[Acute primary ischemic enteritis and colitis. Clinico-pathological and physio-pathological findings].

By opposition to acute post-operative ischaemic enterocolitis, the authors isolate, with the aid of seven cases, the intestinal lesions which spontaneously occur on the small intestines and on the colon and due to an ischaemic mechanism without thrombosis of the mesenteric vessels. After the description of clinical and anatomical features, they point out the main part of the vascular factor in the genesis of the lesions.


[A new aspect of physiology of the bile ducts (author's transl)].

After evaluation of the force necessary for filling of the gall bladder, it seemed to us difficult to admit that the sphincter of Oddi was the only mechanism necessary for filling, which occurs perfectly without this sphincter. This is why our attention was drawn to the possible role of cystic duct circular muscle which has an important neuro-muscular supply and a known peristaltic activity. Studying the anatomical structure of the region, we examined the various routes which may be followed by the bile during filling and emptying. Filling follows a very particular course, like a cork screw, between the wall of the cystic duct and the lower surface of Heisster's value in which the neuro-muscular mechanism is sufficient to ensure peristaltic movements which may pump the bile across Lutken's sphincter into the gall bladder.


[Isotopic angiography. Method of early post-operative control in peripheral vascular surgery. Report of 200 cases (author's transl)].

The authors report their experience of isotopic angiography as means of post-operative control in peripheral vascular surgery in 200 cases. This investigation is very simple and non-traumatic. It gives very satisfactory morphological information and a good idea of the hemodynamics of the acts carried out.


[Osteoblastoma of the patella (author's transl)].

Osteoblastoma is a rare bony tumour. Its localisation at the level of the patella seems exceptional. Our case is the third published case. Wide curetage was a failure, and did not permit histological diagnosis. A cure was obtained by patellectomy, after which the diagnosis of the lesion was made without any doubt.


[The functional cervico-diaphyseal approach. A new route of approach to the hip for surgery of cervico-trochanteric fractures by diaphyseal prosthesis (author's transl)].

The authors report a new route of approach to the hip, specific to cervico-diaphyseal region. Its main application seems to be for the insertion of diaphyseal prostheses in cervico-trochanteric fractures in the eldery. The lack of damage to the capsule, the reconstruction of a solid weight-bearing point on the trochanter, the precise repair of the joint cavity and of muscle continuity make this a simple route of approach with minimal shock, permitting rapid rehabilitation of the patient with immediate weight-bearing.


[Traumatic lesions of the ureter in pelvic surgery. Apropos of 10 cases].

For ureteral lesions without loss of substance our preferences are, at the level of the lesion, either for end-to-end ureteral suture, or antireflux uretero-vesical reimplantation. For ureteral lesions with loss of substance we prefer the psoas bladder, if the bladder is healthy, large and supple, or inter-ureteral anastomosis if the bladder for some reason (radiotherapy, retracted bladder, small "blocked pelvis") is not available. Synthetic ureteral prosthesis may be a rapid and elegant solution in cancer patients with a limited hope of survival. Guided by these principles, we have repaired 10 ureters : 1 by ureterolysis, 2 by end-to-end suture, 3 by inter-ureteral anastomosis, 4 by antireflux uretero-vesico reimplantation. These 10 repairs gave 9 successes. The only failure (end-to-end ureteral suture) was due to our lack of experience, for in a similar case we would now perform an inter-ureteral anastomosis.


[Comparative study of the fate of a pancreatic stump treated by ligature or by pancreatico-jejunal anastomosis (author's transl)].

The authors studied in a series of 23 dogs divided up into two groups the fate of the pancreatic stump treated either by pancreatico-jejunostomy with a Y loop, or by a simple ligature. They note that although the mortality is slightly higher in the anastomoses, histological lesions are constant in both series and are fairly similar. This agrees with the findings in man by Goldsmith and justifies ligature of the remaining pancreatic stump after cephalic duodeno-pancreatectomy.


The synthesis of glycosaminoglycans by cultures of corneal stromal cells from patients with keratoconus.

Keratoconus is a disease that results in thinning and ectasia of the central cornea. Cultures of corneal stromal cells from patients with keratoconus were established and the synthesis of glycosaminoglycans compared with the synthesis of glycosaminoglycans by normal human corneal stromal cells in culture. Keratoconus and normal control cell cultures were incubated with sodium [(35)S]sulfate and [(3)H]glucosamine for 4 h. After incubation, the labeled glycosaminoglycans were isolated from the medium fractions and cells. Keratoconus and normal control cultures synthesized similar amounts of sulfated glycosaminoglycans independent of the age of donors and(or) the number of subcultures. In contrast to normal control cultures, most of the newly synthesized glycosaminoglycans produced by keratoconus cells were found in the growth medium and much less were in the cell layer. Treatment with glycosaminoglycan-degrading enzymes followed by paper chromatography showed that keratoconus cells, as normal control cells, produced hyaluronic acid and various sulfated glycosaminoglycans. The production of cell layer-related heparan sulfate was markedly reduced in keratoconus cultures. Because heparan sulfate has been shown to be associated with cell surfaces, the decreased heparan sulfate content could reflect changes at this location.


Erythrocyte membrane proteins in hereditary glucosephosphate isomerase deficiency.

Erythrocytes (approximately equal to 50% reticulocytes) obtained from a splenectomized patient with a thermolabile variant of glucosephosphate isomerase (GPI) deficiency showed a striking degree of crenation and decreased filterability through 3-micrometer Nuclepore filters  (Nuclepore Corp., Pleasanton, Calif.). Membranes prepared by hypotonic lysis of such erythrocytes were found to contain a high molecular weight aggregate which was probably disulphide-bonded. The 10% most dense erythrocyte fraction showed an accentuation of aggregate formation while aggregates could not be detected in the 10% least dense erythrocyte fraction. The aggregate consisted mainly of spectrin (band 1) and a protein with the mobility of 4.2. "Extractability" of spectrin from these membranes was also markedly diminished. Incubation of the erythrocytes for 24 h in substrate-free medium caused more pronounced spectrin aggregation than in low or high reticulocyte controls. Incubation of low or high reticulocyte controls for 24 h in medium that contained glucose completely prevented the formation of the high molecular weight aggregate. GPI-deficient erythrocytes incubated with glucose  in the medium showed an accentuation of membrane protein aggregate formation; however, this was almost completely reversed by the addition of adenine and inosine to the incubation medium or by the use of fructose, the intermediate just distal to the "block" in glycolysis, as the sole substrate. ATP and reduced glutathione levels in the GPI-deficient erythrocytes incubated with glucose were similar to that found in the low and high reticulocyte controls. Our findings suggest that only a proportion of erythrocytes (the older, more dense population of cells) are susceptible to the formation of disulphide-bonded aggregates, and that this is directly related to an impairment of substrate flow through the glycolytic sequence. The exact mechanism of aggregate formation in these erythrocytes remains to be elucidated.


Sympathetic control of lower esophageal sphincter function in the cat. Action of direct cervical and splanchnic nerve stimulation.

The purpose of this study was to determine the effect of direct stimulation of the sympathetic nerves on the lower esophageal sphincter (LES) in the anesthetized cat. Neither unilateral nor bilateral cervical sympathectomy, or splanchnicectomy significantly modified basal LES pressure in animals with intact vagi, or animals having undergone bilateral cervical vagotomy. Electrical stimulation of the cut, peripheral, cervical sympathetic trunk increased mean arterial blood pressure, but had no effect on LES pressure or LES relaxation as induced by vagal stimulation. Stimulation of the central end of the cervical sympathetic trunk had no effect on LES pressure. Stimulation of the central end of the cut splanchnic nerve produced a decrease in LES pressure with a maximal response of 69.1+/-16.0% (mean+/-SEM). This inhibitory response was not modified by either propranolol or bilateral cervical vagotomy. Stimulation of the peripheral end of the cut, greater splanchnic nerve gave an increase in LES pressure with a maximal response of 38.2+/-7.19 mm Hg. Guanethidine, in the presence or absence of the adrenal glands, significantly augmented this excitatory response. This response was also slightly increased by phentolamine alone at 10 V, 1 Hz, but was not altered by propranolol. The excitatory response was completely antagonized by atropine or by trimethaphan camsylate. Stimulation of the peripheral end of the splanchnic nerve inhibited LES relaxation as induced by vagal stimulation. The results of this study suggest that: (a) the LES in the cat is not affected by either central or peripheral stimulation of the cervical sympathetic trunk; (b) the central portion of the splanchnic nerve carries an afferent inhibitory response to the LES through yet unknown pathways; (c) the peripheral splanchnic nerve carries an atropine-sensitive excitatory response to the LES; and (d) the splanchnic nerves may modulate LES relaxation as induced by vagal stimulation.


Effect of cytochalasin B and D on groups of insulin receptors and on insulin action in rat adipocytes. Possible evidence for a structural relationship of the insulin receptor to the glucose transport system.

The possible physiological importance of the groups of insulin receptors on rat adipocytes and the relationship of these groups to insulin action were investigated. The effect of cytochalasin B and D on biological actions of insulin was measured and compared with the effect of these agents on the ultrastructural distribution of groups of insulin receptors. Cytochalasin B had no effect on epinephrine-stimulated lipolysis, insulin inhibition of epinephrine-stimulated lipolysis, or insulin stimulation of protein synthesis. Cytochalasin B, over a concentration range of 50 nM to 5 muM, progressively inhibited the basal glucose transport system, as measured by glucose oxidation, 2-deoxyglucose transport, and 3-O-methylglucose transport. Insulin was capable of fully stimulating remaining basal transport at submaximal concentrations of cytochalasin B. Insulin pretreatment of adipocytes partially protected the glucose transport system from inhibition by cytochalasin B. Cytochalasin B markedly altered the distribution pattern of insulin receptors, which caused an increase in the number of single receptor molecules by decreasing the number of larger groups. A significant correlation (r = 0.964; P < 0.001) was found between the percent increase in single receptors and the percent decrease in glucose transport. Ferritin-insulin pretreatment of adipocytes prevented disruption of the groups of insulin receptors by cytochalasin B. Cytochalasin D had no effect on the biological actions of insulin or on the groups of insulin receptors. These data suggest that the ability of insulin to affect adipocyte metabolism is independent of the hormone occupying adjacent, grouped receptor sites. The marked contrast in effects of cytochalasin B and D on groups of insulin receptors and glucose transport suggests that the microfilament system is not involved in insulin action or in holding the groups of insulin receptors together, as both agents are known disrupters of microfilaments and inhibitors of actin gelation. The correlation between the effects of cytochalasin B on insulin receptor distribution and glucose transport leads to the speculation that the glycoprotein molecules containing the insulin receptor are functionally linked with the glucose transport system.


Excretion-reuptake route of beta-hexosaminidase in normal and I-cell disease cultured fibroblasts.

It has been proposed that in cultured fibroblasts the final packaging of enzymes in lysosomes requires excretion followed by pinocytosis by neighboring cells via a carbohydrate-specific receptor mechanism. It has also been proposed that the abnormally high activity of lysosomal enzymes in the medium of cultured fibroblasts from patients with I-cell disease (mucolipidosis II) results from an altered carbohydrate recognition residue on the enzymes which prevents reuptake into the cells. With beta-hexosaminidase as a marker, and competitive inhibition of uptake by 2 mM mannose-6-phosphate, we have determined that only 12% of the total (intra- and extracellular) beta-hexosaminidase in normal fibroblasts is channeled through the excretion-reuptake route. After 9 d of exposure to mannose-6-phosphate, normal fibroblast cultures accumulated in the medium only a fraction of the enzyme excreted by I-cell disease fibroblasts in the same period. Furthermore, this minimal loss of enzyme to the medium did not result in a decrease of intracellular enzyme activity. Finally, if the defect in I-cell disease were only because of an impairment of a reuptake mechanism that involves only 12% of the total enzyme, then 88% of the newly synthesized enzyme should be retained by I-cell fibroblasts, resulting in intracellular activity three to nine times higher than that which is observed. These data are consistent with our previous proposal that excessive lysosomal enzyme activity in the medium of I-cell disease fibroblasts results from preferential exocytosis.


Pre- and postoperative studies of plasma calcitonin in primary hyperparathyroidism.

The importance of calcitonin in the homeostatic response to the chronic hypercalcemia of primary hyperparathyroidism is uncertain. To clarify this issue, we have used a new, sensitive radioimmunoassay for human calcitonin to measure basal plasma calcitonin concentrations in 50 patients with primary hyperparathyroidism (32 female, 18 male). We assayed calcium-stimulated calcitonin concentrations preoperatively in 22 of the patients (16 female, 6 male) and postoperatively in 6. Finally, we assayed pentagastrin-stimulated calcitonin concentrations preoperatively in eight of the patients (three female, five male). Plasma calcitonin values after an overnight fast were indistinguishable from those in normal subjects (mean+/-SE, males, 48+/-3 normal and 46+/-5 pg/ml hyperparathyroid, females, 31+/-2 normal and 37+/-3 pg/ml hyperparathyroid.) Among hyperparathyroid patients of both sexes, increases of calcitonin during Ca infusion (15 mg Ca/kg in 4 h) were within normal limits. However, the mean maximal increase of calcitonin was significantly lower in hyperparathyroid than in normal subjects (P < 0.05). In six patients normocalcemic 5-15 mo after parathyroid surgery, fasting plasma calcitonin values were not significantly different, but responses to Ca infusion were greater than preoperatively (Delta calcitonin +/-SE: 13+/-4 preoperatively and 53+/-35 pg/ml postoperatively). The mean maximal increase of calcitonin after pentagastrin (0.5 mug/kg i.v.) was slightly lower than normal in the patients (mean+/-SE, males, 45+/-8 normal and 38+/-10 pg/ml hyperparathyroid, females, 6+/-2 normal and 0 pg/ml hyperparathyroid). Thus, primary hyperparathyroidism is accompanied by normal steady-state concentrations of circulating calcitonin, and normal-to-blunted C-cell responses to pentagastrin or induced hypercalcemia, the response to calcium generally increasing after successful parathyroid surgery. These results clearly show that primary hyperparathyroidism is not characterized by hypercalcitoninemia. The seemingly paradoxical absence of elevated steady-state calcitonin concentrations may be accounted for partly by decreased secretory reserve. However, primary hyperparathyroidism may also be accompanied by an increase in the threshold of sensitivity for calcium stimulation of calcitonin secretion.


Polymorphonuclear leukocyte and monocyte chemoattractants produced by human fibroblasts.

The elaboration of leukocyte chemotactic factors by human fibroblasts was studied. 12 lines of normal fibroblasts obtained by skin biopsy and then cultured in vitro produced chemoattractants (assessed by modified Boyden-chamber techniques) for both peripheral blood polymorphonuclear leukocytes and monocytes (obtained by Hypaque-Ficoll and dextran sedimentation). Chemotactic activity was not present performed in fibroblasts, and cycloheximide blocked its elaboration. The chemotactic activity of crude-culture supernate was heat stable (56 degrees C for 30 min), trypsin- and pronase-sensitive, and neuraminidase resistant. Characterization of the chemotactic activity by gel filtration (Sephadex G-75) showed two active fractions, one with mol wt greater than 100,000 and the other less than 10,000. In studies designed to relate these chemotactic factors to collagen, we have confirmed that type I collagen and alpha 1-chain; are chemotactically active for monocytes but not polymorphonuclear leukocytes. However, the chemotactic activity in fibroblast-culture media was media was distinct from collagen in that it attracted neutrophils, it was not precipitated by 25% ammonium sulfate, and it was resistant to collagenase treatment; ascorbic acid, in concentrations known to stimulate fibroblast collagen synthesis, had no effect on the elaboration of the chemotactic factors. Furthermore, amino acid analysis of Sephadex G-75 fractions with chemotactic activity failed to reveal amino acids such as hydroxyproline characteristic of collagen. In addition to the chemotactic factors secreted by fibroblasts, a heat-resistant factor (30 min at 56 degrees C) which generated the chemotactically active fragment of C5 (C5a) from human serum was also secreted. The elaboration of mediators of the inflammatory and immune responses by fibroblasts may initiate and(or) modulate local skin inflammatory reactions and play a protective role in vivo.


Plasma acetone metabolism in the fasting human.

The metabolism of acetone was studied in lean and obese humans during starvation ketosis. Acetone concentrations in plasma, urine, and breath; and rates of endogenous production, elimination in breath and urine, and in vivo metabolism were determined. There was a direct relationship between plasma acetone turnover (20-77 mumol/m(2) per min) and concentration (0.19-1.68 mM). Breath and urinary excretion of acetone accounted for a 2-30% of the endogenous production rate, and in vivo metabolism accounted for the remainder. Plasma acetone oxidation accounted for congruent with60% of the production rate in 3-d fasted subjects and about 25% of the production rate in 21-d fasted subjects. About 1-2% of the total CO(2) production was derived from plasma acetone oxidation and was not related to the plasma concentration or production rate. Radioactivity from [(14)C]acetone was not detected in plasma free fatty acids, acetoacetate, beta-hydroxybutyrate, or other anionic compounds, but was present in plasma glucose, lipids, and proteins. If glucose synthesis from acetone is possible in humans, this process could account for 11% of the glucose production rate and 59% of the acetone production rate in 21-d fasted subjects. During maximum acetonemia, acetone production from acetoacetate could account for 37% of the anticipated acetoacetate production, which implies that a significant fraction of the latter compound does not undergo immediate terminal oxidation.


Binding of immunoglobulin G aggregates and immune complexes in human sera to Staphylococci containing protein A.

Using the Cowan I strain of Staphylococcus aureus, we compared the binding properties of human monomeric immunoglobulin (Ig)G and oligomeric or complexed IgG. Heat-aggregated IgG served as a model for complexed IgG and heat-killed, formalin-fixed S. aureus (StaphA) as a cellular receptor for IgG, in determining the parameters for oligomeric and monomeric binding. Because of its capacity for multipoint attachment, complexed IgG binding was favored over monomeric IgG binding, and this preferential binding was demonstrated kinetically in equivalent forward rates of binding but in a much slower rate of release from StaphA receptors. From binding studies, we determined which conditions maximize complexes IgG binding and minimized monomeric IgG binding and applied them to the development of an assay for aggregated IgG and immune complexes in human sera. The StaphA binding assay that was devised is quantitative, sensitive, and not complement dependent. It is relatively unaffected by factors such as heparin, complement fixation, native antibodies, and immunoglobulin concentrations, but is affected by the presence of rheumatoid factors. It compares favorably with two other complement-dependent assays of immune complexes, the 125I-Clq binding assay and the Raji cell assay, in terms of sensitivity and the size of immune complexes detected. Studies on the potential of the assay for detecting, isolating, and characterizing immune complexes in biological fluids are presented.


Morphologic-physiologic correlates of the severity of fibrosis and degree of cellularity in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of lung parenchyma characterized by a chronic inflammatory cellular infiltration and varying degrees of interstitial fibrosis. Current data indicate that the severity of fibrosis and the degree of cellularity determine, in part, the prognosis of IPF and the response to therapy. Whereas lung biopsy gives the best assessement of fibrosis and cellularity, physiologic studies are used to stage and monitor the disease process. To determine which physiologic studies correlate best with severity of fibrosis and degree of cellularity, these parameters were graded in lung biopsies of 23 patients with IPF and compared with a variety of physiologic studies. Although vital capacity, total lung capacity, and diffusing capacity are commonly used as objective monitors of the disease process, none of these parameters correlated with either the severity of fibrosis or the degree of cellularity in biopsy specimens. In contrast, almost all parameters of lung distensibility correlated with the morphologic assessment of degree of fibrosis; compliance had the best correlation. Parameters of distensibility, however, correlated poorly with the degree of cellularity. In comparison, gas exchange during exercise correlated with both morphologic parameters; the exercise-induced changes in arterial oxygen pressure per liter of oxygen consumed had a high correlation with the degree of fibrosis (r = 0.89; P less than 0.001) and correlated to a lesser extent with the degree of cellularity (r = 0.56; P = 0.009). In contrast, neither the resting arterial oxygen tension nor the arterial oxygen tension at maximal exercise correlated with the morphologic assessment of degree of fibrosis or the degree of cellularity. These morphologic-physiologic comparisons suggest that (a) lung volumes and diffusing capacity are poor monitors of both the degree of fibrosis and the degree of cellularity; (b) the fibrotic process contributes, at least in part, to parameters of lung distensibility, and both fibrosis and cellularity contribute to gas exchange alterations during exercise; and (c) parameters of lung distensibility and exercise-induced gas exchange alterations may be useful in staging the severity of disease in IPF.


Thymosin-induced suppression of proliferative response of human lymphocytes to mitogens.

The proliferative response of human peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and pokeweed mitogen were suppressed by thymosin. Greatest decreases were observed when cells were preincubated with thymosin for 18 h before a 3-d culture with mitogen in the presence of thymosin. However, significant suppression also occurred when lymphocytes were preincubated for 2 h and cultured with thymosin or preincubated for either 2 or 18 h and washed free of thymosin before culture. These effects were related to the concentration of thymosin and time of exposure to thymosin but not merely to a delay in the response to mitogen or to toxicity. The suppression of mitogen-induced proliferation by thymosin appeared to result from effects of thymosin on a suppressor cell because lymphocytes incubated with thymosin did not acquire increased responsiveness to mitogens as did cells incubated for 18 h in its absence and because mixing thymosin-pretreated lymphocytes with cells not preincubated with thymosin resulted in decreased responsiveness to photohemagglutinin.


Regulation of hepatic transport of bile salt. Effect of protein synthesis inhibition on excretion of bile salts and their binding to liver surface membrane fractions.

The overall transport of bile salts across the hepatocyte is characterized as a carrier-mediated process whose rate-limiting step is biliary secretion. Specific bile salt binding proteins have been identified in liver surface membrane fractions and were postulated to represent the initial interaction in bile salt translocation across both the sinusoidal and canalicular membranes. To test this hypothesis, cycloheximide was administered to rats to inhibit hepatic protein synthesis. 16 h after cycloheximide administration [14C]leucine incorporation into hepatic protein was inhibited by 93% at 1 h and 47% at 12 h. However, values of liver function tests were not increased, although serum albumin, serum alanine amino-transferase, and alkaline phosphatase were significantly decreased. Light and electron microscopy did not demonstrate necrosis or fat accumulation. The latter demonstrated minimal disorganization of rough endoplasmic reticulum and occasional lamellar whorls. 16 h after cycloheximide administration bile salt independent bile flow, basal bile salt excretion, and basal bile flow were unaltered, but the maximum bile salt transport capacity was reduced to 62% of control and 24 h later to 38%. Decreased bile salt transport was reversible, for it returned to control values after 48 h, when hepatic protein synthesis was also normal. Maximum bromosulfophthalein (BSP) transport, on the other hand, was reduced after 16 h to only 85% of control. Both bile salt and BPS maximum transport capacities decreased with time during inhibition of protein synthesis, apparently following first order kinetics. It was estimated that their half-lives are 20 h for bile salt transport and 55 h for BSP transport. These different turnover rates suggest that cycloheximide does not decrease active transport through generalized hepatic dysfunction or alteration of high energy sources possibly required for transport. The maximum number of [14C]cholic acid binding sites in liver surface membrane fractions was determined by an ultrafiltration assay. They were reduced to 68% of control after 16 h of cycloheximide and to 25% after 24 h. This reduction in the number of binding sites is apparently selective, for the activities of the liver surface membrane enzymes (Na+-K+)ATPase, Mg++-ATPase, and 5'-nucleotidase were not significantly changed. The associated alterations in bile salt transport and the maximum number of binding sites after cycloheximide administration suggests that these receptors may be the bile salt carriers.


Glomerular permeability of macromolecules. Effect of molecular configuration on the fractional clearance of uncharged dextran and neutral horseradish peroxidase in the rat.

Molecular parameters other than size and charge are likely to influence the filtration of macromolecules across the glomerular filter. We have studies, therefore, the glomerular permeability of macromolecules with widely different molecular configuration such as horseradish peroxidase, a plant glycoprotein with an isoelectric point in the physiologic pH range, and dextran, an uncharged sugar polymer of D-glucopyranose. Simultaneous fractional clearances were determined for both test macromolecules in five Wistar-Furth rats. The results indicate that for a molecular radius of 28.45 A, as measured by gel filtration, the sugar polymer has a fractional clearance of 0.483 on the average, exceeding that of the protein tracer, with a value of 0.068, by a factor less than 7. We conclude that other molecular parameters such as shape, flexibility, and deformability play important roles in the transport of macromolecules across the extracellular matrix that constitutes the glomerular filter.


Activity of [des-aspartyl1]-angiotensin II in primary aldosteronism.

This study describes the effects of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6+/-1 to 14+/-3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33+/-8 to 65+/-13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III.Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history.


Effects of metoclopramide and bromocriptine on the renin-angiotensin-aldosterone system in man. Dopaminergic control of aldosterone.

This study was designed to investigate the possible role of dopaminergic mechanisms in the control of the renin-angiotensin-aldosterone system in normal man. Six normal male subjects in metabolic balance at 150 meq sodium, 60 meq potassium constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. or placebo followed by angiotensin II infusion 1 h later on 2 consecutive days. Metoclopramide increased plasma aldosterone concentration from 8.2+/-2.2 to 21.0+/-3.3 ng/100 ml (P < 0.005) and plasma prolactin concentration from 18.0+/-4.0 to 91.7+/-4.0 ng/ml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrations remained elevated at 16.8+/-2.1 ng/100 ml (P < 0.01) and 86.8+/-15.9 ng/ml (P < 0.005), respectively. Angiotensin II at 2, 4, and 6 pmol/kg per min further increased plasma aldosterone concentration to 27.2+/-3.4, 31.9+/-5.7, and 36.0+/-6.7 ng/100 ml (P < 0.02), respectively. Placebo did not alter plasma aldosterone or prolactin concentrations, but angiotensin II increased plasma aldosterone concentration to 13.7+/-2.4, 19.0+/-1.9, and 23.3+/-3.2 ng/100 ml (P < 0.005). The increment of plasma aldosterone concentration in response to angiotensin II was similar after metoclopramide or placebo. The six subjects also received the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. followed by angiotensin II infusion on 2 consecutive d. Bromocriptine suppressed prolactin to <3 ng/ml. After placebo, plasma aldosterone concentration increased from 5.2+/-1.4 to 12.3+/-1.7, 17.2+/-2.2, and 21.8+/-3.5 ng/100 ml (P < 0.01) and after bromocriptine from 7.2+/-1.0 to 14.7+/-3.0, 19.8+/-3.2, and 23.4+/-1.6 ng/100 ml (P < 0.001) with each respective angiotensin II dose. No difference in the response to angiotensin II after bromocriptine or placebo was observed. Plasma renin activity, free 11-hydroxycorticoid concentration, and serum potassium concentration were unchanged by metoclopramide or bromocriptine. The results suggest that aldosterone production is under maximum tonic dopaminergic inhibition which can be overridden with stimulation by angiotensin II in normal man.


Defects in DNA and globin messenger RNA in homozygotes for hemoglobin Lepore.

Globin messenger RNA (mRNA) isolated from three patients homozygous for hemoglobin Lepore is shown to have a marked reduction of the amount of beta-like globin mRNA (Lepore-globin mRNA sequences) compared with alpha-globin mRNA by molecular hybridization. The relative amounts of alpha- and Lepore mRNA are similar to the amounts of alpha- and Lepore globin synthesized in intact cells and by isolated mRNA in a cell-free system. It is also demonstrated that Lepore-globin mRNA can completely hybridize to full-length or nearly full-length beta-globin specific complementary DNA and protect it from nuclease digestion, indicating close homology between the delta-mRNA sequences present in Lepore mRNA and the beta-complementary-DNA probe. We have also quantitated the numbers of beta-like globin gene sequences in genomic Lepore DNA by molecular hybridization and demonstrated a reduction in their number consistent with the Lepore gene being a delta beta-gene fusion product.


Immunoglobulin G independent activation of the classical complement pathway by monosodium urate crystals.

10 mg of monosodium urate crystals reduced the CH50 of 1 ml of human serum by 57% after 30 min at 37 degrees C. C1, C4, and C3 depletion of 52, 68, and 46% were typical of classical pathway activation. C1 binding and activation occurred when urate crystals were incubated with isolated precursor C1, and required the intact macromolecule, C1qrs. Activation of isolated C1 by urate crystals was not diminished by F(ab')2 anti-Fc under conditions in which C1 activation by aggregated immunoglobulin (G) was blocked by the F(ab')2 antibody.


Hypoxanthine uptake in isolated rat renal cortical tubule fragments.

Isolated renal tubule fragments prepared from adult Sprague-Dawley rats were used to study the cellular uptake of hypoxanthine. This uptake was rapid, reaching a steady state after 30 min of incubation. Analysis of the intracellular pool during the initial uptake and at the steady state revealed a concentration gradient of hypoxanthine consistent with active transport, although only one-third of the transported hypoxanthine remained unmetabolized. The remainder of the transported hypoxanthine was converted to inosine and inosinic acid, but detectable conversion to uric acid was not noted. A kinetic analysis of uptake revealed that two systems for cellular entry of hypoxanthine existed with K(m1) = 0.005 and K(m2) = 0.80 mM. Hypoxanthine uptake at physiologic concentrations was oxygen, sodium, and temperature dependent, but the addition of metabolic fuels and alteration of the medium pH over the range of from 6.1 to 7.4 had no effect. Adenine, guanine, and inosine inhibited the uptake of hypoxanthine via the low-K(m) system which mediates the majority of uptake at physiologic levels. Xanthine, uric acid, and probenecid inhibited uptake via the high-K(m) system, but did not affect uptake via the low-K(m) system. The data indicate that hypoxanthine at physiologic levels is transported into the renal tubule cell via a system different from that for other oxypurines.


Cyclic hematopoiesis. Effects of endotoxin on colony-forming cells and colony-stimulating activity in grey collie dogs.

Cyclic changes in blood neutrophil counts of grey collie dogs with cyclic hematopoiesis can be eliminated by daily endotoxin injections. Studies were performed to determine the mechanism whereby endotoxin alters this disease. Bone marrow granulocyte-macrophage progenitor cells (colony-forming cells [CFUc]) showed cyclic variation in the untreated grey collie, which was eliminated by chronic endotoxin treatment (Salmonella typhosa lipopolysaccharide W, 5 microgram/kg per day). Similar cyclic variation in blood CFUc was eliminated by this treatment. Tritiated thymidine suicide of the marrow colony-forming cells failed to show cyclic changes to explain the marked swing in CFUc numbers in untreated grey collies. The thymidine suicide rates were not significantly changed by chronic endotoxin treatment. Similarly, serum colony-stimulating activity did not show cyclic variation with the cyclic neutrophil counts in untreated grey collies and was not altered by chronic endotoxin treatment. We suggest that endotoxin eliminates neutrophil cycling in cyclic hematopoiesis by a direct effect on the flux of pluripotent stem cells into the committed stem cell compartment and that this occurs independent of changes in serum colony-stimulating activity.


Corticosteroids inhibit complement-induced granulocyte aggregation. A possible mechanism for their efficacy in shock states.

Granulocyte (PMN) aggregation and embolization may underlie complement (C)-mediated organ dysfunction in such syndromes as hemodialysis neutropenia and Purtscher's ischem;c retinopathy. Because of clinical and pathologic parallels, we have further suggested a role for this phenomenon in the genesis of the adult respiratory distress syndrome (ARDS). Because corticosteroids are commonly used in immune diseases, and have particularly been claimed efficacious in shock and ARDS, we tested the capability of methylprednisolone (MP), hydrocortisone (HC), and dexamethasone (DEX) to inhibit PMN aggregation. Aggregation engendered in vitro by zymosan-activated plasma (ZAP) was inhibited by MP and HC at concentrations approximating plasma levels achieved with the large bolus (30 mg/kg i.v) therapy advocated in shock states; DEX was almost without effect. Using intravital fluorescence microscopy, we observed PMN aggregation and embolization in the mesenteric vessels of rats given intra-arterial infusions of ZAP; this was also prevented by pretreatment with 30 mg/kg MP. Steroid inhibition of aggregation seemed not to involve disruption of receptor function, because aggregation induced by alternative agents, n-formyl-Met-Leu-Phe and the ionophore A23187, was also inhibited by MP. Moreover, corticosteroid inhibition of PMN prostaglandin synthesis is also an unlikely explanation for our results, since aspirin and ibuprofen failed to block aggregation and arachidonic acid neither effected aggregation itself nor ameliorated the steroid effect. Our studies provide a plausible rationale for the empiric observation that high-dose corticosteroids may benefit patients with syndromes associated with microvascular leukostasis.


Hemoglobin biosynthesis in individual erythropoietic bursts in culture. Studies of adult peripheral blood.

By using a methylcellulose clonal assay, we cultured peripheral blood erythropoietic precursors from a patient with sickle cell anemia, a patient with sickle cell hemoglobin C disease, and a normal volunteer. We then analyzed the synthetic rates of adult and fetal hemoglobins (Hb) in individual erythropoietic bursts. Bb were labeled with 14C-amino acids in culture, separated by slab gel isoelectric focusing techniques, and quantitated by fluorographic methods. All bursts exhibited both fetal and adult Hb in varying ratios. Frequency distributions of the individual burst differing in percentage of BbF biosynthesis approached normal distributions. Further stimulation of HbF synthesis by higher erythropoietin in culture was associated with increased HbF biosynthesis in individual bursts. Augmentation of human HbF synthesis in culture appears to be controlled by qualitative intracellular changes rather than by changes in cellular population.


An approach to quality and performance control in a computer-assisted clinical chemistry laboratory.

A locally developed, computer-based clinical chemistry laboratory system has been in operation since 1970. This utilises a Digital Equipment Co Ltd PDP 12 and an interconnected PDP 8/F computer. Details are presented of the performance and quality control techniques incorporated into the system. Laboratory performance is assessed through analysis of results from fixed-level control sera as well as from cumulative sum methods. At a simple level the presentation may be considered purely indicative, while at a more sophisticated level statistical concepts have been introduced to aid the laboratory controller in decision-making processes.


Urinary total porphyrins by ion exchange analysis: reference values for the normal range and remarks on preformed prophyrins in acute porphyria urine.

Determination of total porphyrin with a rapid and east method (ion exchange; spectrophotometry) was performed on 57 morning urine samples from laboratory personnel, 59 arbitrary day urine samples from blood donors, and 90 24-hour urines from medical inpatients. The upper reference limit for morning urine was 0.32 mumol/l but even a value as high as 0.7 mumol/l was found. In the donor urines the upper limit was 0.155 mumol/l. The 24-hour urines showed an upper reference limit of 271 microgram/24 h. These values are in good agreement with values from the literature, mostly based on extraction analyses. Tracings of the absorption curves in the region of 380--430 nm were performed in all analyses and showed that the non-porphyrin absorption was close to linear in most cases. Studies of porphyric urines gave no support to the claim that preformed porphyrins not formed from porphobilinogen are excreted in this disease.


Serum protein profile in sickle cell disease.

The total protein, albumin, globulin, and immunoglobulin levels of sera from 96 children with homozygous sickle cell disease were studied. A comparison of the results with the levels found in a control group of normal children of the same age shows that the sicklers have higher total protein, globulin, and IgM levels. The amounts of albumin and IgA seen were almost the same in both groups. The IgG levels differed considerably, the sicklers having only about half the quantity seen in normal children.


Comparison of passive haemagglutination and haemagglutination-inhibition techniques for detection of antibodies to rubella virus.

Because of the technical problems and length of time involved in the satisfactory performance of the haemagglutination-inhibition test for detection of rubella-specific antibodies, a commercially available passive haemagglutination (PHA) kit utilising rubella antigen-sensitised human erythrocytes was tested for its suitability for use in diagnostic laboratories. The immune response to acute rubella infections as measured by PHA was considerably delayed compared to the response measured by haemagglutination-inhitition. Titres of rubella-specific antibody only became comparable six months after the infection. The commercially available PHA kits is a useful addition to diagnostic laboratories for the determination of immune status and, in conjunction with the haemagglutination-inhibition test, can be an indicator of recent rubella infection.


Anaerobic organisms in postoperative wounds.

A survey of the bacteria found in postoperative wounds was undertaken during a 14-month period. The yields of aerobic and anaerobic bacteria in 65 appendicectomy wounds were compared; 42 wounds yielded aerobes and 51 anaerobes. Seventy-eight other operation wounds yielded anaerobes, and, overall, 33 wounds yielded anaerobes only. Bacteroides sp were the most common anaerobic organisms isolated from all operation sites except the lung.


Anti blood group-M autoantibodies with livedo reticularis, Raynaud's phenomenon, and anaemia.

A 63-year-old woman presented with Raynaud's phenomenon and extensive cold-induced livedo reticularis. A skin biopsy showed no abnormality of the blood vessels but the blood contained high titres of a very unusual autoantibody against the M blood group, most active at low temperatures. An IgM cryoglobulin was detected, and anti-M activity was found in this fraction. The cells of the patient were grouped as MM. The direct antiglobulin test was positive due to C3 component of complement bound to the red cells. The haematological and biochemical results indicate a mild haemolytic process, which is at present well compensated.


Gastin cells and fasting gastrin levels in duodenal ulcer patients: a quantitative study based on multiple biopsy specimens.

The number of gastrin-producing cells in biopsy specimens from the gastric and duodenal mucosae in 19 duodenal ulcer patients was quantitated using a morphometric method. The level of immunoreactive gastrin in a sample of fasting serum obtained at the time of the biopsy was measured by radioimmunoassay. The results show no significant difference when compared with those from a group of normal control volunteers. Moreover, there was no correlation between the numbers of gastrin-producing cells and the fasting serum gastrin level in either controls or duodenal ulcer patients.


Histological appearances of the gastric mucosa 15--27 years after partial gastrectomy.

Sixty-three patients, who had had a partial gastrectomy 15--27 years previously, were examined by endoscopy and multiple mucosal biopsies. No patient had a completely normal gastric mucosa; they showed varying degrees of gastritis, intestinal metaplasia, and dysplasia: 21% had significant dysplasia, and these are regarded as an 'at-risk' group requiring frequent follow-up examinations. One patient had severe dysplasia (carcinoma-in-situ), but no case of infiltrating carcinoma was found.


The priority test request form: a method for improving communication between the physician and the Emergency Clinical Biochemistry Laboratory.

Two forms--a priority test request form and a telephone results form--provide improved communication between the physician and the emergency laboratory of the Clinical Biochemistry Department. The priority test request form contains a list of available tests and it allows the physician to tell the laboratory exactly when emergency test results are required. The telephone results form ensures that the physician will receive a report, by telephone, of a test result although it may not be an urgent test. This allows a greater control of work flow, both routine and emergency, through the laboratory.


Enhanced transformation of digitoxin to dihydrodigitoxin in humans with renal failure.

A gas-chromatographic mass-spectroscopic technique was used to identify dihydrodigitoxin, a metabolite of digitoxin, in the plasma of healthy volunteers and patients with renal failure. Digitoxin and dihydrodigitoxin were extracted from plasma and derivatized with heptafluorbutyric anhydride. In normal subjects, only minimal concentrations of dihydrodigitoxin in plasma could be determined (1 ng/ml) after an intravenous bolus injection of digitoxin. Under a chronic treatment with a daily dose of 0.1 mg digitoxin in three out of seven individuals, detectable dihydrodigitoxin plasma levels were observed (0.7, 1.5, and 1.7 ng/ml) (Table I). On the other hand, in seven patients with renal failure, high dihydrodigitoxin plasma concentrations (8.9 +/- 0.9 ng/ml) were shown which were in a similar range as those of the parent compound (8.7 +/- 2.2 ng/ml) under a maintenance treatment with digitoxin.


Effect of furosemide on serum clearance and renal excretion of digoxin.

Serum turnover and urinary excretion of digoxin with or without oral furosemide were studied in six healthy subjects who received 0.006 mg/kg body weight digoxin intravenously. During furosemide treatment, the total amount of urinary digoxin did not change but the digoxin clearance during the diuretic phase and the digoxin excretion after the diuresis decreased significantly. The average serum half-life was prolonged from 37 hours in the control period to 86 hours in the furosemide period. Decreased glomerular filtration rate by volume depletion might have been responsible for the decreased excretion of digoxin, but there was no significant difference in urine volume after diuresis between the two periods, suggesting the possibility of inhibition of tubular secretion of digoxin by furosemide. It is also possible that serum digoxin concentration may be elevated if furosemide were given more frequently.


The respiratory effects of dezocine and pentazocine in man.

The respiratory effects of dezocine and pentazocine were studied in five volunteers. Based on their effects over a 3-hour period, it was found that dezocine was 8.6 times as potent as pentazocine in terms of their respiratory depressant effects. The clinical significance of these findings remains to be determined.


Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride.

A pharmacokinetic study of the antidiarrheal agent loperamide hydrochloride (Imodium) was conducted in six male subjects. The study utilized a random crossover design and employed a 2-mg capsule and a 0.2-mg/ml syrup formulation. Each treatment consisted of a single oral dose of 8 mg loperamide HCl followed by a two-week interval before the next treatment. Serum and urine samples obtained at various times after drug administration were assayed for loperamide using a radioimmunoassay specific for the drug. The mean biologic half-life, calculated from the elimination phase of the log serum concentration-versus-time data, was 10.8 +/- 0.6 hours for the overall study, 10.2 +/- 0.6 hours for the syrup formulation, and 11.2 +/- 0.8 hours for the capsules. The loperamide from the syrup was absorbed more rapidly than from the capsule formulation, with the peak serum levels observed at a mean time of 2.4 +/- 0.7 hours for the syrup and 5.2 +/- 0.3 hours for the capsule formulation. The relative areas under the serum loperamide concentration-versus-time curves suggested that the two formulations have comparable physiologic availability. The maximum observed serum concentrations were also similar, indicating the safety of the syrup formulation. Excretion of approximately 1 per cent of the dose in the urine as unchanged loperamide after seven days was observed independent of the particular dosage form that was administered.


Hemodialysis of theophylline in uremic patients.

Hemodialysis of theophylline was studied in three uremic patients. The dialysis clearance ranged from 75.6 to 97.9 ml/min and averaged 88.1 ml/min. A much smaller value of 32.8 ml/min was reported by Levy and associates. The difference may be attributed to the two monitoring factors during hemodialysis, namely, blood and dialyzate flow rates. Both were higher in our study. Analysis of the semilogarithmic plots of the arterial plasma concentration versus time over a 3-hour period gave apparent half-lives of 3.15, 2.04, and 2.73 hours, respectively, for the three patients. Half-life of theophylline in normal subjects ranged from 4 to 6 hours or even longer. A prolonged half-life of theophylline in uremia could be expected. Our kinetic study indicated an approximately 50 per cent reduction in terminal half-life during hemodialysis. Hourly dialyzate was collected from one patient to account for drug recovery in the dialysis fluid. Forty per cent of the administered dose was recovered in the dialyzate during a 3-hour dialysis period, indicating effective removal. Dialysis clearance for creatinine was calculated by arterial-venous difference and correlated with that of theophylline. We found that theophylline was cleared by the dialyzer at a rate approximating 63 per cent of creatinine removal.


The relationship between information transfer and speech intelligibility of dysarthric speakers.

The purpose of this study was to determine the relationship between information transfer and speech intelligibility, as measured by single-word and paragraph transcription across a wide range od dysarthric speakers. Nine dysarthric speakers, including ataxic, spastic, and hypokinetic types, participated in the study. Their performance was judged by 108 listeners. The correlations between information transfer and paragraph and transcription scores and between information transfer and word transcription scores were high, i.e., 0.95 and 0.90, respectively. Word transcription scores tended to be slightly lower than information transfer scores for mildly dysarthric speakers. Clinical implications of these findings were discussed.


Semantic paraphasia.

In the present paper a large corpus of semantic word selection errors from a severe Wernicke's aphasic is analyzed in accordance with a taxonomy recently proposed in the literature. In an attempt to demonstrate the systematicity of the aphasic substitutions, the errors are classified along a wide range of conceptual spheres. In addition, recent theories of the Russian neuropsychologist A. R. Luria are considered in providing an explanation for lexical selection deficits. Finally, comparisons are made between aphasic errors and similar errors seen in "slips-of-the-tongue" in non-brain damaged normal subjects.


Cortical word deafness in a child: a case history.

Despite the recent report of Goldstein et al. (1975) on pure word deafness in an adult, it still seems worthwhile to study the case of cortical deafness in a child, not only because we believe this to be one of the very few cases duly reported upon, but also because of its interesting pathological history, its implications for the existence of specific speech sound detectors, and its evidence of pathological communicative behavior which deviates from that of a deaf child.


Social class, defective hearing, and language.

Linguistic behavior of lower class normal-hearing children is less developed than that of higher class children. This study tests the hypothesis that the same applies to hearing defective (h.d.) children. Ninety-six h.d. children were tested with a linguistic ability test. The h.d. chiren scored lower than the higher class h.d. children. Within their own class the difference between the higher class h.d. and normal-hearing children was larger than that between lower class h.d. and normla-hearing children.


Interaction of deaf and hearing preschool children.

Hearing and hearing-imparied children attending an integrated preschool were observed in a free-play situation. The principal objective was to discern how hearing and deaf children interacted and modified their communication skills as a function of hearing status. The data indicate that hearing children interact more frequently with other hearing children on several behavioral categories (approaches, vocalizations, social play, and physical contact). Although there was a tendency for deaf children to approach other deaf children more frequently than they approached hearing children, they showed no preferences for other interactions as a function of peers' hearing status. These findings are consistent with those of research on other exceptional children, such as the mentally retarded, in showing that, while hearing-impaired children showed no peer preference, they were least preferred by normal peers.


Description and evaluation of structured speaking and listening activities for hearing-impaired adults.

This study was designed to evaluate improvement in word comprehension, pronunciation, and auditory discrimination as a result of structured group experience in speaking and listening. Subjects included 75 college students with hearing impairment and auditory discrimination for speech. Subjects were divided into three groups matched on the basis of hearing characteristics. Groups A and B received 20 hours of instruction over a 10-wk interval. Group A was evaluated relative to word comprehension, word usage in writing, and pronunciation. Group B was evaluated relative to auditory discrimination before and after training. Group C (control) did not receive training but auditory discrimination was evaluated over the 10-wk interval. Significant improvements in word comprehension, word usage in writing, pronunciation, and in auditory discrimination were achieved as a result of training. No significant change in auditory discrimination was observed in the control group.


Vocal register effects on vowel spectral noise and roughness: findings for adult females.

The effects of vocal register (vocal fry, modal, and falsetto) on the relative roughness and spectral noise level (SNL) of isolated test vowels (/u/ and/ae/) were investigated. Each of the three vocal registers; the obtained samples were magnetically recorded. A panel of 11 listeners independently verified by perceptual judgments that each recorded sample was produced in the "desired" vocal register. Also, they independently rated (on a 5-point equal-appearing intervals scale) the roughness of each test production. A median of the 11 roughness ratings (MRR) available was then obtained as an index of the roughness of each vowel sample. Additionally, a narrow-band (3 Hz) acoustic spectrum of each test production was made in which measures of vowel spectral noise were obtained. A mean over 25 noise measures per test production (from 100 to 2600 Hz) served as an index of the spectral noise level (SNL) for each vowel sample. The major finding in the study was that the MRR and the SNL for productions of both test vowels diminished significantly across vocal registers, from fry, to modal, to falsetto.


The relevance of body motion cues to both functional and dysfunctional communicative behavior.

This study assessed the extent ot which a speaker's visible, spontaneous body movements can contribute to the speech process. An experiment was conducted where subjects responded to videotaped verbal stimuli in one of three conditions (audiovisual, audiovisual without lip and facial cues, and audio alone) over four signal-to-noise ratios. The results indicated that: (1) visual cues can at times significantly improve comprehension scores, even with lip-facial cues not present; (2) visual cues significantly retard decay of comprehension as noise is increasingly introduced; (3) visual cues assist the comprehension of certain types of verbal segments, regardless of the information content expressed in those types of segments. A model of the bimodal aspect of the speech process is developed which illustrates both the cognitive and message-content dimensions. Possible future applications and research objectives are discussed in terms of normal and dysfunctional communicative behavior.


The morphology of the hippocampus and dentate gyrus in normal and reeler mice.

The morphology of the hippocampus and dentate gyrus in normal and reeler mice has been studied in Nissl, myelin, Golgi, Timm's sulfide silver and gold chloride-sublimate preparations. It is evident from both cell-and fiber-stained sections that despite the obvious defect in the positioning of the hippocampal pyramidal and dentate granule cells in the reeler mouse within the radial dimension, the hippocampal formation as a whole shows a normal and consistent progression of cytoarchitectonic fields along its transverse axis, and a normal and consistent progression of changes in the structure of the hippocampus and dentate gyrus along their longitudinal axes. Thus, at least in these structures, the reeler gene seems to exert its effect only in the radial dimension. Cell counts in the area dentata indicate that the number of dentate granule cells in the reeler mouse is reduced compared to that found in normal or heterozygous animals. Although it has been known for some time that the number of granule cells in the reeler cerebellar cortex is markedly reduced, this appears to be the first evidence for a reduction in cell number in a forebrain structure. All the major cell types normally found in the hippocampus and the dentate gyrus are recognizable in Golgi-stained preparations from the brains of reeler mutants. However, in both regions there are a number of abnormalities in the appearance of the cells which seem to be related to the cellular ectopia. Thus, whereas most of the pyramidal and granule cells which attain a normal position in the mutant usually have normal, or near-normal dendritic arbors, the dendrites of nearly all ectopic cells are severely distorted, both in their orientation and general configuration. In preparations stained by the Timm's sulfide silver technique it is evident that the general lamination pattern seen in normal mice is retained in the reeler hippocampus and dentate gyrus despite the gross malpositioning of many of the relevant neurons. However, although the overall laminar arrangement is preserved, there are some fairly consistent abnormalities; for example, the normal trilaminar staining pattern seen in the stratum moleculare of the dentate gyrus is replaced in the reeler by a bilaminar pattern. In gold chloride-sublimate impregnated preparations there is no obvious alignment of the astrocytes in the stratum moleculare of the dentate gyrus in either normal or reeler mice. Moreover, the distribution of the astrocytes within this zone is fairly normal in the reeler mouse, although, in general, these cells appear to be more consistently stellate in form than in normal animals.


The organization of certain afferents to the hippocampus and dentate gyrus in normal and reeler mice.

The organization of certain of the major afferents to the hippocampus and dentate gyrus has been studied in normal and reeler mutant mice using the autoradiographic and the anterograde degeneration methods. The distribution of the hippocampal and dentate afferents which arise in the medial and lateral parts of the entorhinal cortex and the hippocampus of both sides, has been found to be generally similar to that previously described in the rat, but there are a few minor differences that are discussed in the text. Despite the marked ectopia of many of the neurons in the hippocampal formation in the reeler mouse, the principal afferents to the hippocampus and the dentate gyrus maintain many of the features seen in normal mice. In particular, they maintain a normal radial sequence and a characteristic laminated and complementary arrangement. However, there are a number of significant differences in their distribution; for example, in the reeler mouse, the entorhinal afferents occupy the entire radial extent of the stratum moleculare of the dentate gyrus, whereas in normal mice they are restricted to the outer four-fifths of this layer. Furthermore, in the mutant the commissural and associational afferents to the dentate gyrus do not occupy the inner one-fifth of the molecular layer (as they do in normal animals) but rather are spread throughout the zone containing granule cells, which includes both the poorly-defined stratum granulosum and most of the hilar region of the dentate gyrus. Some of the developmental and functional implications of these and other abnormalities in the organization of the afferents to the hippocampus and dentate gyrus are discussed.


The morphological and physiological properties of a regenerating synapse in the C.N.S. of the leech.

Regeneration of an electrical synapse between particular interneurons in the medicinal leech was traced physiologically and morphologically using intracellular recording the horseradish peroxidase (HRP) injection. The synapse between S-cell interneurons lies in the connective midway between segmental ganglia, so crushing near one ganglion severs only one S-cell's axon. The severed distal stump remains connected to the adjacent uninjured S-cell and continues for weeks to conduct impulses. The injured cell regenerates, while its uninjured "target" neuron in the next ganglion does not grow. After the sprouts of the regenerating neuron cross the crush, one or a few branches grow along the surviving distal stump toward the original synapse. After about one month when the region of original synapse has been reached, regenerating neurons form electrical junctions and stop growing. Thereafter electrical coupling improves in stages. Within two months the regenerated neuron attains full caliber, the stump degenerates and function is normal. In some instances within days or weeks of crushing, the regenerating neuron forms a basket of synapses upon its severed distal stump and then continues growing to synapse with the target. When this occurs, electrical coupling and subsequent impulse transmission between S-cells rapidly resumes. These experiments indicated that the regenerating neuron is guided to its proper synaptic target by recognizing and following its severed distal stump. Sometimes the distal stump itself becomes an intermediate synaptic target.


Opening of tight junctions in cerebral endothelium. I. Effect of hyperosmolar mannitol infused through the internal carotid artery.

Infusion of 1.8 M mannitol solution into the internal carotid artery of Wistar rats allows horseradish peroxidase (HRP) to cross cerebral vascular endothelium via intercellular pathways. This was made evident by density gradients of HRP observed in consecutive tight junctional compartments following in vivo administration, and by the passage of colloidal lanthanum through junctional membrane appositions of glutaraldehyde fixed cerebral endothelium. Three hours after mannitol infusion, small non-capillary vascular segments were still focally permeable to HRP. Twenty-four hours after the osmotic insult, the tracer was absent in the affected hemisphere. Water and electrolyte assays indicated absence of brain edema during the period of observation of blood-brain barrier opening.


Opening of tight junctions in cerebral endothelium. II. Effect of pressure-pulse induced acute arterial hypertension.

Acute arterial hypertension was produced in male Wistar rats by pressure pulse through the right internal carotid artery. The pressure pulse was induced by infusion of physiological saline as a bolus, at a rate of 0.63 ml per second by syringe pump. Evans blue (Eb) was used to visualize the areas of blood-brain barrier opening. Intravenously injected horseradish peroxidase (HRP) was used to study the ultrastructural basis of permeability changes in cerebral endothelium. Eb outlined circumscribed areas of blood-brain barrier opening. HRP extravasation was found mainly around small arteries. The capillary network was affected to a much lesser extent. Electron microscopy showed that HRP crossed the endothelial cell layer by intercellular routes. Glutaraldehyde fixed brain samples permeated with colloidal lanthanum supported these observations.


Quantitation in positron emission computed tomography: 1. Effect of object size.

The effect of object size on the capability of positron emission computed tomography to measure isotope concentrations in a cross section was studied. The relationship between the apparent isotope concentration in an image and the true concentration was measured as a function of object size for three instrument resolutions and four convolution filters. The relationship between image size and object size was also measured under the same conditions. Depression of apparent isotope concentration in an image for objects equal in size to the instrument resolution (FWHM) was significant (50% for a cylinder and 25% for a bar). For objects larger than 1.0 FWHM, accurate object sizes can be estimated from the images. Thus, reasonably accurate and practical schemes of compensation for object size effects can be implemented for objects larger than 1.0 FWHM. Accuracy in quantitating isotope concentrations in smaller objects is seriously compromised by the loss of sensitivity to the object size and the large correction factors required to compensate for instrument response. The results of the measurements were found to be in good agreement with theoretical predictions for ideal systems of comparable resolution.


Sphenoidal mucoceles with intracranial extension.

Two cases of sphenoid sinus mucocele with intracranial extension are presented. Multiplanar computed tomography scans delineated the extent of these lesions, facilitating both preoperative diagnosis and proper clinical management. One lesion was isodense and the other hyperdense (98 Hounsfield units: 1,000 scale). Neither demonstrated significant enhancement after the administration of contrast medium.


Incidence of basal ganglia calcifications on computed tomography.

In a group of 3,800 computed tomography examinations, 14 patients (0.4%) were found to have high attenuating lesions suggesting calcifications within the basal ganglia. The lesions were bilateral in all patients. A majority of the patients had psychic symptoms and convulsions. Electroencephalographic changes were frequent and extrapyramidal symptoms occurred. Until now only three patients have been endocrinologically examined. One of them had hypoparathyroidism. Since parathyroid dysfunction frequently is associated with calcifications of the basal ganglia, these patients should be referred for endocrinological evaluation.


Visualization of the longitudinal fold of the duodenum by computed tomography.

The longitudinal fold of the duodenum can be visualized by computed tomography (CT). Visualization of the fold helps localize the hepatopancreatic duct entrance into the duodenum. Many pathological processes of the head of the pancreas such as pancreatitis or malignancy can produce swelling involving the longitudinal fold, which can be visualized by CT.


The right posterolateral tracheal band.

Changes in the right posterolateral tracheal band and the right retrotracheal recess are reliable parameters for evaluating pathology in the right superior mediastinum. We have measured the posterolateral tracheal band at the sternal notch and 2 cm below the sternal notch in computed tomograms. At the sternal notch, the average thickness was 8.4 +/- 3.8 mm. At the level 2 cm below the sternal notch, the posterolateral band was 6.4 +/- 1.8 mm. This represents measurements from 100 normal patients. Pathology in the lungs, pleura, esophagus, soft tissues, and other mediastinal structures can clearly affect the posterolateral tracheal band, causing abnormal contours and widening of the band.


The subtrapezial space.

The subtrapezial space as it is depicted on computed tomography scans of patients positioned with their arms above their heads is described and illustrated. Knowledge of the outline and contents of this area is useful in the recognition of enlarged lymph nodes.


Diving-type injury of the cervical spine: contribution of computed tomography to management.

We have utilized computed tomography (CT) in addition to conventional radiography for evaluation and as a guide to management of serious diving injuries to the cervical spine. This technique has proven to be invaluable in the initial assessment and further clinical management of this type of injury. A classification of these injuries and associated fractures is presented based on CT appearance. Representative cases are presented comparing standard radiography and CT.


Demonstration of beam hardening correction in computed tomography of the head.

The efficacy of a method of removing artifacts due to beam hardening in computed tomography of the human head is demonstrated on a realistic, mathematically described phantom. An efficient implementation is discussed.


Utilization of cross-plane rays for three-dimensional reconstruction by filtered back-projection.

Present popular computed tomography (CT) algorithms reconstruct an object from the ray measurements lying on a set of parallel planes. This paper presents an algorithm that can also utilize "cross-plane" rays (i.e., rays that cross through many planes) to reconstruct the object. In this reconstruction algorithm, the ray measurements are grouped into two-dimensional projections, filtered, and stored. The filtered projections can then be back-projected onto a three-dimensional matrix or any plane through the three-dimensional volume. General theoretical aspects are presented and then applied to the special case in which ray measurements have been made in all directions. The algorithm is tested using computer-generated data. Expressions for the noise power spectrum and the variance in the reconstruction are derived. It is shown that the noise-to-signal ratio per detected photon for this reconstruction method is close to a theoretical limit, as it also is for normal CT. The ability to use ray measurements that cross many planes is especially useful in emission CT, where order-of-magnitude improvements in image quality per unit dose can be achieved.


Sarcoidosis of the central nervous system.

A case of central nervous system sarcoidosis verified by direct biopsy and skin tests and without evidence of any other system involvement is reported. The computed tomography findings are described in detail.


Computed tomography changes in neurosarcoidosis clearing with steroid treatment.

Contrast enhancement computed tomography (CT) in a patient with central nervous system (CNS) sarcoidosis revealed increased densities particularly in the frontal and temporal areas. Treatment with prednisone improved the condition, and the CT abnormality disappeared. These previously undescribed findings can be of help in establishing the diagnosis and in following the patient's response to treatment.


Traumatic diaphragmatic hernia into the pericardium: verification of diagnosis by computed tomography.

Computed tomography (CT) is a useful modality in the evaluation of mediastinal abnormalities and in the assessment of mediastinal masses for fat content. A case of posttraumatic herniation of the omentum and large bowel into the pericardial sac is presented. The mediastinal configuration, depicted on a CT scan, is thought to be diagnostic of this extremely rare abnormality.


Intrathoracic kidney.

An asymptomatic, posterior mediastinal mass first appeared in a routine chest X-ray film of a 43-year-old woman. Computed tomography (CT) permitted the diagnosis of intrathoracic kidney to be advanced. Intravenous urography confirmed the CT diagnosis.


Computed tomography in preoperative diagnosis of conjoined twins.

A case of thoracoomphalopagus twins diagnosed preoperatively by computed tomography is described.


Cerebral toxoplasmosis in the adult.

We report a case of cerebral toxoplasmosis in an adult patient. The diagnosis was established by demonstration of Toxoplasma gondii in the cerebrospinal fluid, and the patient was evaluated by computed tomography.


Cerebral phycomycosis.

The incidence of phycomycotic infections of the central nervous system (CNS) remains high in diabetic and immunosuppressed patients. Despite increasing awareness of possible CNS fungal infections, the diagnosis during life remains difficult and is most often made at postmortem examination. The present report describes a histologically confirmed case of cerebral phycomycosis diagnosed in life. The findings on computed tomography as well as other radiological diagnostic procedures are discussed.


Cervical computed tomography in multiple sclerosis with spinal cord involvement.

We present the computed tomography findings in a young man with known multiple sclerosis during an acute phase of recrudescence. An enhancing lesion is demonstrated in the brain with a possibly enhancing focus in the spinal cord.


Receiver operating characteristic curves in the evaluation of hard copies of computed tomography scans.

Receiver operating characteristic curves have been used to compare a variety of pictures derived from a number of hard copy devices used with EMI computed tomography scanners. The pictures examined were obtained from (a) a Shackman camera with bromide paper, (b) a Polaroid camera and Polaroid film, (c) a Shackman backed camera with radiographic film, and (d) an EMI multiformat imager. The results show no significant difference in detectability of an experimental object close to noise values using the various hard copies. It is concluded that the choice of a hard copy device might be based on considerations other than its physical performance.


Early histopathology of the cutaneous capillary fragility test (Rumpel-Leede).

The characteristic histologic change seen at 2 h in the Rumpel-Leede (Hess) test is, in addition to focal hemorrhage in the upper dermis, a perivascular lymphocyte infiltrate with focal areas of lymphocytic epidermal invasion. The histologic findings, even with the liquefaction degeneration, are similar to those of purpura simplex and indicate that, early in many forms of vasopermeability, the lymphocyte may be a primary inflammatory cell.


Pitted keratolysis (keratolysis plantare sulcatum). Ultrastructural study.

Biopsies from typical lesions of pitted keratolysis from five patients have been investigated by electron microscopy to provide information on colonization and morphology of the microorganisms involved in this disease. A part of the biopsies was inoculated in culture media, and Corynebacteria were selected for further examination. Electron microscopy revealed a great variability in the morphologic feature of bacteria concerning size, shape, capsule, cell wall, cross wall formation, plasma membrane, nucleoplasm, cytoplasmic organelles and constituents including mesosomes, ribosomes, volutin granules, and glycogen particles. The pleomorphism is thought to be due in part to the diversity of preparation techniques used in this study and in part to different growth conditions in vivo and in vitro. As a consequence the present findings are only partly comparable with previously published data on bacteria involved in skin diseases. Evidence is presented that bacteria inducing pitted keratolysis may be able to destroy keratin by means of hydrolytic enzymatic activity.


Systemic mastocytosis and the mastocytosis syndrome.

A patient with extensive systemic mastocytosis and the mastocytosis syndrome was studied by light and electron microscopy. Mast cell proliferation was found in the bone marrow, the liver, spleen and lymph node. In addition, the patient had telangiectasia macularis eruptiva perstans and elevated histamine levels.


Skin storage in liquid nitrogen. An ultrastructural investigation.

The problem of cell survival as well as the biochemical and histological effects on skin of low temperature storage in liquid nitrogen has already received attention. However, little is known of the submicroscopic alterations induced by such treatment. Our study shows that rapid or slow freezing, direct or mediate contact with the liquid nitrogen, pretreatment before freezing, type and concentration of cryoprotectants, all have various effects on the fine morphology of epidermal cells. Glycerol is shown as having better cryoprotective activity than DMSO at concentrations of 15% or less. Our data are examined taking into account all available reports on the problem of cryopreservation and the use of cryoprotectants.


The dermal component in melanosis naeviformis Becker.

Histological investigations were performed in 11 subjects suffering from melanosis naeviformis Becker. Apart from the well-known epidermal alterations such as basal hyperpigmentation, slight acanthosis and growth of coarse hair, dermal changes were found in each case. The dermis was considerably thickened and contained numerous small and/or large bundles of smooth muscle without relation to cutaneous adnexa. Thus, melanosis naeviformis Becker can be considered an organoid nevus with epidermal, melanocytic and dermal components.


Lichenoid delayed hypersensitivity reactions in tattoos.

Two patients with an inflammatory reaction in a red tattoo had histopathologic changes of lichen planus. The lesions demonstrated a lymphocytic bandlike infiltrate, liquefaction degeneration, acanthosis, hypergranulosis, and orthokeratosis and many hyaline bodies. Metal particles were observed in the region of the dermal-epidermal reaction. This probably is another example of the lichenoid reaction produced by delayed cellular hypersensitivity.


Febrile ulceronecrotic Mucha-Habermann's disease with interstitial pneumonitis.

A case of febrile ulceronecrotic Mucha-Habermann's is presented. This disorder is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) characterized by the sudden eruption of diffuse coalescent ulcerations associated with high fever. In the present case the disease was preceded by the milder typical form of PLEVA. Histologically a leukocytoclastic vasculitis was seen in addition to the usual lymphocytic perivascular and lichenoid infiltrate. During the course of the disease the patient developed an interstitial pneumonitis which resolved concomitantly with the cutaneous lesions. Adenovirus type II recovered at the height of the illness from the patient's urine may have etiologic implications in the pathogenesis of the disease.


Chromomycosis. Successful treatment with 5-fluorocytosine.

A case of chromomycosis, caused by Fonsecaea pedrosoi, was treated with 5-fluorocytosine. After 18 weeks of treatment the initial lesions had largely resolved, and no evidence of active disease was observed clinically, histologically or from fungal cultures of the biopsy material. Further resolution of the remaining hypertrophic scar was achieved by intralesional injections of triamcinolone acetonide. Minimal side-effects were encountered during the therapy, and no recurrence during an 18-month follow-up period was observed. The results of this study indicate that 5-fluorocytosine is an effective and relatively safe mode of therapy in chromomycosis.


Separation of a guanine nucleotide regulatory unit from the adenylate cyclase complex with GTP affinity chromatography.

We studied the relationship between guanine nucleotide binding proteins and adenylate cyclase activity of solubilized turkey erythrocyte membranes with GTP affinity chromatography. Solubilized adenylate cyclase from untreated membranes or membranes pretreated with GMP only (GMP prep) responded poorly to GTP or Gpp(NH)p but were markedly stimulated by fluoride. The solubilized enzyme from membranes pretreated with isoproterenol+GMP (ISO+GMP prep) did not respond to GTP but was markedly stimulated by Gpp(NH)p. Fluoride-stimulated activity of the ISO+GMP prep was reduced by comparison with the GMP prep but could be increased significantly by addition of GTP. GTP hexane agarose (GTP linked to matrix via morpholine derivative of ribose) failed to interact specifically with either the GMP or ISO+GMP prep. Incubation of ISO+GMP prep with GTP-gamma-agarose (GTP linked to matrix via terminal phosphate) reduced the Gpp(NH)p response and the GTP-dependent fraction of the fluoride response. GTP-gamma-agarose did not reduce the fluoride response of the GMP prep. Following incubation with ISO+GMP prep, GTP-gamma-agarose beads were eluted with buffer containing Gpp(NH)p. The eluate had only slight intrinsic adenylate cyclase activity but was able to increase significantly the activity of GTP-gamma-agarose-treated ISO+GMP prep as well as untreated GMP prep. An eluate from GTP-gamma-agarose beads incubated with GMP prep did not possess activity. Our results suggest that the guanine nucleotide-regulatory unit is reversibly associated with the adenylate cyclase complex of turkey erythrocyte membranes.


Inhibitory effect of adrenaline on oxytocin release in the ewe during the milk-ejection reflex.

Milk-ejection activity was determined in the blood plasma of ewes during normal milking and during milking when adrenaline was injected intravenously before or after udder stimulation. It was found that administration of adrenaline either before or after udder washing, decreased the oxytocin concentration and milk yield but increased the yield by hand-stripping. Adrenaline also retards the average time for peak oxytocin concentration. These results and the use of a beta-receptor blocker to inhibit the effect of adrenaline at the myoepithelial cell level indicate that in ewes adrenaline can prevent the release of oxytocin from neurohypophysis.


Metabolism of [U-14C; 2,3-3H]-L-valine by the isolated perfused goat udder.

Two lactating mammary glands excised from 2 goats were perfused for several hours in the presence of [U-14C; 2,3-3H]-L-valine and received adequate quantities of glucose, acetate and amino acids. In the synthesized milk 96 and 89% respectively of the casein valine was derived from free plasma valine. Valine was extensively catabolized by mammary tissue, resulting in a considerable 14CO2 production and in the incorporation of 14C into milk citric acid and to a lesser extent into casein aspartic acid and glutamic acid. About 30% of the valine molecules which were taken up by the mammary gland were oxidized to CO2 and 70% were incorporated in casein as valine residues. About 10% of the plasma valine molecules were reversibly transaminated during one passage through the udder. An important amount of radioactivity of plasma was present in unknown metabolites. Only 7% of this activity was localized in isobutyrate. The radioactivity of total milk fat was very low. Mainly iso-14:0, iso-16:0 and 15:0 were labelled.


Effects of increased supply of essential amino acids on the metabolism of the isolated perfused guinea-pig mammary gland.

The effects of high rates of infusion of essential amino acids on amino acid uptake by the isolated perfused guinea-pig mammary gland were studied. Infusion of methionine, tyrosine, phenylalanine, histidine and tryptophan (designated group 1) resulted in significant increases in the uptakes of tyrosine, phenylalanine and histidine. Methionine, tryptophan and other essential amino acids were not significantly affected. Infusion of threonine, valine, isoleucine, leucine, lysine and arginine (designated group 2) resulted in significant increases in uptake of all these amino acids. Group 1 amino acid uptake was not significantly affected. Infusion of all the essential amino acids (i.e. groups 1 and 2 together) resulted in significant increases in all their uptakes. Using as index 'the predicted rate of protein synthesis', infusion of group 1 and 2 together led to an apparent 27% increase in protein synthesis. The above results are discussed in relation to the control of milk protein synthesis by limiting essential amino acids.


Effects of restriction of amino acid supply to the isolated perfused guinea-pig mammary gland.

When individual essential amino acids were omitted for periods of 40--100 min from the infusate substrate solution in isolated perfused guinea-pig mammary gland experiments, uptake of methionine, tyrosine, phenylalanine, histidine and tryptophan (group 1) was significantly depressed by a mean of 49.8%, whereas the remaining essential amino acids (group 2) showed no significant decrease in uptake. During depletion periods oxidation of [14C]amino acids was increased. The possible significance of the differences in absorption between the 2 groups of amino acids is discussed.


Benign follicular neoplasias.

The generality of benign epithelial neoplasias of follicular origin or with differentiation toward follicular structures is briefly reviewed. Recently delineated examples of this group are more extensively discussed.


Local anesthesia of the face.

The principles and practice of local anesthesia on the face are discussed in terms of preoperative preparation of the patient, effective topical and injectable local anesthetics, innervation of the face, and techniques of topical application and injection of local anesthetics.


Primary cutaneous squamous-cell carcinoma on the face: penetration to the base of the brain.

A recurrent squamous-cell carcinoma that was found clinically to have metastasized to regional lymph nodes was managed by a surgeon skilled in Moh's techniques, a plastic surgeon, and a radiotherapist in a premeditated plan. The malignancy was further found to have extended to the base of the brain. As much surgery as was deemed feasible, still short of complete ablation of the malignancy, was performed. Radiotherapy to the neck prior to radical lymphadenectomy and to the base of the brain subsequently was administered. After one year of follow-up, the patient is well, though prognosis is guarded.


Controversies in dermatopathology.

Five controversial topics in dermatopathology are discussed. Penile lesions with atypical epidermal cells in young men, neoplasms with intraepithelial cellular nests, neoplasms with a trichilemmal outer layer, neoplasms with eddies of squamous cells, and the origin of seborrheic keratoses are analyzed to suggest a means of clinical recognition and understanding.


Hyponatraemia in patients with head injury.

Three patients with head injury are described to illustrate certain features of the development, treatment and recovery of hyponatraemia. The hyponatraemia is initially due to water retention but true sodium depletion may develop because of an associated urine sodium loss. The mechanism of the latter is discussed.


Conservative management of patent ductus arteriosus in preterm infants.

We report our experience of medical treatment, chiefly based on prolonged artificial ventilation, of 33 preterm infants with PDA and heart failure whose survival rate was 88%. All of them had clinical criteria used by others to indicate surgical ligation of the ductus arteriosus. This conservative approach seems to give better results than surgical ligation, despite a high frequency of bronchopulmonary dysplasia among survivors.


Guide wire-sheath technique for pulmonary artery catheterization and central vein cannulation.

The combination of a spring guide wire with a sheath introducer system has been successfully used for the routine placement of pulmonary artery and central venous catheters. The method, which is described is simple, quick, and safe. It is applicable to the initial placement of the catheter, to any necessary alterations in its position, and to its eventual replacement with a central venous cannula.


Evaluation of a simple device for regulating intravenous infusions.

Dial-A-Flo, an infusion control device, is assessed for accuracy, in vitro and in vivo. The unit did not permit accurate control and particularly so at lower flow rates. The normal spontaneous variations in venous pressure that occur around an infusion cannula tip, further increase the error of gravity-fed infusions. Dial-A-Flo has no advantage over a standard administration set alone, and should not be used for controlled administration of cardiac drugs.


Description and evaluation of a preventive mental health program for preschoolers.

A school-based model of preventive intervention is described which identified and significantly overcame school maladaptation among preschool children enrolled in a Detroit Public School Title I Program. Children were screened by teachers for learning and behavioral difficulties using the AML Scale, the Classroom Adjustment Rating Scale, and the Caldwell Preschool Inventory. Sixty-four children were identified on the basis of these instruments as exhibiting some form of school maladaptation. These children were randomly assigned to an experimental condition (N = 32) or placebo control (N = 32). Individually designed prescriptive techniques were developed for high-risk children in the experimental group and were implemented by college student aides after training by the project staff. A multivariate analysis of variance and follow-up univariate analyses, testing differences between experimental and control groups on the posttests, were performed. The difference between the groups on all three criteria measures was significant and favored the experimental children.


The discriminative efficiency of the Bayley Scales of Infant Development.

This study was designed to determine the discriminative efficiency of the Bayley Mental and Motor Scales for classifying infants as neurologically suspicious and neurologically normal. The two groups employed in the study were formed on the basis of the results from comprehensive neurological examinations performed at ages 1 and 7. Three discriminant function analyses were conducted, one for each scale separately and a third incorporating both scales using a stepwise procedure. Efficiency was measured in terms of number of correct and incorrect classifications, false positive and false negative errors, and validity coefficients. Comparisons among the analyses were examined by means of relative discrimination power and incremental validity. The findings suggested that the Motor Scale provides the most accurate identification of infants with suspected neurological impairments. A statistically significant likelihood discriminant function derived from both scales yielded some additional discriminative power. The law of parsimony, however, dictated the use of the single Motor Scale.


An adolescent symptom checklist for juvenile deliquents.

A rating instrument was developed to assess the personality functioning of problem adolescents who have a brief history of official delinquency. Subjects were 186 residents at a short-term diagnostic detention facility. The instrument that emerged from a factor analysis was tested for reliability, validity, and cross-situational generality. Two major orthogonal factors emerged, Apathy-Withdrawal (I) and Anger-Defiance (II). Each factor was found to be congruent with the corresponding dimension on behavior rating instruments that had previously yielded two orthogonal factors and that had been shown to be relevant to a large number of psychological and educational issues. Significant correlations between the factors and a series of global ratings measuring behavior and measures indicative of the frequency and seriousness of official delinquency provided further evidence of construct and discriminant validity as well as evidence of cross-setting consistency of personality functioning.


An analysis of observational learning in autistic and normal children.

The present investigation studied observational learning in autistic children. Fifteen autistic and 15 normal children watched an adult model engage in a set of behaviors under specific verbal instructions. After observing this situation, the children were tested to determine what they had acquired through observation. The results showed that (1) the majority of the autistic and the youngest normal children acquired only some limited features of the observational situation and (2) chronological age was related to the amount of learning through observation in the normal children but not in the autistics. The deficit that the autistic children showed in observational learning may be related to a failure to discriminate or attend to the total stimulus input presented. Their failure in observational learning can be seen to contribute in a major way to the severely impoverished behavioral repertoires of these children.


Test anxiety and evaluation threat: children's behavior in the classroom.

Children differing in test anxiety level were observed in two art classes, one immediately preceding a classroom examination, the other when no examination was expected. The observational analyses indicated the following: (a) When an examination was expected there were general increases both in children's task orientation and in their concern with other's evaluations, and a decrease in general activity level. It was suggested that future research examine the effects of additional situational variables on children's classroom behaviors. (b) Highly test-anxious children were generally hardworking and inactive. They reacted to examination expectancy with a decrease in task orientation, reduction in communications, and attentional constriction. Less anxious children reacted to examination expectancy by working harder, eliminating task-irrelevant behaviors, and seeking feedback. These results were interpreted as supporting a cognitive theory of test anxiety.


Behavior problems of preschool children: dimensions and congenital correlates.

Factor analysis of a revised Behavior Problem Checklist for a sample of preschool children yielded six oblique primary factors and two orthogonal second-order factors. Scores on these factors were correlated with activity level, gross- and fine-motor incoordination, minor physical anomalies, and sociability. There were sex differences and factor differences in the resulting patterns of correlations. The patterns of correlations also indicated that the six primary factors could be collapsed into two broad (Conduct and Personality) and two narrow (Distractibility and Attention Seeking) factors.


Relationship among environmental and demographic variables and teacher-rated hyperactivity.

This study assessed the role of environmental and demographic factors in the occurrence of teacher-rated hyperactivity. The subject group consisted of 79 hyperactive and 81 nonhyperactive children ranging from 5 to 12 years of age. Parents of the subjects were interviewed to obtain information regarding the environmental and demographic factors of sex, race, birth order, number of siblings, frequency of change of residence, income level, mother's age, father's age, educational level of mother, educational level of father, parents' marital status, and the method of child discipline used in the home. Comparison between the the hyperactive and nonhyperactive groups suggested nonsignificant differences with the exception of sex (p less than .001), in which the ratio of hyperactive males to hyperactive females was 5:1.


An interview with a child to assess psychiatric disturbance: a note on its reliability and validity.

Forty-six children with enuresis were given a psychiatirc interview. The two writers made independent ratings of 10 behavioral variables. Seven of these showed satisfactory interrater reliability. No relationship was established between child psychiatric disturbance assessed in this way and estimates of disorder obtained from information given by mothers and teachers.