[Segmental pancreatic lesions after partial or total splenectomy in rabbits]. Previous experiments on compensatory hypertrophy of the splenic parenchyma after partial splenectomy, permitted us to observe lesions of the part of the pancreas in contact with the spleen.  This part of the gland is supplied only by the splenic artery and suffers from some degree of ischemia during splenectomy.  The object of this research was to seek, as a routine, pancreatic disease after splenectomy.  32 adult rabbits were used.  Partial splenectomy carried out in 15 cases, removed about 2/3rds of the spleen and involved ligature of 4 or 5 splenic and mesenteric arterio-venous pedicles.  Total splenectomy, carried out in 17 cases, included ligature of the splenic arteriovenous trunk and 3 or 4 spleno-gastric and spleno-mesenteric arterio-venous pedicles.  These operations were followed by more or less intense stasis extending to the splenic part of the pancreas.  The animals were examined one week and 8 months afterwards.  All the rabbits, except one, had pancreatic lesions.  The most severe and extensive lesions, including large areas of cytosteato-necrosis with, in 11 cases, pseudo-cysts, with caseation, followed total splenectomy.  Partial splenectomy gave rise to 6 pseudocysts including 2 containing blood and 9 cases with milder lesions including involution, rarefaction and sometimes disappearance of the gland which had suffered from ischemia.  In these splenectomies, ligature of the splenic arterio-venous pedicles supplying the pancreas were responsible for pancreatic disease.


[Anatomopathological aspects and treatment of sternitis and sternochondritis after cardiac surgery]. The authors report their experience of the treatment of sternitis on a surgical unit.  They analyse here 23 case records out of 31 cases of sternitis treated on their unit.  Out of these 23, there were 3 deaths (13 p. 100) and 16 cures (69,5 p. 100) with an average follow up of 20 months.  The solutions adopted, including extremely wide exposure and, in some cases, removal of infected bone, are justified by the fact that these patients were admitted from other surgical units.  The diagnosis was facilitated by the fact this unit includes a clinical bacteriology research unit.  The authors make no apologies for using very classical surgical methods and attempt to demonstrate that these extreme cases require radical surgery.  Their original contribution consists of the rational use of antibiotics, but the surgical solution is pre-eminent.


[Autotransfusion in acute hemoperitoneum]. This procedure is well known, there were 2 000 cases reported in the literature with a very small number of complications.  Is autotransfusion really efficacious?  According to the author's results in 9 cases of hemoperitoneum, the red cells obtained by this method are quantitatively valid, but hemolysis starts early (6 hours) and the disappearance of the platelets and coagulation factors occurs even more early (2 hours).  However, clinical tolerance is perfect, thus confirming the good experimental results obtained in animals.  The true limits are hemolysis and the risk of contamination but, with appropriate apparatus and precise indications, and unsoiled blood, less than 24 hours old, autotransfusion is a good method which may provide a solution in certain emergencies.


[Osteosynthesis of trochantero-diaphyseal and sub-trochanteric fractures.  (Apropos of 57 osteosyntheses)]. The authors report 57 cases of osteosynthesis for trochanterodiaphysial and subtrochanteric fractures.  They analyse the types of fracture in relation to age, methods of treatment used and the results.  They emphasize the poor prognosis after 70 years.  They suggest close wound intramedullary nailing whenever possible and osteosynthesis on non-fractured metastasis in order to prevent fracture.


[Treatment of fractures of the humerus by intramedullary fixation]. The Hackethal's technique of intramedullaring wiring for humeral fracture represents the immobilisation procedure particularly convenient for this bone.  This procedure can be realised without special instrumentation with Kirschner's wires and image intensifior.  To allow the approach of the fracture, the patient's position is choosed upon the topography of the lesion.  The intramedullaring wiring is always done from down to up.  Indications for this procedure are: humeral shaft fracture, humeral neck fracture, and fractures of the shaft and of the neck.  During the reduction of the fracture, the immoderate use of a image intensifior seams to be the major risk.  Hackethal's technique for medullary wiring was used in 21 patients, only one pseudarthrosis was noted.  The fonctionnal recovery of the arm is usually realised in three months.


[Disunion of colo-rectal anastomosis after surgery]. Breakdown of sutures is the main complication of colonic and rectal surgery.  The percentage of breakdowns is between 5 and 10 p. 100.  The latter may be obvious as shown by a fistula or by peritonitis.  But they may also be latent and present with septicemic shock.  One must then detect the breakdown by the association of clinical, radiological and laboratory signs in order to re-operate immediately.  Intensive care plays a very important role in the treatment of this lesion.  Suture breakdown is sometimes unforseeable, but it may be avoided by taking into consideration certain prophylactic rules which are analysed here.


Gas chromatographic resolution of enantiomeric amphetamines and related amines. I. Structural effects on some diastereomer separations. Eight structurally related enantiomeric primary amines including several amphetamines were resolved as distereomers by gas chromatography. Optically active acylated amino acid chlorides were reacted with the amine racemates to yield volative diastereomers which were chromatographed on polar and on nonpolar columns. Selectivity of diastereomeric pair separations was found to be dependent on substitution at the chiral centers of both the amino acids and the amines. Baseline resolution was achieved on a 6-ft. diethylene glycol succinate column at 200 degrees for seven of the eight amines. The polar stationary phases yielded higher relative separation factors than the nonpolar phase in all cases for the same chromatographic conditions. The effects of varying the perfluoroacyl group of the amino acid resolving agent from trifluoroacetyl to pentafluoropropionyl to heptafluorobutyryl was to significantly decrease the retention times without significantly decreasing these separation factors.


Automation of multiple sephadex LH-20 column chromatography for the simultaneous separation of plasma corticosteroids. An automated method of Sephacex LH-20 chromatography has been developed for the simultaneous and complete separation of corticosterone, 11-deoxycortisol, aldosterone, cortisone and cortisol from a small plasma sample prior to radioimmunoassay. Using a controlled elution flow-rate of 40 ml/h and automated programme tape-controlled collection of the eluates from six columns eluted simultaneously, excellent reproducibility of elution patterns with minimal day-to-day and column-to-column variations could be achieved. The method can be easily extended and permits the reliable, rapid and easy routine separation of individual steroids from a single plasma or tissue extract on a multi-column scale.


Direct quantitative thin-layer chromatographic determination of prostaglandins A2, B2, E2 and F2 alpha. A direct method for the determination of prostaglandins (PG) A2, B2, E2 and F2 alpha by thin-layer chromatography (TLC) is described. The TLC development is carried out on silica gel 60 F254 plates so that PGA2, PGB2 and PGE2 can be directly determined together by chromatogram spectrodensitometry using the reflection method. PGE2 must be converted into pgb2 so that it can be measured at lambda max. 224 nm and after conversion into PGB2 by spraying with potassium hydroxide solution. PGF2 alpha is measured after spraying with methanolic sulphuric acid and subsequent heating at lambda max. 530 nm. The method of determination described here is characterized by a short analysis time and good accuracy, and it is therefore suitable for quality control and stability investigations with these prostaglandins. The coefficient of variation is plus or minus 3.5 percent.


Empirical quantum chemical approach to structure-gas chromatographic retention index relationship. I. Sterol acetates. It has been found possible to correlate chromatographic retention parameters directly with molecular electronic structure by means of a linear relationship. The empirical parameters used are total energy and localized charge, calculated by the method of Del Re. They are deduced directly from the molecular structure and they permit the retention index to be calculated theoretically with an acceptable error.


[Structure-mobility relationships in thin-layer chromatography. Applications to some progestogens (author's transl)]. A study has been made on the quantitative relationship between the chromatographic mobility and the structure of progestogenic steroids. The coefficient K, corresponding to the fundamental skeleton, and the parameters of different substituents were calculated from the RM values. The results obtained with eighteen steroids tested in two solvent systems of low dielectric constant and low polarity have been improved satisfactorily.


Pituitary-gonadal relations in infancy. I. Patterns of serum gonadotropin concentrations from birth to four years of age in man and chimpanzee. Mixed cord sera (27 male, 28 female) and sera from 105 male and 93 female children aged 5 days to 4 yr were assayed for FSH, LH and hCG. Cord hCG was similar in both sexes (median 58 mIU/ml; range 20-9000), and fell to less than 5 mIU/ml by 5 days of life, a value which is below the limit of detectable cross reactivity in the LH radioimmunoassay. Cord FSH was less than 5.5 mug LER-907/100 ml in both sexes. In boys there was a rapid rise of FSH in early postnatal life, with peak levels up to 55 mug/100 ml between 1 week and 3 months, followed by a decline by 4 months reaching the low values seen in older prepubertal subjects. This postnatal FSH rise was both more marked in females with peak values at 2-3 months up to 169 mug/100 ml, and also more sustained with levels staying above those of older prepubertal children until 4 yr of age. Serum LH levels in the boys were in the adolescent range by 1 week of age, peaked at 1 month and then declined to the usual childhood range by 4 months. A similar pattern, though with lower peak LH values, was seen in the female infants. A longitudinal study of serum FSH and LH values in one male and one female chimpanzee from 17 to 456 days of age showed patterns in serum gonadotropins which paralleled those seen in the human cross-sectional study.


A modified hemagglutination inhibition test for estimating human follicle-stimulating hormone (hFSH) in unprocessed urine. The development of a hemagglutination inhibition test for urinary human follicle stimulating hormone (hFSHu) is described. Antisera were raised in rabbits and absorbed immunochromatographically with crude preparations of human chorionic gonadotrophin (hCG). hFSHu was coupled to erythrocytes by means of bis-diazobenzidine. The reagents, alone or in combination were subjected to various specificity tests such as reactions of hFSHu-coated erythrocytes with antisera against different antigens, reactions of anti-hFSHu with erythrocytes coated with different antigens, and reaction of "non-FSH" preparations on different test combinations of anti-hFSHu sera and hFSHu-coated erythrocytes. A comparative assay of an hFSHu preparation with different reagent combinations appeared to give the most stringent criterion for specificity. A modified hemagglutination inhibition test system was developed according to the principle reported earlier for urinary human luteninizing hormone (hLHu). Its sensitivity was fixed at 2 mIU FSH/ml which is sufficient for the estimation of hFSH in unconcentrated urine.


The insulin response to intravenous fructose in relation to blood glucose levels. The insulinotropic action of intravenous fructose was examined in 24 subjects without known metabolic disease. When blood glucose values before the fructose infusion were at or below normal fasting levels, fructose elicited only a small plasma insulin response. In contrast, the insulin response was strikingly augmented when preinfusion blood glucose and plasma insulin levels were moderately elevated. The insulinotropic action of fructose appears closely related to the preinfusion blood glucose level. Fructose has little or no insulinotropic action in the absence of glucose but potentiates glucose-mediated insulin release. The insulinotropic potency of other glucose analogues in vivo may show a similar dependence on concomitant blood glucose levels.


Plasma estrogen and androgen concentrations in children during adolescence. Using Sephadex LH-20 chromatography and a radioimmunological technique, the simultaneous measurement of estrone, estradiol, testosterone and dihydrotestosterone was performed in a single extract of peripheral plasma in children. In 44 boys and 43 girls, the mean plasma concentration of estrone rose steadily in both sexes, though more pronounced in the girls. For estradiol, this increment was noted only for the girls. For testosterone, the boys showed a spurt after pubertal stage 3, whereas the girls did not show any rise throughout the developmental phases. The girls, however, showed increment in dihydrotestosterone, concentration from pubertal stage 1 to 3, and plateaued thereafter. The boys showed marked increment in the concentration of this steroid throughout development, although less pronounced as that seen for testosterone. Plasma estrogens correlated better with the clinical evaluation of sexual maturation than with chronological ages in the girls. Similarly, the boys showed better relationship between the androgens and maturational stages than with chronological age. The girls also demonstrated a steep increment in the SDs for the estrogen values with sexual maturation (at stages 3 and 4, the SDs for estrone and estradiol were 0.26 and 0.80 respectively, at stage 5 they were 0.82 and 1.49 respectively) reflecting perhaps the onset of cyclic activity. When the estrogen values were related to the androgen values, the boys demonstrated a high association (r equals 0.78). This correlation was absent in the girls.


Suppression of renin and aldosterone by small amounts of DOCA in normal man. Previous investigators have suggested that low renin hypertension may be due to an unknown mineralocorticoid. This investigation was designed to simulate the effect of an unknown mineralocorticoid by administration of small amounts of desoxycorticosterone acetate (DOCA) in three normal subjects. The response of 2-h upright plasma renin activity (PRA), plasma aldosterone concentration (PA), and urinary aldosterone excretion (UA), as well as extracellular fluid volume, (ECFV) was determined on a high and low salt diet before and during the administration of DOCA for 13 days. After 9 days of DOCA, ECFV increased approximately 2 liters and PRA decreased to levels found in our patients with LRH. PA and UA decreased appropriately as PRA was suppressed. We would expect an unknown mineralocorticoid to have similar effects on the reninangiotension-aldosterone system. Thus, these results would suggest that in LRH the normal levels of PA and UA are inappropriately elevated in relation to the low PRA.


Spontaneous remission of Cushing's syndrome in a patient with an adrenal adenoma. A 23-yr-old male student presented with clinical and biochemical evidence of Cushing's syndrome. One month later, his elevated plasma and urinary adrenal steroids had returned to normal. At surgery, an adrenal adenoma was removed from his right side. We postulate that he either underwent a temporary spontaneous remission of his disease without treatment, prior to surgery, or that his adenoma secreted glucocorticoids in a cyclical fashion.


A diphasic pattern of gonadotropin secretion in patients with the syndrome of gonadal dysgenesis. Cross sectional and longitudinal studies of plasma FSH and LH in 58 patients, age 2 days of 20 yr, with the syndrome of gonadal dysgenesis show a diphasic pattern of gonadotropin secretion. The mean basal plasma FSH level is 43 plus or minus 7 (SE) ng/ml (LER-869) in patients from 2 days to 4 yr, which is strikingly elevated. Thereafter, a decline in plasma FSH to a mean level of 4 plus or minus 0.7 (SE) ng/ml occurs between 4 and 10 yr, followed by a rise after 10 yr to 61 plus or minus 4 (SE) ng/ml. The pattern of LH (LER-960) secretion is qualitatively similar to that of FSH, although quantitatively the values for LH are 1/3 to 1/10 those for FSH. The similarity of pattern of gonadotropin secretion observed between patients with gonadal dysgenesis and normal children suggests that gonadal function does not play a decisive role in the pattern of gonadotropin secretion from infancy through adolescence, but exercises striking effects on the quantity of gonadotropin secreted.


Formation of 6-hydroxylated progesterone in the human placenta and response to hCG. The in vitro metabolism of 7alpha-3-H-pregnenolone by five term human placentas obtained from repeat cesarean section was studied. Incubations were carried out either with minced tissue for 1 h or by organ culture for 6 h and 24 h. Twenty-one experiments were performed to determine the effect of human chorionic gonadotropin (hCG), human placental lactogen (hPL), and heat-inactivated hCG on the metabolism of pregnenolone. The major radioactive product was progesterone (40-60%); unchanged pregnenolone accounted for only 5-15% of the radioactivity. 3-H-6beta-OH-progesterone was found and rigorously identified. In control experiments 6beta-OH-progesterone was 2-4% of the radioactivity. In the presence of hCG there was a significant (P smaller than 0.005) 2-3-fold increase of 3-H-6beta-OH-progesterone in the 1-h mince incubations and the 24-h organ cultures. There was no increase of 3-H-6beta-OH-progesterone over control values with hCG after 6-h organ cultures; with heat-inactivated hCG; or with hPL. These findings provide additional data that hCG affects steroid metabolism in the human placenta. In addition, 3-H-6alpha-OH-progesterone was found and rigorously identified in yields of approximately 0.5-1%. The effect of hCG on 6alpha-hydroxylation was not determined. This appears to be the first demonstration of 6alpha-hydroxylation of C21 steroids by human tissue.


Stable reduction of plasma growth hormone (hGH) levels during chronic administration of 2-Br-alpha-ergocryptine (CB-154) in acromegalic patients. In 7 acromegalic patients in whom plasma hGH concentrations had dropped acutely after a single dose of 2-B r-alpha-ergocryptine (CB-154, 2.5 mg orally) chronic CB-154 treatment (10 mg orally for 30 days) was also accompanied by a significant and stable reduction of hGH. Withdrawal of the drug was followed by a rapid return of hGH to pretreatment values. Reinstatement of oral CB-154 treatment resulted again in suppression of hGH levels measured 30 and 60 days later. In 5 patients, unresponsive to acute administration of CB-154, no appreciable variation in hGH levels was present after 30 days of treatment. These results suggest that 2-Br-alpha-ergocryptine offers a new approach to the medical treatment of acromegaly.


The stimulation of human prolactin secretion by 3-Iodo-L-tyrosine. Oral administration of a single 1 g dose of MIT to 10 normal male and female subjects resulted in a rise in serum prolactin in each subject. The mean peak level of serum prolactin attained by the 10 subjects was 36.3 plus or minus 7.9 ng/ml which was highly significantly elevated (P smaller than 0.0005) above the mean basal level of 5.3 plus or minus 1.0 ng/ml. While there was no significant difference between the basal serum prolactin levels of male and female subjects, the mean peak level attained by male subjects following MIT (18.8 plus or minus 3.3 ng/ml) was significantly less (P smaller than 0.0025) than that recorded for the female group (62.5 plus or minus 9.1). Serum levels of growth hormone (GH), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), triiodothyronine (T3), thyroxine (T4) and cortisol were not significantly altered following MIT administration. The complete absence of side effects due to MIT make it a suitable drug for the acute clinical assessment of pituitary prolactin reserve.


Adrenal response to tolbutamide-induced hypoglycemia in high altitude dwellers. Adrenal response to tolbutamide-induced hypoglycemia was studied in 23 normal men born and living at high altitude (Morococha, Perú, 4,540 m) and compared to 23 men born and living near sea level. Fasting blood sugar was significantly lower in the high altitude dwellers (HAD) and this difference persisted throughout the test period. The blood glucose decrement at 30 min was significantly less in the HAD. Plasma cortisol response was significantly higher at 30 and 60 min in the HAD. Peak cortisol level occurred earlier in the HAD than in men living at sea level. The absolute cortisol increment at 30 min was significantly greater in the HAD.


Measurement of serum clogestone acetate (AY-11,440) by a radioreceptor assay: a practical approach to the quantitative determination of synthetic progestins. A novel method is described for the measurement of nanogram quantities of clogestone acetate (3beta, 17alpha-dihydroxy-6-chloropregna-4,6-dien-20-one 3,17-diacetate) in serum:clogestone acetate (CgAc) is converted to chlormadinone acetate in the presence of wheat germ lipase and hydroxysteroid dehydrogenase. The ketonic steroid formed is then incubated with rat uterine cytosol and 3-H-progesterone. The concentration of 3CgAc is estimated from a standard curve derived by incubating cytosol with 3-H-progesterone and varying amounts of chlormadinone acetate. The statistically validated method has been used for the estimation of serum CgAc in humans and dogs given an oral dose of the steroid. The radioreceptor assay (RRA), has practical advantages over related techniques such as radioimmunoassay (RIA) especially with respect to the developmental work. This is the first time that a quantitative assay of a progestin by the tissue receptor approach has been described.


Altered tissue response to glucagon in obesity. The tissue response to exogenously administered glucagon was examined in 5 obese subjects (180 plus or minus 20 percent ideal body weight) and compared with the response in 5 normal weight controls (plus or minus 10 percent of ideal body weight). In all control subjects, glucagon (1 mug/kg) caused an increase in plasma free fatty acids and betahydroxybutyrate concentrations. In contrast, not only did the obese subjects fail to demonstrate a similar catabolic response, but 4 of the 5 obese subjects actually responded with a depression of plasma free fatty acid concentration and 3 of the 5, a decrease in betahydroxybutyrate. The potential mechanisms responsible for this defect are discussed, and it is suggested that the observation of an abnormal tissue response to a pharmacological stimulus warrants further investigation utilizing physiological lipolytic stimuli.


Somatomedin activity in cerebrospinal fluid. Somatomedin activity has been demonstrated in the cerebrospinal fluid (CSF) of 12 normal subjects and one patient with acromegaly. In all cases the concentration was lower in the CSF than in the corresponding serum, and a significant correlation was demonstrated between the somatomedin activity in the two body fluids (p smaller than 0.01).


Hypercalcitoninemia in acute pancreatitis. Calcitonin was measured in four patients with acute pancreatitis with hypocalcemia. A marked elevation of this hormone was noted in each case and persisted over several days. The peak level of calcitonin preceded the maximum fall in calcium. Among the various factors affecting calcium balance in pancreatitis, calcitonin probably plays an important role.


Stimulation of aldosterone production by angiotensin II peptides in vitro: enhanced activity of the (1-sarcosine) analogue. The biological activity of angiotensin agonists has been determined in a highly sensitive in vitro assay system, based upon aldosterone production by isolated dog adrenal cells. The responses to angiotensin II and the heptapeptide [Des-Asp-1]-angiotensin II are identical, while the [Des-Asp-1, Des-Arg-2]-hexapeptide and the [Des-Phe-8]-heptapeptide are almost completely inactive. By contrast, [Sar-1]-angiotensin II, a potent agonist upon vascular smooth muscle, is also about 10 times more active than angiotensin II in stimulating the production of aldosterone by dog adrenal cells. The increased agonist activity of [Sar-1]-angiotensin II is attributable to increased binding affinity as well as increased efficacy at the adrenal receptor site. These results also suggest that conversion to the [Des-Asp-1] heptapeptide is not an important intermediate step in the action of angiotensin II upon the zona glomerulosa.


The effect of hypoglycemia on TSH release in man. The effect of insulin-induced hypoglycemia on TSH release was studied in 7 normal subjects (Group I), 5 patients with sellar enlargment, 1 patient with idiopathic panhypopituitarism (Group II-A) and 2 acromegalic patients (Group II-B). Serial measurements of TSH, GH and corrtisol, after a bolus of insulin (0.1 U/kg body weight), were made over a period of 120 min. The peak TSH value of 8.3 plus or minus 0.9 pU/ml (mean plus or minus SEM) did not differ statistically from the basal value of 6.0 plus or minus 1.3 pU/ml in Group I. GH levels, however, increased from 1.0 plus or minus 0.0 ng/ml to 28.1 plus or minus 4.3 ng/ml, which was highly significant (P less than 0.001). In contrast, Group II-A patients had an increase in serum TSH from 4.3 plus or minus 1.4 pU/ml to 28.6 plus or minus5.7 pU/ml (P less than 0.02). The peak GH levels of 4.0 plus or minus 1.7 ng/ml did not differ significantly from the basal value of 1.2 plus or minus ng/ml. In group II-B, the untreated acromegalic patient (G) did not show alterations in TSH levels consonant with the increase in GH from a basal value of 34.9 ng/ml to a peak of 46.9 ng/ml with the induction of hypoglycemia. In the treated acromegalic subject (H), basal GH increased from 7.8 ng/ml to 11.4 ng/ml with no significant changes in TSH. Serum cortisol levels in Groups I, II-A and II-B did not show consistent inverse relationship to circulating TSH. The observations in this study suggest that hypoglycemia may stimulate TSH release in certain pituitary disorders. Through GH release might play an inhibitory role on TSH secretion, the results suggest other unidentified factor(s).


The effect of acute hypercalcemia on growth hormone release in man. The growth hormone response to acute hypercalcemia was studied in 9 normal subjects. Growth hormone, calcium, glucose, phosphate and magnesium levels were determined at 30-min intervals during 4-h infusions. Infusions, performed in random order in the subjects, consisted of either normal saline at 3 ml/min for / h or 15 mg calcium/kg (calcium gluconate at 3 ml/min for 3 h followed by normal saline for the fourth hour. Significant hypercalcemia (P less than 0.05) was achieved within 60 min and maintained throughout the infusion. No change in calcium concentrations occurred during normal saline infusions, and phosphate, glucose and magnesium were unchanges in all studies. Growth hormone levels were significantly higher (P less than 0.05) at 60 min and all subsequent determinations during calcium infusion when compared to normal saline infusions. In 6 of the subjects, standard l-dopa provocative testing with an oral dose of 500 mg was preformed during normal saline and calcium infusions identical to those described above. Peak growth hormone responses did not differ significantly following l-dopa during saline or calcium infusion. These results suggest that an acute increase in circulating calcium promotes greater basal growth hormone secretion without a synergistic increase in hypothalamic mediated growth hormone release by l-dopa.


Fetal protection against masculinization with hyperreactio luteinalis and virilization. In a unique patient with secondary amenorrhea and hirsutism prior to pregnancy, lutein cysts with hyperreactio luteinalis enlarged the ovaries to a diameter of 25 cm during pregnancy. The purpose of the study was to explore the possibility that placental aromatization of androgens may be a metabolic barrier that offers protection against masculinization of a female fetus. Maternal serum, umbilical cord serum and lutein cyst fluid were analyzed for testosterone, progesterone and estradiol content. The cardinal clinical findings were marked maternal virilization but no fetal masculinization. At the time of delivery, massive ovarian production of testosterone and a large maternal-fetal testosterone gradient were found. The maternal arm vein testosterone level, 15,000 ng/dl, was about 100 times normal level, the material ovarian vein level was 51,800 ng/dl, while the cord blood level was only 465 ng/dl. At the same time there was an increase in fetal cord blood estradiol to 33 ng/ml, a 7-fold increase compared to normal cord levels. A protective mechanism for the fetus may exist when maternal androgens are markedly elevated due to a maternal endocrinopathy concurrent with pregnancy. Our data are compatible with the concept that placental aromatization of androgens may function as a metabolic barrier, thus offering protection to the fetus from excessive maternal androgens. Another facet of the protective mechanism may be increased fetal exposure to potent estrogens, which may buffer the influence of androgens reaching the fetus.


Ultrastructure of the human mammary gland. II. Postpartum lactogenesis. The history and fine structure of 7 human mammary glands were studied in the post partum. Widespread hypertrophy and hyperplasia of the mammary acini were observed accompanied by dilatation and engorgement of the lumen by milk. Loose strands of connective tissue surrounding the mammary lobules and ductules contained dilated, engorged vascular channels. The lactogenic epithelial cells displayed rich cytoplasm containing prominent layering stacks of rough endoplasmic reticulum closely related to the enlarged oval mitochondria, on occasion surrounding their entire circumference. Also noted were numerous ribosomes and polyribosomes. The markedly hypertrophied golgi apparatus revealed cisternae containing particulate electron dense material and vesicles with dense granules. The latter were frequently seen being discharged in the lumen devoid of limiting membrane. Abundant fat droplets were present in the basal and apical regions and "pinched off" into the lumen, apparently surrounded by a limiting membrane. The lactogenic cells were richly endowed with slender microvilli in their luminal pole and related to one another by cytoplasmic prolongations, desmosomes and tight junctions. The myoepithelium was stretched and thinned out toward the periphery of the acini between the lactogenic epithelium and the basement lamina. Abundant myofilaments were present in the myoepithelial cells. Pinocytotic vesicles were also present, although not very numerous, in both the lactogenic and the myoepithelial cells. In general the human mammary gland during lactopoiesis follows similar structural changes as those previously described in other mammals.


Characterization of human growth hormone preparations used for the treatment of pituitary dwarfism: a comparison of concurrently used batches. Twelve different human growth hormone preparations used concurrently for the treatment of pituitary dwarfism have been studied by gel filtration and radioimmunoassay for GH, FSH, LH and TSH. The GH content of the vials as stated by the manufacturer could be verified by radioimmunoassay in all but one preparation tht contained much less than indicated. All preparations which had been extracted from acetone-preserved glands by various methods were shown to contain large amounts of aggregated growth hormone. By contrast, preparations extraced from frozed pituitaries contained GH mainly in the native monomeric form. FSH, LH and TSH could be detected in all preparations. With the exception of one pre paration containing large amounts of all three glycoprotein hormones, the degree contamination of these hormones was moderate to low. No conclusion could be drawn from the content og glycoprotein hormones as to whether frozen glands or pitutiaries preserved in acetone were used as raw material. The advantage of using growth hormone prepared according to the Roos methods, or any modification of it starting from frozen glands, over preparations made from glands preserved in acetone is discussed.


A nonchromatographic radioimmunoassay for 17alpha-hydroxyprogesterone. A radioimmunoassay is described for the measurement of 17alpha-hydroxyprogesterone in human plasma. We have employed the principle of "immunologic purification." 17-OHP and related steroids are bound to an excess of antiserum. Steroids with a low affinity for the antibody are extracted by ether. The 17-OHP is subsequently freed from antibody by acid hydrolysis and this extract is assayed by radioimmunoassay.


Pituitary secretion of free alpha and beta subunit of human thyrotropin in patients with thyroid disorders. Utilizing sensitive and specific radioimmunoassays, serum concentrations of human thyrotropin (hTSH), the immunologically common alpha subunit of the glycoprotein hormones, and the specific beta subunit of hTSH ( hTSH-beta) have been measured in normal individuals, in patients with primary hypothyroidism, and in patients with other disorders of thyroid function before and after intravenous administration of thyrotropin releasing hormone (TRH). In 29 normal individuals hTSH-beta was not detectable in serum (smaller than 0.5 ng/ml) before or after TRH; alpha was smaller than 0.5-2.0 ng/ml in men and premenopausal women and 1.0-5.0 ng/ml in postmenopausal women and did not increase after TRH. In 20 patients with primary hypothyroidism mean serum hTSH-beta was 1.3 ng/ml and increased to a peak value of 3.7 ng/ml after TRH; mean alpha was 4.3 ng/ml and increased to 6.3 ng/ml after TRH. None of the patients with Graves' disease, a hyperfunctioning thyroid nodule, or hypothyrotropic hypothyroidism had detectable serum hTSH-beta concentrations or alpha concentrations higher than the normals before or after TRH. In 3 patients with primary hypothyroidism given an intravenous bolus of labeled hTSH, no dissociation of hTSH into subunits was detectable for at least 3 h, indicating that the increment in serum alpha and hTSH-beta after TRH represented secretion of free subunits from the pituitary. In addition, L-thyroxine (L-T4) administered to 2 hypothyroid patients decreased the serum concentrations of alpha and hTSH-beta before and after TRH. Serum hTSH-beta was fully suppressed with 100-300 mug L-T4 daily, but there was a residual serum alpha component, which could not be suppressed with thyroid hormone and probably represented alpha subunits arising from gonadotropin-secreting pituitary cells. Normal pituitary glands also contained a predominance of free alpha subunit relative to hTSH-beta, in addition to hTSH. The secretion of free subunits in hypothyroidism may represent only a quantitative difference from the normal state, and subunits of hTSH appear to respond to the same control mechanisms as complete hTSH.


The influence of exogenous estrogen on the circadian periodicity of circulating prolactin in women. Ethinylestradiol (400 pg/day) does not only stimulate prolactin release in normal cycling women but also modifies the pattern of the circadian periodicity of circulating prolactin: the nocurnal rise is of reduced amplitude but covers a larger part of the nyctohemeral period as compared to the situation during a control period in the same subjects. The values start rising long before sleep, i.e., -t 2 pm, under estrogen treatment and during sleep, i.e., at 4 am, during the control period. In both cases, however, the values remain high until 8 am and are minimal at 12 am.


Elevtion of serum testosterone in ovarian hyperstimulation syndrome. Serum testosterone levels were monitored in female subjects who received therapy with human gonadotropins of urinary origin (menotropins) and human chorionic gonadotropin (hCG). Serum testosterone levels were not elevated in those subjects who did not experience side effects with therapy (Group A); among the other 7 subjects (Group B) with either moderate or severe ovarian hyperstimulation, serum testoterone levels rose distinctly (range 1.4 minus 9.0 ng/ml). Total menotropin dosage and serum estradiol-17beta levels were higher in Group B than in Group A. Ovarian hyperstimulation and elevation of serum testosterone were not restricted to patients with the syndrome of polycystic ovaries.


Metabolism of thyroxine and triiodothyronine in patients with chronic granulomatous disease. Normal human leukocytes can degrade thyroid hormones in vitro especially during phagocytosis. To test whether the leukocyte system plays a significant role in hormone economy in vivo, studies of the metabolism of labeled T4 and T3 granulomatous disease, whose leukocytes had earlier been shown to have a reduced ability to degrade the thyroid hormones. Hormone turnover rates in the 3 subjects were similar to those reported for normal children by various investigarors. Also, normal ratios between fecal and urinary excretion of radioactivey were observed, suggested that deiodination was the major route of hormone breakdown, as it is in normal subjects. Our interpretations of these findings are: 1) an intact leukocyte hormone degrading system is not essential for normal rates of thyroid hormone metabolism in vivo; 2) the leukocyte defect in chronic granulomatous disease is not accompanied by a general defect in mechanism for thyroid hormone degradation in other tissues.


Treatment of acromegaly with bromocryptine. Four men and 4 women with active acromegaly were treated with bromocryptine for 4 to 5 weeks. Serum growth hormone levels response to a glucose load were measured before and in the last weed of treatment. In only 1 patient was the grwotoh hormone response rendered normal by the drug. This patient, but none of the others, also showed an improvement in glucose tolerance and a reductin of the raised serum insulin levels during the glucose load. In three of the 8 patients vomiting was troublesome side effect of treatment.


Comparison of cylic and linear forms of somatostatin in the inhibiton of growth hormone, insulin and glucagon Secretion. The relative potency of cyclic and linear somatostatin in their inhibitory action on GH, insulin and glucagon secretion was assessed in 7 normal adult men. Administration of linear or cyclic somatostatin as a single intravenous bolus (50 mug) resulted in a prompt and concomitant decline in both insulin and glucagon. While both peptides elicited a quantitatively similar suppression of glucagon secretion, the decline in basal insulin level was greater with the cyclic than with the linear preparation. Both the linear and cyclic form of somatostatin appears to be more potent in the inhibition of insulin than glucagon. No discernable change in plasma glucose and GH levels was observed.


Control plasma renin activity and changes in sympathetic tone as determinants of minoxidil-induced increase in plasma renin activity. A study was made of the possible mechanism(s) underlying minoxidil-induced increase in plasma renin activity (PRA). 10 patients with essential hypertension were treated with minoxidil and subsequently with a combination of minoxidil plus propranolol. Minoxidil lowered mean arterial pressure 31.6 plus or minus 3.3 mm Hg, mean plus or minus SEM. There was an associated increase in both PRA, 6.26 plus or minus 2.43 NG/ML/H, and heart rate, 21.4 plus or minus 2.7 beats/min. The changes in PRA and heart rate were positively correlated, r, 0.79. Addition of propranolol reduced mean arterial pressure by a further 10.1 plus or minus 1.5 mm Hg and returned heart rate to control levels. Propranolol reduced PRA significantly but not to control levels. Control PRA positively correlated with PRA on minoxidil, r, 0.97, and with PRA on minoxidil plus propranolol, r, 0.98. We conclude that control PRA is a major determinant of change in PRA with minoxidil. Minoxidil increased PRA by at least two mechanisms: (a) an adrenergic mechanism closely related to change in heart rate and blocked by propranolol, and (b) a mechanism(s) not sensitive to propranolol and possibly related to decrease in renal perfusion pressure.


The influence of the extracellular fluid volume on the tubular reabsorption of uric acid. Changes is tubular reabsorption of uric acid in response to alterations in the extracellular fluid volume (ECFV) were examined in rats by clearance studies and by direct intratubular microinjections. Contraction of the ECFV led to a rise in the serum uric acid concentration and a 47% decrease in the clearance of uric acid. The ratio of uric acid to inulin clearance also fell, indicating an increase in the net tubular reabsorption of urate. Volume expansion resulted in an increase in the urate clearance and a 37% decrease in the net tubular reabsorption of uric acid. To localize the site in the nephron where these changes occur, microinjections of [2-14C]urate were performed. The lack of conversion of radioactive urate to allantoin after microinjections was demonstrated by thin-layer chromatography. After contraction of the ECFV, urinary recoveries of uric acid were significantly decreased after microinjections into proximal tubular sites. In contrast, recoveries were increased from these proximal sites after volume expansion. No evidence for distral reabsorption was obtained in any group of animals. These studies demonstrate that net urate reabsorption is influenced by the state of hydration of the ECFV and that these alterations are mediated by changes in the rates of reabsorption in the proximal tubule.


Determinants of glomerular filtration in experimental glomerulonephritis in the rat. Pressures and flows were measured in surface glomerular capillaries, efferent arterioles, and proximal tubules of 22 Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). Linear deposits of rabbit and rat IgG and C3 component of complement were demonstrated in glomerular capillary walls by immunofluorescence microscopy. Light microscopy revealed diffuse proliferative glomerulonephritis, and proteinuria was present. Although whole kidney and single nephron glomerular filtration rate (GFR) in NSN (0.8 plus or minus 0.04 SE2 ml/min and 2 plus or minus 2 nl/min, respectively) remained unchanged from values in 16 weight-matched NORMAL HYDROPENIC control rats (0.8 plus or minus 0.08 and 28 plus or minus 2), important alterations in glomerular dynamics were noted. Mean transcapillary hydraulic pressure difference (deltaP) averaged 41 plus or minus 1 mm Hg in NSN versus 32 plus or minus 1 in controls (P LESS THAN 0.005). Oncotic pressures at the afferent (piA) end of the glomerular capillary were similar in both groups ( 16 mm /g) but increased much less by the efferent end (piE) in NSN (to 29 plus or minus 1 mm Hg) than in controls (33 plus or minus 1, P less than 0.025). Hence, equality between deltaP and piE, denoting filtration pressure equilibrium, obtained in control but not in NSN rats. While glomerular plasma flow rate was slightly higher in NSN (88 plus or minus 8 nl/min) than in controls (76 plus or minus 6, P greater than 0.2), the failure to achieve filtration equilibrium in NSN rats was primarily the consequence of a marked fall in the glomerular capillary ultrafiltration coefficient, Kf, to a mean value of  0.03 nl/(s times mm Hg), considerably lower than that found recently for the normal rat, 0.08 nl/(s times mm Hg). Thus, despite extensive glomerular injury, evidenced morphologically and by the low Kf, GFR remained normal. This maintenance of GFR resulted primarily from increases in deltaP, which tended to increase the net driving force for filtration, and thereby compensate for the reduction in Kf.


The urinary concentrating defect in the Gunn strain of rat. Role of bilirubin. The role of high serum and tissue levels of unconjegated bilirubin in the pathogenesis of the impaired urinary concentrating ability was investigated in homozygous (jj) Gunn rats with the congenital absence of hepatic glucuronyl transferase. Continuous phototherapy with blue fluorescent lights at a wave length of 460 nm or oral cholestyramine feeding or both reduced serum levels of unconjugated hilirubin to levels consistently below 3.0 mg/100 ml for several weeks in both weanling and adult jj Gunn rats. The renal concentrating defect was already present in weanling jj Gunn rats by 21 days of age. In treated weanling jj animals, maximum concentrating ability and the concentration of urea and nonurea solutes in the papilla and medulla, determined after 24 h of fluid deprivation, were normal when compared to unaffected heterozygous (Jj) littermates. Solute-free water reabsorption which is reduced in jaundiced jj Gunn rats was restored to normal in treated weanling jj rats. The tissue concentration of unconjugated bilirubin was reduced throughout the papilla and inner and outer medulla in the treated jj rats in comparison with untreated jj littermates. The defect in urinary concentrating ability was only partially reversible and sometimes irreversible in adult jj rats, probably because of permanent renal parenchymal damage occurring secondary to massive crystalline deposits in the papilla and medulla. It is concluded that unconjugated bilirubin is directly involved in the pathogenesis of the concentrating defect in jaundiced jj Gunn rats.


Increased sensitivity to stimulation of acid secretion by pentagastrin in duodenal ulcer. The effect of graded doses of pentagastrin (2.7-6,000 ng/kg times h) on gastric acid secretion was measured in 20 duodenal ulcer (DU) and 20 non-DU subjects. Confirming many previous studies, the mean observed highest response and the mean calculated maximal response were significantly greater in DU than in non-DU subjects. The mean dose (plus or minus SE) in ng/kg times h for half maximal response, calculated from responses corrected for basal secretion and normalized for maximal secretion, was 92.1 plus or minus 1.7 in DU and 246.8 plus or minus 24.6 in non-DU subjects, a significant difference. By parallel line bioassay non-DU subjects required 2.8 times more pentagastrin (95% confidence limits 2.1-3.7) than DU highest response. Thus, this study shows that, compared with non-DU subjects, DU patients not only secrete more acid in response to stimulation by pentagastrin but also are more sensitive to stimulation by pentagastrin, that is, need smaller doses to achieve the same fraction of maximal response.


The effects of age and liver disease on the disposition and elimination of diazepam in adult man. This study investigates the separate effects of age and hepatocellular liver disease on the disposition and elimination of diazepam (Valium) in man. The drug was given either by rapid intravenous injection (0.1 mg/kg) or orally (10 mg) to 33 normal volunteers rnaging in age from 15 to 82 yr as well as to 9 individuals with alcoholic cirrhosis, 8 with acute viral hepatitis, and 4 with chronic active hepatitis. In the normal individuals, the terminal plasma half-life of diazepam, (t 1/2 (B)) exhibited a striking age-dependence; at 20 yr the t 1/2 (beta) was about 20 h, but it increased linearly with age to about 90 h at 80 yr. The plasma clearance of diazepam in the majority of the normal subjects was between 20 and 32 ml/min and showed no significant age-dependence. Cigarette smoking did not affect the half-life or the clearance. Additionally, neither the plasma binding (97.4 plus or minus 1.2%, mean plus or minus SD) nor the blood/plasma concentration ratio (0.58 plus or minus 0.16) of diazepam showed any age-related changes (P greater than 0.05). By contrast, analysis of the intravenous data according to a two-compartment open model indicated that both the initial distribution space (V1) and the volume of distribution at steady state [Vd(ss)] of diazepam increased linearly with age (P less than 0.005). The increase in Vd(ss) was secondary to the change in V1. It appears then that the prolongation of t 1/2 (beta) of diazepam with age is primarily dependent on an increase in the initial distribution volume of the drug. The plasma concentration/time course of the metabolite, desmethyldiazepam, was also affected by age. In older individuals, the initial presence and the peak values of desmethyldiazepam were observed later and the metabolite was present in lower concentrations. Despite the profound prolongation of t 1/2 (theta) with age, the constancy of diazepam clearance indicates that drug plasma concentrations will not accumulate any more in the old than the young, and chronic dosage more in the old than the young, and chronic dosage modifications based on pharmacokinetic considerations are unnecessary. Data obtained in patients with liver disease were compared with those found in age-matched control groups. Patients with cirrhosis showed a more than twofold prolongation in the half-life of diazepam (105.6 plus or minus 15.2 vs. 46.6 plus or minus 14.2 h, P less than 0.001).


Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils. The cytophilic activity of human myeloma proteins of different classes and subclasses for lymphocytes, monocytes, and neutrophils was investigated. Binding of both unaggregated immunoglobulins (Ig) and Ig aggregated with rabbit F(ab)2 anti-Fab fragment sera was determined. Lymphocytes bound unaggregated IgG1 and IgG3 proteins, but none of the proteins of the other classes. In contrast, after aggregation, IgG of all subclasses and IgE proteins bound to lymphocytes; aggregated proteins of the other classes did not bind. Monocytes bound unaggregated IgG1 and Ig3 better than Ig4 whereas the binding of proteins of other classes was insignificant. Neutrophils bound unaggregated IgG1 and IgG3 proteins and, in addition, IgA1, IgA2, secretory IgA, and IgG4 proteins. After aggregation, the neutrophils bound more Ig of all classes; however, the differences between the amounts bound remained similar to the amounts of unaggregated proteins. The native structure of the Ig molecule is necessary for the maintenance of complete activity, because Fc fragments bound less than intact Ig, and reduction and alkylation abolished cytophilia. The Fc receptors on all cell types tested showed no specificity for any of the respective cytophilic IgG subclasses; however, neutrophils appear to have separate receptors for IgG and IgA proteins.


The postnatal decline of hemoglobin F synthesis in normal full-term infants. Studies were carried out during the 1st yr of life in normal infants born at term to determine the proportions of fetal hemoglobin (Hb F) and adult hemoglobin (Hb A) being synthesized, in order to describe the complete switchover from Hb F to Hb A synthesis during postnatal life. 53 blood samples from 37 infants were incubated in an amino acid mixture containing [14C]leucine and chromatographed on DEAE-Sephadex for separation of Hb F and Hb A fractions. The completeness of the CEAE-Sephadex separation of Hb A and Hb F at an age when the major portion of synthesis was of the adult type of hemoglobin was confirmed by globin chain chromatography with the use of carboxylmethyl cellulose. There was a rapid decline in Hb F synthesis postnatally until 16-20 wk of age when levels of 3.2% plus or minus SD 2.1% were reached. By combining this data with that previously published, the complete switchover from Hb F to Hb A synthesis can be described in humans in relation to postconceptional age. It follows a sigmoid curve; the steep portion, which lies between the 30th and 52nd postconceptional week, is preceded and follwoed by plateaus averaging 95% and 7% Hb F synthesis, respectively.


The effect of urea infusion on the urinary concentrating mechanism in protein-depleted rats. To explore the role of urea in the urinary concentrating mechanism, the contents of vasa recta, Henle's descending limbs and collecting ducts were sampled by micropuncture of the renal papilla before and after infusion of urea in 10 protein-depleted rats. Eight protein-depleted rats not given urea were similarly studied as a control group. After urea administration, osmolality and the concentrations of urea and nonurea solute of urine from both exposed and contralateral kideny increased significantly. The osmolality and urea concentration of fluid from the end of Henle's descending limb and vasa recta plasma and the tubule fluid-to-plasma inulin ratio in the end-descending limb all increased significantly after urea infusion. We interpret these observations to indicate that urea enhances urinary concentration by increasing the abstraction of water from the juxtamedullary nephron (presumably the descending limb), in agreement with the prediction of recent passive models of the urinary concentrating mechanism. However, the concentration of urea in fluid from the descending limb after urea infusion was high (261 plus or minus 31 mM) and the difference in solium concentration between descending limb fluid and vasa recta was small and statistically insignificant.


Hepatocellular uptake of taurocholate in the dog. The purpose of this study was to examine the hepatocellular extraction of taurocholate and to determine the kinetic characteristics of the uptake process. The uptake of taurocholate by the liver of the intact dog was studied by the multiple-indicator dilution method. 51Cr-labeled red blood cells (a vascular indicator), 125I-labeled albumin (an extravascular reference), and [14C]taurocholate were injected into the portal vein. Different doses of unlabeled taurocholate were included in the injection mixture. Hepatic venous dilution curves were obtained. As a consequence of the hepatic uptake, the outflow recovery of [14C]taurocholate was much reduced when compared to that of albumin, but its recovery increased with increasing doses of taurocholate, suggesting a progressive saturation of the uptake process. The analysis of the dilution curves fitted a three-compartment model system well and no return of the extracted taurocholate to the extracellular space could be detected. The initial space of distribution of taurocholate was 1.22 plus or minus 0.12 (SD) times greater than that of albumin. Analysis of the data for uptake was consistent with Michaelis-Menten kinetics. The calculated initial maximal velocity of uptake (Vmax) was 4.53 mumol times s--1 times 100 g of liver--1 and the dose yielding half-maximal velocity (DK) was 7.11 mumol times 100 g of liver--1. These results are consistent with the hypothesis that the uptake of taurocholate is carrier-mediated. The maximal vilocity of uptake was about six times the known maximal capacity of biliary secretion of taurocholate in the dog.


Observer error in histological assessment of marrow hypocellularity. Observer error in the assessment of marrow hypocellularity was studied by examining histological sections from 37 mice having normal or reduced marrow cellularity and comparing the estimated cellularity with a previously measured value. For marrows or mild or moderately reduced cellularity the subjective estimate of cellularity was almost valueless both in terms of accuracy and reproducibility. Only severely hypocellular marrows, having a cellularity of less than 17% of normal, could be recognized as being abnormal with some degree of accuracy and reproducibility.


Strains of Pseudomonas putrefaciens from clinical material. Eight strains of Pseudomonas putrefaciens have been received from among 466 strains of Pseudomonas submitted to the Computer Trials Laboratory for identification over the last eight years. Two of the strains of P. putrefaciens from patients with otitis media and otitis externa respectively appear to have played a pathogenic role. The biochemical characteristics of these eight strains were compared with those of seven culture collection strains.


The measurement of iron-binding capacity in serum and purified transferrin with the aid of chemical affinity chromatography. In a mew method for the estimation of transferrin by iron-binding capacity iron is added as the tartrate in NaCl with about 10 mM bicarbonate. The excess iron is removed by passage through DEAE-Sephadex A-50 previously treated with the iron chelator disodium catechol-3,5-disulphonate. The iron remaining bound to transferrin is measured without protein precipitation by the use of ferrozine. The method is applicable to fresh, frozen, or lyophilized serum, purified transferrin, and some quality control preparations. Validation experiments confirm that transferrin in serum and in pure solution is saturated with iron and give some evidence of specificity. The possible use of commercially available transferrin preparations as analytical reference standards is discussed.


Computer card morphometry of jejunal biopsies in childhood coeliac disease. The histological changes in 95 jejunal biopsy specimens from children have been analyzed by a new mporphometric technique. The microscope image of the specimen is traced directly onto computer data cards. A simple sketch records accurate quantitative data in a matrix of 840 points, retaining the spatial arrangement of the tissue components. The data are fed via an optical mark data card reader, into a mini-computer. FORTRAN IV programs allow calculation of surface area, villous heights, and component volumes in metric units, and of volume proportions, volume-to-volume ratios, and surface-to-volume ratios. Pictorial and numerical printouts are produced, which are suitable for inclusion in the patient's notes. Jejunal biopsies from 37 controls and 26 untreated coeliac patients were clearly distinguished morphometrically. Sixteen pairs of biopsies from coeliac patients on long-term gluten-free diets before, and 12 weeks after, the reintroduction of dietary gluten significantly reflected the effects of gluten challenge. Comparison of control and abnormal biopsies showed a spatial redistribution of the components, more than a change in their absolute amounts. There was no significant differences in the total epithelial volumes in controls, treated or untreated patients, suggesting that the mucosal lesion in coeliac disease is not a true atrophy.


The predictive value of histometry of thyroid tissue in anticipating hypothyroidism after subtoatl thyroidectomy for primary thyrotoxicosis. Thyroid tissue removed at partial thyroidectomy from primary thyrotoxicosis patients, after preparation for operation with carbimazole and Lugol's iodine, was studied with the histometric technique. In patients with little or no evidence of autoimmunity before operation, the chance of developing postoperative hypothyroidism was approximately 1 in 2 in those who had volume percentage of epithelium greater than 40, but only approximately  1 in 10 in those who had volume percentage of epithelium less than 40. This approach may ultimately prove of predictive value in a substantial proportion of patients for anticipating hypothyroidism after subtotal thyroidectomy for primary thyrotoxicosis.


Hepatitis in clinical laboratories: a three-year survey. In a survey of laboratories where members of the Association of Clinical Pathologists worked, hepatitis was reported from 5 percent of 244 in 1970, 7 percent of 215 in 1971, and 2 percent of 337 in 1972. Of the 36 laboratories reporting hepatitis, a modest excess tested specimens from haemodialysis, transplant, and haemophilia units and performed tests for HB Ag. The average annual attack rate for staff of all types was 111 per 100,000 with higher rates for biochemists (268 in science graduates and 204 in technicians) and medical haematologists (258). Tests for HB Ag were positive in 17 cases ans negative in 15; nine were untested. No case was fatal and only 10 of the 41 required admission to hospital. Fourteen had a history of contract with 'high-risk (haemodialysis) specimens' but the most frequently suspected source of infection was personal contact with jaundiced or HB Ag-positive individuals and only in three cases were laboratory accidents suggested as the suspected source of infection. The findings indicate a need for caution and sensible safety precautions but not for exaggerated alarm.


Electron microscopy of serum of healthy hepatitis B antigen carriers. The sera of 36 blood donors who are established HBsAg carriers were examined with the electron microscope. The findings were correlated with the histological and electronoptic appearances of the liver and the titre and subtype of the antigen. Antigen-antibody complexes could not be detected. Dane particles constituted 2 percent or more of the total particle count in five of the 36 sera, including three sera from five carriers with chronic aggressive hepatitis and two sera from 11 carriers with chronic persistent hepatitis. In sera from carriers with normal histology or the minimal histological lesion of focal parenchymal necrosis they were detected very infrequently or not at all. Three biopsies revealed intranuclear inclusions when examined electronoptically and the corresponding sera all contained greater than 2 percent Dane particles. Where greater than 2 percent Dane particles were seen the antigen titre tended to be high. The predominant subtype was ad. There was no correlation between the number of Dane particles and the antigen subtype nor between subtype and histology.


ECHO 9 infection in pregnant women with suspected rubella. Both rubella virus and Echovirus 9 (ECHO 9) were epidemic in Scotland during the summer of 1973; both viruses can cause a mild febrile illness with rash. Sera from 286 rubella-negative pregnant women were tested for neutralizing antibodies to ECHO 9 virus; 40 women had antibody titres suggestive of recent infection. Prospective studies on the outcome of these pregnancies are in progress but preliminary results suggest no connexion between fetal damage and ECHO 9 infection.


Coagulase-negative staphylococci and micrococci in urinary tract infections. One hundred catalase-positive, coagulase-negative, Gram-positive cocci isolated in significant numbers from the urine of patients with urinary tract infections, provisionally subdivided by their sensitivity to nonoviocin, were classified according to a slightly model version of Baird-Parker's schemes (1965 and 1972). It appeared that strains of Micrococcus were nearly all of sub-group 3, and that these were important pathogens of young women presenting with urinary infections in general practice. All such strains were resistant to novobiocin. Strains of staphylococcus were heterogeneous, and were found principally in infections arising in hospital, among older prople. Most staphylococci were sensitive to novobiocin. It is suggested that it is easy and sufficiently accurate to separate staphylococci and micrococci isolated from cases of urinary tract infection on the basis of their sensitivity or resistance to novo-biocin. The distinction is useful because of its therapeutic and epidemiological significance.


Serological tests in the differentiation of staphylococcal and tuberculous bone disease. The haemagglutination test for antileucocidin is frequently positive in cases of bone tuberculosis in the absence of obvious staphylococcal infection. This test is therefore of little practical use in the differentiation of staphylococcal and tuberculous bone disease, and its use has been discontinued at the Royal National Orthopaedic Hospital. The antigamma haemolysin test in bone tuberculosis appears to give rise to few false positive results. Our observations confirm that the anti-alpha haemolysin and antigamma haemolysin tests used together reveal about 80 percent of cases of staphylococcal bone infection on first presentation or relapse.


Bilateral adrenal medullary hyperplasia: a clinicopathological entity. A 36-year-old white patient is described. He received treatment for hypertension and showed slightly increased excretion of 17-OHCS- and 17-ketosteroids but no increase in values for 3-methoxy-4-hydroxymandelic acid in the urine. He was admitted to hospital for a myocardial infarction, which was found to be situated in the anterior wall. During his stay in hospital a sudden increase in blood pressure occurred, together with a typical attach of perspiration, loss of consciousness, and ventricular fibrillation. The assay by 3-methoxy-4-hydroxymandelic acid now showed markedly increased amounts. A phaeochromocytoma was thought to be the most probably diagnosis, but now withstanding therapy the patient died from cerebral lesions. At necropsy a recent anteroseptal myocardial infarction and some minor lesions were found but no tumour and notably no phaechromocytoma, neither in the adrenals nor elsewhere. Using Dobbie's morphometric technique, as described by Munro Neville (1969), changes in the adrenals were demonstrated, which were considered to represent primary adrenal medullary hyperplasia. Criteria for the diagnosis of this syndrome are discussed. Until now it had been presumed to be present in a number of cases but never convincingly demonstrated.


Crosslink in bone collagen in Paget's disease. The crosslink in bone collagen was analysed in specimens of bone obtained at necropsy from cases of Paget's disease and compared with normal bone collagen of the same age. The specimens were stored at -20 degrees C before analysis. The predominant crosslink in a normal bone collagen was hydroxylysinohydroxynorleucine (di OH-LNL) (F1), which was designated syndesine in the past; another fraction, hydroxylysinorleucine (HLNL) (F2), musch less prominent than di OH-LNL, was also noted in a normal bone collagen. Both fractions were reduced in bone tissue of advancing age. The peak corresponding to HLNL was considerably increased in Paget's disease. This abnormality was constantly seen in specimens of bone from cases of Paget's disease, but the significance of the finging could not be assessed from the present investigation. Calcitonin has been shown to produce complete remission in Paget's disease and the crosslink pattern was found to be normal in specimens examined froma calcitonin-treated patient. This shows that calcitonin has some effect on the metabolism of collagen and a normal crosslink in such a situation lends support to this idea.


A new cause of haemolytic anaemia in the newborn. A description of an unstable fetal haemoglobin: F Poole, alpha2-G-gamma2 130 trptophan yeilds glycine. In a newborn twin with haemolytic anaemia an unstable fetal haemoglobin was found to be the cause. The anaemia improved spontaneously with the disappearance of the fetal haemoglobin. The new Hb F (alpha2gamma2) variant was shown to have a glycine at position 130 of the 146 residues of the gamma chain. This portion is inside the globin molecule and in all known normal globins it is occupied by a residue with a bulky hydrophobic side chain. Its replacement by glycine which has no side chain would be expected to cause instability. The human gamma-chains may either have a glycine or an alanine at position 136. Evidence is brought forward to suggest that in the abnormal chain position 136 is occupied by glycine.


Unusual megaloblastic anaemia wiht multinucleate erythroblasts: two cases with septicaemia and acute renal failure. The case histories and blood pictures of two patients who had cardiac lesions, septicaemia, and renal failure and terminally developed a leucoerythroblastic anaemia with megloblastic features associated with multinucleate erythroblasts, are described. Though folate deficiency may have made a minor contribution to the blood abnormalities, it is considered that some other disturbance in erythropoiesis was responsible for the bizarre blood and bone marrow changes in these patients. Similar cases reported in the earlier literature are reviewed.


In vitro antibacterial activity of amikacin, a new aminoglycoside, against clinical bacterial isolates from children. Four hundred and fifty-eight clinical bacterial isolates from a children's hospital were examined for antibiotic susceptibility to amikacin (BB-KS) in comparison with a number of other antibiotics by the disk diffusion and agar dilution methods. The wide spectrum of activity of amikacin against Gram-negative bacteria was confirmed; it included E. coli, Proteus species, Enterobacter species, and Pseudomonas aeruginosa. Staphylococci were highly sensitive, but other Gram-positive bacteria tested were resistant. A disk zone diameter of 10 mm effectively separated resistant form sensitive bacteria in a standard disk diffusion test.


The effect of pharmacologic doses of steroids on atrioventricular conduction in man. His bundle electrograms were performed in ten patients with organic heart disease. Recordings were made at various rates using right atrial pacing. Two grams of methylprednisolone were infused intravenously over a 20-minute period. The PI-A, A-H, H-Q, and H-S intervals were obtained before and up to 1 hour after the infusion of the steroid. The maximum effect was seen at 1 hour. All patients showed a significant prolongation in the A-H interval with negligible effects on other intervals. At the atrial pacing rate of 120 beats/minute, the average A-H interval increased from control of 119 milliseconds to 159 milliseconds after steroids (P smaller than 0.01). Second-degree heart block occurred at lower pacing rates after steroids in six patients as compared with the control state. The postsuppressive sinoatrial node recovery time was increased in seven cases after steroid infusion. Pharmacologic doses of steroids can impair conduction through the atrioventricular node.


Naproxen metabolism in man.

Naproxen metabolism in man. In summary, naproxen is an acidic, highly albumin-bound drug. After oral administration, it is promptly and fully absorbed. The mean half-life of the drug in man is 13 hours, close to ideal for twice-daily administration. The only metabolite detected in man is the 6-desmethyl compound. Both it and naproxen itself are excreted in the urine, primarily as conjugates. The kinetics of naproxen binding to serum albumin tend to limit attainable plasma levels. They increase little if the dose is increased beyond 500 mg twice daily, since greater concentrations are rapidly cleared. Albumin binding and competitive displacement are also responsible for potential interactions of naproxen with drugs such as warfarin, sulfonylureas, and aspirin. Experience thus far does not indicate that any of the potential interactions are clinically meaningful.


Clinical evaluation of d-2-(6'-methoxy-2'-naphthyl)propionic acid (naproxen) in rheumatic conditions. A double-blind, crossover trial with 40 patients suffering from classic or definite rheumatoid arthritis was undertaken to obtain a clinical evaluation of naproxen in the disease. Each patient received either naproxen (500 mg/day) or placebo for 20 days and was then switched to the other compound for 20 days. For final evaluation, 22 cases were eliminated for various reasons, leaving 18 patients: seven cases of classical rheumatoid arthritis and 11 cases of definite rheumatoid arthritis. Optimum or very good efficacy of the active compound was present in 66.6 per cent of the cases versus 11.1 per cent of the placebo group. Doubtful or nil activity was observed in 66.6 per cent of the cases receiving placebo versus 16.6 per cent for naproxen. In addition, of the 22 cases that were eliminated from the final evaluation, but which were seen for the first ten-day follow-up visit while taking the active drug, optimum or very good efficacy was seen in 13. Therefore, this trial showed that naproxen achieved antiinflammatory and analgesic activity far superior to that observed with placebo.


New approaches to trials of antirheumatic drugs in rheumatoid arthritis. While drug trials can be performed in different designs and sequences, the paramount consideration is careful definition of limited trial objectives such as efficacy, tolerance, and safety. Efficacy variables might include tests for analgesic effect, antiinflammatory activity, or specific antirheumatic action. Unless a drug has remarkable therapeutic effect, double-blind comparison with placebo or a standard reference drug such as aspirin is mandatory. Random assignment of patients to treatment groups must be assured and patients should not receive other antirheumatic drugs unless the trial is specifically designed to study drug interactions. Drug dosage poses a problem because average doses are usually employed. Compliance is monitored by several techniques including measurement of blood levels of test drugs in all study patients. Multicenter trials have several advantages: (1) averaging patient selection, (2) minimizing observer bias, (3) shortening time of trial by rapid entry of patients, (4) entering large number of patients, which can permit examination of "responders" versus "non-responders." Data analysis should employ proper statistical evaluations (nonparametric tests for nonnormally distributed variables). Duration of study period, trials to evaluate drug interactions, and variables used to measure drug effects will be discussed.


Anatomical evidence for cone and rod-like receptors in the gray squirrel, ground squirrel, and prairie dog retinas. In the gray squirrel (Sciurus carolinensis), the prairie dog (Cynomys ludovicianus), and the Mexican and 13-line ground squirrels (Citellus mexicanus and C. tridecemlineatus) there exist two distinct classes of photo-receptors that have cone-like and rod-like anatomical features respectively. These two receptor classes were previously known to exist in the gray squirrel, but only the cone-like (C) receptor had been observed in the other species. We have now found small numbers of rod-like (R) receptors in the other species as well. R-receptors comprise about 40% of the receptors in the gray squirrel, 10% of the receptors in the prairie dog, and 4-5% of the receptors in the two species of ground squirrel. This paper describes certain light and electron microscopic features of these two receptor classes including their synaptic connections with second-order cells and with each other. We find that the C-receptor has a morphology and synaptic organization characteristic of other mammalian cones. However, the R-receptor differs from other mammalian rods in certain morphological respects, and its synaptic organization has both cone and rod characteristics as well as some unusual features.


Electrophysiological evidence for rod-like receptors in the gray squirrel, ground squirrel and prairie dog retinas. Spectral sensitivities of the gray squirrel, Mexican and 13-line ground squirrel and prairie dog were determined by electroretinography under both dark- and light-adapted conditions. The dark-adapted spectral sensitivity function obtained from intact eyes of these species peaks between 515-525 nm; however, when corrected for lens absorption or recorded from the lensless eye, it peaks near 500 nm and closely matches in shape a rhodopsin nomogram curve (lambda max equals 502 nm). Upon light adaptation all these retinas become relatively more sensitive to long-wave stimuli (i.e., they show a small Purkinje shift). The light-adapted spectral sensitivity function is broader than that obtained from the dark-adapted eye, especially toward the longer wavelengths. Weconclude that in all these species the dark-adapted spectral sensitivity is mediated by a single, rhodopsin-like photopigment and that light-adapted sensitivity is mediated by two (or more) photopigments.


Nerve fiber hypertrophy in posterior tibial nerves of mice in response to voluntary running activity during aging. Three-month-old male C57BL/10 mice were exercised by voluntary running activity in vertically revolving wheels for two hours each day until 24 months of age. Activity scores were recorded each day and the animals were regularly weighed and inspected for abnormalities. Control animals were similarly treated except that the activity wheels were immobilized. At the end of the exercise period, survival was 84% for the exercise group and 64% for the controls. Light microscopic examination of the posterior tibial nerve of the surviving animals showed a significant fiber hypertrophy in response to the exercise. The number of myelinated fibers in nerves from exercised animals did not differ from those of the controls. On the basis of these data, it is suggested that prolonged exercise does not prevent the loss of peripheral nerve fibers associated with age but rather, may exert an effect on the nervous system by modifying the surviving cells.


Projections from the nucleus and tractus solitarius in the cat. After lesions in the nucleus of the tractus solitarius (NTS) in cats and kittens, the termination of degenerating fibers was localized using the Nauta and the Fink-Heimer techniques. The distribution of degenerating fibers was compared with that seen after lesions of the dorsal nucleus of the vagus (DNV) and after section of the ninth and tenth cranial nerves. The projection from the NTS is to the nucleus ambiguus (A), the other divisions of the NTS including the medial NTS and the ventrolateral NTS, and DNV, the medial reticular formation ventral to the NTS (probably the paramedian reticular nucleus), the nucleus intercalatus (INC), and the intermediate nucleus (INT). The probable functional significance of projections from the NTS to these medullary nuclei is discussed in relation to pathways of cardiovascular reflexes. Of particular note is the projection to the INT which may be part of a descending pathway to spinal cardiovascular neurons in the intermediolateral horn.


Behavioral and morphological evidence for binocular competition in the postnatal development of the dog's visual system. Two normally-reared dogs and five dogs reared with monocular eyelid closure were studied. The two normal dogs and three of the deprived dogs were tested with a perimetry technique for the extent of behavioral visual field, and all of the dogs were studied histologically to determine the size of cell somata in the lateral geniculate nucleus. Behaviorally, the normal dogs saw with each eye approximately from 120 degrees ipsilateral to 30 degrees contralateral. The deprived dogs had a normal field of view for the non-deprived eye, but with the deprived eye they saw only in the monocular segment (i.e., approximately 120 degrees to 30 degrees ipsilateral). Histologically, geniculate cells in the monocular segment of deprived dogs were of normal size. In the deprived laminae of the binocular segment, however, cells averaged about two-thirds normal size, and in non-deprived laminae of this segment, neurons were hypertrophied. The hypertrophy was greater for cells in lamina A (40%) than for those in lamina A1 (17%). These data indicate that in monocularly deprived dogs, the monocular segment of the visual system develops normally, but the binocular segment does not. Therefore, we conclude that binocular competition operates in the developing dog's visual system much as it does in the cat's.


Scanning electron microscopy of epiplexus macrophages (Kolmer cells) in the dog. Young dogs (6-14 weeks) were perfused with buffered aldehydes by standard techniques. The inferior medullary velum and tela choroidea were removed intact from the fourth ventricle, post-osmicated, dehydrated, critical point dried, coated with palladium-gold and examined in a Cambridge Stereoscan S4 scanning electron microscope. Selected samples after thorough scanning were routinely prepared for transmission electron microscopy (TEM). This study depicts numerous epiplexus (Kolmer cell) macrophages that exhibit extreme polymorphism. Because of the pleomorphic nature of these cells and their processes, classification based on external morphology is not practical. TEM shows their internal structure to be that of a macrophage. Bleb-like structures and bulbous projections appear to emerge from certain ependymal cell surfaces which seem to be completely or partially devoid of cilia.


Late ultrastructural changes in neuronal mitochondria after lonizing radiation of the brain. Brain tissue was examined for morphological changes at 12 and 16 months after focal irradiation of the brain in female mice. Irradiation was performed with deuteron beams derived from the 60-inch Brookhaven cyclotron at a rate of 1925 rad second -minus 1 though an anti-Bragg device which produced uniform exposure. Experimental animals received a dose of 10,000 rad, covering a 9 by 5 mm area over the skull and extending into the brain from a depth of about 2 mm. An additional group of animals served as sham-irradiated controls. Histological studies revealed extensive cell loss, vacuolation, and prominent vascular changes in irradiated regions of the brain at 16 months post-irradiation. Ultrastructural examination of brain tissue at 12 and 16 months after irradiation revealed the presence of unusual elongated mitochondria with parallel arrays of cristae. Altered mitochondria were more prevalent at the longer post-irradiation interval.


On the absence of a rubrothalamic projection in the monkey with observations on some ascending mesencephalic projections. In order to determine whether there is a rubrothalamic projection in the rhesus monkey, the ascending degeneration resulting from electrolytic lesions made in the red nucleus and adjacent mesencephalon in animals surviving at least one year after bilateral interruption of the superior cerebellar peduncles (PCS) was studied by means of the Fink-Heimer technique. In a necessary preliminary step it was shown that virtually all of the degeneration disappeared from the thalamus within twelve months after PCS interruption so that degeneration resulting from the subsequent electrolytic mesencephalic lesions could be attributed to interruption of non-cerebellar ascending fibres. The results show that degeneration was present in the thalamus following the electrolyte mesencephalic-diencephalic lesions but it could be accounted for on the basis of damage either to residual PCS fibres, to somatosensory pathways, to intrathalamic connections or to cell groups or projection fibres of the reticular formation, substantia nigra or globus pallidus. It is concluded that there is no direct rubrothalamic projection in the monkey and, in particular, no evidence of a projection from the red nucleus to the ventral lateral or ventral anterior thalamic nuclei. The results also indicate that the mesencephalic reticular formation is the main source of ascending afferents to the nucelus reticularis thalami. Some observations were made concerning nigrostriatal and nigrothalamic projections. Retrograde cell changes resulting from unilateral lesions made caudal to the red nucleus were studied in three animals. The observed cell changes are interpreted as being consistent with the conclusion that there is no rubrothalamic projection.


Effects of moderate heat and milk yield on plasma thyroxine in cattle. The effects of milk yield (lactational intensity) and short (18 h) moderate heat exposure (30 C) on plasma thyroxine were studies in spring (March) and fall (October) in the University of Missouri dairy herd. Spring and fall thyroxine did not differ at thermoneutral temperature of 15 C. The relatively short moderate heat exposure had no effect within production groups either in the spring or fall sampling. As stage of lactation progressed, thyroxine also increased. The effect of stage of gestation was an elevation in the first trimester (compared to nonbred) that progressed into the second and third trimesters. In both spring and fall (15 C), the high production group (adjusted and unadjusted) had lower plasma thyroxine compared with middle and low production groups, while no difference in adjusted means was significant between middle and low production groups. Correlations were --.51 between plasma thyroxine and lactational intensity in both spring and fall. The short exposure to moderately high environmental temperature intensified the relationship of lowered plasma thyroxine in hibh producing cows, and thyroxine was negatively correlated (--.63 and --.64) with lactational intensity. Because total plasma thyroxine is inversely related to lactational intensity, studies are warranted to quantitate free hormonal concentrations and utilization by dairy cattle with varying productivity.


Feeding and temperature changes in sheep following injections of barbiturates, Ca-++, or Mg-++ into the lateral, third, or fourth ventricle or cerebral aqueduct. Eleven sheep were prepared with cannula guides directed toward four areas within the ventricular system to determine effective sites of action of chemicals which when injected into the cerebrospinal fluid produce changes in feeding behavior and temperature regulation. Pentobarbital, barbital, calcium chloride, and magnesium chloride elicited feeding in sheep when injected into the third ventricle or into the cerebral aqueduct; however, feeding response was less after injections into the latter. Pentobarbital and magnesium chloride elicited an increase in body temperature when injected into the third ventricle but not when injected into the cerebral aqueduct. Perfusions (push-pull) of the lateral and third ventricles with calcium chloride and magnesium chloride solutions (50 mM) resulted in feeding while similar perfusions of the fourth ventricle resulted in no response. Responses to lateral and third ventricular injections presumably involved effects on both anterior and posterior hypothalamic areas while injections into the cerebral aqueduct, due to the caudal flux of the cerebrospinal fluid, may have affected primarily only the posterior hypothalamus and more caudal structures. The feeding response probably resulted from depression of neural fibers which inhibit feeding.


Adverse effect of excess methionine or methionine hydroxy analog on feed consumption in cattle. The toxicity of DL-methionine and methionine hydroxy analog infused into the rumen or abomasum was gauged by relative feed consumption. A continuous intraruminal infustion of at least 3 days' duration of DL-methionine equalent to about 2.5% or more of dietary dry matter intake was required to reach a toxic amount. This was approximately four times the amount necessary when it was infused into the abomasum. Methionine hydroxy analog equalent to about 1% or more of dietary dry matter intake was toxic when infused into either rumen or abomasum. This is in large excess of suggested amounts of analog supplementation. Reduced palatability is likely to occur in advance of reduced intake due to toxicity.


Effect of thyroid status and thiocyanate on absorption and excretion of iodine by cattle. Effects of throidectomy or iodine-131, thyroprotein feeding, and thiocyanate dosing on radioiodine metabolism in the bovine were studied in 34 animals. Two thyroidectomized calves excreted 44% more radioiodine in urine and 38% less in feces than two thyroid-tact calves. Oral thiocyanate increased urinary radioiodine 32% in throidectomized and 46% in intact calves while reducing fecal radioiodine 48% in throidectomize and 11% in intact calves. Urninary radioiodine clearance of two heifers was increased 52% by thiocyanate, but urine flow was not affected. Percentages of radioiodine doses cycled through the abomasum daily and recovered from digestive tracts at slaughter, respectively, were: 12 thyroid-intact cows, 468 and 77; two intact cows fed 10 g sodium thiocyanate daily,64 and 41; 10 thyroid-damagedcows, 506 and 149; and four thyroid-damaged cows fed 8 g thyroprotein daily, 372 and 93. Thyroid damage had little effect on gastric radioiodine secretion but increased total digestive tract radioiodine because of greater volume of tract contents. Inhibition of gastric radioiodine secretion by thiocyanate reduced the digestive tract radioiodine pool. The digestive tract iodine pool may conserve iodine by reducing loss in urine.


Modified fluorometric determination of vitamin A in milk. A modified fluorometric procedure for determination of vitamin A in milk was developed to provide rapid analysis of large numbers to samples.. Saponification and a single extraction in a reaction vessel without transfer provided simplicity and standardization. Time and temperature of saponification and time of extraction were studied. Fifteen replicates of four different milks gave standard deviations of .71, .82, 1.26, and .71 on samples with 29, 26, 38, and 26 mug retinol per 100 ml. Recovery of added vitamin A in six amounts in two experiments gave ranges of recovery of 96.0 to104.0 and 95.2 to 105.3% with average recoveries of 100.0 and 99.9%.


Detection of rapidly labeled phosphatidic acid in lactating mammary gland of the intact rat. Within 10 min following intravenous injections of phosphorus-32 labeled phosphoric acid into lactating rats, an intensely labeled pool of phosphatidic acid could be demonstarated in the mammary tissue. This finding provides supporting evidence for existence of the glycerol-3-phosphate pathway of milk triglyceride synthesis in the intact animal.


Pregastric esterase in milk sham fed to adult jersey steers. Pregastric esterase activity was detected in reconstituted nonfat milk sham fed from a nipple pail to two 4-yr-old rumen-fistualted steers. Lipolytic activity, determined in a medium containing 5% tri-n-butyrin, averaged 8.6 plus or minus .4 lipase units. Further assays, in which activitiy was measured by free fatty acids released from a condensed milk substrate, averaged 166.9 plus or minus 9.2 mumol. These values are higher than those noted for young calves, indicating that secretion of pregastric esterase may persist in cattle beyond calfhood. Esterase activity in one of the steers fed whole milk until he was 2 yr of age showed no marked residual effect of earlier intake of milk fat.


Orientation of cattle fetuses in utero in relation to stage of pregnancy. The orientation in utero of cattle fetuses was studied in 494 pregnant cows (478 singly pregnany; 16 twin pregnant). Fetuses were in anterior presentation if the head was oriented toward the cervix and in posterior presentation if the head was oriented toward the uterotubal junction. Data were considered for 10 day stages of gestation (Day 40 to 170) and for 15 day stages (Day 171 to 280). Before 100 days and between 101 and 200 days of pregnancy the proportion of fetuses in anterior presentation approximated 50%. After 201 days of pregnancy 82.7% of fetuses were in anterior presentation, and orientation was different (x-2 equals 16.49:1 df) from random (50:50). After 216 days all fetuses were in anterior presentation. Data from twin pregnancies were too few to be conclusive, but no trends were dissimilar from those in singly pregnant cows. Anterior presentation of fetuses is assumed not later than 216 days of gestation in normal pregnancies.


Evaluation of protein nutrition by metabolizable protein and urea fermentation potential. Metabolizable protein and selected metabolizable amino acid requirements for lactating cows were described, and tentative values were established for differnt yields of milk.A new expression"urea fermentation potential of feeds," describes urea use in lactation rations for partial satisfaction of protein and amino acid requirements. Tentative urea fermentation values were established for the more common cattle feedstuffs. Four lactation rations were formulated with different fermentation values to illustrate the variable feeding value of urea in satisfying amino acid requirements at different yields of lactation. Urea had the highest feeding value in lower-protein rations when fed to cows with medium to low yields of milk.Conversely, urea, by the metabolizable protein system, had little or no feeding value in lactation rations having more than about12% protein on a dry matter basis or in rations supporting lactations in excess of 25 to 30 kg of milk per cow per day.


Triiodothyronine turnover in hospitalized psychogeriatric patients. In a group of 12 hospitalized psychogeriatric patients, the fractional triiodothyronine (T3) turnover rate was significantly higher than in healthy control subjects of the same age, whereas the thyroxine (T4) turnover rate and other aspects of pituitary-thyroid function were virtually similar in both groups.  Despite the presence of manifestations of sympathetic overactivity or hypermetabolism, the patients did not have true hyperthyroidism, as verified by the laboratory findings and the results of antithyroid treatment.  The increases T3 turnover in aged hospitalized patients with brain disorders may be a compensatory mechanism which develops under these particular circumstances in order to maintain neurohormonal homeostasis.  An alternate possibility is that the increased T3 turnover is secondary to hyperkinesis.


Improvement of physical function after stroke: surgical and orthotic management. Initial and subsequent programs for the orthotic and surgical management of the post-stroke patient are outlined, particularly with regard to impairmant of the lower extremities in hemiplegic patients.  New developmentsin functional electrical stimulation are described.


Communication for the aphasic stroke patient: assessment and therapy. Loss of communicative ability is one of the most devastating handicaps associated with stroke.  The goals of therapy require continuous adjustment.  Early ambulation facilitates breathing, chewing and swallowing, which are important factors in voice control.  Hearing and vision should also receive concentrated attention.  Formal speech therapy should begin when the patient shows an interest in regaining speech.  Even before that, however, family members and friends can be of great help in laying the foundation for a good prognosis.


Changes in elderly welfare hotel residents during a one-year period. After a one-year interval, a structured interview designed to assess the quality of life was again conducted with most of the tenants in a single-room occupancy hotel in New York City. Comparisons was made between the two sets of findings. During the year, a program had been in effect to provide social, psychiatric, recreational, medical and other services to all the tenants at the hotel. Of the original 181 interviewees, 100 completed the second interview. Statistically significant changes occurred in 9 of the 35 variables assessed for the one-year period. There was significant improvement in the self-care index, but some negative mood changes were also found. The subgroup of identified alcholics showed the most positive improvements of any of the subgroups.


Day care services: an alternative to institutional care. The day care program at St. Camillus Nursing Home in Syracuse, New York is described.  The growth rate of the program,, the observed benefits to the participants, and acceptance by their family members indicate its value to the community.  The admission criteria are well defined and non-restrictive, and there is a wide scope of services.  However, a greater number of participants and expansion of the services would be feasible if Medicare patients could be included in the program besides the present Medicaid and private physician referrals.  Such reimbursement should be provided for the sake of participants and their families, as well as for the economics of the total health structure.  This would open the doors for day care programs in many other communities across the nation.


Auditory and visual memory losses in aging populations. Seventy-four men and women (age range, 44-77 years) were tested for short-term auditory and visual memory as part of a larger series of memory and cognitive function tests.  All test scores for visual memory, including facial photograph recognition when a sequence requirement was adhered to, showed a significant decline (p smaller than .05) in a comparison of subjects aged 44-54 and subjects aged 55-64.  This decline was not observed with the two tests of auditory memory.  Thus the data indicate that short-term visual memory may be more susceptible to aging than is auditory memory.


Morphology and development of Philometra cylindracea (Ward and Magath, 1916) (Nematoda: Philometridae). A description of the male and a redescription of the female of philometra cylindracea, a parasite of yellow perch (Perca flavescens), are presented. Philometra cylindracea has a one-year development cycle starting as infective larvae in June and becoming mature, larvigerous worms at the end of next June. Cyclops vernalis was found to be a suitable intermediate host under experimental conditions;


Studies on Brugia pahangi 9. The longevity of microfilariae transfused from cat to cat. Microfilariae in whole uncentrifuged cat blood were transfused from infected to normal cats. The recipient cats were bled frequently and the life-span of the microfilariae in the peripheral circulation was determined; The life-span on microfilariae in different cats was ver variable. Microfilariae were detected fro 2-136 days after inoculation. In immunized cats microfilariae could not be detected 18 hours after inoculation. Any attempt to concentrate or clean the microfilariae caused them to disappear from the circulation more quickly.


Studies on Onchocerca cervicalis Railliet and Henry 1910: V. The development of Onchocerca cervicalis larvae in the vectors. Colonies of Culicoides nubeculosus and C; variipennis were established at Winches Farm Field Station, St. Abans. Both species of midge were found to be susceptible to infection with Onchocerca cervicalis microfilariae. Infection was achieved either by engorging through a chick skin membrane on a suspension of microfilariae in blood, or by feeding upon a horse naturally infected with O. cervicalis microfilariae. A large proportion of the microfilariae ingested by the midges penetrated into the haemocoel and migrated first to the thoracic flight muscles and then to the head. Larval development occurred during migration and 3rd stage (infective) larvae of O. cervicalis reached the head of infected midges (kept at 23 degrees C.) 14-15 days after engorgement.