Collaborative study of the colorimetric determination of zirconium in antiperspirant aerosols.

A previously published method for determining zirconium in antiperspirant aerosols was collaboratively studied by 7 laboratories. The method consists of 2 procedures: a rapid dilution procedure for soluble zirconium compounds or a lengthier fusion procedure for total zirconium (soluble and insoluble compounds), followed by colorimetric determination. The collaborators were asked to perform the following: Spiking materials representing 4 levels of soluble zirconium were added to weighed portions of a zirconium-free cream base concentrate and the portions were assayed by the dilution procedure. Spiking materials representing 4 levels of zirconium in either the soluble or the insoluble form (or as a mixture) were also added to portions of the same concentrate and these portions were assayed by the fusion procedure. They were also asked to concentrate and assay, by both procedured, 2 cans each of 2 commercial aerosol antiperspirants containing zirconyl hydroxychloride. The average per cent recoveries and standard deviations for spiked samples were 99.8-100.2 and 1.69-2.71, respectively, for soluble compounds determined by the dilution procedure, and 93.8-97.4 and 3.09-4.78, respectively, for soluble and/or insoluble compounds determined by the fusion procedure. The average per cent zirconium fouund by the dilution procedure in the 2 commercial aerosol products was 0.751 and 0.792, respectively,with coefficients of variation of 2.94 and 2.53%, respectively. Insufficient collaborative results were received for the fusion procedure for statistical evaluation. The dilution procedure for statistical evaluation. The dilution procedure has been adopted as official first action.


Separation and analysis of the pyrethrins by combined gas-liquid chromatography-chemical ionization mass spectrometry.

Pyrethrins, the 6 naturally occurring insecticidal esters of pyrethrum extract, were analyzed by combined gas-liquid chromatography-chemical ionization mass spectrometry. Separation was best on an OV-25 column with temperature programming; The chemical ionization mass spectra for the 6 esters as well as for the thermally isomerized pyrethrins I and II are reported and discussed. Using selective ion monitoring, a lower limit of detectability of all 6 esters was 114 ng of total extract injected on the column.


Rapid preparation of micro sample and gas-liquid chromatographic determination of methoxychlor residues in animal tissues and water.

Methods are described for analyses of methoxychlor (2,2-bis(p-methoxyphenyl)-1,1,1-trichloroethane) in tissues of fish and invertebrate animals and in water samples. These micro methods offer economy in solvents and materials, and reduce health and fire hazards. Furthermore, the methods sufficiently reduce sample weights to allow analyses of small animals (mayflies) or animal organs. Samples are extracted in a ball-mill with n-hexane, and lipids are removed from fatty samples by freezeout. Small Florisil columns give final lipid cleanup and partial separation of methoxychlor from interfering materials. Methoxychlor is determined on a short gas-liquid chromatographic column (retention time 2.2 min). Animal tissue samples as small as 0.1 g and water samples of 5 ml can be analyzed at sensitivities of 10 and 1 ppb, respectively. Methoxychlor recoveries were 84-101% (fish and crab tissue), 92-100% (cod liver oil), and 98-107% (water) over a concentration range of 0.-10 ppm. Results obtained for fish tissue by using micro procedures agreed to within 20% of results reported by an independent laboratory using an established method.


Quantitative determination of thiourea in citrus fruits.

A quantitative method for thiourea determination in orange peels is proposed, with direct reflectance spectrometric measurements on chromatoplates. Thiourea is separated on a silica gel plate with methanol-chloroform (10 + 90), and the spots are characterized with 2,6-dichloroquinone chloroimide; this colorimetric reaction is unstable, so thiourea is quantitated on the chromatogram by direct ultraviolet reflectance spectrometric measurements at 240 nm. Comparison between this method and the AOAC colorimetric method shows interferences and higher results in the colorimetric assay. By slightly modifying the extraction technique, such as purifying the extract on an alumina column, it is possible to decrease these interferences and to avoid erroneous results with the AOAC colorimetric method. For both methods, colorimetry in solution and reflectometry on chromatoplates, applied after the proposed extraction technique, the sensitivity is about 1 ppm and the reliabilities are similar.


Comparison of semiautomated and manual methods for the determination of thiamine in baby cereals and infant and dietary formulas.

Using a semiautomated method, the mean thiamine content of specific products ranged from 88 to 101% and 83 to 93% for baby cereals and infant and dietary formulas, respectively, of those obtained with the AOAC manual method. The best results were obtained when data for the semiautomated method were calculated from a standard curve obtained by using thiamine solutions which had been digested and hydrolyzed along with the samples.


Aflatoxin in Tunisian aleppo pine nuts.

Twenty-six of 50 Aleppo pine nuts samples collected throughout Tunisia showed relatively high levels of contamination by aflatoxin. Some samples contained as much as 2000 ppb aflatoxin B1, and very few contained less than 100 ppb. Total aflatoxins as high as 7550 ppb were found. A traditional pudding, widely consumed in Tunisia, which was prepared from contaminated nuts still contained more than 80% of the aflatoxin originally present in the nuts.


Radiology of airway foreign bodies in children.

Among 91 children with airway foreign bodies there were 10 with radiopaque foreign bodies. Seventy-four of the cases of non-opaque foreign bodies were unilateral. Seventeen had pulmonary consolidation or loss of volume and 33 had a unilateral hyperlucent lung. In 18 of the latter there was unilateral overinflation, but in 15 the hyperlucency was the result of pulmonary vasoconstriction. Twenty-three patients had normal routine inspiration radiographs; in 14 of these fluoroscopy or expiration films were obtained and air-trapping was demonstrated in 13. In twenty-three of the children the diagnosis was delayed. Fifteen of these had normal chest radiographs or unilateral hyperlucency alone. Since normal inspiration chest radiographs are frequently seen in cases of airway foreign bodies even when the diagnosis is delayed, it is strongly recommended that fluoroscopy or expiration films be obtained in any patient where the diagnosis is in doubt.


The variable roentgen appearance of traumatic diaphragmatic hernia.

Alteration of the diaphragmatic contour should be added to the list of radiographic signs of traumatic diaphragmatic hernia (TDH). Such changes may sometimes be appreciated prior to gross herniation of abdominal viscera into the hemithorax. Alterations of the hemidiaphragmatic contour are non-specific, but suggestive of TDH in the appropriate clinical setting.


Epidermoid cysts of the spleen.

In the two cases presented here, the sonographic findings were unique. At low gain settings the rounded masses appeared sonolucent and smooth walled. As the gain was increased, multiple internal echoes appeared close to the inner wall, indicating the thick and irregular wall lining. It is presumed that these echoes were produced by the trabeculae. It is felt that the sonographic findings in epidermoid cysts of the spleen may be diagnostic, obviating the need for arteriography.


Crossed, fused renal ectopia with severe hydronephrosis: angiographic diagnosis.

The authors describe two children with crossed, fused renal ectopia in whom severely damaged hydronephrotic ectopic kidneys were not shown by intravenous urography. Aortography confirmed the diagnosis in both patients. Aortography is of great value if a diseased ectopic kidney must be resected; demonstration of the vascular supply to both kidneys enables the surgeon to preserve all of the normal renal tissue.


Small nuclear RNA localization during mitosis. An electron microscope study.

The localization of small nuclear ribonucleic acids (snRNAs) during mitosis in Amoeba proteus was studied by high voltage (1,000 kV) electron microscope autoradiography. By suitable micromanipulations, the snRNA's, labeled with [3H]uridine, were made to be the only radioactive molecules in the cell and thus easy to follow autoradiographically. During interphase the snRNA label, which is almost exclusively nuclear, is distributed fairly uniformly through the nucleus with a slightly higher amount of label over chromatin than over nonchromatin areas. During prophase the snRNAs, which continue to be largely nuclear, become highly concentrated in the condensing chromosomes. At metapase, almost all of the snRNAs are cytoplasmic and essentially none are associated with the maximally condensed chromatin. Beginning in early anaphase, the snRNAs resume their association with the chromosomes, with the degree of association increasing throughout anaphase. Most of the snRNAs are back in the nuclei by telophase, but the intranuclear localization is hard to determine. We conclude that snRNAs have a great affinity for the partially condensed chromosomes of prophase and anaphase, but none for the maximally condensed chromosomes of metaphase. A minor amount of snRNA localizations in association with nucleoli and the nuclear  envelope are also reported. On the basis of these findings a role of snRNAs in genetic "reprogramming" or chromosome organization is proposed.


Spatial relationship of photosystem I, photosystem II, and the light-harvesting complex in chloroplast membranes.

We have previously demonstrated (Armond, P. A., C. J. Arntzen, J.-M. Briantais, and C. Vernotte. 1976. Arch. Biochem. Biophys. 175:54-63; and Davis, D. J., P. A. Armond, E. L. Gross, and C. J. Arntzen. 1976. Arch. Biochem. Biophys. 175:64-70) that pea seedlings which were exposed to intermittent illumination contained incompletely developed chloroplasts. These plastids were photosynthetically competent, but did not contain grana. We now demonstrate that the incompletely developed plastids have a smaller photosynthetic unit size; this is primarily due to the absence of a major light-harvesting pigment-protein complex which is present in the mature membranes. Upon exposure of intermittent-light seedlings to continuous white light for periods up to 48 h, a ligh-harvesting chlorophyll-protein complex was inserted into the chloroplast membrane with a concomitant appearance of grana stacks and an increase in photosynthetic unit size. Plastid membranes from plants grown under intermediate light were examined by freeze-fracture electron microscopy. The membrane particles on both the outer (PF) and inner (EF) leaflets of the thylakoid membrane were found to be randomly distributed. The particle density of the PF fracture face was approx. four times that of the EF fracture face. While only small changes in particle density were observed during the greening process under continuous light, major changes in particle size were noted, particularly in the EF particles of stacked regions (EFs) of the chloroplast membrane. Both the changes in particle size and an observed aggregation of the EF particles into the newly stacked regions of the membrane were correlated with the insertion of light-harvesting pigment-protein into the membrane. Evidence is presented for identification of the EF particles as the morphological equivalent of a "complete" photosystem II complex, consisting of a phosochemically active "core" complex surrounded by discrete aggregates of the light-harvesting pigment protein. A model demonstrating the spatial relationships of photosystem I, photosystem II,  and the light-harvesting complex in the chloroplast membrane is presented.


Basal lamina of embryonic salivary epithelia. Nature of glycosaminoglycan and organization of extracellular materials.

The ultrastructural organization and the composition of newly synthesized glycosaminoglycan (GAG) in the epithelial basal lamina of mouse embryo submandibular glands were assessed. The labeled GAG accumulating in the lamina is distinct from that in its tissue of origin, the epithelium, or from that in the surrounding mesenchyme. In the lamina, hyaluronic acid accounts for approximately 50% of the labeled GAG, chondroitin-4-sulfate is twice the chondroitin-6-sulfate, and there is a low proportion of chondroitin. This composition is constant regardless of whether the lamina is labeled by whole glands or, in the absence of mesenchyme, by isolated epithelia retaining a lamina and by isolated epithelia generating a lamina de novo. The results andicate that the labeled GAG are bona fide components of the lamina, and suggest that laminar GAG is deposited in units of constant composition. Ultrastructural observations following ruthenium red staining or tannic acid fixation extablish that the lamina is a highly ordered specialization of the basal cell surface. Discrete structures in macroperiodic arrays apparently attached to the plasmalemma are visualized. This organization is seen in intact glands and in the laminae produced by epithelia in the absence of mesenchyme or biological substrate. The data are interpreted as indicating that the basal lamina contains supramolecular complexes of hyaluronic acid and proteoglycan which are organized into an extracellular scaffolding which imposes structural form on the epithelium.


The electrolytic conductivity detector as an element-selective gas chromatographic detector.

The response and elemental selectivity of the electrolytic conductivity detector (E1CD) to nitrogen-, chlorine-, and sulfur-containing compounds has been investigated as a function of chemical structure, furnace chemistry conditions (i.e., reaction gas, furnace temperature, catalyst, and post-furnace chemical abstractors), and solubilization-and-ionization processes (electrolytic chemistry and electrolytic conductance). The "profiling" of detector response for the gas-liquid chromatographic-E1CD analysis of selected compounds under defined furnace chemistry reaction conditions and electrolytic chemistry included the determination of detector signal to noise ratio, peak tailing, and elemental selectivity. Detector response and conductivity phenomena are discussed in terms of gas-phase furnace chemistry reactions, post-furnace reaction or abstraction processes, and solution-phase ionization and neutralization processes occurring in the conductivity cell.


A microcomputer-directed mass spectrometer as a compound-selective detector for gas chromatography.

Determination and quantitation by mass spectrometry can be difficult for compounds in complex biological mixtures where chromatographic interferences are frequently encountered. A gas chromatographic-mass spectrometric system is described which utilizes reverse spectral search and retention time screening to provide a high degree of compound specificity. Computer control of instrument operation, and of data acquisition, analysis and printout allows technologist operators to obtain highly reliable, precise quantitative results using relatively crude sample preparation procedures and short chromatographic times.


Positive peak identification in liquid chromatography using absorbance ratioing with a variable-wavelength spectrophotometric detector.

It is frequently necessary to confirm the identification of component peaks isolated in high-performance liquid chromatograms. The UV spectrum of the pure compound is usually a very powerful signature for most compounds. For liquid chromatographic instruments that permit stop-flow operation, a simple approximation is obtained with a variable wavelength UV detector by determining the absorbance ratios at several specific wavelengths to characterize the compound. If the wavelengths are well chosen, these absorbance ratios provide a very specific and a very reliable technique for peak identification. The absorbance ratios are independent of the concentration of the compounds in the detector flow cell. Identity or purity of individual peaks can be confirmed when absorbance ratios are taken from the peaks of individually injected pure standards. Flow can be stopped several times on the leading and trailing edges of broad peaks, and ratios calculated. If the ratios are identical, the peak can be considered to be pure; if ratios differ, the presence of unresolved components can be suspected. Stop-flow ratioing can be performed during gradient elution: standards are injected under rapid elution conditions and the resulting ratios are compared with those of the peaks from the gradient run. Ratios are found to be identical for similar components, regardless of the differences in retention time, thus providing rapid identification of the compounds in the gradient chromatogram. Factors that influence the overall precision of the method are: ability to stop and re-start eluent flow without loss of chromagraphic efficiency, ability to obtain numerical absorbance data from the detector, the wavelength repeatability of the detector, and the requirement that the detector cell design allow slow interruptions without baseline upset.


The sampling and determination of halocarbons in ambient air using concentration on porous polymer.

The levels of halocarbons have been determined in rural air in central Michigan using a sampling procedure employing pre-concentration on a porous polymer. The samples were analyzed by gas chromatography (GC) with an electron capture detector. Both qualitative and quantitative confirmation of the results were achieved by GC-mass spectrometry. Trichlorofluoromethane, chloroform, 1,1,1-trichloroethane, carbon tetrachloride, trichloroethylene and perchloroethylene were determined in the range of 30-130 parts per trillion. These concentrations agree well with data obtained by others in Washington state and Ireland indicating even distribution of the halocarbons in these latitudes.


Epoxide-diol pathway in the metabolism of 5H-dibenzo[b,f]-azepine (iminostilbene).

5H-Dibenzol[b,f]azepine-10,11-epoxide and 10,11-dihydro-10,11-dihydroxy-5H-dibenzo[b,f]azepine were identified by gas chromatography-mass spectrometry in rat urine as the main biotransformation products in the metabolism of 5H-dibenzo[b,f]azepine (iminostilbene). The presence of these metabolites was confirmed in vitro by incubating iminostilbene with rat liver microsomal enzymes.


Gas chromatographic and mass fragmentographic assays of carcinogenic polycyclic hydrocarbon epoxide hydratase activity.

A specific and very sensitive procedure for the determination of epoxide hydratase activity in hepatic microsomes is described. Any polycyclic hydrocarbon epoxide can be used as a substrate; in this study, benzo(a)anthracene-5,6-oxide, benzo(a)pyrene-4,5-oxide and 3-methylcholanthrene-11,12-oxide were utilized. The corresponding trans-diols formed during incubation are separated and evaluated using either an electron-capture gas chromatographic method for the determination of their chloromethyldimethylsilylated derivatives or gas chromatographic-mass fragmentographic measurement of their trimethylsilylated derivatives. Concentrations as low as 1 ng per millilitre of incubation mixture can be estimated.


Thin-layer chromatography of chlorophylls and their derivatives on cellulose layers.

A method for the separation and identification of chlorophyll a and b, pheophytin a and b, pheophorbide a and b, chlorin e6, rhodin g7, and the corresponding chlorophyll a' and b' derivatives, as well as the saponification products of pheophorbide a and b, by thin-layer chromatography on commercial cellulose layers on the micro-scale has been developed. Two solvent systems were used: light petroleum (b.p.60-80 degrees)-pyridine (9:1, v/v) and n-heptane-pyridine (7:3, v/v). The former was suitable for chlorophylls, pheophytins and pheophorbides, and the latter for pheophorbides, chlorin, rhodin and their esters. The separation of the derivatives was good and no chemical alteration of the derivatives could be observed. The method is rapid and easy to use and is therefore suitable for checking the purity of derivatives during the preparation of chlorophylls and their derivatives.


Reversed-phase high-performance liquid chromatographic determination of tetracyclines in urine and plasma.

The high-performance liquid chromatographic separation and quantitative analysis of oxytetracycline, tetracycline, and chlortetracycline from urine and plasma were effected on an octadecylsilane reversed-phase packing. The calcium complexes of the tetracyclines were extracted from urine and plasma with ethylacetate and then reextracted into hydrochloric acid. Following the injection of the hydrochloric acid extracts onto the column, the individual tetracyclines were eluted isocratically and quantitated spectrophotometrically. Concentrations of less than 1 microng/ml in urine and 1.5 microng/ml in plasms were quantitatively determined with a relative standard deviation of less than 5%.


Stimulation of growth hormone secretion by desimipramin and chlorimipramin in man.

In twelve healthy male subjects 75 mg desimipramin (DMI) administered intramuscularly and 100 mg DMI given orally led to a prompt rise in serum growth hormone (GH) levels. The maximum level of serum GH was observed 60 min after the i.m. and 150 min after the oral administration of DMI. Chlorimipramin (CI) administered in the same manner and in the same dosages resulted in a significant increase in GH in only six out of twelve subjects. The maximum level was observed 60 min after the i.m. and 150 min after the oral administration of DMI. There was no change in the prolactin (PRL) levels after administration of DMI and CI.


The effect of sodium restriction and prostaglandin inhibition on the renin-angiotensin system in man.

To investigate the possible interrelationship between the renin-angiotensin and prostaglandin systems, two groups of normal men were evaluated under conditions of varied sodium intake and after indomethacin, an inhibitor of prostaglandin synthesis. Eight subjects were placed on a 200 mEq Na diet and given 45 min infusions of prostaglandin A1 (PGA1) at 0.075 microng/kg/min and angiotensin II at 10 ng/kg/min on separate mornings. PGA1 produced a significant rise in both plasma renin activity (PRA) and aldosterone. Angiotensin II caused a similar rise in aldosterone. The patients were then placed on a 10-20 mEq Na diet and the infusions repeated. PGA1 again induced a further increase in both PRA and aldosterone. Angiotensin II produced the expected increase in aldosterone while PRA decreased. Body weight and 24 h sodium excretion were not different from control days on either diet. When indomethacin was administered to patients on the low sodium diet, PRA fell significantly and there was an increased pressor responsiveness to angiotensin. In a separate group of 4 patients on a low salt intake, basal PRA fell significantly during a 4 day period of indomethacin administration and returned to control values within 48 h after discontinuing the drug. These studies suggest that PGA1 infusions stimulate renin release independently of sodium balance. Inhibition of prostaglandin synthesis lowers PRA and increases pressor responsiveness to angiotensin. The data provide further evidence that vasodepressor prostaglandins may play a role in renin release and blood pressure homeostasis.


The effects of ovine prolactin on water and electrolyte excretion in man are attributable to vasopressin contamination.

Prolactin is an important osmoregulatory hormone in several lower vertebrate species. The present study was undertaken to clarify the effects of prolactin, if any, on human renal function. Eight normal adult male subjects on a 150 mEq sodium (Na), 60 mEq potassium (K) diet for 5 days were studied during 12 h of oral water (H2O) loading on 2 consecutive days. On day 1, after a 6 h control period, a 1 ml normal saline placebo was given im; on day 2, 25 mg of ovine prolactin (OP) was substituted. The subjects were supine and received a constant infusion of Na and K. After OP, serum prolactin rose from 6.9+/-0.8 ng/ml to 15.0+/-2.5 ng/ml (P less than .01) at 1 h, 27.6+/-4.0 ng/ml (P less than .002) at 2 h, 33.1+/-4.3 ng/ml (P less than .001) at 3 h and remained elevated for the remaining 3 h of study. The ovine prolactin had 20-25% of the potency of human prolactin in the human prolactin radioimmunoassay system. In response to OP, free H2O clearance (CH2O) promptly decreased from 10.1 +/- .06 ml/min to 6.1 +/- .05 ml/min (P less than 0.1) at 1 h, to a nadir of 5.1+/-.3 ml/min (P less than .001) at 2 h, and returned to control levels by 4 h. CH2O was unchanged after placebo, and urinary Na and K excretion, creatinine and osmolar clearance (COSM), plasma Na, K, osmolality and aldosterone were unchanged after OP or placebo. Control plasma vasopressin was 1.0+/-0.1 micronU/ml and was not changed after prolactin (1.1+/-0.1 micronU/ml at 1 h, 1.1+/-0.1 micronU/ml at 2 h and 1.1+/-0.1 micronU/ml at 3 h). The ovine prolactin contained 2 micronU of immunoassayable vasopressin per microng of powder. Aqueous vasopressin, 50 mU (containing in 25 mg of ovine prolactin), produced a decrease in CH2O not significantly different from prolactin in 6 water loaded subjects. Four different subjects given 100 mg of OP had decreased CH2O from 8.3+/-0.3 to 2.7+/-0.7 ml/min at 1 h (P less than .001) and to 2.8+/-0.7 ml/min at 2 h (P less than .01). Control plasma osmolality was 301+/-4 mOsm/1 and decreased to a maximum of 288+/-5 mOsm/1 4 h after OP (P less than .001). After prolactin administration, plasma vasopressin rose from 0.44+/-0.15 to 0.80+/-0.41 micronU/ml (P =NS) at 1 h. The transient antidiuresis in response to ovine prolactin is due to contamination of the preparation with vasopressin. Prolactin does not acutely influence renal electrolyte excretion and probably does not influence water excretion in man.


Sleep-wake patterns of LH and testosterone release in prepubertal boys.

Ten prepubertal boys who ranged in age from 6 11/12 to 14 2/12 years were studied for 2 consecutive nights. The subjects went to sleep at their usual times and sleep patterns were monitered polygraphically. Each night blood samples were drawn every 30 min from 1800 to 0600 h and plasma LH and testosterone (T) levels were measured on each sample. During evening wakefulness the mean LH (range 2.8-5.1 mIU/ml) and T (range 31-116 pg/ml) levels were in the normal prepubertal range for each subject. In the 5 youngest subjects (age 6 11/12 to 10 8/12 years) the mean hormone levels during sleep were significantly higher than the wakeful levels in 2 of 9 and 0 of 9 study nights for LH and T, respectively. In contrast, in the older prepubertal boys (age 13 2/12 to 14 2/12 years) the mean levels during sleep were significantly higher than wakeful values during 8 of 9 and 5 of 9 study nights for the same respective hormones. These data suggest that in young prepubertal subjects the sleep related rises of LH and T are either absent or not discernible in the peripheral blood. The prepubertal pattern of sleep-entrained LH and T release may be seen in prepubertal boys approaching the time of puberty and these hormonal rhythms are antecedent to the physical changes of puberty.


The diabetogenic action of somatostatin in healthy subjects and in maturity onset diabetics.

To determine whether cyclic somatostatin (GH-RIH) interferes with glucose utilization and gluconeogenesis we studied levels of blood glucose (BG), immunoreactive insulin (IRI), immunoreactive glucagon (IRG) and of human growth hormone (GH) after iv glucose (330 mg/kg) and iv arginine (0.5 g/kg) in healthy subjects (n=8) and in maturity onset diabetics (n=8; fasting BG less than 200 mg/dl) both in the presence and in the absence of GH-RIH (500 microng/h iv). GH-RIH caused a reduction of glucose utilization in healthy subjects as shown by the decrease of the k-value from 2.08+/-0.22 (SE) % per min to 0.61+/-0.06 (SE) % per min (P less than 0.0005). No significant change of the glucose disappearance rate was observed in maturity onset diabetics by GH-RIH (kI=0.55+/-0.14 (SE) % per min; kII=0.42+/-0.03 (SE) % per min). The response of insulin to glucose was abolished by GH-RIH. The glucose induced suppression of IRG was in part significantly enhanced by GH-RIH in maturity onset diabetics (P less than 0.01). BG rises seen after iv arginine were increased by the administration of GH-RIH both in healthy subjects (P less than 0.001) and in maturity onset diabetics (P less than 0.05). Somatostatin abolished IRI and GH responses to arginine in both groups studied (P less than 0.001). IRG increases after arginine administration were diminished by GH-RIH in both groups (P less than 0.01). Our data demonstrate that GH-RIH impairs the iv carbohydrate tolerance in healthy subjects and facilities an increased hepatic glucose output upon administration of arginine both in controls and in maturity onset diabetics. We attribute the diabetogenic effect of somatostatin to suppression of IRI release rather than to changes in the IRG/IRI ratio in favor of IRG.


Characterization of a protein in mid-term human amniotic fluid which reacts in the somatomedin-C radioreceptor assay.

Amniotic fluid contains materials other than insulin which react in a somatomedin C radioreceptor assay using human placental membranes. The material in mid-gestational amniotic fluid which reacted with the somatomedin C radioreceptor assay eluted slightly after albumin from a Sephadex G-150 column equilibrated with 0.1M NH4HCO3. Neither boiling nor treatment of this fraction with 1% formic acid yielded small molecular weight somatomedin-like peptides. Separation of the somatomedin reactive material (Sm RM) from albumin was achieved by gel filtration through Ultrogel AcA44 in 3.1M NH4HCO3. The active product had an apparent molecular weight of 33,000 to 35,000 Daltons; its isoelectric point determined by focusing was between 4.1 and 5.1. The purified amniotic fluid protein displaced somatomedin C in the somatomedin C radioreceptor assay but did not compete with insulin in the insulin radioreceptor assay. Sm RM produced only a slight stimulation of thymidine uptake in human fibroblasts but was inactive in stimulating sulfate uptake in hypox rat costal cartilage. In human fibroblast cultures Sm RM inhibited the stimulation of thymidine uptake induced by human serum and by purified rat somatomedin. When Sm RM was added to the 125I somatomedin C, some of the radioactivity eluted from gel filtration at pH 8.6 was converted to a molecular weight complex of about 43,000. We conclude that the material which we have isolated from mid-gestational amniotic fluid is a protein which may bind somatomedin and make it unavailable to the somatomedin receptor of human placenta and human fibroblasts.


Evidence for an unidentified steroid in a child with apparent mineralocorticoid hypertension.

A unique syndrome in a three-year-old American Indian girl was characterized by signs and symptoms of mineralocorticoid excess in the absence of excessive secretion of any known sodium-retaining steroids. Hypertension and hypokalemic alkalosis were corrected by spironolactone or a low sodium diet. Plasma renin activity was suppressed but the secretion of aldosterone was undetectable and was not stimulated by salt depletion. There was no evidence of abnormal accumulation of aldosterone precursors and metabolism of a tracer dose of the hormone was normal. Secretion rates of cortisol, corticosterone, deoxycorticosterone, deoxycortisol and aldosterone were very low and did not increase normally with ACTH administration. However ACTH administration aggravated hypertension and hypokalemia. Dexamethasone did not improve hypertension. Despite low secretion of glucocorticoids and mineralocorticoids, the patient showed no addisonian features and survived severe illness. Secretion of a factor of adrenocortical origin was suggested by the exacerbation of the syndrome of ACTH. The unidentified factor appears to be both a potent glucocorticoid and mineralocorticoid.


Prolactin and growth hormone responses to psychological stress in normal and neurotic subjects.

In order to study the response of plasma prolactin (PRL) to acute psychological stress and to compare it with that of growth hormone (GH), the mirror drawing test (MDT) was performed in 20 normal controls (11 male, 9 female) and 22 neurotic patients (12 male, 10 female). Plasma PRL and GH were measured serially before, during and after the test. In controls, the test caused no significant change in plasma levels of either hormone. In neurotic males, the response of PRL to the test was not consistent, whereas, in neurotic females, plasma PRL level rose significantly following the test. Increase of GH, on the other hand, was apparent in the  neurotics of both sexes. The correlation between the responses of the two hormones in the neurotics was low and non-significant. The results indicate that although the psychoendocrine coping mechanism in the neurotics works less effectively for both PRL and GH, the two hormones may have different psychological correlates.


Immunoreactive glucagon (IRG) responses to intravenous glucose in prediabetes and diabetes among Pima Indians and normal Caucasians.

Immunoreactive glucagon (IRG) response to a 3 min iv infusion of 25 g glucose was examined in 7 nondiabetic Caucasians, 8 nondiabetic, 8 prediabetic and 16 diabetic Pima Indians to define the normal IRG response and to determine if abnormalities of IRG suppression occur in diabetic and prediabetic Pima Indians. Fasting IRG levels were similar in the 3 nondiabetic groups. In response to the glucose infusion the maximum percentage fall in plasma IRG concentration was similar in the normal Caucasians (37+/-4%) and the normal (42+/-2%) and prediabetic Indians (43+/-3%). In the diabetic Indians the relative fall was less at all sampling times than among the prediabetic or normal Indians. No evidence of any differences in IRG suppression in prediabetic and normal Indians or normal Caucasians was found. Without detectable change in insulin levels during the first 10 min following the glucose infusion, IRG levels in the diabetics fell but to a lesser degree than that in the other groups.


Adrenergic modulation of growth hormone secretion in acromegaly: alpha- and beta-adrenergic blockade produce qualitatively normal responses but no effect on L-dopa suppresion.

The serum GH response to oral L-Dopa during the separate infusions of saline, phentolamine and propranolol was exmined in 12 acromegalic patients. In six L-Dopa responsive patients, serum GH concentrations rose during propranolol infusions (and fell during phentolamine infusions as previously reported). There was no effect of propranolol or phentolamine on the fall in serum GH following oral L-Dopa in this group of patients. Thus, beta-adrenergic, as well as alpha-adrenergic, mechanisms are involved to the regulation of GH secretion in a qualitatively normal fashion in  some acromegalic patients. However, the qualitatively abnormal suppressive effect of L-Dopa on GH secretion seen in some acromegalic patients does not appear to be mediated through either alpha-adrenergic or beta-adrenergic mechanisms.


Seasonal variation in serum T3 and T4 levels in man.

In a group of 13 healthy male adults in the Netherlands, a seasonal variation in circulating serum thyroxine (T4) and triiodothyronine (T3) levels was found, inversely correlating with the seasonally altering environmental temperature. Lowest serum T4 and T3 levels were found in the summer.


Allescheria (Petriellidium) boydii sinusitis in a compromised host.

The first case of Allescheria (Petriellidium) boydii sinusitis is reported. The organism was isolated from the maxillary sinus in an elderly, diabetic, chronic alcoholic man on maintenance hemodialysis who developed a syndrome resembling mucormycosis. Infections with A. boydii are infrequent and are most commonly limited to Madura foot. In addition, several cases of pulmonary and central nervous system involvement have been described. There is no established therapy for A. boydii, since the published data on antimicrobial sensitivity are limited. Our organism was inhibited by 1.25 mg of amphotericin B per ml and 0.15 mg of miconazide per ml.


Schizophrenic cognitive dysfunction: a deficit in rule transfer.

This study examined conceptual rule learning (RL) deficit in male schizophrenic Ss categorized into three groups as defined by Whitaker Index of Schizophrenic Thinking (WIST). Ss were administered a conjunctive, disjunctive, conditional or biconditional rule learning task, WIST, and Shipley-Hartford Memory Scale. It was shown that: (a) the WIST reliably differentiates among three levels of thought disorder as reflected by a deficit in inter-problem transfer of rule learning; (b) certain WIST and Shipley parameters reliably predict RL performance; and (c) phenothiazine dosage levels show no influence on the WIST and no correlation with RL. The findings indicate that cognitive dysfunction in schizophrenics is evidenced by limited inductive reasoning, insufficient channel capacity for filtering out irrelevant information, and inability to gain from antecedent RL experience. Principal locus of schizophrenic thought disorder is examined within a stimulus encoding-information processing paradigm.


Differential effectiveness of informal group procedures in weight control.

This article is the latest in a series that deals with psychological factors connected with obesity and its management in women members of the TOPS ("Take Off Pounds Sensibly") organization. Successful weight losers have MMPI profiles that differ from those of non-losers, and both show "normalization" of MMPI profiles and improvement in weight control after 16 weeks of group therapy. The present investigation attempted to assess the effectiveness of different types of nonprofessional "therapy" (the interactions of members at local TOPS chapter meetings) in helping members to achieve greater weight control. Nineteen TOPS chapter meetings were rated on 18 scales descriptive of member interaction, leader behavior, stress on nutrition, exercise, psychological factors in weight control, group and individual attitudes toward each other and toward the TOPS organization, and the like. Twelve of the 18 scales showed significant interjudge reliability, and for 10 chapters on which complete data were available (N = 108) 5 of these 12 scales significantly differentiated relatively successful from unsuccessful chapters. Those 5 were "attitudinal" or "interactional" variables such as emotional concern and enthusiasm rather than "content" or "procedural" variables such as emphasis on diet or exercise or reinforcement procedures.


The wish to die and the wish to live in attempted suicides.

The internal struggle hypothesis of suicidal behavior suggests that suicidal individuals wish both to die and to live. To test this hypothesis, spearate self-ratings of the Wish to Die and the Wish to Live were obtained from 64 women and 42 men hospitalized for suicide attempts. The dependent variable was the severity of suicidal intent assessed by a quantitative instrument. The results indicate that 50% of the sample experienced internal debates over death and life, 40% wanted to die, and 9% wanted to live. Internal struggle over the issues of death and life was related to lower suicidal intent scores than a unidirectional motivation toward death. It also appeared that the actual magnitudes of death and life wishes were not as crucial to suicidal intent as the degree of congruence between them. However, two-way analysis of variance yielded only a significant Wish to Die main effect. The discussion centers on the heterogeneity of the sample's motivational stance and the therapeutic and empirical usefulness of the scales to identify ambivalent and monambivalent patients.


Prior event uncertainty reduction under two different levels of time uncertainty of foreperiod duration in schizophrenia.

Schizophrenic and alcoholic Ss judged stimulus durations of .50 and .55 seconds. Stimulus was 1, 3 or 5 dark dots and was preceded by variable foreperiod duration of 1, 3 or 5 seconds. Judgment of stimulus duration was found to be a monotonically increasing function of both foreperiod duration and numerosity of dots. When pitch of sound, which functioned as a warning signal, was correlated with numerosity of dots, the monotonic relation between numerosity of dots and estimation of stimulus duration was eliminated for alcoholics, but not for schizophrenics, only when foreperiod duration was constant from trial to trial. The effect of prior information as to numerosity of dots was negligible for both schizophrenics and alcoholics when foreperiod duration was variable from trial to trial.


Evidence for a dual-factor concept of psychopathological emotional deficit: anhedonia and sensation-seeking.

Correlations between measures of anhedonia and sensation-seeking were calculated in two psychiatric samples. The correlations indicated that, despite their conceptual similarity, the two represent different motivational deficits. Ther correlates appeared to indicate that sensation-seeking represents neurotic inhibition, while anhedonia reflects a separate motivational deficit apparently characteristic of process schizophrenics.


Now I lay me down for keeps: a study of adolescent suicide attempts.

From a nationwide study of 830 white, emotionally disturbed adolescents, ages 12 to 18, three samples were selected for study. One consisted of all boys (N = 31) and girls (N = 67) referred for treatment after suicide attempts. The second included those boys (N = 7) and girls (N = 22) referred for suicidal thoughts and threats, as well as suicide attempts. The third was comprised of those boys (N = 13) and girls (N = 12) referred for suicidal thoughts and threats, but who had made no known suicide attempts. Both self- and psychotherapist ratings on 1,250 variables were examined by comparing the endorsement rates for boys and girls in each criterion group separately with those of the remaining sample of distrubed adolescents who had not been referred for suicidal behavior. Our results confirm some past findings and introduce a large number of new correlates of adolescent suicidal behavior. They indicate that there is little difference between teenagers who attempt suicide and those who think about it or threaten it. The findings also highlight the necessity of studying the sexes separately.


The adult self expression scale: validation by the multitrait-multimethod procedure.

The present studies were designed to provide further validation of the Adult Self Expression Scale as a measure of assertive behavior for adults in general. Validation was approached by the Campbell and Fiske multitrait-multimethod procedure and was concerned with the convergent relationship of assertion as measured by the Scale with measures of dominance and abasement as well as the discriminant capability of the instrument in terms of its relationship to various types of aggression, both verbal and physical. A variety of self-report, peer-rating, and unobtrusive measures were obtained from four distinct samples: participants in avocational interest classes at a technical institute, adults enrolled in an evening course in counseling theories at a state university, psychiatric inpatients, and convicted male felons. The results indicated that the Adult Self Expression Scale exhibits moderately strong convergent validity and moderate discriminant validity. The utility of the scale as a measure of assertive behavior for use with adults in general was supported.


Psychological assessment of the burn patient.

Emotional and intellectual responses of 25 burn patients, 16 males and 9 females, were assessed with the MMPI and the six verbal subtests of the WAIS. These measures were administered upon hospital admission and 11 to 12 months after discharge. Data analysis entailed Hotelling's T2 tests for paired observations, paired t-tests and product-moment correlations. Results did not reveal the emotional and intellectual deterioration commonly reported in the literature. The composite group MMPI profiles were essentially normal at both administrations with significant pre-post increments on the L Scale, Scale 9 and Scale 0, p less than .05. Male patients did not show significant pre-post changes, while females showed a significant pre-post increment on Scale 0, p less than .05, which indicates increased social orientation and gregariousness. Patients as a group showed significant pre-post increments on the Information (p less than .05) and Digit Span (p less than .01) subtests of the WAIS. Males demonstrated more dramatic increases than did females. Discrepancies between these findings and those reported by other investigators are attributed to the use of young children as participants in other studies, the absence of discernible premorbid factors that have been associated with post-trauma adjustment difficulties in other investigations and possible differential effectiveness of psychological intervention during hospitalization. The WAIS and MMPI were found to be sensitive to the emotional and intellectual changes experienced by participants, which suggests their application to assess the psychological aspects of the burn patient's recovery.


Comparison of MMPI scores of pregnant women and female medical patients.

The MMPIs of 94 women who were in the first trimester of pregnancy were compared with the MMPIs of 1,690 female medical patients who were between 20 and 29 years old. Pregnant women obtained significantly lower scores on indices of subjective distress, somatic complaints, and general maladjustment. They obtained significantly higher scores on the Ego Strength scale, which reflects good psychological adjustment. The interpretation of Hooke and Marks (1962) that pregnancy is a period of good psychological adjustment and emotional health is supported.


Factor analysis of the items of the State-Trait Anxiety Inventory.

The present investigation was designed to determine by factor analysis the nature of the items that comprise the A-State and A-Trait scales of the State-Trait Anxiety Inventory. Three factors were identified. Factor I was defined exclusively by items from the A-State scale. The underlying dimension tapped by the scale was interpreted as state anxiety (how one feels at a particular moment in time); support thus was provided for Spielberger's A-State concept. Items from the A-Trait scale, however, identified two separate factors, neither of which was clearly consonant with Spielberger's concept of A-Trait. Factor II appeared to tap state anxiety according to how the individual generally feels or a typical level of state anxiety as remembered over an indefinite period of time. Factor III was interpreted as a measure of neuroticism.


Cross-cultural study of the factorial dimensions of the NOSIE.

The NOISE is a rating scale designed for use with long-stay schizophrenic patients with six scales derived from a series of factor analyses of data from American patients. The present paper reports an attempt to replicate these scales in a British setting. After factor analysis five NOSIE scales showed identical item content across the two cultures. In the British analysis the items of the Retardation scale were factorially complex so that the scale was not replicated. It was concluded that most of the NOSIE was cross-culturally robust and relevant to its declared purpose.


A comparison of the Stanford-Binet abbreviated and complete forms for developmentally disabled children.

Three abbreviated versions of the Stanford-Binet were reviewed and compared for 50 children with developmental disabilities. The children ranged in age from 6 years - 0 months to 15 years - 11 months. While the IQs obtained from the abbreviated forms correlated highly with the complete Binet IQ, it was felt that the 2-item test yielded too many "misses" both in terms of IQ and classification to be of significant value for use with developmentally disabled children. Although the Terman and Merrill 4-item and Wright versions both yielded considerable "misses" in classification, they were believed to be of definite value to the time-harried examiner. Caution was advised, however, in the use of abbreviated-form IQs as a basis for important diagnostic decisions.


Patterns of emotional disturbance on the WISC-R.

Fourteen WISC subtest patterns that purport to differentiate behavioral disorders were applied to the WISC-R. Forty-one adolescent males referred as a result of conduct disorders were administered the WISC-R. In general, a group analysis showed a depression of verbal functions and satisfactory reliability. The majority of signs investigated were shown to be as effective with nonschizophrenic emotionally disturbed children as with the specific clinical picture they were designed to predict. Evidence pointed to a number of patterns of subtest scatter useful in the diagnosis of a generalized state of emotional disturbance. Implications for clinical practice were discussed.


A programmed training technique that uses reinforcement to facilitate acquisition and retention in brain-damaged patients.

Hospitalized brain-damaged patients were Ss in a study designed to evaluate the effectiveness of a treatment technique used with contingent reinforcement to facilitate acquisition and retention of environmentally relevant information. Ss were divided into three groups that were equated diagnostically and demographically. Group I received the treatment technique with contingent material and verbal reinforcement. Group II received the treatment technique with only contingent verbal reinforcement, and Group III was a control. Both treatment groups showed significant acquisition of the experimental information, and 1 week after training the two treatment groups showed no significant loss of acquired information. None of the groups showed any significant change in ward behavior during the experiment. It was concluded that the treatment technique used with contingent reinforcement can be used in the retraining of memory in brain-damaged patients.


Therapists prophesy.

Therapists' expectancies for therapeutic gain in patients reputedly are linked to the actual outcome of treatment for their patients. Theoretical papers have suggested that therapists' expectancies may cause or facilitate patient therapeutic response to treatment. Unfortunately, empirical data related to these notions are greatly lacking. The present study tested the relationship between therapist expectancy and treatment outcome for hospitalized schizophrenic patients. It also tested two opposing hypotheses re the nature of the link between therapist expectancy and outcome (causative vs. predictive). Multiple regression analyses revealed that therapists' expectancies are multi-dimensional, formed partly on the basis of therapists' knowledge of psychopathology in general and partly on their perception of their patients' pretreatment adjustment. The analyses also revealed that therapists' expectancies were associated significantly with treatment outcome; the data supported a predictive, not causative, interpretation of the nature of therapists' expectancies.


Accuracy of perception of psychotherapeutic content as a function of observers' level of facilitation.

Eight high-functioning and eight low-functioning Master's-level psychologists viewed 11 1-hour individual therapy sessions. The level of functioning of the psychologists was determined by ratings based on the Carkhuff global level of facilitation scale. After each session the observers completed a Therapy Session Report questionnaire that asked them to indicate what the patient and therapist were feeling and concerned with during the session. Analysis of variance indicated that high-functioning observers were more accurate in their perceptions than low-functioning observers and that all observers were more accurate with regard to their perceptions about the therapist. Results were discussed in terms of the validity of the Carkhuff scales.


Treatment of sexual dysfunction: a review of outcome studies.

Studies that have reported the outcome of treatment of various sexual dysfunctions are reviewed. While the number of published studies is limited, the results are remarkably consistent. By use of a variety of techniques, the prognosis for successful treatment of primary orgasmic dysfunction in women and premature ejaculation in men is quite good. The treatment of secondary or situational orgasmic dysfunction is more difficult and results in much lower success rates. Variables that affect treatment outcome and implications for future research and treatment are discussed.


Should fearful individuals be instructed to proceed quickly or cautiously?

Snake or cockroach phobic Ss were given opportunities to approach a live specimen. Those instructed to go "as far as they could" made significantly more progress in overcoming their fear than Ss asked to proceed cautiously. They also did better than the group especially urged to push themselves, although this difference was not significant. Implications for treatment strategies are discussed.


A study of pretherapy role induction as an influence process.

It is not clear whether the effectiveness of role induction procedures derives from the fact that they (a) provide clients with information about therapy; or (b) serve as a vehicle for influencing attitudes and beliefs about treatment. In this study 17 clients were assigned to one of two pretherapy interview conditions or to a control (no interview) group. In one condition, social influence aspects of the interview were maximized, while in the other they were minimized. Information given about therapy was the same in both circumstances. Results suggest that therapeutic gains were greatest for patients in the high influence condition. Implications are drawn for the conceptualization of role induction procedures.


Responses of high- and low-emotional deficit patients to exciting, grating, and neutral stimuli.

The preferences of high- and low-anhedonia and sensation-seeking psychiatric hospital groups for music rated as exciting, grating, and neutral, and the tendencies of these groups to modify the volume level at which they were exposed to these pieces, were compared. Volume-level choice was unrelated to anhedonia and sensation-seeking, which casts doubt on the theory that these affective deficits are mediated by efforts to reduce the quantity of incoming emotional stimulation. Anhedonia scores were not related to preferences for the three types of music. However, in contrast to high sensation-seekers, low sensation-seekers tended to dislike all types of music, and especially those rated as grating.


Pain adaptation and emotional deficit.

The pain adaptation rates of high- and low-emotional deficit schizophrenics were compared. Electrical stimulation pain thresholds were calculated and retaken at four intervals after administration of shocks in a learning task. Low scorers on the General Sensation-Seeking and Thrill/Adventure Seeking scales showed significantly less pain adaptation than did their high sensation-seeking counterparts. No differences in level of adaptation appeared between high and low scorers on the Anhedonia scale or three other sensation-seeking scales. The results suggested that the neurotic emotional deficit defined by the sensation-seeking scales may be mediated by inadequate adaptation to painful stimuli.


Physiognomic form perception: a comparison of normal and schizophrenic subjects.

The following reports the findings of a study that tested the hypothesis that schizophrenics--contrary to what has been suggested in the literature--are deficient, rather than superior, in perception of physiognomic properties. The Physiognomic Form Perception Test (RFPT), developed for the purpose and found reliable, was administered to 19 normal and 19 schizophrenic Sc. Results were in support of the hypothesis: normal Ss scored significantly higher than schizophrenics (t = 3.01, p less than .01). In addition, a qualitative analysis of verbalizations showed, as predicted, that schizophrenics gave significantly fewer "physiognomic-expressive" responses and significantly more of those rated "associations-rationalizations," as well as more "personalized and self-referent" responses.


Perceived locus of control as a function of level of depression among alcoholics and nonalcoholics.

This study investigated perceived locus of control as a function of level of depression among 39 alcoholics and 39 matched nonalcoholic controls. Ss completed the Rotter I-E scale and the Beck Depression Inventory. Initial analyses of variance indicated a lack of difference between groups on the I-E scale; however, alcoholics were significantly more depressed than were controls. A correlational analysis indicated a significant relationship between an external locus of control and higher levels of depression. When level of depression was controlled statistically, an alalysis of covariance indicated that the alcoholic samples was significantly more internal than the nonalcoholics. These data tend to cross-validate Lamont's (1972) findings of an item-mood response bias in the I-E scale. These data further support the contention that caution must be used in interpreting comparative locus of control results derived from samples that have differential base rates of depression.


A rating scale for the selection of internship applicants.

This study evaluated the utility of a rating scale for selecting clinical psychology interns. Forty-five applicants were rated by five staff psychologists. Variables rated included previous clinical experience, academic record, scholarly productivity, letters of recommendation, and intangibles. Majority agreement was found for 80% of the applicants for academic record and for scholarly productivity, for 73.3% of the applicants for clinical experience and for letters of recommendation, for 40% of the applicants for intangibles. Overall majority agreement was found for 64.8% of the candidates. All of the variables correlated positively and significantly with the total score. Scholarly productivity was weighted highest as a predictor of the applicant's total score followed by clinical experience, intangibles, letters of recommendation, and academic record. Advantages of the use of the rating scale by training centers in the selection of interns were discussed.


Interocular transfer of visual discriminations in goldfish after selective commissure lesions.

Goldfish with transections of the intertectal commissure learned but failed to transfer interocularly a simple visually cued avoidance task in a shuttle box, whereas posterior commissure lesions had no effect on this simple transfer task. However, fish with tectal commissure lesions could show normal interocular transfer of a shape discrimination, once discrimination pretraining with color cues had been carried out with each eye separately. Lesions of anterior commissure had no effect on either shape or color transfer, but fish with intended cuts of the postoptic commissures showed striking deficits of interocular transfer. As with comparable studies in the pigeon, it is concluded that postoptic, but not tectal, commissures are required for interocular transfer in the goldfish.


Interaction of hunger and thirst in the motivational arousal underlying hoarding behavior in the rat.

Rats were studied in which hoarding of food could be elicited by a 16-hr food deprivation schedule. It was found that (a) prolonged water restriction, with food ad lib, failed to induced hoarding in spite of a spontaneous reduction in food intake and a fall in body weight to below levels normally critical for the onset of hoarding. Thus, different physiological deficits are not necessarily equivalent or additive in the elicitation of food hoarding, and water lack may suppress it. (b) Hoarding behavior was released in water-deprived animals by a brief drink of water. A 30-min delay to allow absorption of the ingested water significantly enhanced the release of hoarding. Air drinking by water-deprived rats did not release hoarding. Thus, the absence of hoarding during water lack may be caused by an active inhibitory process that can itself be inhibited or canceled by postingestional effects of drinking but not by oropharyngeal stimulation mimicking water signals. (c) Although water lack prevented hoarding in response to concomitant self-imposed fasting, hoarding ensued at maximal rates when a further mild degree of food deprivation was superimposed. Thus, the inhibition of hoarding by dehydration operates subtractively, not multiplicatively, and, with free access to food, the inhibition of hoarding by thirst tends to be balanced, exactly, by the facilitatory effect of concomitant fasting; thus superadded food deprivation can take full effect. It is concluded that in states of motivational arousal, specific inhibitory mechanisms may inhibit, subtractively, certain activities biologically irrelevant to prevailing physiological needs.


Comparison of ovarian and hypothalamic obesity syndromes in the female rat: effects of diet palatability on food intake and body weight.

Both ovariectomy and hypothalamic knife cuts produced hyperphagia and obesity in adult female rats. The ovarian obesity, however, unlike hypothalamic obesity, was virtually independent of diet palatability. Ovariectomized rats became obese on quinine-adulterated diets, which completely blocked hypothalamic obesity, and they displayed little further weight gain when given a high-fat diet, which greatly potentiated hypothalamic obesity. Ovarian and hypothalamic obesity were also found to be additive irrespective of diet condition when both surgical treatments were combined in the same animal; that is, ovariectomy increased the food intake and body weight of knife-cut animals given the quinine or high-fat diet. In contrast to their dissimilar feeding effects, ovariectomy, hypothalamic cuts, and the combined surgeries, did not differentially alter the aversion to a .01% quinine solution. The results indicate that ovarian obesity and hypothalamic obesity represent two different feeding disorders and are mediated by separate neural mechanisms. The functional nature of these disorders is discussed in light of recent body weight set point interpretations.


Unit activity in cingulate cortex and anteroventral thalamus of the rabbit during differential conditioning and reversal.

Multiple-unit activity was recorded from the rabbit anterior cingulate cortical area (AC) and from the anteroventral nucleus of the thalamus (AV) during differential avoidance conditioning and reversal. The positive and negative conditioned stimuli were tones of different frequency, and the unconditioned stimulus (UCS) was shock delivered through the grid floor of a rotating-wheel conditioning apparatus. Conditioning was preceded by pretraining with tones and noncontingent presentations of the shock UCS. The results showed associative (differential) neuronal activity in both AC and AV during differential conditioning. The effect in AC occurred in the intermediate and final sessions of conditioning. A very large differential effect appropriate to original conditioning occurred in AC in the first two sessions of reversal training. The differential effect in AV occurred in the final session of conditioning when the behavioral response was well learned. There was no clear neuronal reversal in AC or AV.


Postoperative pedal edema.

Careful preoperative evaluation and precise surgical technique are important in the prevention of postoperative edema, which can alter surgical results functionally or cosmetically. If the lymphatics become occluded or injured, interstitial fluid protein concentration increases, and edema will probably result. Even mild or moderate edema may prolong healing time, and if edema persists for several weeks or months, recurrent or severe edema may result.


Calcaneal osteotomy.

The calcaneal osteotomy for the correction of valgus and varus deformities of the foot is a relatively simple and effective procedure. Since the main theme of the seminar was "Practical Reconstructive Foot Surgery," Dr. Sullivan's comments were limited to the principles of osteotomy with a brief discussion of the procedural techniques. The principles which he discusses relate to the goals to be achieved by osteotomy based on biomechanics. He also covers instrumentation, postoperative management, complications, tissue handling and choice of osteotomy sites.


The effects of ephedrine and theophylline on dexamethasone metabolism in bronchial asthma.

The effect of ephedrine (nine patients) and theophylline (seven patients) on dexamethasone metabolism was studied before and after three weeks of drug therapy in 16 asthmatics. Five patients were studied similarily but treated with placebo. After treatment with ephedrine, there was a mean decrease in plasma dexamethasone half-life (t1/2) of 132 minutes, or 36 per cent (P less than 0.025), and mean increase in metabolic clearance rate (MCR) of 148 liters/day, or 42 per cent (P less than 0.001). Increase in the excretion of urinary radioactivity, predominantly in the conjugated fractions, was noted. In contrast, theophylline and placebo therapy resulted in no significant changes in dexamethasone t1/2 or MCR. The rate of urinary excretion of radioactivity was reduced after theophylline treatment. Since ephedrine accelerates labeled dexamethasone clearance while theophylline does not, caution is necessary when prescribing ephedrine for asthmatics requiring long-term therapy with dexamethasone and probably other corticosteroids. It would appear from the present investigation that theophylline is a more appropriate bronchodilator for these patients.


Political psychiatry: a post-Watergate perspective or the revolution of falling expectations.

The social contract is a concept equally vital to philosophy and psychology in terms more relevant to this presentation, to politics and psychiatry. From the Hobbesian point of view, the contract has to do with the rights and responsibilities of different components and classes of society vis á vis one another. From the psychodynamic point of view, the social contract has to do with the way individuals relate to each other. Common to both perspectives is the implicit recognition that certain rules will be followed and that penalties will ensue when they are not, or, at the very least, that the prospect of penality will serve as a deterrent. These two notions of social contract converge in the actual regulation of our individual and collective behavior. Governance is impossible without trust in either the rules (more commonly known as the law, or the rule of law) or the people who administer them, whether parent, judge, or senator. Laws that are accepted and a corresponding "care that those laws are failfully executed" both are necessary to a good and just society. Perhaps I can demonstrate these concepts by paraphrasing the nobel Prize winning Japanese novelist who used as a title of his prize winning novel, The Sound of the Mountain. The tearing of the social fabric is the sound of loss of trust in our government, governors, and governance. If that trust is lost, it is but a step to loss of faith in self. For me, the test of these envolving concepts is their usefulness in predicting or at least in coping with the near future. To re-establish trust is our major task. My view may be too narrow and parochial, but I think it is more than coincidental that two of the groups under severest attack as untrustworthy are politicians and psychiatrists. The response of these two groups have some dramatic and meaningful similarities. In politics or, at least, in campaign rhetoric we are seeing fewer promises and more candor; mor emphasis on truthfulness, personal integrity, and character and fewer offers to solve difficult problems. In psychiatry, and somewhat in psychology and the other behavioral and social sciences, we see a demand to reduce the role of scope of the profession, particularly in dealing with "social issues," such as poverty and racism, which commentators and critics consider to be outside the proper sphere of competence and propriety. As a political psychiatrist, I am deeply concerned. In order to avoid the pitfalls of over-promising, we are overreacting; we are movinginto a trap that combines anti-intellectualism and anti-idealism. It can be summarized briefly in what I would call "the revolution of falling expectations." This is wrong. I protest. At the risk of being accused of hubris and hutzpah, I feel that nothing less than the best intellectual capacities and abilities and the deepest and widest experience are needed to deal with our problems in both politics and psychiatry...


Policy responses to complex issues: the case of black infant mortality.

There is a considerable body of literature that documents the higher infant mortality among American Blacks. This disparity has been attributed to many socioeconomic factors such as poor pre- and postnatal maternal health care, poor nutrition, inadequate housing, and so forth. Yet a careful examination of the data reveals that infant mortality is higher for Blacks regardless of socioeconomic condition. The present paper explores possible roots of this higher mortality rate in the centuries of nutritional deprivation suffered by Blacks in America. If a sizeable fraction of the higher black rates is a result of historical forces, it is questionable if traditional social welfare approaches and programs will markedly improve the situation. Indeed, a new set of interventions are called for to attack the picture of inequality and injustice that emerges from current U.S. infant mortality figures.


From "pressure group politics" to "medical-industrial complex:" the development of approaches to the politics of health.

This paper analyzes the development of the study of the politics of the health. In doing so it explores the connection between the changing conceptions of the politics of health and actual changes in the health systems of the western world. Three stages are identified in the development of health care systems. These are labelled the eras of benign neglect, health insurance and government regulation. It is then noted that three basic approaches to the politics of health have been taken over the years. These are labelled the group, modified group and holistic approaches. The article then argues that these three approaches tend to reflect the basic assumption explicit and implicit in the three stages of the development of the actual health systems of Canada, the United States and the United Kingdom. After critically commenting upon the value of each of the approaches, the paper notes that very few political scientists have used anything other than a rather narrow group approach to analyze the politics of health and therefore have failed to explain the dynamism of health care field. Then a few explanations for this unhappy state of affairs are ventured and the conclusion states a case for eclecticsm in the study of the politics of health.


Social class, political power, and the state: their implications in medicine--part III.

This is the third part of an article on the distribution of power and the nature of the state in Western industrialized societies and their implications in medicine. Parts I and II were published in the preceding issue of this Journal. Part I presented a critique of contemporary theories of the Western system of power; discussed the countervailing pluralist and power of elite theories, as well as those of bureaucratic and professional control; and concluded with an examination of the Marxist theories of economic determinism, structural determinism, and corporate statism. Part II presented a Marxist theory of the role, nature, and characteristics of state intervention. Part III focuses on the mode of that intervention and the reasons for its growth, with an added analysis of the attributes of state intervention in the health sector, and of the dialectical relationship between its growth and the current fiscal crisis of the state. In all three parts, the focus is on Western European countries and on North America, with many examples and categories from the area of medicine.


Alkaline phosphatase activity in human bladder tumor cell lines.

The cellular localization and isoenzyme pattern of alkaline phosphatase in five cell lines derived from human bladder carcinomas (T24, RT4, RT112, J82, EJ) shown not to be HeLa cells has been established. RT112 cells had a high level of alkaline phosphatase. RT4 had a moderate amount of alkaline phosphatase but in the other three lines, levels were extremely low. Prednisolone caused a small (2 to 3-fold) increase in total alkaline phosphatase in T24 and RT112 lines only. Electrophoretic separation of isoenzymes showed that RT112 and RT4 cells (derived from more highly differentiated tumor types) had three heat stable bands equivalent to placental alkaline phosphatase and three slower bands of a modified placental type. Prednisolone increased only the former. In T24 cells the enzyme resembled the liver-type alkaline phosphatase in electrophoretic mobility and sensitivity to heat denaturation. Cytochemical studies confirmed the presence of cell surface-associated extramembraneous placental type enzyme in RT112 cells. All five cell lines had small deposits of intramembraneous alkaline phosphatase in the plasma membrane and deposits associated tith the mitochondrial membranes and the endoplasmic reticulum that were not completely inhibited by phenylalanine or Levamisole.


Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice.

NZW F1 (B/W) mice were subjected to sham surgery or neonatal thymectomy and/or splenectomy and studied for immunoglobulin class of antibodies to double-stranded DNA and polyadenylic acid (Poly A) at 4 to 13 months of age. These antibodies occur spontaneously during the course of autoimmune disease in B/W mice. Sera were fractionated by sucrose density gradient ultracentrifugation and assayed for antibodies by a filter radioimmunoassay method. IgM was recovered in the 19S region and IgG in the 7S region as demonstrated by immunodiffusion. In sham-operated controls, at all ages studied, anti-DNA antibodies were both IgM and IgG, with the former predominating in males, and the latter in females. In both sexes, anti-Poly A antibodies were primarily IgM in young mice. There was a sequential switch from IgM to either enhanced or new IgG production in the following sequence: female anti-DNA and anti-Poly A (6 months), male anti-DNA (9 months), and male anti-Poly A (11 months). Both thymectomy and splenectomy caused earlier death in male mice, whereas females lived significantly longer after thymectomy. Neonatal thymectomy in males caused a premature switch from IgM to IgG antibodies to DNA, but it had a transient effect in females. Thymectomy almost completely prevented the late switch to IgG antibodies to Poly A in both sexes. By contrast, splenectomy promoted the formation of IgG antibodies to Poly A in male mice. These results suggest that the newborn B/W thymus and spleen contain regulatory cells and/or factors exerting different controlling influences on spontaneous antibodies to DNA and Poly A. Male B/W mice appear to be under the regulatory influence of suppressor cells, whereas the predominant regulation in female B/W mice appears to be a helper effect.


Morphology of delayed-type hypersensitivity reactions in the guinea pig cornea.

Guinea pigs sensitized with several soluble protein antigens in incomplete Freund's adjuvant (IFA) and tested at 5 to 7 days developed basophil-rich corneal reactions characterized by minimal edema and fibrin deposition. These lesions resembled the skin reactions of cutaneous basophil hypersensitivity (CBH) in their immunization requirements, time course, and character, but differed in that basophils were relatively less frequent and eosinophils and neutrophils more numerous in ocular than in cutaneous reactions developing simultaneously in the same animal. In contrast, animals immunized with antigens such as ovalbumin in complete Freund's adjuvant (CFA) developed much more severe delayed-type ocular reactions whether tested at early or late intervals after sensitization. These intensely injected, chemotic reactions exhibited an extensive cellular infiltrate of mononuclear cells as well as marked corneal edema accompanied by extensive fibrin deposition. Hence, these ocular reactions were similar to the classic indurated tuberculin-type delayed hypersensitivity (DH) skin reactions except that neutrophils were more numerous. These data indicate that in the eye as in the skin two distinct patterns of delayed-onset, cell-mediated hypersensitivity may occur to the same antigen, depending on the mode of immunization and the time of testing. However, significant differences were found in the frequency with which the various granulocytes infiltrated reactions elicited simultaneously in the eye and skin. Therefore, the character of immune expression may vary in different parts of the body and local factors, such as the local microvasculature, evidently contribute to these differences.


Inflammatory cells in solid murine neoplasms. III. Cytotoxicity mediated in vitro by macrophages recovered from disaggregated regressing Moloney sarcomas.

Macrophages (Mphi) were recovered from disaggregated, spontaneously regressing Moloney sarcomas for in vitro testing of their cytotoxic capabilities. At a 3:1 ratio, Mphi in monolayers efficiently killed (51Cr release) a variety of tumor target cells without regard to antigenic specificity. Within 24 hr most of their cytolytic potential was lost. Killing could be restored, however, if Mphi were replated at higher cell densities. A soluble, heat-stable, dialyzable inhibitor of thymidine incorporation, which did not interfere with cellular proliferation, also was produced by Mphi recovered from Moloney sarcomas. The finding of such a competitive inhibitor, probably cold thymidine, in supernatants further opened to question the validity of radioisotope incorporation into DNA as a measure of Mphi-mediated cytostasis. The data presented suggest that Mphi may participate in the regression process by directly killing tumor cells, thus complementing the antigen-specific cytolytic capabilities of the T lymphocytes that are also found in large numbers within regressing Moloney sarcomas.


Sequential proliferation induced in human peripheral blood lymphocytes by mitogen. II. Suppression by PHA-activated cells.

Human peripheral blood cells from cultures stimulated by phytohemagglutinin (PHA) for 3 days suppressed continued proliferation when added to feeder layer cultures of autologous lymphocytes previously stimulated with mitogen. Proliferation 1 day after the addition of inhibitory cells was reduced 50 to 60% as measured by tritiated thymidine (3HTdR) uptake and mitotic index. It is suggested that a similar suppressive phenomenon may be acting in most standard mitogen-stimulated cultures to limit cell division after only a few days of culture. Suppression of continued lymphocyte proliferation in the feeder layer cultures by cells from PHA-stimulated cultures was not due to cell crowding, carry-over of mitogen, or nutrient depletion; nor was it an artifact of thymidine incorporation. Apparent suppression of proliferation by an extract of these cells, however, was artifactual; the extract inhibited 3HTdR uptake but did not reduce mitotic activity. It is not known whether the inhibition exerted by the PHA-activated cells is mediate through a discrete subpopulation of "suppressor cells" or represents a regulatory function of any mitotic or post-mitotic cell, or both.


Biosynthesis of pyrrolidone carboxylic acid in hairless mouse epidermis.

[3H]Glutamic acid (PCA) was followed with time after a single subcutaneous injection. PCA specific activity increased slowly, reaching a peak at 3 to 4 days after injection of the labeled amino acid, after which it slowly decline. Incorporation of [3H]glutamic acid into epidermal PCA was markedly inhibited by a single topical application of cycloheximide. Topical application of cycloheximide 2 hr prior to [3H]glutamate injection caused a significantly greater reduction in PCA specific activity (determined 3 days after injection) than cycloheximide treatment 3 hr after administration of the labeled amino acid. Ninety-seven percent of the PCA content of hairless mouse epidermis was shown to reside in the stratum corneum. These observations indicate the involvement of protein synthesis in the formation of PCA from glutamic acid rather than a direct conversion of the amino acid. The high level of PCA in mammalian epidermis appears to be caused by its accumulation in the stratum corneum accompainied by a relatively slow rate of PCA turnover in comparison to other tissues.


The epidermal response to change in thyroid status.

Epidermal dimensions, replication, and anabolic activity have been studied before and after treatment in 10 patients with thyrotoxicosis and 7 patients with hypothyroidism. Following treatment of thyrotoxicosis there was a significant decrease in epidermal thickness, and also in cell replication as measured by an autoradiographic labeling index technique. The rates of anabolic activity in the epidermis, as estimated by measuring the rates of incorporation of tritiated precursor compounds, were significantly reduced after treatment in the thyrotoxic group. There were increases in these same measurements in the hypothyroid group following treatment although their magnitude was not as great as that seen after treatment of thyrotoxicosis. There was a significant positive correlation between serum triiodothyronine and epidermal thickness, labeling index and proline incorporation, but no correlation could be detected between serum thyroxine iodine and any of the epidermal measurements. These findings indicate that the eidermis changes in structure and activity in thyroid disease, and that the changes are rapidly reversible. Furthermore, the correlations we have found suggest that the receptors for thyroid hormone in human skin are specific for triiodothyronine.


Local regulation of blood flow in subcutaneous tissue in generalized scleroderma.

The effect of orthostatic changes in vascular transmural pressure on blood flow in subcutaneous tissue was studied in 10 patients with the acrosclerotic type of generalized scleroderma. Blood flow was measured on the back of the hand by the local 133xenon washout technique. The blood flow remained constant when the hand was elevated 20 cm above the jugular notch, indicating that there is autoregulation of blood flow, When the hand was lowered 40 cm below by 50% observed in normals. Thus, intrinsic vascular reactions responsible for the autoregulator response are present, whereas the normal "vasoconstrictor response" to an increase in venous transmural pressure is almost abolished in tissues with sclerodermic changes. The abolition of the vasoconstrictor response is probably due to sympathetic neuropathy associated with the sclerodermic changes.


An attenuated influenza virus vaccine: protection against homologous and heterologous strains of virus.

An effective influenza virus vaccine should be capable of inducing protection against both the homologous strain of virus and the heterologous strains representing antigenic drift. For evaluation of the protection provided by an attenuated influenza virus vaccine, volunteers were immunized intranasally with either placebo or influenza A/England/42/72 (H3N2) virus vaccine in a double-blind fashion in two doses administered two weeks apart. Forty-seven subjects were challenged 30-100 days after the second dose with either the homologous or a virulent heterologous strain of virus [A/Dunedin/73 (H3N2)]. The vaccine resulted in good clinical protection against challenge with both the homologous and heterologous strains of virus. The rates of protection against infection (as judged by antibody responses, irrespective of signs and symptoms) were also good (72% and 60% against the homologous and heterologous strains, respectively). Thus, immunity induced by this attenuated influenza virus vaccine extends to provide protection against a related but nonidentical influenza virus.


Effect of folate deficiency of the intestinal mucosa on jejunal transport in the rat.

The role of folate deficiency in the pathogenesis of the abnormalities of structure and transport of the small intestine that are often present in certain disorders such as alcoholism is unclear. One reason for this is that the folate status of the intestinal mucosa has never been ascertained in humans. Previous investigations have shown that a deficient diet supplemented with sulfa does produce folate deficiency of the intestinal mucosa in weanling rats and that this is associated with diarrhea and structural abnormalities of the jejunum. In the present study, we used then in vivo marker perfusion technique to examine the jejunal transport of water, sodium, xylose, glucose, and L-leucine in such folate-deficient rats. Supplementation of the normal diet with sulfa did not produce folate deficiency of the intestinal mucosa, but it was associated with a moderate reduction in water absorption; this was attributed to cecal enlargement in these rats. Rats placed on a folate-deficient diet plus sulfa developed markedly depressed serum and jejunal folate concentrations, net secretion of water and sodium, and persistent diarrhea; absorption of xylose, glucose, and L-leucine remained normal, however. Folate repletion of these rats by water and sodium transport to absorption ano cessation of diarrhea. These observations indicate that folate deficiency of the intestinal mucosa alters the transport of water and electrolytes but not that of such solutes as xylose, glucose, and L-leucine. They suggest that when transport abnormalities of these solutes occur in folate-deficient alcoholics, this in not due to the folate deficiency but rather to other pathogenic factors such as ethanol.


Role of renal vasodilatation in the blunted natriuresis of saline infusion of dogs with chronic bile duct obstruction.

Since part of the natriuresis of the extracellular fluid volume expansion (ECVE) is due to renal vasodilatation, it is possible that the blunted natriuresis during ECVE in dogs with chronic ligation of common bile duct (CBD) is due to gailure to renal arteries to dilate. Studies were carried out to investigate this question in normal dogs, sham-operated animals, and dogs with acute and chronic legation of CBD. ECVE with 0.45 percent saline caused a significant rise in renal plasma flow (RPF) and urinary sodium excretion (UNaV) in all animals except those with chronic ligation of CBD. In the latter dogs, the increment in UNaV was significantly less than that observed in the other groups of animals, and RPF did not increase significantly following saline infusion in dogs with CBD ligation. The intrarenal administration of acetylcholine produced a significant and comparable increase in RPF in all animals, including those with chronic ligation of CBS, but the rise in UNaV in the latter was significantly less than that in the other groups of dogs. The data indicated that (1) ECVE is not associated with renal vasodilatation in dogs with chronic ligation of CBD, (2) this abnormality is not due to a defect of the renal arteries to respond to vasodilators, and (3) the lack of renal vasodilatation may be partly responsible for the blunted natriuresis, but other sodium-retaining forces may also be operative.


Severe generalized glutathione reductase deficiency after antitumor chemotherapy with BCNU" [1,3-bis(chloroethyl)-1-nitrosourea].

Patients receiving BCNU [1,3-bis(2 chloroethyl)-1-nitrosourea] acquire a profound deficiency of erythrocytic oxidized glutathione reductase (GSSG-R) within minutes after the first intravenous injection of a single therapeutic dose (75 mg/M.2) of the drug. This effect is not accompanied by changes in the activites of 19 additional erythrocytic enzymes tested, is reproducible in vitro in a dose-related manner, and is not caused by the antitumor agents administered concurrently with the nitrosourea. The inactivation of erythrocytic GSSG-R results in decreased levels of reduced glutathione (GSH), marked GSH instability and disturbed hydrogen peroxide removal with a positibe ascorbate cyanide test and leads to increased susceptibility to oxidative hemolysis, particularly in glucose-6-phosphate dehydrogenase (G-6-D)-deficient patients. BCNU inhibits GSSG-R irreversibly, probably through alkylation rather than carbamylation, and the reappearance of enzyme activity in vivo after each chemotherapy pulse depends on the capacity of the marrow to release erythrocytes with normal activity formed during the drug-free interval. BCNU inhibits GSSG-R not only in erythrocytes but also in human leukocytes and platelets, as well as in yeast, monkey erythrocytes, and all the organs tested in the mouse. This generalized, severe, and specific GSSG-R deficiency caused by therapeutic doses of BCNU may enhance or mediate the toxic and antitumor effects of the nitrosourea and provides a simple yet sensitive biochemical means of monitoring bone marrow reserve in patients receiving multiple courses of chemotherapy with this agent.


A rapid radioimmunoassay for serum unconjugated estriol with a directly iodinated estriol radioligand.

Radioiodinated estriol not previously derivatized was found to be immunoreractive and is shown to possess Sephadex-adsorptive characteristics similar to those of tritium-labeled estriol and nonlabeled estriol. Because of these characteristics, radioiodinated estriol is shown to be an acceptable radioligand for use in a rapid and reliable column radioimmunoassay for determination of unconjugated estriol in serum. An evaluation of the estriol column RIA assay with this radioligand is presented.


Comparison of subcutaneous and intraportal insulin administrations on adenylate energy charge of the liver in diabetic rats.

Effects of subcutaneous and intraportal administrations of insulin on adenine nucleotide metabolism of the liver and oxidative phosphorylation of the isolated mitochondria were investigated in alloxan-diabetic rats. The diabetic rats were classified into two groups according to the severity of impaired insulin response to oral glucose: diabetic rats with only minor impairment of insulin response and those with severely defective response. The energy charge levels (ATP + 1/2ADP)/(ATP + ADP + AMP) of the liver both groups were not significantly different from those of controls. In the first group, the oxidative phosphorylation of liver mitochondria was within normal limits and was enhanced significantly by subcutaneous administration 4 U. of insulin (p less than 0.005). In the secong group, the mitochondrial oxidative and phosphorylative activities were inhibited severely and did not recover even with subcutaneous administration of 20 U. of insulin. Intraportal administration of insulin doses (4 to 8 U.) insufficient for normalization of hyperglycemia produced a decrease in the energy charge of the liver to a considerably lower level than normal (p less than 0.01), whereas larger doses (20 U.) of insulin raised the energy charge to normal levels, with a concomitant recovery of mitochondrial oxidative phosphorylation. It is suggested that subcutaneous administration of insulin is effective for hepatic energy metabolism only if insulin response to glucose loading is still present but that only intraportal administration of insulin can exert a beneficial effect in diabetic rats without insulin response.


Demonstration of gastric glucagon hypersecretion in insulin-deprived alloxan-diabetic dogs.

The contribution of the gastric fundus to the hyperglucagonemia of poorly controlled diabetes was studied in insulin-deprived alloxan-diabetic dogs by simultaneously measuring plasma glucagon in the venous effluents of the fundus and the pancreas, and the inferior vena cavae plasma. In the basal state, mean glucagon averaged 411 +/- 45 pg./ml. in the gastric vein and 941 +/-161 in the pancreaticoduodenal vein; both values were significantly above the vana caval level of 281 +/-35 (p less than 0.01). Intravenous arginine infusion to 1,180 +/- 432 after 1.5 minutes; this was significantly above the mean vena caval glucagon concentration which reached a peak of only 352 +/- 74 (p less than 0.01 to 0.05). Intragastric instillation of arginine was followed by a doubling of gastric vein glucagon within 10 minutes, and the increases in the gastric vein were significantly greater than in the peripheral plasms at several points. The infusion of insulin at a rate of 0.0015 u./kg./min. rapidly lowered glucagon in the gastric and pancreaticoduodenal veins, abolishing the gradient across the stomach and reducing the transpancreatic gradient. The studies raise the possibility that extrapancreatic glucagon may contribute to the hyperglucagonemia of insulin deficiency.


Mechanism of inhibition of hemoglobin S polymerization by cyanate.

We have studied the effect of carbamylation on hemoglobin S (HbS) polymerization with the use of a new quantitative gelling technique. HbS gels fromed in the presence of nitrogen and dithionite (with or without carbon monoxide) at pH 7 in 0.15M phosphate were separated into sol and gel phases by centrifugation at 130,000 g. Hb concentration to the sol phase ([Hb]sol) of nonligated HbS was found to be constant (10.5 +/- 092 mM heme) over a range of original Hb concentrations from 11 to 17 mM at 24degrees C. This suggests that the HbS sol-gel equilibrium behaves as simple two-phase system. Increasing levels of total carbamylation from 0.65 to 3.65 moles CNO-/mole Hb tetramer (0.36 to 2.2 moles N-terminal/mole Hb4) progressively increases [Hb]sol. Specific activity of 14CNO-HbS was similar in the sol and gel phases, whereas COHbS appeared to be completely excluded from polymer structure of the gel. A comparison of the solubility of uncarbamylated and heavily carbamylated HbS at Co saturations ranging from 3 to 61 percent showed that the larges difference in [Hb]sol occured at the lowest ligand saturation rather than at intermediate states of ligation. Inhibition of HbS polymerization by carbamylation under these conditions, therefore, is not primarily the result of an effect on the T in equilibrium R comformational equilibrium. Our findings indicate that cyanate can interfere with HbS polymerization directly, possibly by alteration of surface binding sit(s) which are critical to aggregation. This direct action of cyanate may contribute significantly to the hematologic improvement achieved by cyanate treatment in sickle cell disease.


Experimental production of manifest and concealed ventricular rhythms in man.

Analysis of clinical ventricular ectopy has provided deductive evidence for the existence of concealed ventricular rhythms. Studies in the experimental animal have demonstrated that when ventricular extrastimuli are applied near the ventricular effective refractory period of consecutive sinus beats, extrastimuli may not be conducted after sinus beats immediately following the post-estrasystolic pause. This sequence may be due to a prolongation of the effective refractory period of ventricular muscle produced by the increased cycle length resulting from the post-extrasystolic pause. The purpose of this study was to extend these observations to the human ventricle in an attempt to produce concealed ventricular rhythms by programmed ventricular extrastimuli. Twelve patients with normal PR intervals and QRS complexes with a mean age of 49 years were studied with ventricular extra-stimuli at programmed intervals following normally conducted sinus impulses. Premature ventricular impulses were introduced after every sinus beat at intervals 10 to 120 msec outside the effective refractory period. In eleven patients without ventricular interpolation, stimuli applied within 40 msec of the effective refractory period produced from one to three concealed (non-conducted) ventricular stimuli following the post-extrasystolic pause; stimuli applied greater than 40 msec outside the effective refractory period at identical current levels produced manifested bigeminy in all cases. In one patient with interpolated premature ventricular beats without a compensatory pause, programmed ventricular extrastimuli produced manifest bigeminy at all coupling intervals. This study demonstrates the experimental production of concealed and manifest ventricular rhythms in man and confirms the importance of the relationship between the ventricular effective refractory period, the timing of the premature ventricular impulse, and the occurence of a compensatory pause.


Differences in the T lope in males and females with angina pectoris.

In cases with angina pectoris, the location and configuration of the T loop in a male group and a female group were compared. In the male group, the types of abnormal T loop were mainly an anterior displacement type (the AD type) and an abnormal shape type (the AS type). On the contrary, a posterior displacement type (the PD type) was found in most cases in the female group. The movement of the T loop after exercise test or exacerbation was also different in the two groups. In the male group, an anterior displacement or increase of W/L of the T loop was observed, but in the female group, the T loop was dislocated more to the left and posteriorly. The reason for these differences in the T loop in both groups is discussed.


The vectorcardiogram in subjects with sex chromosome aneuploidy.

Vectorcardiographic variables have been studied in patients with sex chromosome abnormalities and compared with normal controls. Several of these variables were found to be correlated with the number of sex chromosomes in the karyotype, some being related to the number of X chromosomes, some to the number of Y chromosomes, and others to both. The variables concerned included time intervals and vector magnitudes in both the QRS and ST-T wave complexes. The heart rate itself proved dependent on both the X and the Y chromosome complements. The correlations could not be explained by age, height, or weight differences between the seven different karyotype groups studied. The dependences of variables other than the heart rate remained after correction for between-group heart rate differences. The findings are discussed.