and lowered the levels of TSH, possibly decreasing the risk of thyroid carcinoma. Both patients showed gratifying responses to therapy.


Strabismus and pseudostrabismus with retrolental fibroplasia. Three patients with temporal displacement of the macular secondary to retrolental fibroplasia had true strabismus in associations with amblyopia and pseudostrabismus related to a large, positive angle kappa. In one case, a headturn associated with the neutral point of nystagmus was also a presenting problem. Ocular deviation was measured by the light reflex test and the prism cover test, with particular attention paid to adequate cosmetic alignment. Large amounts of prism placed before the fixating eye resulted in loss of visual acuity, while eyes placed in a parallel position by surgical means may not appear to be straight. Thus, surgery can result in parallel ocular alignment while prismatic therapy may be required to center the pupillary light reflex and to provide satisfactory cosmetic appearance.


Malignant lymphoma presenting as unilateral eyelid mass. A 58 year-old man presented with a large mass in the upper eyelid of his only eye. He had no systemic symptoms, but his physical examination revealed slightly enlarged preauricular and axillary lymph nodes. Biopsies of the upper eyelid mass and the ipsilateral preauricular lymph node revealed a poorly differentiated lymphocytic lymphoma. This case is of ophthalmic interest because the eyelid mass was the initial manifestation of the lymphoma.


Effect of pituitary gonadotrophins on tritiated thymidine uptake by rat ovary. An autoradiographic study. The effect of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on the follicular growth in the ovary of the hypophysectomized rat was investigated using autoradiography. The numbers of DNA-synthesizing nuclei in the granulosa cell were measured by autoradiography after flashlabelling with tritiated (3-H) thymidine. The frequency of 3-H-thymidine labelled nuclei in the granulosa cell enhanced in the presence of FSH. In contrast, LH had no significant effect on thymidine uptake. The result suggests that FSH stimulates follicle cell division, whereas LH does not.


[The effect of cyclophosphamide on tumors in the sensitivity-test (author's transl)]. The sensitivity of tumors to cyclophosphamide was tested in vitro. For this purpose, the urine of cyclophosphamide-treated rats (90 min., 500 mg/kg) was used. This method of activating cyclophosphamid proved more advantageous than other methods; all cytostatically effective metabolites can be used in the test and the production of metabolites can easily be standardized. Consequently results with good reproducibility can be obtained. In various long-term and short-term test models with animal transplantation-tumors in vitro, the effects of the cyclophosphamide metabolites depended on the dose used. This test results in the various test models are comparable. In the tissue-culture of tumors (long-term test) sensitivity was evaluated by using morphological criteria as well as by counting cell numbers. In the short-term test the sensitivity of tumors was found out by influencing the nucleic acid syntheses (3-H-thymidine-, 3-H-uridine-incorporation). As the tissue-culture meets with difficulties as a routine clinical examination, the use of the short-term test is recommended. Using as model the fast proliferating WALKER-256-carcinosarcoma and a slowly proliferating rat adenocarcinoma, the results of the sensitivity-test in vitro were compared with the effects of therapy in animal tests. Tumor remissions corresponding with the results reached in vitro, which depended on dosis, could also be achieved in both transplantation-tumors. Human tumors, tested in in vitro studies (short-term-test), show a different sensitivity to cyclophosphamide.


[Regional different cell-proliferation in placetones (materno-fetal circulation-units) of mature human placenta (author's transl)]. The examinations presented are based on earlier histological, histochemical, ultra-histochemical and biochemical studies about regional differences of placental villi in the center and the periphery of the placentons (materno-fetal circulation-units) of mature human placentas. In this study the question was followed up whether the morphological "immature" imposing villi lying in the centers of the circulation-units are immature like the villi of placentas of earlier stages of pregnancy also referring their proliferation. Autoradiograms were made from specimens of placentas of 38.-41. weak of uncomplicated pregnancies. The degree of nuclear labeling was higher in the villi situated in the center of the placentons. By these findings the centers of the placentons are interpreted to be not areas of lower metabolism - possibly conditioned by maternal blood flow - but regions of growth and regeneration. The results comply well with our up to date conception of formation and growth of the placentons.


[LH, FSH and ovarian steroids in serum during normal menstrual cycles and cycles with corpus luteum insufficiency in the human female (author's transl)]. LH, FSH, estradiol-17beta, progesterone, 20alpha-dihydroprogesterone, 17alpha-hydroxyprogesterone, delta4-androstenedione and testosterone are determined by radioimmunoassay in serum daily during 11 menstrual cycles. Three of them had to be considered as cycles with corpus luteum insufficiency on the basis of basal body temperature, length of the luteal phase and the pattern of progesterone concentration in serum. One woman conceived during the investigated cycle. The present concepts of the regulation of ovulation are discussed on the basis of the chronological relationshp of changing endocrine parameters in serum during the cycles. The analysis of the hormone concentrations in serum during the cycles with corpus luteum insufficiency supports the view that corpus luteum insufficiency could be caused by an insufficient stimulation of the growing follicle, but other ethiological factors have also to be considered.


The amniotic fluid foam test and fat cell count in malnourished and well-nourished fetuses. A malnourished fetus has a higher concentration of pulmonary surfactant in the amniotic fluid than its well-nourished contemporary. The clinical value of this observation is discussed. Malnourished fetuses have higher "fat cell" counts in their amniotic fluid than well-nourished contemporaries. Well-nourished fetuses, at the same gestational age have high fat cell counts when the surfactant concentration is high, and low fat cell counts when the surfactant concentration is low. The relationship between surfactant concentration and the fat cell count is discussed.


Palmitic acid and lecithin measurements in amniotic fluid. A method is described for the rapid and quantitative estimation of total amniotic fluid palmitic acid. Palmitic acid and lecithin were measured in 140 samples of amniotic fluid in normal and abnormal pregnancy, and the correlation coefficient between the two parameters was 0.93. It is concluded that amniotic fluid palmitic acid measurements are of value in the prenatal determination of fetal pulmonary maturity.


Deuterium order parameters in relation to thermodynamic properties of a phospholiped bilayer. A statistical mechanical interpretation. The physical properties of bilayers of dipalmitoyl-3-sn-phosphatidylcholine are analyzed in terms of a statistical model proposed by Marcelja (S. Marcelja (1974), Biochim. Biophys. Acta 367, 165). The model is used to calculate the segmental order parameters of the hydrocarbon chains, the transition temperature of the crystalline leads to liquid crystalline phase transition, the entropy change of the transition, the bilayer thickness, and the linear thermal expansion coefficient. The theoretical predictions are in excellent agreement with experimental results obtained by deuterium magnetic resonance, differential scanning calorimetry, and X-ray diffraction. The model yields the probabilities of trans and gauche conformations and also those of more specific conformational defects like kinks or jogs.


Cleanup of extracts using sweep co-distillation adapted to gas chromatograph. An adaptation of the Varian Aerograph gas chromatograph to the sweep co-distillation cleanup using the modified Storherr tube is described. The recoveries of this cleanup technique were evaluated for the mixture of four organophosphoru pesticides added to extracts from ten crop and milk. Pesticides were analyzed by gas chromatography with a cesium thermionic detector.


The SUNY biomedical communication network: six years of progress in on-line bibiographic retrieval. The SUNY Biomedical Communication Network became operational in 1968 as the first on-line bibliograhpic retrieval service for biomedical literature. Since 1968, the SUNY/BCN has grown in size from nine to thirty-two medical and university libraries and has expanded its data base coverage to include the ERIC and Psychological Abstracts data bases in addition to the full ten-year retrospective MEDLARS data base. Aside from the continuous provision of an on-line searching system, the SUNY experience over the last six years has yielded valuable information in the following areas of: (1) monograph indexing and retrieval, (2) shared cataloging, (3) user interaction and education in on-line systems, and (4) member participation in Network policy-making processes. The continued success of the SUNY/BCN  is evidence that it is possible to provide a high quality on-line bibliographic retrieval system at cost to academic institutions. SUNY's success in this effort is the result of centralized resource sharing and effective regional networking, combined with thoughtful planning by user advisory committees.


Renal tubular excretion of triethylcholine (TEC) in the chicken: enhancement and inhibition of renal excretion of choline and acetylcholine by TEC. 1. [3H]-triethylcholine (TEC) was actively transported by the renal tubule of the chicken at a rate 85% that of simultaneously administered p-aminohippuric acid (PAH). 2. TEC was demonstrated to be transported by the organic cation transport system in the kidney through inhibition with quinine and the bio-cation choline. 3. When the infusion of TEC was increased to 2 times 10(-6) mol kg(-1) min(-1) reaching the infused kidney, the transport of [3H]-TEC was inhibited, suggesting that an excretory transport maximum for TEC in the renal tubules had been reached. 4. The excretion of both choline and acetylcholine was enhanced by TEC loads as low as 1 times 10(-18) mol kg(-1) min(-1). Enhancement continued as TEC infusion was increased up to approximately 1 times 10(-7) mol kg(-1) min(-1) at which point this enhancement was converted to inhibition. 5. Possible mechanisms for the biphasic effect of TEC on organic cation transport are discussed.


Placental transmission of thyroid-stimulating immunoglobulins. Long-acting thyroid stimulator (LATS) and LATS protector (LATS-P) were assayed at or near delivery in serum from 18 pregnant women with a history of past or present thyrotoxicosis. The results suggested that neonatal thyrotoxicosis may be predicted prenatally if maternal serum LATS and LATS-P concentrations near delivery are above certain levels.


How useful are our present statistics on sexually-transmitted diseases? Various aspects of the British statistics relating to sexually-transmitted diseases are examined. Defects in these are illustrated by data from a series of surveys. It is suggested that the information being collected and published is incomplete by an unknown amount, inadequate because it tells only of laboratory diagnoses, and unusable at a local level because it relates to no identifiable population. Some suggestions are made as to how the data collected might be made more useful: the first and most important is that a working party should decide for what purposes the statistics are required.


Laryngeal sarcoma.

Laryngeal sarcoma. Of the 6,067 malignant laryngeal tumors treated at the Ear, Nose and Throat Clinical Hospitals in Yugoslavia, a total of 20 were sarcoma. Eighteen of these patients were men. The most frequent forms were chondrosarcoma and fusocellular sarcoma - four cases of each. A survival rate of more than five years was seen in only four patients (one fibrosarcoma, two lymphosarcomas, and one chondrosarcoma).


Normal total plasma calcium in the newborn. The first week of human life is characterized by rapidly changing plasma calcium levels, as well as low concentrations in comparison with adults. Whereas the infant's cord blood has a higher concentration than the mother's blood, the level drops precipitously in the first 24 hr (first drop) after birth and reaches a minimum level (second drop) at about 48 hr. A third drop may follow between the fourth and seventh days, but is different from the other two in that it is generally preventable with proper milk feeding. The level is markedly influenced by starvation, diet, and age. During the first week, the full-term newborn may show calcium levels in the range of 1.75 to 3.00 mmol/1, whereas the premature newborn shows values of 1.50 to 2.50 mmol/1. The low birth weight infant displays intermediate values. The literature on diseases involving calcium in the newborn, particularly neonatal tetany, is especially helpful in establishing a concept of normal levels, providing clinically supported upper and lower values. Calcium studies on the new born have been notably advanced by use of sound ultramicrochemical analytical methods.


Effect of acute hypobaric hypoxia on 32-P incorporation into phospholipids of alveolar surfactant, lung, liver and plasma of rat. Exposure of adult rats to hypobaric hypoxia caused hypolipidemia, hypotriglyceridemia and hypophospholipidemia. Hypobaric hypoxia produced an increase in liver triglyceride and cholesterol levels and a decrease in lung triglyceride, total phospholipid and phosphatidyl choline. The proportion of phosphatidyl choline in the pulmonary surfactant fraction I phospholipids (responsible for reducing surface tension) decreased (55.2% as compared to 80.4% in control animals). Incorporation of 32-P into liver phosphatidyl ethanolamine was significantly increased, incorporation into lung phosphatidyl choline and phosphatidyl ethanolamine was increased whereas a decreased incorporation into plasma phosphatidyl choline was observed. The data suggest an enhanced lipid synthesis in liver with a probable impairment of mobilization into plasma.


[Prevention of respiratory distress syndrome with betamethasone. Preliminary communication]. A controlled trial of antepartum glucocorticoid treatment for prevention of respiratory distress syndrome in premature infants was carried out. 37 mothers, in whom premature delivery threatened between 28 and 37 weeks of gestation, were given intramuscular injections 8-12 mg of betamethasone as well as medication inhibiting uterine activity and strict bedrest to delay premature delivery for at least 24 to 48 hours. In comparison with a control group of 16 mothers, who received tocolytic and sedative medication and were on strict bedrest and another control group of 42 untreated patients, there was no difference in the 3 groups concerning the incidence of respiratory distress syndrome in premature infants, but there was a lower perinatal mortality rate of respiratory distress syndrome in the betamethasone treated group, than in the controls, possibly due to a milder course of respiratory distress syndrome disease by accelerating functional maturation of the fetal lung with betamethasone.


Leucémogénése et régénération du systémé lymphoïde chez des hybrides f1 (c3h x akr/t1ald) restaurés par des cellules médullaires et thymiques parentales. Luekaemogenesis and repopulation of the lymphoid system have been studied in sub-lethally irradiated (c3h x akr/t1ald) f1 hybrids which have been restored with parental Bone Marrow (BM) cells with or without thymic cells. The metacentric marker of the T1ALD sub-strain made it possible to identify the host or donor orgin of leukaemias. Leukaemias occur either in the thymuc (lymphosarcomas) or in the other lymphoid tissues (extra-thymic leukaemias). After irradiation, the precentage of lymphosarcomas increases from 5 to 95%. The rate of leukaemias in hybrids which have been restored only with BM cells is 55, 56 and 100% respectively depending on the origin of BM: syngenic, C3H and AKR. In this last group 75% of the lymphosarcomas originate from donor cells. The inhibitory efficiency of the three kinds of BM on luekaemogenesis seems to be related to their respective abilities to spontaneous malignant transformation. When AKR or C3H thymic cells are injected together with BM cells, leukaemogenesis is altered. The effect is indirect as these cells are not actually concerned by the malignant transformation. The percentage of LS is significantly reduced and the mean survival improved in hybrids restored with C3H thymic, mixed AKR or C3H BM cells. AKR thymic cells are less efficient. In both cases, the percentage of extra thymic leukaemias increases at the expense of lymphosarcomas. Thymic cells do not change the kinetics of repopulation in thymus and lymph-node by the BM cells, except when C3H thymic cells are mixed with T1ALD BM cells; in this case, the lymph-node repopulation is temporarily enhanced. Different hypotheses might explain the effect of thymic cells on leukaemogenesis: enhanced recovery of the postirradiation immunological deficiency, transfer of virus by the AKR thymic cells, and more probably influence of the thymic cells on the maturation or/and differentiation of the lymphoid cells.


An additional younger-age peak for cancer of the nasopharynx. The age distribution of 666 masopharyngeal cancer patients attending the Tata Memorial Hospital, Bombay, during 1941-72 was found to show an additional younger-age peak in the age-group 13-22. The peak was found in both sexes, in different communnities, at two time periods and in histologically proved cases. One hundred cases of nasopharyngeal lymphosarcoma showed no deviation from a uniform age distribution. Pooled incidence data for 48 population groups showed the peak in the age-group 15-19 for males and in the age-group 10-14 for females. No such peak was observed for malignancies of the nose, sinuses, etc. (ICD NO:160)


Gastric neoplasms in the dog: a report of 20 cases. Twenty dogs with gastric tumors were admitted to the University of Minnesota Veterinary Hospital and Diagnostic Laboratory from 1951 to 1974. The tumors included 14 carcinomas, 3 lymphosarcomas, 2 leiomyomas, and 1 leiomyosarcoma. The carcinomas were categorized morphologically as carcinoma (5), adenocarcinoma (2), scirrhous carcinoma (5), and scirrhous adenocarcinoma (2). Most of the tumors were located in the body and pylorus. Ulceration occurred in 11 dogs, with 2 ulcers penetrating and resulting in peritonitis. Metastasis occurred in 4 of the dogs. The mean age of the dogs was 9.7 years. The male-to-female ratio was 12 to 8. There was no significant breed predominance. The mean duration of illness was 2.14 months. Radiographic features were consistent with gastric neoplasia in 2 of 6 dogs radiographed.


Determination of hexachlorobenzene and mirex in fatty products. A procedure is described for the isolation and cleanup of hexachlorobenzene (HCB) and mirex in fats and oils for gas-liquid chromatographic (GLC) analysis. The fat or oil is distributed on unactivated Florisil, and the HCB and mirex are eluted with acetonitrile. The pesticides are then partitioned into petroleum ether. Elution through activated Florisil with methylene chloride-hexane (20+80) is used for the final cleanup. HCB and mirex are then measured by GLC, using the appropriate electron capture conditions with a 15% OV-210 column for HCB and a 3% OV-101 column for mirex. The method demonstrates recoveries greater than 90% for HCB and mirex and allows screening at or below the 0.1 ppm level in fats with a 3 mg fat injection.


Collaborative study of the glass wool filtration method for the recovery of virus inoculated into ground beef. A method for estimating viral population levels in ground beef was studied collaboratively in 7 laboratories. The collaborators recovered virus from 6 inoculated samples. Three samples were replicates of the high virus concentration 050 plaque-forming units (pfu)/g) and 3 replicates represented the low concentration (10 pfu/g). Six of the 7 collaborators recovered acceptable levels of virus from the samples. The per cent of variation was 30.6 for the high concentration and 18.5 for the low concentration. Collaborators did not differ from one another significantly in the results obtained for the 10 pfu/g samples, but results from one collaborator were significantly low for the recovery of virus from the 50 pfu/g samples. The results indicate that the glass wool filtration method is adequate for the detection of a number of viruses that may be found in foods. The method has been adopted as official first action.


Age and type of onset as critical variables in early infantile autism. A retrospective study of 131 autistic children was made in which 2 groups, Natal and Acquired, were defined on the bases of age at onset and type of onset. Prenatal and perinatal variables were found to be significantly related to Natal onset, whereas in the Acquired group the significant variables were those occurring in early childhood, between years 1 and 3. Follow-up data on intellectual functioning and language development indicated a better prognosis for the Acquired group. An inability to cope with stress is postulated as an underlying feature in both instances, present from birth in the Natal group and occurring in the face of developmental stresses in the Acquired group.


Multiple response to sound in dysfunctional children. Methods and findings derived from over a decade of linguistic-kinesic microanalysis of sound films of human behavior were appled to the analysis of sound films of 25 dysfunctional children. Of the children, 17 were markedly dysfunctional (autistic-like) while 8 had milder reading problems. All of these children appeared to respond to sound more than once: when it actually occurred and again after a delay ranging from a fraction of a second up to a full second, depending on the child. Most of the children did not seem to actually hear the sound more than once; however, there is some indication that a few children may have done so. Evidence was also found suggesting a continuum from the longer delay of autistic-like children to the briefer delay of children with reading problems.


Increasing isolate and social play in severely disturbed children: intervention and postintervention effectiveness. A group treatment procedure was instituted in Study 1 to increase the isolate and social play of 4 severely disturbed children. The results indicated that play behavior could be increased significantly by the use of food and social reinforcement and by the use of passive shaping, but that it quickly declined when the intervention was terminated. Social play, however, did remain above baseline levels during extinction. Study 2 replicated the results of Study 1 with a second group of older children, also severely disturbed. However, the procedure of fading adult intervention proved an effective method for increasing the resistance of social play to extinction relative to Study 1. A PROCEDURE OF CONtinuous and multiple-observer reliability assessment was employed for both studies, and the positive results and the methodological implications of the procedure are discussed.


The pathology of the degenerate meniscus lesion. The incidence of horizontal cleavage lesions of the menisci was studied in 100 random necropsy examinations. Sixty per cent of subjects had at least one such tear, the incidence being 29 per cent out of the 400 menisci. Eighty-five per cent of the subjects showed changes of osteoarthritis in the patello-femoral or tibio-femoral joint compartments. The coincidence of horizontal cleavage lesion and osteoarthritis was frequent. Horizontal cleavage lesions were commoner in medial or larger menisci and in males. Eighteen per cent of the menisci were calcified and this was twice as common in those menisci with a degenerate tear. Because the horizontal cleavage lesion was so common in the older knee, it must usually remain unrecognised clinically with other factors causing symptoms of night pain and tenderness.


Animal experiments in radiotherapy III: large versus small animals. An evaluation is made of the conflicting claims of large and small animals as models in experimental radiotherapy. The pro's and con's of each are examined in relationship to both tumor and normal tissue studies. It is concluded that there are few, if any, tumor-related studies in which large animals are preferable, and that a somewhat similar situation exists with investigations of early reactions on normal tissues (at least to the extent that these are governed by the cell survival curve). The conclusion emerges, however, that a large animal may be required in certain investigations of late effects. Examples of the very different late effect tolerance levels between mouse and man are given.


Altering iodine metabolism in the calf by feeding iodine-binding agents. Effects of feeding cottonseed meal and anion-exchange resin on iodine absorption and excretion by calves were investigated. Each additional amount of resin fed from .3 to 3.5 g/kg body weight further increased fecal excretion from single oral iodine-131 and intravenous iodine-125 doses. By feeding 3 to 10 g cottonseed meal/kg body weight, excretion of oral iodine-131 given daily was increased 7 to 94% in feces and reduced as much as 35% in urine, but plasma iodine-131 was not changed. Introducing 1 g resin/kg body weight daily into the diet increased fecal iodine-131 excretion three to five times that with cottonseed meal alone and reduced both plasma and urinary iodine-131. The same amount of resin fed daily had similar effects on excretion of iodine-131 injected subcutaneously each day. Although iodine depletion by a highly efficient iodine binder (resin) in the gastrointestinal tract is probable, iodine binding by a natural feed constituent (cottonseed meal) was relatively inefficient.


Bilateral lymphosarcoma of the breast.

Bilateral lymphosarcoma of the breast. A case is presented of bilateral lymphosarcoma of the breast in a 77-year-old woman. The pre-admission surgical history recorded a mastectomy in July 1972, for lymphosarcoma of the right breast. She had been well until shortly before admission in March 1974 because of a tumor in her left breast. This proved to be lymphosarcoma. Treatment consisted of a left mastectomy. At that time there were no signs of axillary or systemic involvement. Later, evidence of systemic lymphosarcomatosis necessitated starting chemotherapy.


Hypercalcaemic stupor as a presentation of lymphosarcoma. A case is reported of a 32 year old woman with a two year history suggestive of schizophrenia who presented in stupor. This proved to be due to hypercalcaemia with a concomitant high cerebrospinal fluid calcium concentration associated with previously unsuspected lymphosarcoma. Necropsy revealed no significant intracranial abnormality, and mechanisms that may have been involved in the production of the impaired consciousness are discussed.


Drug absorption VII: influence of mesenteric blood flow on intestinal drug absorption in dogs. Intestinal absorption of sulfaethidole and haloperidol was determined using an in situ canine intestinal preparation. Intestinal absorption of sulfaethidole was determined at three or four mesenteric blood flow rates in each dog, ranging from unaltered flow (100%) to no flow (0%). A relatively small change in absorption rate occurred when the splanchnic blood flow rate was decreased about 35%. Further reductions in mesenteric blood flow resulted in progressive impairment of sulfaethidole absorption. The simultaneous measurement of sulfaethidole intestinal disappearance and appearance in blood indicates that sulfaethidole disappearance is equivalent to absorption. Haloperidol absorption also decreased with decreased intestinal perfusion but differed from sulfaethidole in that membrane storage of haloperidol appeared to take place during its absorption.


Respiratory stimulant effects of ethamivan and picrotoxin. The respiratory stimulant effects of ethamivan and picrotoxin were studied in unanesthetized decerebrate cats. It was found that neither compound exhibited selective stimulant action on the respiratory neurons. Ethamivan evoked increases in respiratory rate but not in tidal volume, whereas picrotoxin profoundly altered both of these variables. The increases in respiratory rate evoked by ethamivan required intact vagus nerves since midcervical vagotomy abolished this effect. It is conceivable that ethamivan stimulated pulmonary chemoreflexes which then led to increased respiratory rate. Picrotoxin had no discernible effect on peripheral chemoreflexes. It altered, however, the central respiratory rhythmicity, or rate, depth and rhythm of respiration. There was a marked effect on central respiratory control which led to cycling between slow and deep, and rapid and shallow breathing. These were interspersed with periods of rapid and deep respiration.


Charge pulse studies of transport phenomena in bilayer membranes. I. Steady-state measurements of actin- and valinomycin-mediated transport in glycerol monooleate bilayers. A charge pulse technique has been applied to studies of transport phenomena in bilayer membranes. The membrane capacitance can be rapidly charged (in less than a microsecond). The charge then decays through the membrane's conductive mechanism-no current flows through the solution or external circuitry. The resulting voltage decay is thus a manifestation of membrane and boundary layer phenomena only. There are a number of advantages to this approach over conventional voltage or current-clamp techniques: the rise-time of the voltage perturbation is not limited by the time constant deriving from the membrane capacitance and solution resistance, thus permitting study of extremely rapid rate processes; the membrane is exposed to high voltage for relatively short times and thus can be subjected to higher voltages without breakdown; the steady-state current-voltage behavior of the membrane can be deduced from a single charge pulse experiment; the charge (and therefore the integral of the ion flux through the membrane) is monitored allowing detection of rate processes too rapid to follow directly. In this paper we present what is primarily a steady-state analysis of actin (non-, mon-, din-, trin-)-mediated transport of ammonium ion and valinomycin-mediated transport of cesium and potassium ions through glycerol monooleate bilayers. We introduce the concept of the "intercept discrepancy", a method for measuring charge lost through extremely rapid rate processes. Directly observable pre-steady-state phenomena are also discussed but will be the main subject of part II.


Preparing sections of skeletal muscle for transmission electron analytical microscopy (TEAM) of diffusible elements. Comparative morphological examination and elemental analysis were carried out in structural compartments of sections of skeletal muscles. These had been prepared either by conventional plastic embedding technique or by various methods of cryo-ultramicrotomy. The analyses were performed in a Philips EM 301 with an Edax energy-dispersive X-ray spectrometer. Spectra obtained from sections of plastic-embedded muscle depended on the reagents used for fixation and staining and were absent if these were omitted. Brief fixation with glutaraldehyde resulted in gross ionic changes, and sectioning of frozen material with trough liquid led to extraction of elements. Sections cut from unfixed and frozen muscle without trough liquid showed numerous peaks. (Mg, P, S, Cl, K, Ca). In the superficial parts of the fibres of freeze-dried sections reproducible spectral differences were found between different structures. Thus, rapid freezing of unfixed tissue, dry cutting in the frozen state, and freeze-drying should be the procedure of choice if data on diffusible ions are desired.


Tungsten coating--a method of improving glass microtome knives for cutting ultrathin sections. Glass knives for ultramicrotomy were considerably improved by coating the cutting edge with a film of evaporated tungsten metal. Knives treated by this method gave up to tem times as many acceptable sections as uncoated glass knives. They could also cut thinner sections and harder tissues than ordinary glass knives, and eliminated some of the cutting artefacts produced by them. No explanation for this improvement was found although several possibilities were examined.


A microspectrofluorometer with on line real time correction of spectra. A microspectrofluorometer incorporating analogue computing segments and suitable for recording corrected spectra instantaneously on an X-Y recorder is described.


High resolution electron microscope study of lattice images in biological apatites. Lattice (Fourier) images of crystallites in human bone and teeth, and calcified atherosclerotic plaque were studied using high resolution transmission electron microscope techniques. The lattice images observed in the normal and diseased calcified tissue were compared with the images of synthetic hydroxyapatite crystallites.


A wet stage modification to a scanning electron microscope. A modification to the vacuum system of a JSM2 scanning electron microscope has enabled hydrated specimens to be placed inside the specimen chamber of the instrument and to be surronded by water vapour at a pressure up to approximately I 3-kPa (10 Torr). The surface topography was observed by detecting the backscattered electrons using a wide angle backscattered electron detector placed close to the specimen. The microscope was operated in the normal scanning mode which allowed the examination of the surface topography of the specimens, whilst still retaining the depth of focus which is a feature of the SEM. This modification has enabled a resolution of approximately 0.2 mum to be obtained from biological specimens partially immersed in water at temperatures just above 0 degrees C.


Photographic aspects of scanning electron microscopy. Factors governing photographic image quality in the scanning electron microscope are discussed with particular reference to the commonly used EXA camera on the Cambridge Stereoscan IIa. It is shown that the small image on the medium speed film suffers considerable loss of information due to the turbid nature of the photographic emulsion. Inexpensive modifications to the oscilloscope camera supplied with the Stereoscan are described which enable the superior quality of a larger format to be utilized. Appropriate settings of the brightness and contrast controls of the image tube with respect to the photographic system is discussed and the results illustrated in a series of micrographs.


Treatment of chronic pain with acupuncture. We performed 979 acupuncture treatments in 261 patients with chronic pain.  A substantial number of patients stated that they had relief immediately following a series of four acupuncture treatments.  It did not matter whether the needles were placed in the traditional meridian locations of in arbitrary fixed control points.  Four weeks following treatment, 65% of the patients reported little or no reduction in the  intensity of their pain, 17% reported a 50% reduction, and 18% at least a 75% reduction.


Hazards of overconcentrated milk formula.  Hyperosmolality, disseminated intravascular coagulation and gangrene. Severe hypertonic dehydration with hyperglycemia developed in a 7-week-old infant girl after she was fed an overconcentrated milk formula for five days.  Renal failure,disseminated intravascular coagulation, gangrene of the legs, and coma were added complications.  Intravenous rehydration, peritoneal dialysis, and heparin administration corrected the metabolic and coagulation derangements, and renal function returned to normal.  Bilateral below-the-knee amputations were performed and the child subsequently learned to walk with artificial limbs.  The dangers of overconcentrated formulas in infant feeding should be widely publicized through warnings printed on all commercial milk preparations.


Career decisions of unaccepted applicants to Medical School. To investigate the admissions process to medical school and the post-rejection behavior of unaccepted applicants, a national sample of the 16,837 such applicants to the entering medical school class of 1971-1972 was studied in 1973.  The majority of the 1,933 respondents had reapplied to medical school following rejection, and 27% had gained entrance to either US or foreign schools by the time of study.  Of those still unaccepted, about half were studying or working in health-related fields of study or occupations at least 2 1/2 years following the initial rejection.  We conclude that unaccepted applicants demonstrate considerable variance in postrejection behavior, which is associated with both personal and institutional factors.


Fetal alcohol syndrome:  Report of a case. A boy born to a known alcoholic mother demonstrated the fetal alcohol syndrome.  Although considerably postterm, he weighed less than 1.5 kg (3 lb) at birth and has failed to catch up at 2 1/2 years of age.  In addition to continuing prenatal and postnatal growth and developmental deficits, he has many of the other stigmata described as characteristic of this syndrome.  To this list have been added other findings from our case.


Acute rheumatic fever in adults.

Acute rheumatic fever in adults. Acute rheumatic fever (ARF) in 53 adults was characterized by a severe, febrile migratory polyarthritis involving primarily large joints in the lower extremities, with evidence of an antecedent streptococcal infection. Carditis, present in only eight (15%) of the adults, was mild and transient. The characteristic abnormality in laboratory findings was an erythrocyte sedimentation rate (Westergren) greater than 100 mm/hr. Response to high-dose aspirin therapy was prompt and dramatic in all patients. Mild andevanescent abnormalities of both renal function and hepatic function (not aspirin-mediated) were detected in 51% and 64%, respectively. A common disorder in San Antonio, ARF has distinctive symptoms. It can be readily diagnosed and promptly treated. In the adult, it is almost exclusively a syndrome of events severe but transient in the joints, and mild and transient in the heart, kidneys, and liver.


Posterior fossa hemorrhage. Localization by computerized tomography. The differentiation between pontine and cerebellar hemorrhage is important both prognostically and therapeutically but is often very difficult. Computerized axial tomography of the brain is a new, rapid, nonivasive method of studying intracranial disease. This technique proved useful in making this important differential diagnosis in the case reported here.


Erythroplasia of Queyrat. Treatment with topically applied fluorouracil. Three patients with biopsy-confirmed erythroplasia of Queyrat were treated with topically applied fluorouracil. The lesions cleared completely, and recurrence-free follow-up periods ranged from 20 to 60 months. There were normal histological findings in posttreatment biopsy specimens in two of the patients. A literature review yielded five additional cases successfully treated with fluorouracil applied topically. Patients with histologically confirmed erythroplasia of Queyrat should be afforded treatment with topically applied fluorouracil, as results appear to be superior to those of surgical or radiological treatment, with less morbidity.


Voodoo in the general hospital. A case of hexing and regional enteritis. We have observed the case of a hexed patient that emphasizes the interplay between modern medical practice and the influence of a supernatural voodoo subculture. Psychosocial stresses involved in the patient's illness (regional enteritis) added to the complexity of the clinical problem. The presence of ambivalence in the patient and her mother concerning their systems of belief, and their unwillingness to accept totally the treatment modalities of either modern medicine or voodoo, probably prevented the patient's predicted death.


Elevated carcinoembryonic antigen levels and biliary tract obstruction. Circulating carcinoembryonic antigen (CEA) levels and their relation to liver function test values were studied in 29 jaundiced patients with benign extrahepatic biliary tract obstruction and inflammation. During the obstructive and inflammatory phase, 15 (52%) of the patients had CEA levels greater than 2.5 ng/ml. Elevated CEA levels were associated more frequently with common bile duct stones (and cholangitis) than with gallbladder stones (and cholecystitis) alone, although this difference was not statistically significant. The former often had values greater than 5.0 ng/ml. The highest values were found in two patients with liver abscesses. T'HE CEA levels returned to normal following relief of obstruction in seven of ten patients and increased in two patients who had progressive inflammation. Serum alkaline phosphatase and bilirubin levels were significantly higher in the patients with elevated CEA levels (p smaller than .05). Serum alkaline phosphatase levels showed a significant positive correlation with CEA levels (p smaller than .02). Patients with obstructive jaundice and elevated CEA levels do not necessarily have cancer.


Air-rinsing after dialysis. A mode of transmission of hepatitis virus. During a recent outbreak of hepatitis B among patients receiving dialysis, georgraphic and temporal distribution of cases in the absence of exposure to blood products suggested patient-to-patient transmission. The patients who contracted hepatitis used Kiil dialyzers with a single-pass dialysate system, while patients who used hollow-fiber dialyzers appeared to be protected. Blood was returned to patients after Kiil dialysis by the air-rinse technique with the use of a nonsterile plastic tube attached to a manometer bulb. Laboratory experiments demonstrated that Staphylococcus aureus and poliovirus became widely distributed throughout the Kiil dialyzer when introduced during the rinse phase by contaminating the air-rinse tubing.


Beverage can pull-tabs. Inadvertent ingestion or aspiration. Potential medical hazards are involved in the procedure of dropping the "pull-tab" into an aluminum beverage can before drinking the contents. We have seen two cases of inadvertent ingestion and one of inadvertent aspiration of the pull-tab. One of the patients who had ingested a pull-tab required endorcopic extraction of the pull-tab from the esophagus, and the patient who had inhaled a pull-tab required an open thoracotomy for removal of the foreign body from the bronchus. Aluminum is not as dense as radiopaque or other metals and is, therefore, frequently difficult to identify on standard roentgenograms.


Recurrent acute renal failure with idiopathic paroxysmal myoglobinuria. A second episode of myoglobinuric renal failure requiring dialysis developed in a muscular 30-year-old man. His first episode, which was not exercise-related, had occurred in childhood and was accompanied by chills, fever, and leukocytosis, whereas the second followed unaccustomed exertion 15 years later. Despite two occurrences of severe renal failure and intermittent episodes of myoglobinuria, renal function is presently normal. Idiopathic paroxysmal myoglobinuria may produce recurrent life-threatening acute renal failure; however, the prognosis for recovery, as evidenced by this case, appears favorable.


The toxicity of intravenously used marihuana. While no unanimity of opinion exists regarding the risk to physical health from smoking marihuana, we have seen four cases that demonstrate clearly that intravenous usage is hazardous. The severity of the multisystemic involvement is dose-related. On initial examination, signs of most severe overdosage included fulminant gastroenteritis, hypoalbuminemia, toxic hepatitis confirmed by serial biopsy, acute renal failure, electrolyte disturbances, leukocytosis, anemia, and a relative thrombocytopenia. In three patients who shared a common needle, gingivostomatitis also developed.


Evaluation of ibuprofen (Motrin). A new antirheumatic agent. Ibuprofen is a new, mild analgesic agent that may be useful in the symptomatic treatment of rheumatoid arthritis and osteoarthritis. Results of clinical studies have shown that its beneficial effects in these conditions are comparable, but not superior, to those of aspirin. However, at recommended doses it has less anti-inflammatory effect than aspirin. Its usefulness as an analgesic in the treatment of other types of pain and as an antipyretic has not yet been established. Ibuprofen causes fewer adverse effects on the gastrointestinal system, including occult bleeding, than aspirin. Serious adverse reactions have not been reported. Thus, ibuprofen may be acceptable for use in patients who cannot tolerate aspirin or other antirheumatic drugs.


Preoperative bone scans. Use in women with early breast cancer. Strontium nitrate Sr 87m bone scans were made preoperatively in a group of women with suspected breast cancer, 35 of whom subsequently underwent radical mastectomy. In 3 of the 35 (9%), the scans were abnormal despite the absence of clinical or roentgenographic evidence of metastatic disease. All three patients has extensive axillary lymph node involvement by tumor, and went on to have additional bone metastases, from which one died. Roentgenograms failed to detect the metastases in all three. Occult bone metastases account in part for the failure of radical mastectomy to cure some patients with breast cancer. It is recommended that all candidates for radical mastectomy have a preoperative bone scan.


Primary hyperparathyroidism. Laboratory and clinical data in 73 cases. The serum calcium level measured in the research laboratory was 10.8 mg/100 ml or more in all of 73 patients with primary hyperparathyroidism, though many of the values were normal when measured in the hospital laboratories. Postoperatively, all patients successfully operated on showed an immediate increase in renal phosphorus reabsorption to 95% to 100%, and a decrease, which averaged 54%, in urinary hydroxyproline levels. Seven patients who had hyperplasia had no clinical or laboratory features distinguishing them from those with adenomas. Uremia, an ominous sign, was found in six patients, five of whom died.


[Effect of rubratoxin B on the respiration of liver mitochondria in the rat]. The in vitro effect of rubratoxin B on the electron transport system of rat liver mitochondira was investigated. This mycotoxin depressed oxygen consumption in ADP-lacking mitochondira and in ADP-coupled mitochondria, using succinate or beta-hydroxybutyrate as substrats. Rubratoxin B is neither an oxidative-phosphorylation inhibitor nor uncoupling agent. Its effect is compared with aflatoxin B1.


Proximal small bowel transit pattern in patients with malabsorption induced by bovine milk protein ingestion. Seven allergic patients with bovine milk or milk protein-inducible transient intestinal malabsorption exhibited radiologic signs of rapid transit of ingested barium through the proximal small intestine hours following oral challenge with bovine milk or milk protein solution. Control studies in the same patients without prior milk challenge revealed significantly more leisurely progress of contrast medium in the proximal small bowel. The possible pathogenetic role of such hasty transit through the functionally most effective portion of the digestive tract in patients with malabsorption points up the physiologic importance of roentgen examination of motility patterns in this particular segment of small bowel.


Intrarenal mycotic (false) aneurysm secondary to staphylococcal septicemia. Report of a case detected arteriographically in a 10-month-old infant. Gross hematuria, a flank mass, and a nonfunctioning kidney were seen at excretory urography in a 10-month-old infant with staphylococcal pneumonia and septicemia. Selective renal arteriography revealed a mycotic (false) intrarenal artery aneurysm with an intrarenal and perinephric hematoma.


A natural anti-A agglutinin in the serum of the brown trout (Salmo trutta). 20% of normal serum samples from adult brown trout (Salmo trutta) possess an agglutinin for human erythrocytes with anti-blood-group A specificity. This agglutinin has properties which clearly distinguish it from the agglutinin with anti-(B+'P') specificity found in ova from fish of the same species and from anti-blood A antibodies found in human serum.