Pharmacokinetics of motilin in man.

The study provides pharmacokinetic data for exogenous synthetic and endogenous natural motilin in man. Synthetic 13-norleucine-motilin was infused into 6 healthy volunteers at a dose of 0.6 and 2.4 (pmoles per kg) per min over 60 min and plasma motilin was measured by radioimmunoassay. During the infusions mean plasma levels of 124.8 +/- 14.8 and 360 +/- 19.6 pmoles per liter, respectively, were achieved. Disappearance half-time on stopping the infusion was 4.36 min. The apparent volume of distribution was calculated to be 49.4 +/- 3.3 ml per kg, and the metabolic clearance rate was 7.8 +/- 0.5 (ml per kg) per min. To measure the decay of endogenous motilin somatostatin was used in the same 6 subjects. A bolus of 100 mug and a subsequent 15-min infusion of 15 mug per min of somatostatin suppressed the fasting motilin level by 50%. The disappearance half-time was 4.56 min. It is concluded that both synthetic and endogenous motilin are eliminated by first order kinetics with very similar half-times. Our data also suggest that the previously reported motilin infusions at these dose levels gave plasma concentrations within the physiological range and that the effects noted may thus have reflected the physiological actions of motilin.


Discharge of newly synthesized proteins in pure juice collected from the human pancreas. Indication of more than one pool of intracellular digestive enzymes.

The pancreatic secretion of 6 normal human volunteers was collected by endoscopic cannulation of the main pancreatic duct. The appearance of newly synthesized proteins was monitored at 1-min intervals after labeling with [75Se]methionine. The minimum transit time of these proteins from their site of synthesis to the acinar lumen was 36 +/- 8 min. Stimulation of protein secretion by a rapid intravenous injection of caerulein (40 ng per kg), 1 hr after [75Se]methionine administration, greatly decreased (by 73% on an average) the specific radioactivity of the discharged proteins. These data support the concept of a functional heterogeneity of proteins secreted by the human pancreas.


Effect of small bowel resection on the gastric mucosa in the rat.

Male Sprague-Dawley rats (120 to 130 gm), unoperated, sham-operated, and those with a 50% resection of the proximal small intestine, were studied after periods of 3, 6, 9, or 12 months. Differences in body weight and in the surface area, thickness, volume, and cellular content of the gastric mucosa between these three groups of animals were compared and statistically analyzed. After an initial loss in body weight, animals with small bowel resection and sham-operated animals attained weights equivalent to unoperated controls. Comparison of the groups for mucosal surface areas of the body of the stomachs showed no significant differences at the 3-, 6-, or 9-month periods. However, 12 months after surgery, the mucosal surface area of stomachs from resected animals was significantly greater than in corresponding controls. At 3, 6, and 9 months after resection, the thickness and volume of the gastric mucosa and the epithelial cell populations (parietal and nonparietal) of the gastric glands were significantly greater than in controls. However, at 12 months, there was no significant difference in any of these parameters between the controls and the experimental animals. The DNA content of the gastric mucosa was significantly greater for animals with small bowel resection than for corresponding controls at 1 and 6 months after surgery. It is concluded that hyperplasia of the gastric glands exists for at least 9 months after proximal small bowel resection in the rat. This hyperplastic response may be responsible for the previously observed (N Engl J Med 272:509-514, 1965; Surgery 65:292-297, 1969) gastric hypersecretion associated with extensive small bowel resection.


Duodenal-gastric reflux and slowed gastric emptying by electrical pacing of the canine duodenal pacesetter potential.

In 6 (10 to 12 kg) mongrel female dogs, silver electrodes for recording electrical activity and for pacing of pacesetter potentials (PP) were implanted on the stomach and duodenum and a catheter for intraluminal instillations was inserted into the duodenum. Beginning 2 weeks after operation, electrical recordings were made intermittently from the fasted, conscious dogs with no pacing and during pacing of the PP in the proximal and in the distal duodenum. A suspension of BaSO4 injected into the unpaced duodenum and observed cinefluoroscopically was swept quickly from the duodenum into the jejunum; little or none passed orad into the proximal duodenum, and BaSO4 rarely entered the stomach. Only 1 to 3% of a duodenal infusate of 154 mM NaCl with [14C] polyethylene glycol (2 ml per min) appeared in the stomach after 15 min. The results during proximal duodenal pacing were the same as with no pacing. However, distal duodenal pacing, which reversed the direction of propagation of the duodenal PP's, caused duodenal-gastric reflux of BaSO4 in every dog and forced about 30% of the duodenal infusate into the stomach during fasting and during gastric emptying of 400 ml of 154 mM NaCl; at the same time, the rate of emptying of the gastric instillate was slowed about 25%.


Sequential uptake of horseradish peroxidase by lymphoid follicle epithelium of Peyer's patches in the normal unobstructed mouse intestine: an ultrastructural study.

Membranous epithelial or "M" cells in lymphoid follicle epithelium of Peyer's patches extend between the adjacent columnar cells, forming a membrane separating lymphocytes in the epithelial cell layer from the intestinal lumen. They lack developed microvilli, glycocalyx, or terminal web but contain numerous vesicles. Transport of particles from ligated intestinal loops by such cells without evidence of further uptake of these particles by lymphocytes has been described by others. Horseradish peroxidase (HRP), an enzyme known to function orally and parenterally as a foreign protein antigen, was injected into the unligated intestines of fasted healthy 2-month-old white Swiss mice to determine if HRP would be absorbed in detectable quantities by M cells, and whether subsequent uptake of HRP by lymphocytes could be documented. At intervals from 1 to 60 min the most distal ileal Peyer's patch was fixed, removed, reacted with H2O2-3,3'-diaminobenzidine and examined by light and electron microscopy for HRP reaction product. At 1 min HRP adhered to surfaces of columnar cells and M cells and extended down into surface pits in the M cell. After 5 min HRP was found in vesicles of M cells but not in columnar cells. At 1 hr HRP was detected in the extracellular space between M cells and their enfolded lymphocytes, as well as in vesicles within these lymphocytes. Transport of intestinal luminal material by M cells with subsequent uptake by lymphocytes provides a specific route for antigen uptake into the intestinal lymphoid system.


Transmissible gastroenteritis: sodium transport and the intestinal epithelium during the course of viral enteritis.

Sodium transport, mucosal structure, and epithelial enzymes were studied in piglets killed 10, 25, 40, 72, or 144 hr after infection with a standard dose of transmissible gastroenteritis virus. Glucose-stimulated Na transport measured in short-circuited jejunal epithelium and suspensions of villous enterocytes became progressively more abnormal during the first 40 hr, but recovered completely by 144 hr. As Na transport deteriorated, jejunal mucosal villi shortened and crypts deepened; cells isolated from the villi became more crypt-like in their enzyme profile, with high levels of thymidine kinase and low levels of sucrase activity 40 hr after infection. At 40 hr, when diarrhea is severe, little if any virus has been found in the epithelium. Our data suggest that the relatively undifferentiated crypt type enterocytes on the villi constitute an important determinant of altered Na transport and diarrhea in this invasive viral enteritis.


Effects of partial surgical pancreatectomy in rats. I. Pancreatic regeneration.

The capacity for pancreatic regeneration in male Wistar rats of average weight 176 g was determined after surgical resection of 50, 70, or 90% of the pancreas. In control animals of this weight pancreatic growth was still taking place but ceased after 2 months. Growth of the residual pancreas in resected animals over this period was greater than in controls and the final weight of the residual pancreas was 21, 32, and 78% greater than that of the corresponding segments in sham-operated animals after 50, 70, and 90% resection respectively. Proliferation of acinar cells was assayed by autoradiographic detection of tritiated thymidine incorporation in controls and after 90% resection. Proliferation of acinar cells in control animals during the first 2 weeks of the experiment was significantly higher than at later times when it fell to very low levels. Proliferation in 90% resected animals was markedly higher than in controls from 2 to 5 days after resection and, together with the limited hypertrophy occurring at this time, adequately accounted for the increase in weight of the residual pancreas during the first 2 weeks. We were unable to explain the increase in pancreatic weight in control or resected animals between 2 weeks and 2 months either in terms of hypertrophy or hyperplasia of acinar cells.


Plasma amino acid patterns in hepatic encephalopathy of differing etiology.

Plasma amino acids were measured in 18 patients with hepatic encephalopathy on a protein-restricted diet of 20 g or less daily. Plasma aminograms tended to group into two distinct patterns depending on the etiology of the patients' hepatic pathology. Patients with chronic liver disease with superimposed acute insults, i.e., gastrointestinal bleeding, infection, alcoholic hepatitis, had elevated levels of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, as well as methionine, glutamate, and aspartate, whereas levels of the branched chain amino acids, valine, leucine, and isoleucine, were consistently depressed. Those patients with previously normal livers and acute hepatic necrosis, i.e., "fulminant hepatitis," had grossly elevated levels of all amino acids except the branched chain amino acids, which were normal. Elevations of amino acid levels in this patient group tended to correlate with extent of hepatic necrosis and hence had prognostic significance. Additionally, the different patterns seen in these two groups tend to suggest the indicated therapy as well as predict its efficacy.


Study of an epidemic of jaundice, presumably due to toxic hepatitis, in Northwest India.

An epidemic of jaundice probably due to toxic hepatitis occurred in three adjoining districts of Northwest India during the period November and December, 1974. The dogs of the villages were affected first, then the human beings. Detailed clinical features, appropriate laboratory tests, and liver biopsies were studied. A retrospective epidemiological survey was carried out. The disease had a subacute onset starting with high fever, followed by rapidly progressive jaundice. Ascites appeared simultaneously and soon became quite massive. Hepatomegaly was recorded when ascites decreased. Liver function tests suggested cholestatic jaundice. The mortality rate in the hospital was 10%. Clinical features in dogs were similar, but mortality was almost 100%. Liver histology was characterized by (1) edema and collagenization of the central veins, never with thrombosis, (2) cholangiolar proliferation, (3) moderate to severe ballooning of the hepatocytes, (4) perisinusoidal fibrosis, (5) cholestasis, and finally, (6) cirrhosis with reverse lobulation. Etiology of this epidemic of hepatitis could not be unequivocally established. Critical analysis of the data suggests that some food toxin may have been a factor in the outbreak of this unusual epidemic of toxic hepatitis.


Pigment versus cholesterol cholelithiasis: identification and quantification by infrared spectroscopy.

We previously reported that 27% of 92 cholecystectomized patients had pigment stones (Am J Dig Dis 19:585-590, 1974). Using standard biochemical methods, we found that cholesterol accounted for an average of 77% of the dry weight of cholesterol stones, but that unconjugated bilirubin represented a mean of only 7% of pigment stones. This quantitation of pigment stones was limited because approximately 66% of their weight was insoluble. To characterize pigment and cholesterol stone composition further, we used infrared spectroscopy--a technique requiring neither crystallinity nor solubilization--to quantitate pigment, carbonate, and cholesterol in gallstones. Other organic and inorganic components of stones were measured by standard methods. By infrared spectroscopy, two types of pigment stones were identified: carbonate-containing and noncarbonate pigment stones. Carbonate pigment stones contained significantly more calcium, carbonate, and phosphate, but less pigment than noncarbonate stones. Compared to our initial report, the total measured components of all pigment stones were increased 6-fold from 10 to 63%. Cholesterol was the major component of cholesterol stones by chemical assay or infrared spectroscopy. Among five cholesterol stones with limited solubility, 80% of the insoluble residue was identified as cholesterol by infrared spectroscopy. This study extends our knowledge of pigment stone and cholesterol stone composition by the use of quantitative infrared spectroscopy in conjunction with standard biochemical methods; furthermore, it confirms that pigment and cholesterol stones differ in composition and form by different mechanisms.


Dynamics of the enterohepatic circulation of the glycine conjugates of cholic, chenodeoxycholic, deoxycholic, and sulfolithocholic acid in man.

Highly sensitive and specific radioimmunoassays for cholylglycine, chenodeoxycholylglycine, deoxycholylglycine, and sulfolithocholylglycine have been used to study the kinetics of the enterohepatic circulation of these conjugated bile acids in 8 healthy subjects. Venous blood samples were collected over a 32-hr period, during which time the subjects ate three meals. Serum levels of cholylglycine and chenodeoxycholylglycine rose after each meal, and reached their maximum level within 30 to 60 min. A second chenodeoxycholylglycine peak occurred 2 to 3 hr after the first two meals in all subjects; a second peak was also found for cholylglycine in 3 of the 8 subjects. Serum deoxycholylglycine levels also rose postprandially; the peak level generally occurred 30 min later than that of cholylglycine. Serum sulfolithocholylglycine levels did not alter significantly after meals. The data indicate that the dynamics of the enterohepatic circulation of individual serum bile acids differ both quantitatively and qualitatively.


Effect of ethanol on collagen formation in dietary cirrhosis in the rat.

Ethanol (10 or 15% in the drinking water) was found to increase the amount of collagen in the livers of rats receiving a cirrhogenic diet. This effect of ethanol was most striking in the animals receiving 10% ethanol. Ethanol lowered the amount of labeled proline incorporated into hydroxyproline and, therefore, into collagen. The amount of labeled hydroxyproline remaining in the liver 7 days after injection was greater in the rats receiving 10% ethanol than in the pair-fed controls. A net increase in collagen deposition attributable to ethanol was associated with lowered rate of collagen synthesis. The main action of ethanol in increasing the rate of collagen deposition, therefore, must be inhibition of collagen breakdown.


A cause of hyperamylasemia associated with chronic liver disease.

The cause of hyperamylasemia associated with chronic liver disease is unclear. In an attempt to identify the tissue of origin of hyperamylasemia in 3 patients with chornic active hepatitis their serum was isoelectrically focused. The isoamylase patterns obtained were compared to those of pancreatic and salivary amylase. The apparent salivary gland origin of the excessive blood amylase in the patients studied was substantiated by radiological demonstration of parotid sialoectasia in one patient and histological evidence of sialoadenitis in another. Further evidence was the coincident isoelectric points of the predominant isoamylase in the sera of the liver disease patients and of patients with parotid inflammatory disease. Hyperamylasemia associated with chronic liver disease may be of salivary gland origin and as such forms part of the spectrum of extrahepatic manifestations of chronic active hepatitis.


Endoscopic appearance of colonic lymphoid nodules: a normal variant.

A patient undergoing routine colonoscopy was observed to have multiple white nodules scattered diffusely throughout the colon. Endoscopic biopsy revealed normal lymph tissue. The endoscopic appearance is described to avoid misdiagnosis and inappropriate therapy.


A case of chronic oropharyngo-esophageal candidiasis with immunological deficiency: successful treatment with miconazole.

The case of a 38-year-old male patient with chronic recurrent oropharyngo-esophageal candidiasis since early childhood, resistant to topical therapy with nystatin, is reported. The disease had resulted in impressive oropharyngeal lesions and stricturing of the midesophagus. Extensive in vivo and in vitro immunological studies done before and after successful treatment with miconazole showed a persistent partial deficiency of the cell-mediated immune system, in particular that directed toward candida antigens. Miconazole, a new potent antifungal drug, proved effective in controlling the candidiasis, which had become resistant to conventional treatment.


Dispensability of both the amide of phenylalanine and the carboxyl group of aspartic acid for the stimulation of gastric acid secretion by gastrin peptides in dogs.

Two derivatives of the C-terminal tripeptide of gastrin devoid of -NH2 from the phenylalanyl residue and of -COOH from the aspartic acid, MBOC-Met.Asn.Phe-OH (I) and MBOC-Met.Asp-OBenz.Phe-OMe (II), stimulated gastric acid secretion in the dog when infused intravenously at doses of 100 to 400 mug/kg-hr. Maximal responses induced by I and II were about 30-40% of that induced by the C-terminal tetrapeptide of gastrin. At a dose of 600 mug/kg-hr, I had an inhibitory action while II initially augmented and then inhibited acid production. Neither the C-terminal amide nor the carboxyl group of the aspartyl residue is essential for the gastric stimulatory activity of gastrin peptides.


[Tobacco use in adolescence].

Different studies in North-Switzerland showed that 9% of young boys and 3% of young girls tried to smoke cigarettes the first time with or before six years of age. Boys in the age of 17 to 21 from rural districts smoked cigarettes in 23%, girls in the equal age from rural regions in 14%. 17% of the non-smokers and only 2% of the smokers did not drink any alcohol. In Berne, 23% of the cigarette smokers and only 3% of non-smokers had ever taken drugs (marihuana, LSD) in their life.


[Problems in nonsmoker training].

As results of long experiences with patients who urgently need to stop smoking and in group therapy the practical problems of such trials are discussed: the different reasons and problems for addicts and habitual smokers, "pseudoalibis", analysis of the predominant motivation, the different steps of cessation and the problems of the ex-smoker in his surroundings.


[Ventilation distribution disorders. Evaluation based on nitrogen elimination curves of the lung and on an inspiratory gas-distribution index derived from it].

An uneven distribution of the inspiratory gas volume to the alveolar volume leads to disturbances of the ventilation/perfusion ratio VA/Q with resulting arterial hypoxemia. These ventilatory disturbances can be verified by nitrogen-washout-curves and an inspiratory gas distribution index derived from those curves. Preoperative diagnostic and the control of respiratory diseases during intensive therapy are possible without technical difficulties.


[Therapy of migraine. Clinical experience with Migraeflux, a new migraine drug].

The new migraine preparation Migraeflux has been subjected to clinical trial in a double-blind cross-over study in 32 single tests. Compared with other products, the 2-phase-preparation Migraeflux is distinguished--due to its antihistaminic ingredient--by the capacity of preventing in 2/3 of the cases the formation of a migraine attack if applied soon during the prodromal phase. If the attack is not prevented, the intensity of pain is lessened in 70% of the remaining cases and the duration of attack is markedly reduced. The preparation proved to be tolerated very well.


[Coprolith-ileus of the small intestine].

The case of a 71 year old man is reported, in which coproliths developed in the small intestines over a period of 13 years and which finally lead to a complete ileus. This condition is discussed in connection with other rare forms of ileus; specific clinical phenomena are pointed out, which might be helpful in establishing a correct diagnosis. Among the transient forms of ileus associated with food intake, which may cause the patient only slight discomfort, one should bear in mind a corpus alienum-ileus. Only operative therapy of ileus is promising success.


[Nutrition in infant enteritis].

The effects of two different formulas in the treatment of acute diarrhea were tested in a prospective study with 40 infants. The formulas differ in content of lactose, fructose, starch, sodium and potassium. Both groups reached normal food intake at the same time and could be discharged from clinical observation. The patients were divided into two groups with equal degrees of diarrhea. During nutrition with lactose-reduced formula, body-weight was rising and the water-binding capacity of chymus seemed to be better. From significant higher percentages of prae-beta-liproproteins in electrophoresis better endogenous metabolic efficiency could be derived. Phospholipids were also significantly increased when lactose-reduced formula was given. The comparative formula led, due to the higher content of potassium to significantly higher serum levels. The results of this investigation indicate, that reduction of lactose in the formula for infants with diarrhea has some advantages. Whether more effectiveness of formulas in diarrhea could be expected from addition of medium chain triglycerides (Gracey et al. 1970, Schreier und Porath 1971) requires further investigations.


[Use of xylitol as sugar substitute in diabetic children].

In 24 diabetic children treated with insulin xylitol was used as a sugar substitute for four weeks in an amount of 30 gms/day. In one case only the xylitol application was terminated before the end of the dietetic period because of diarrhoea. The other children tolerated xylitol fairly well, three of the children found the polyol too sweet. Because of incomplete data, the values of only 18 children were compiled. A significant increase of serum uric acid concentration measuring 1 mg/100 ml was the main side effect of xylitol usage. This effect was favoured by the fact that diabetic children do not use sucrose. As was shown earlier, a sucrose free period is the precondition for the possibility to find a xylitol induced hyperuricemia. In metabolically healthy children the existence of a sucrose induced hyperuricemia is also to be expected, this xylitol effect is, therefore, obviously without pathophysiological significance. Xylitol is suited for use as a sugar substitute in diabetic diet and in caries prophylaxis if the limited dose is observed.


Demographic and clinical characteristics of black psychiatric patients in a private general hospital.

A study of 419 first admissions to a private general hospital psychiatric inpatient unit showed that only 8.8 per cent were blacks, while 23 per cent of the population in the community were blacks. When compared to white patients, blacks were much less likely to be rerred for hospitalization by private sources, were substantially younger, and had shorter hospitalizations. The most common diagnosis for blacks was paranoid schizophrenia. The authors conclude that despite the widespread availability of third-party insurance coverage, blacks use the private general hospital less ofter than whites and their patterns of use are substantially different.


Analysis of a decision framework for prepared food systems.

Each of the major decision areas that is covered in this article is multi-dimensional in nature, and each could be developed into a lengthy and meaningful discussion. However, the basic purpose of this article has been to suggest a framework for evaluating and making decisions that are associated with planning prepared food systems. We have attempted to underscore the importance of making basic procedural and conceptual decisions related to prepared food systems before deciding the subcomponents of each decision area. Perhaps the most important element of the decision-making process is a thorough understanding of the interrelationships between each of the five major decision areas. This understanding, when it is combined with the suggested decision framework, should contribute to a well-planned, smoothly operating prepared food system.


Immunogenic activity of a ribosomal fraction obtained from Pasteurella multocida.

The cells of P. multocida strain P-1059 were destroyed with the French pressure cell; the ribosomal fraction proven to be homogeneous by analytical ultracentrifugation was obtained from the product by centrifugal fractionation, zonal electrophoresis, and Sephadex G-200 gel filtration. The ribosomal fraction exhibited intense protective antigenicity in mice and chickens, but the lipopolysaccharide (endotoxin) and the other bacterial cell fraction obtained in this experiment did not. Sodium deoxycholate treatment of the ribosomal fraction resulted in only a 13% loss in immunological activity, and ribonuclease treatment caused a 60% loss of activity.


Effects of tobacco smoke on chemotaxis and glucose metabolism of polymorphonuclear leukocytes.

The effect of tobacco smoke on in vitro chemotaxis of human polymorphonuclear leukocytes (PMN) was determined. Whole tobacco smoke, gas phase of smoke, and water-soluble fraction were potent inhibitors of PMN chemotaxis. The results indicated that PMN chemotaxis was inhibited in a dose-dependent manner by water-soluble fraction and that this suppression was not a result of cytotoxicity. In an attempt to determine the mechanism of chemotaxis inhibition, the effect of tobacco smoke on glucose metabolism of PMN was studied. Exposure of PMN to whole smoke, gas phase, or water-soluble fraction resulted in an increase (twofold) in glucose catabolism via both glycolysis and the hexose monophosphate shunt, with no apparent effects on the metabolism of glucose via the tricarboxylic acid cycle. These results suggest that the inhibitory effects of tobacco smoke on PMN chemotaxis were not directly attributable to effects on glucose metabolism of these cells. Further, the inhibitory effects of water-soluble fraction on PMN chemotaxis were shown to be largely irreversible and preventable in the presence of cysteine. Thus, the major inhibitory effects of tobacco smoke probably result from the direct action of oxidants and/or thiol-reactive substances on PMN.


Angiostrongylus cantonensis: phospholipase in nonsensitized and sensitized rats after challenge.

Rats given an initial infection with Angiostrongylus cantonensis had moderately elevated phospholipase B activity in the lungs at 8 and 15 days after challenge, and greatly elevated levels were evident at 35, 43, and 49 days. In the brain, the values were elevated at 15 through 35 days. These periods of increased activity in the lungs and brain coincided with the migration patterns of the third stage larvae and the adult worms in this host. The elevated enzyme levels also were were correlated with increased numbers of eosinophils in the bone marrow at 8 and 15 days and again at 36, 43, and 49 days after infection. Similarly infected rats exhibited leukocytosis at 1 through 10 weeks of observation after challenge, and striking eosinophilia at 1, 7, 8, and 9 weeks. Rats reinfected after removal of the worms of the initial infection by thiabendazole treatment showed an anamnestic response characterized by (i) elevated enzyme values in both the lungs and brain at 1 day after reinfection and (ii) eosinophilia in the bone marrow by day 4. These accelerated responses were accompanied by a significant reduction in the worm burden of the rats. The results, which support our hypothesis that inflammation, elevated phospholipase B activity, and reduction in worm burden are causally related, are discussed in light of similar findings reported earlier from our studies with Trichinella spiralis and Nippostrongylus brasiliensis.


Influence of temperature on opsonization and phagocytosis of staphylococci.

The effect of incubation temperatures of 41, 37, and 4 degrees C on phagocytosis was investigated using human neutrophils and [3H]thymidine-labeled staphylococci. Depressed phagocytosis was observed at 41 and 4 degrees C. At 41 degrees C diminished staphylococcal uptake resulted from decreased attachment of bacteria to leukocytes; the inhibitory effect at 4 degrees C was secondary both to decreased opsonization and to reduced attachment to leukocytes. In contrast to the findings with normal serum, opsonization with heat-inactivated serum appeared to be relatively intact at 4 degrees C. By incubating samples in lysostaphin, it was determined that the process of bacterial ingestion as well as that of attachment was adversely affected by incubation temperatures of 41 and 4 degrees C.


Effects of low- and high-passage influenza virus infection in normal and nude mice.

A human isolate of type A Hong Kong influenza virus (H3N2) was adapted to mice by serial passage. Lung homogenates from mice who received low passage levels contained about the same quantity of virus (10(6.2-6.95) 50% tissue culture infective doses/ml) as those from mice who received high passage levels (10(5.95-6.45) 50% tissue culture infective doses/ml); however, death occurred only in animals given high-passage virus. Passage 3 (P3) and passage 9 (P9) viruses were selected as representative of low-passage and high-passage viruses, respectively. Although minimal differences were detected in infectivity for rhesus monkey kidney tissue cultures and mice, P9 virus was at least 10,000 times more lethal for mice (mean lethal dose = 10(4.2)). Infection with P3 virus was accompanied by minimal bronchitis and bronchiolitis only, whereas P9-infected animals exhibited marked bronchitis, bronchiolitis, and pneumonia. Striking thymic cortical atrophy was also demonstrable in the P9-infected animals and, although virus was more commonly recovered from thymuses from these animals, immunofluorescent studies revealed only a few cells containing influenza virus antigens. To further explore the participation of thymus-derived lymphocytes in influenza, athymic nude mice and furred immunocompetent littermates were given 500 50% mouse infectious doses of P9 virus. Nude mice exhibited an increased survival time and, in contrast to the extensive lung pathology seen in furred littermates, manifested minimal cellular infiltration and no tissue destruction in lungs. Brains from nude mice exhibited encephalomalacia with lymphocytic perivascular cuffing, which was not seen in furred animals. Virus was recovered from brains of 6 of 13 nude mice and 1 of 10 furred animals. The contrasting models suggest that thymus-dependent cells play a significant role in the inflammatory response to influenza virus infection and should prove useful for probing host-virus interactions which characterize influenza virus virulence.


Congenital abnormalities in newborn lambs after infection of pregnant sheep with Akabane virus.

Akabane virus (a Bunyavirus) has been associated with epizootics of congenital deformities in cattle, sheep, and goats. Experimental studies using mouse-adapted virus inoculated intravenously into pregnant sheep gave an inapparent infection. Neutralizing antibodies were detected on day 5, and peaks in the titer were seen at days 10 and 48. Ewes infected at day 30 to 36 of pregnancy produced five (31% incidence) deformed lambs. Sera from four of these possessed neutralizing antibodies to Akabane virus before ingesting colostrum. Two lambs had arthrogryposis, hydranencephaly, kyphosis, scoliosis, and brachygnathia; one had micrencephaly; and the other two had porencephaly. The two lambs with arthrogryposis and hydranencephaly also had extensive lesions in other tissues. In the spinal cord there was a marked decrease in the number of ventral horn neurones and a depletion of myelin. Skeletal muscles showed marked atrophy. The medulla of the thymus possessed large Hassall's corpuscles and a reduced number of thymocytes in the cortex. It would appear that the pathogenic effects of Akabane virus are related to the gestational age (30 to 36 days) at which the fetus is infected. Akabane virus can now be included in the growing list of teratogenic viruses and provides an interesting system for studying such congenital diseases.


Determination of molecular weight, isoelectric point, and glycoprotein moiety for the principal skin test-reactive component of histoplasmin.

A purified component designated HPD (histoplasmin-purified derivative) dII was isolated from two different cru-e histoplasmin lots by a combination of gel filtration and polyacrylamide disc electrophoresis (Sprouse, 1969). A 0.05-mug portion of HPD dII was reactive and specific in detection of delayed hypersensitivity in guinea pigs experimentally infected with Histoplasma capsulatum. The objective of this study was to characterize this skin test-reactive component for (i) homogeneity, (ii) molecular weight, (iii) isoelectric point, and (iv) composition. Sephadex chromatography, polyacrylamide disc electrophoresis, sucrose density gradient ultracentrifugation, acid and heat denaturation, and immunoelectrophoresis indicate that HPD dII is (i) homogeneous, (ii) of approximately 12,000 molecular weight, and (iii) a glycopeptide of approximately 60% carbohydrate and 40% proteinaceous composition. The marked acid and heat stability exhibited by the compound probably is attributable to the prominent carbohydrate moiety in the molecule. Isoelectric focusing indicated an isoelectric point of 5.68. This would suggest that dII is an acidic compound with either predominance of acidic amino acid residues in the molecule or, more probably, an abundance of electron donors in the carbohydrate moiety. In summary, HPD dII appears to be a glycopeptide of approximately 12,000 molecular weight, reactive in elicitation of delayed hypersensitivity of histoplasmosis.


Basophil hypersensitivity response in rabbits.

A cutaneous basophil hypersensitivity response has been observed in rabbits immunized with bovine serum albumin and challenged intradermally with this antigen 7 days later. The cellular response appears to be similar to cutaneous basophil hypersensitivity reported in guinea pigs and humans. A basophil response was also observed in rabbits immunized with Staphylococcus aureus and challenged with viable staphylococcal cells 7 days later. A method of observing basophil infiltration in rabbits by means of connective tissue spreads obtained from the subcutaneous connective tissue is described. The rabbit should serve as an excellent model for the study of basophil responses as these animals have a significant basophil component with few if any tissue mast cells which may be confused both morphologically and functionally with the basophil.


Inhibition of glucosyltransferase by human salivary immunoglobulin A.

Purified glucosyltransferase isolated from Streptococcus sanguis OMZ 9 and different immunoglobulin A from saliva, saliva pellet, and dental plaque were used to study enzyme-antibody interactions. A strong inhibition of glucosyltransferase activity was obtained with the different immunoglobulin A fractions.


Adjuvant activity of synthetic N-acetylmuramyl peptides in rats.

The minimal adjuvant-active structure in bacterial cell wall peptidoglycan for the induction of delayed hypersensitivity in rats (WKA) was the N-acetylmuramyl dipeptides (N-acetylmuramyl L-alanyl-D-isoglutamine and N-acetylmuramyl L-alanyl-D-glutamic acid).


Serum opacity factor of Staphylococcus epidermidis.

Three Staphylococcus epidermidis strains produced a factor giving rise to opacity in different sera but not in albumin. Serum opacity factor was resistant to age and heat and active in acidic media.


Protection against endotoxin-induced mortality in mice treated with transition metal salts.

Administration of manganese or chromium chloride 1 h before challenge with a single bolus of Salmonella typhosa endotoxin completely obviated death in endotoxin-challenged mice.


Lipid A antiserum-mediated protection against lipopolysaccharide- and lipid A-induced fever and skin necrosis.

The antiendotoxic activity of lipid A antiserum was studied in rabbits, using lipid A (lipopolysaccharide)-induced fever and skin necrosis as test systems. It was found that lipid A antiserum had no significant antipyretic effect when it was incubated with lipid A or injected intravenously before lipid A challenge. However, in animals that were pretreated (day 0) with a single dose of lipid A (lipopolysaccharide), a significant protective effect of passively transferred antiserum (day 1) to lipid A (lipopolysaccharide fever) (day 2) was observed. Also, the lipid A (lipopolysaccharide)-induced local shwartzman reaction could be prevented by lipid A antiserum. In the fever system, the degree of protection depended on the preparative and the challenge doses as well as on the amount of antiserum transferred. The fever protection mediated by lipid A antiserum seemed to be lipid A (lipopolysaccharide) specific with regard to both the preparative and the challenge injections. Lipid A specificity of the protective factor present in the antiserum was indicated by the fauggest that the factor might be identical with lipid A-specific immunoglobulin. The significance of the preparative injection is not understood at the present time. Iti is concluded, however, that in the fever protection system described, besides specific humoral factors, other factors, perhaps cellular, are involved.


Cell walls of Coccidioides immitis: neutral sugars of aqueous alkaline extract polymers.

The neutral sugar components of hydrolysates of the alkali-soluble and -insoluble fractions of an acid-extracted Coccidioides immitis mycelial cell wall preparation were examined by gas-liquid chromatography. The alkali-soluble fraction was separated into a neutral water-soluble (46% carbohydrate) and a neutral water-insoluble fraction (6% carbohydrate). Glucose was the major neutral sugar constituent of all fractions. Mannose appeared to be a second major component of the alkali-soluble, water-soluble fraction. 3-O-methylmannose was absent. Small amounts of other sugars, including galactose and pentoses, were tentatively identified. Borohydride reduction before alkaline extraction resulted in retention of almost half of the glucose and variable amounts of other components in the alkaline residue, indicating that solubilization of cell wall polymers by alkaline extraction results in significant degradation of the native cell wall polymers.


Interactions between mycoplasma pneumoniae and the first components of complement.

Mycoplasma pneumoniae cells were rounded and killed by fresh guinea pig serum (GPS) which did not contain detectable amounts of antibody. The first component of complement (C1) was bound by M. pneumoniae in considerable amounts from both GPS and purified C1. The C1 bound by the cells was reacting with C4. Sequential addition of C1, C4, C2, and C-ethylenediaminetetraacetate to glass-grown M. pneumoniae cells resulted in rounding of a significant number of cells. M. orale and M. fermentans showed a reduced binding capacity for C1 as compared with M. pneumoniae. Both species were only slowly killed by fresh GPS, whereas M. hominis was as sensitive as M. pneumoniae. The results suggest an antibody-independent interaction between some components of the membrane surface of M. pneumoniae and C1, resulting in an activation of the complement system leading to the killing of the mycoplasma cells.


Effect of Trichinella spiralis infection on passive cutaneous anaphylaxis in mice.

Infection of CFW mice with Trichinella spiralis induced a state of relative unresponsiveness to passive cutaneous anaphylaxis (PCA) induced with hen egg albumin and its corresponding antibodies. The unresponsiveness was to PCA produced either with immunoglobulin G1 (IgG1) or IgE type of antibodies, but was more pronounced with the latter. As few as 25 larvae given by stomach tube 20 days before induced this resistance, although 400 larvae induced a greater resistance. When 400 to 600 larvae were fed to mice, the refractoriness of these mice to PCA was noticed 15 days later. The sera of infected mice had the ability to inhibit mainly PCA induced by IgE. This inhibitory property of sera from infected mice was more pronounced 35 days after infection than 10 months later, when only weak inhibitory activity was detected. Purified rat IgE inhibited the PCA reactions induced in both mice and rats with mouse IgE-type antibody. At high concentrations, evidence of inhibition of the IgG1-induced PCA in mice was also obtained. We believe that the relative unresponsiveness of infected mice is due to an increase in production of IgE which competitively blocks the mast cell sites for other IgE molecules.


Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in vratza district, Bulgaria.

Data on the occurrence of endemic nephropathy (EN) and urinary tract and other cancers in an endemic region of Vratza district, Bulgaria, for the years 1965-1974, are presented. In endemic villages a high incidence of urinary tract tumours, affecting in particular the renal pelvis and ureter, closely correlated with the EN incidence and mortality rates. In the villages with high and moderate EN incidences urinary tract tumours are the most common neoplasms. They account for 25% of all tumour sites in males and 30% in females. In hyperendemic villages age-adjusted incidences in EN and urinary tract tumours were 506/10(5) and 104/10(5) in females, and 315/10(5) and 89/10(5) in males respectively. EN mortality in these villages accounted for over 40% of all deaths in females and about 30% in males. Both diseases displayed peculiar geographic clustering. Females and middle-aged persons were most often affected. Urinary tract neoplasms were often multiple and nearly 90% of them originated in the uro-epithelium. In endemic and non-endemic villages of the region studied, the frequency and pattern of non-urinary tract cancers were rather similar, with statistical values close to those of the rural population of Vratza District and Bulgaria as a whole.


Immunoglobulin complexes in sera of patients with malignancy.

Sera frour 146 patients with malignancy, 59 normal controls and 42 patients hospitalized with non-malignant diseases were examined by a precipitin test with monoclonal rheumatoid factor (mRF) for the presence of circulating immune complexes containing IgG. Forty-two (29%) of the sera from cancer patients but only two of the sera from patients in each of the control groups contained such material. Similar results were obtained with a radioimmunoassay for immune complexes based on the same mRF. Sera from 23 of 65 patients with metastatic malignancy (35%) had elevated levels of immune complexes by this latter test. The presence of the material was not related to the source of malignancy, presence of carcinoembryonic or hepatitis antigens or of such autoantibodies as rheumatoid factor or anti-DNA. By density gradient ultracentrifugation the reacting material was identified as being of molecular size 19s or greater. It has not yet been further characterized with regard to the nature of any antigens present.


Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: sensitivity to asparaginase.

An undifferentiated human pancreatic carcinoma has been established in continuous culture and is grown in Dulbecco's modified. Eagle's medium fortified with 10% fetal calf serum and 2.5% horse serum. The established cell line (MIA PaCa-2) has a doubling time of 40 h. The cells are large with abundant cytoplasm, exhibit a high degree of aneuploidy and have a tendency to grow on top of other cells. MIA PaCa-2 grows in soft agar with a colony-forming efficiency of 19%. Both MIA PaCa-2 cells and a cell line from another pancreatic carcinoma obtained from National Cancer Institute (NCI) are sensitive to asparaginase, a property not shared by several other human tumor cell lines tested.


A dose-response study on urethane carcinogenesis in rats and mice.

Sprague-Dawley rats and NMRI mice were treated with urethane in the drinking water for 2 years. In both species the daily doses were: 100, 500, 2,500, and 12,500 mug/kg. The frequency of animals with malignancies increased steadily with increasing doses, beginning from 500 mug/kg/day for rats, and from 100 mug/kg/day for mice. To evaluate the possible cancer risk for man due to urethane in beverages, the observed response rates were used to extrapolate responses at lower doses. At a daily dose of 0.14 mug/kg/day (corresponding to daily consumption of a beverage with 10 ppb urethane by a 70-kg man) the upper risk limits were estimated to be 3.2 in 100,000 for rats, and 470 in 100,000 for mice (modified Mantel-Bryan procedure). Problems in calculating a possible cancer risk for man on the basis of animal observations are discussed. Since treatment of beverages with diethyldicarbonate leads to the formation of urethane, and since a cancer risk to man from urethane cannot be excluded, replacement of diethyldicarbonate by a toxicologically unobjectionale compound is called for.


Redefining addiction. I. Making addiction a scientifically and socially useful concept.

Addiction is both a more complex-and a more common-phenomenon than either medical personnel or laymen have realized. It is impossible to link addiction as a medical syndrome to any one drug or family of drugs, or to trace it to a specific biological mechanism. As scientists have uncovered more data leading to these conclusions, they have turned away from employing the term "addiction." Yet many drug researchers and workers in the helping professions continue to make incorrect assumptions about both addiction and drug use. In this paper the author attempts to broaden the applicability of the addiction concept in order to give it meaning. With this broader approach, we find that many involvements that people become engaged in follow the pattern of addiction, while some involvements with supposedly addictive drugs do not follow this pattern. The addiction cycle is explored by means of the following psychological definition: An addiction is any compulsive activity or involvement which decreases a person's ability to deal with other aspects of his life to the point where that activity or involvement comprises the dominant source of emotional reinforcement and identity for the person.


Prosperity as a cause of death.

The general death rate rises during business booms and falls during depressions. The causes of death involved in this variation range from infectious diseases through accidents to heart disease, cancer, and cirrhosis of the liver, and include the great majority of all causes of death. Less than 2 percent of the death rate-that for suicide and homicide-varies directly with unemployment. In the older historical data, deterioration of housing and rise of alcohol consumption on the boom may account for part of this variation. In twentieth-century cycles, the role of social stress is probably predominant. Overwork and fragmentation of community through migration are two important sources of stress which rise with the boom, and they are demonstrably related to the causes of death which show this variation.


Sex, stress, and health.

Recent research suggests possible health benefits of sexual activity. Sexual arousal appears to increase testosterone levels in males. (Related effects in females have not been studied.) This article shows that increased testosterone has a number of health-promoting effects and that good sexual functioning is a health issue not only in itself, but also in its effects on general health as well. Both clinical and experimental evidence indicates that stress disrupts the normal sexual response. Combining this with the previous evidence, a general model of reciprural inhibition between sexual and stress effects is proposed, with the implication that sex may be an antagonist to the deleterious health effects of stress. If stress disrupts sex, the result is likely to be indirect negative effects on health. Three basic types of stress which frequently disrupt sexual functioning are described, and it is argued that sex therapy techniques are effective in large part as a result of their ability to reduce these forms of stress. The kinds of stress that lead to sexual dysfunction have clear social roots. A variety of etiological factors are identified. It is argued that movements promoting social change may in fact perform sexual preventive medicine, which may indirectly augment general health as well.


Diagnostic Peritoneal Tap.

Diagnostic peritoneal tap has been an invaluable tool in the early diagnosis of acute abdominal catastrophy. We have discussed the role of abdominal paracentesis in 27 cases of blunt abdominal trauma and acute abdomen, where the diagnosis was in doubt despite clinical and emergency investigations. A simple method of tapping was adopted and there have been no complicatons.


Injuries to the popliteal artery.

We have discussed our experiences in operative treatment of popliteal artery injuries. Healing depends on the elapsed time between injury and operation. Three patients brought to the clinic after eight hours required amputations because of irreversible changes caused by anoxemia.


New technic for surgical treatment of wrist ganglion.

A new technic for surgical treatment of dorsal wrist ganglia is described. Our results are compared with the best results obtained by other authors in the treatment of all types of ganglia.


Solitary bone cyst of the calcaneus.

Ten cases of solitary bone cyst are presented. Nine of the lesions were asymptomatic and were discovered incidentally. Two patients were operated upon while eight were followed for 1 to 14 years. In spite of severe foot injuries that three patients have sustained, no fracture of the calcaneus occurred. We also showed experimentally that the strength of the calcaneus is not significantly reduced by the presence of the cyst. Therefore operative intervention in this lesion is not recommended. Acknowledgements: We wish to thank Dr. M. Carakostas, Consultant Orthopaedic Surgeon at Asclepeion Hospital, Athens, for allowing us to present Case 6 and Mr. St. Paipetis, Professor of the Polytechnic School of Athens, for his adivce during the experimental work.


High friction compression in the treatment of complicated fractures of the lower extremity.

Charnley's compression clamps have hastened the union of cancellous bones but not much success has been obtained in the slender shafts of cortical bones. The principles of biophysics show that a fracture site under compression acts as a hinge joint. If friction is increased in such "joints" along indicated axes, immobility of the fracture fragments can be obtained and lead to bone union. We have developed a modified device based on Charnley's compression clamps to create high friction compression. We successfully applied it in the treatment of eight fractures of the shafts of the femur or tibia which would not unite because of infection, soft tissue interposition or gross incongruity of fragments. The mechanical aspects of creating friction with the device are discussed.


Topical undecylenic acid in tinea pedis: a new look.

One hundred and four patients with mycologically confirmed tinea pedis took part in a controlled clinical trial to determine the efficacy of undecylenic acid powder preparations in the treatment of their fungal infections. Clinical and mycological cures were obtained in 53% of those subjects treated with undecylenic acid powders as compared with 7% of those treated with the talc vehicle or left untreated. Undecylenic acid in a powder vehicle appears to be a safe and effective agent in the treatment of tinea pedis.


Surgery in primary hyperparathyroidism.

Data were reviewed on 26 patients suffering from primary hyperparathyroidism (PHPT). The diagnosis of PHPT is increasing in frequency, due to greater awareness and better methods of detection. Delay in recognition has gradually decreased, thus permitting earlier treatment. No single test or any combination of tests can be considered satisfactorily pathognomonic of PHPT. Hypercalcemia is the most satisfactory finding suggestive of PHPT. Cervical exploration should be an integral part of the diagnostic work-up. Removal of a distinct adenoma is adequate therapy if the other parathyroid glands are normal. Subtotal parathyroidectomy should be performed only in cases of hyperplasia of all parathyroid glands.


Postoperative intrahepatic cholestasis.

Postoperative jaundice is an occasional complication of major surgery. Four illustrative cases are described and a mechanism of development is suggested. The jaundice may seem to be biochemically of the obstructive type. Most of the bilirubin is of the conjugated type. The disturbance of liver function can be caused by several factors, including massive transfusion, hematoma in tissues, shock, heart failure, anoxia, infection and perhaps medications. Postoperative jaundice by itself is not of cardinal importance in deciding the prognosis of the patient.


Biochemical transformation of regenerating ocular surface epithelium.

Several biochemical parameters, including glycogen levels, and the activities of hexokinase, phosphorylase, and lactate dehydrogenase have been compared in regenerating epithelium of conjunctival and corneal origin in rabbits. The study was designed to determine the extent of biochemical transformation of conjunctival into corneal epithelium completed within 6 weeks. Although histological transformation, especially in the case of the chemically damaged eyes, is not. Glycogen and lactate dehydrogenase levels remained well below normal corneal epithelial levels for the period of observation.


Histopathologic changes after thermokeratoplasty for keratoconus.

Six patients had penetrating keratoplasty following thermokeratoplasty (TKP) at different time intervals. The standard temperature used was between 90 degree and 95 degree C. with constant saline irrigation. The corneal buttons were studied by light and electron microscopy. Immediate changes observed included epithelial necrosis, marked degneration of keratocytes, and endothelial edema. After 24 hours, evidence of acute inflammation was noted in the subeptihelial zone and superficial stroma, and the endothelial changes persisted. One month after TKP, there was evidence of cellular regeneration of all the corneal layers. Eight months later, regeneration of the endothelial cells, keratocytes, and epithelium was present. Regeneration of the epithelial basement membrane was defective.


The phacoemulsification procedure. III. Corneal complications.

Persistent corneal edema is one of the complications of phacoemulsification. Five patients underwent this procedure 6 to 8 months before keratoplasty was performed. In addition to bullous keratopathy, two corneas had corneal scarring due to probe overheating or corneal vascularization of the anterior chamber. Electron microscopy of corneal specimens showed that four cases had Fuch's dystrophy without warts and one had guttata. Endothelial cell destruction varied from lessions of small size (15 to 50 mu) to large abrasions. Cases with severe edema and vitreous adhesion showed retrocorneal membrane formation. Surgical trauma seemed to have precipitated decompensation of these dystrophic corneas.


The effect of corneal edema on visual function.

Corneal edema was produced by atmospheric-induced anoxia and the visual effect was assesed by conventional acuity tests and compared with contrast sensitivity measurements. For the degree of edema which this technique produced, contrast sensitivity was depressed for only high spatial frequencies and could be considered in terms of equivalent defocus. This was not the case ofr a greater degree of edema which was simulated by a diffuser with a particle size that mimics the diffraction effects from an edematous cornea. Equivalent blur was not applicable, since low spatial frequencies were also affected and the letter and contrast sensitivity tests gave radically different results. In the light of these findings, the validity of the present letter acuity evaluation of visual function for patients in which intraocular scattering is involved is questioned.


Comparative reproducibility of the digital photogrammetric procedure utilizing three methods of stereophotography.

The reproducibility of digital photogrammetry of optic nervehead photographs taken with the Zeiss fundus camera with Allen stereoseparator, the Donaldson fundus camera, and the Zeiss fundus camera with twin-prism separator were evaluated. Reproducibility of the various quantitative factors was significantly better when the two types of simultantic cups. Larger per cent errors were encountered with shallower optic cups. Substantial improvements in parameter reproducibility were obtained when finer sampling intervals were used during film digitization.


Glucocorticoid responsiveness associated with HLA-B12.

Primary open-angle galucoma (POAG) patients are more responsive to glucocorticoids, and have increased prevalences of the histocompatibility antigens HLA-B7 and HLA-B12. We report herein a comparison of in vitro cellular responsiveness to glucocorticoids and HLA classification for 25 POAG patients, and 25 individuals who respond to topical dexamethasone with intraocular pressure is greater than 31 mm. HG. (GG responders). Within both the POAG and GG groups, significantly greater responsiveness to prednisolone occurs in patients with HLA-B12 antigen. No such association occurs for patients with HLA-B7.


Trabeculotomy in the immature, enucleated human eye.

Greater than 50 per cent of resistance to aqueous outflow was eliminated by internal trabeculotomy covering 30 degrees of the limbal circumference in enucleated, postmorten infant eyes subjected to constant-pressure acqueous perfusion. The proportion of total outflow resistance eliminated after limited trabeculotomy was greater in infant eyes than that observed in eyes of older children andthan that which others have observed in adult eyes. These data suggest that in the infant eye aqueous humor may flow circumferentially in Schlemm's canal but that the capacity for circumferential flow diminishes with increasing age.


Oral vaccination and multivalent vaccine against Pseudomonas aeruginosa keratitis.

Active immunization against Pseudomonas aeruginosa keratitis and systemic disease in mice was studied. In the first series of experiments, monovalent vaccine, administered orally or intraperitoneally, protected against subsequent corneal and intraperitoneal challenge with the homologous strain of P. aeruginosa; however, oral administration of vaccine elicited less protection than intraperitoneal administration. After both routes, protection was observed at 11 and 32 days post-vaccination, but it was greater at 11 days. In the second series of experiments, multivalent vaccine administered intraperitoneally protected against corneal challenge with 56 to 78 percent of 18 strains.


The determination of the diffusion coefficient of krypton in rabbit ocular tissue.

The validity of the inert gas clearance method for measuring choroidal blood flow has recently been demonstrated by studying the diffusion of krypton in ocular tissue. In this study the diffusion coefficients of krypton in rabbit ocular tissue were calculated from measurements of the diffusion coefficients of xenon. The mean values for the diffusion coefficients of krypton obtained in this study were 1.6 X 10(-5), 0.76 X 10(-5), 0.80 X 10(-5), and 1.2 X 10(-5) cm.2 per second for the sclera, choroid, retina, and vitreous, respectively.


Spatio-temporal interactions in anisometropic and strabismic amblyopia.

Contrast sensitivity functions for sinusoidal gratings of different spatial frequencies and stimulus durations have been determined for both eyes of amblyopic subjects. For both long and short stimulus durations, the entire contrast sensitivity function of the amblyopic eyes is lower than that of the nonamblyopic eyes. When the gratings were flickered at 10 Hz, the sensitivity for pattern and flicker detection were similar for both eyes at low spatial frequencies. Possible neural mechanisms for the differences in contrast sensitivity are considered with respect to recent psychophysical and electrophysiological evidence for channels with different spatio-temporal properties in the mammalian visual system.


Correlation of in vitro 32P counts with histologic features of malignant melanoma of choroid and ciliary body.

The radioactive phosphorus uptake of 30 samples fron nine uveal melanomas was determined by liquid scintillation counting. These in vitro measurements correlated positively with clinical (in vivo) 32P values and with the number of mitotic figures and percentage of epithelioid cells (PEC) within the specimens. Three possible explanations were found for the failure of previous workers to demonstrate a correlation between cell type and clinical 32P. (1) Cell type, using Callender's classification, provides only a crude estimate of the PEC within a tumor; in particular, tumors of mixed cell type can vary widely in epithelioid cell content. (2) The rate of 32P absorption is not su-ficiently sensitive to distinguish spindle cell tumors from mixed cell tumors with a low PEC. (3) Clinical 32P measurements may be affected by extraneous factors that cause large deviations from the expected values.


The role of thyroid hormone in the development of the chick corneal endothelium and epithelium.

Previous studies have established that thyroxine or thiouracil treatments affect the development of corneal transparency in the chick. The effects of these drugs on chick corneal epithelial and endothelial development were investigated because in the adult the integrity of these cell layers is necessary for the maintenance of corneal transparency. Chick embryos were treated with thiouracil or thyroxine at stage 36 or 38; the corneas were excised 2 to 12 days after treatment (between stages 38 and 45), and prepared for electron microscopy. The colloidal tracer ruthenium red was added during fixation to study epithelial and endothelial permeability and to stain the intercellular endothelial spaces. At all stages studied, the epithelium was impermeable to ruthenium red and this property was not affected by drug treatment. The epithelial barrier to this tracer is located in the outermost cell layer. The ease of penetration of ruthenium red through the endothelial intercellular spaces indicated the lack of zonular tight functions and the presence of gap functions in this cell layer. Thiouracil treatment delayed the development of the corneal epithelium so that at stage 45 it resembled epithelium from a normal embryo 3 stages younger. In normal animals, chick corneal endothelial development is characterized by an increasing degree of interdigitation of the lateral plasma membranes of adjacent endothelial cells with advancing embryonic age. Thiouracil treatment delayed this progressive development of adjacent cell membrane interdigitation. In contrast, thyroxine treatment accelerated the development of the lateral borders of the endothelial cells. It also appears that thyroid hormone can affect the development of the cell membranes of apposed cells in epithelium as well as the endothelium of the embryonic chick cornea.


In vivo observation of protein diffusivity in rabbit lenses.

We report the in vivo observation of protein diffusivity in rabbit lenses with the use of laser light-scattering spectroscopy. Levels of laser light irradiation, which we estimate to correspond to a level less than that used in routine ophthalmoscopy, were adequate for observation. The in vivo measurements agreed with measurements on the same lens after excision from the animal. Since changes in protein diffusivity reflecting even very small degrees of protein aggregation can be observed by this method, it should make possible quantitative studies of incipient lens opacification.


Kainic acid: neurotoxic effects after intraocular injection.

Intraocular injection of 120 nmol. of kainic acid, a powerful glutamate receptor agonist, induces a marked degeneration of cells in the inner nuclear layer of the retina. Within 2 hours after injection there is a significant decrement in the specific activities of tyrosine hydroxylase, choline acetyltransferase, and glutamic acid decarboxylase; by 48 hours after injection there is nearly a complete loss in the presynaptic neurochemical markers for the cholinergic and GABAergic neurons. The dopaminergic neurons, as assessed by activity of tyrosine hydroxylase and concentration of endogenous dopamine, are reduced only 50% by the kainic acid treatment. Although basal adenylate cyclase activity is unaffected by kainic acid, there is a 90 percent reduction in the activating effects of dopamine on adenylate cyclase in the kainic acid-treated retina.


Blue and green cone mechanisms in retinitis pigmentosa.

Pronounced abnormalities in the increment threshold curves for the blue and green cone mechanisms only 10 degrees above the fovea, and in some cases in the fovea as well, have been found with a 2.5 degrees stimulus in different genetic types of retinitis pigmentosa. Whenever cone thresholds were abnormal, thresholds determined by the blue cone mechanism (pi1 and pi3) were more elevated than those determined by the green cone mechanism (pi4). Thresholds determined by the green cone mechanism were consistently more elevated at low background intensities than at intermediate and high background intensities. Threshold elevations for the blue and green cone mechanisms relative to each other in the perifovea in a given patient tested with the 2.5 degrees stimulus could be simulated in normal observers tested with a single small stimulus. These findings support the idea that the summation pools for blue and green cone mechanisms are proportionally reduced below normal in retinitis pigmentosa, at least in the perifovea, and are compatible with the idea that both mechanisms are comparably involved at the photoreceptor level.


Calcification of soft contact lenses in patient with dry eye and elevated calcium concentration in tears.

Following radiotherapy for an extensive intraepithelial carcinoma of the conjunctiva and eyelid, a patient developed opacification of soft contact lenses used on the same side. Calcilm was demonstrated within the contact lenses by cytochemical methods and by energy-dispersive x-ray microanalysis. The phenomenon was associated with unilateral tear insufficiency and an elevated tear calcium level as determined by atomic absorption spectrophotometry.


Radio telemetry of intraocular pressure in vitro.

A guard ring pressure transensor, using the principles of surface applanation, was used to transmit intraocular pressure (IOP) from a cadaver canine eye. The transensor consisted of a passive resonant coil/capacitor combination, made pressure sensitive by the movement of a small ferrite plate which acted as its applanating surface. Oscillation induced in the transensor by a remote grid dip oscillator (GDO) was monitored by a digital frequency counter (DFC). The resonant frequency of oscillation in the transensor bore a linear relationship to the in vitro IOP in three separate experiments (coefficient of determination for linear regression, r2 equals 0.90). These data indicate that radio telemetry is feasible, using a miniature applanating passive radio telemetric device for continual monitoring of IOP.


Age-related changes in the free amino acid pool of rat lens.

Quite disparate values have been reported by various investigators for the concentrations of free amino acids in the normal rat lens.  To test the possibility that the apparent discrepancies could result from age- or strain-related effects, assays were made on both weanling and mature specimens from two common laboratory strains of rats. Althoug, the levels of free amino acids in the plasma were very similar in all groups, the total free amino acid concentration in the lenses of weanling rats was almost double that found in mature rats. Individual amino acids showed quite varied patterns of age-related changes in concentration. Although there is limited evidence that strain-related differences in the amino acid pool may also exist, it was concluded that age-related alterations pro0ably account for most of the variation present in the previously reported values.


HLA antigens and primary open-angle glaucoma in black Americans.

Black patients with primary open-angle glaucoma, when compared to nonglaucomatous individuals, demonstrate significantly increased prevalences of the HLA antigens B7 and B12 and significantly decreased frequencies of A1 and A11. White patients with primary open-angle glaucoma have in common with blacks the increases in B7 and B12 and the decrease in A11, but present no deficit of A1. In addition, white patients with primary open-angle glaucoma demonstrate a significant increase of A3 and a decrease of Bw35, both of which are not found in blacks.


Inhibition of leukocyte migration with melanoma-associated antigens in choroidal tumors.

Patients with choroidal melanomas and simulating choroidal tumors were tested in a masked manner in a leukocyte-migration inhibition (LMI) assay with a 3M KCl antigen derived from a metastatic choroidal melanoma. Good discrimination petween patient groups was observed with this antigen. The sensitivity and specificity of this assay are discussed.


Retina viability in the Necturus.

Electroretinograms (ERG's) were recorded from the eyes of paralyzed normal and decapitated mudpuppies (Necturus maculosus). Fully dark-adapted responses to a range of stimulus intensities were compiled hourly under both conditions. Statistical analyses indicate no significant change in responsiveness in paralyzed normal animals during periods up to 6 hours. After decapitation, there was a significant decline of sensitivity to light during the first 3 hours. An oxygen-sensitive component similar to the c-wave was observed with DC recording but only in normal eyes. Anoxic mudpuppy eyes show an ERG decline with an average time constant of 1.5 hours.


The rod outer segment phospholipid/opsin ratio of rats maintained in darkness or cyclic light.

Rhodopsin (opsin), lipid, and fatty acids were measured in rod outer segments (ROS's) of rats maintained for at least 2 weeks in continuous darkness or in 12 hours per day cyclic light. Average rhodopsin per eye was 1.8 nmol. for the 5 ft.-c. cyclic light groups compared to 2.4 nmol. for the dark groups of the same age. The phospholipid/opsin ratio was significantly higher after cyclic light maintenance, suggesting that slow adaptive processes control the opsin density of the ROS membranes. Estimates indicate that ROS length also depends on the long-term light environment. ROS lipid and fatty acid composition were not consistently different in dark and light groups.


Experience with a microscopic screening program for sputum specimens.

Microscopic examination of almost 2,000 sputum specimens was performed over a 3 1/2-month period. The specimens were categorized into 6 groups based on numbers of leukocytes (PMN's) and squamous epithelial cells (SEC's) observed at low magnification (X 100). Bacteriologic evaluation of specimens consisted of identification and antimicrobial susceptibility tests of potential pathogens when growth was equal or predominant to the growth of oropharyngeal flora. Specimens containing greater than 25 PMN's and less than 25 SEC's had potential pathogens identified in 51% of the samples. Specimen containing greater than 25 SEC's and any number of PMN's showed a rate on only 19%. Specimens containing less than 25 PMN's and SEC's had a rate of 13%. Since initiating the screening program in which sputum specimens containing greater than 25 SEC's were unacceptable for culture, the per cent of acceptable specimens received by the laboratory nearly doubled.


Evidence against gastrointestinal pseudoparasitism by the land planarian, Bipalium kewense Moseley 1878.

The possibility of gastrointestinal pseudoparasitism by the free-living land planarian, Bipalium kewense, was tested by feeding and survival experiments. The intestinal tracts of three dogs were negative for B. kewense after the individual dogs were fed eight, three, and four large worms and autopsied at 12 h, 3 h, and 45 min, respectively. Survival of the worms in Warburg flasks, under N2, AT 27 C, was 2 h or less.. In Gas Pak jars (CO2 + H2) at 37 C, survival was less than 60 min. Aerobically, at 37 C, survival varied from 45 to 60 min. Attra-tion of the worms to stool material was examined by placing planaria inside square whose boundries were constructed of fecal smears. Bipalium kewense exposed to canine feces showed strong avoidance reactions. Urea, a nitrogen end product of these worms, was also shown to be a negative stimulus for B. kewense. Failure to establish even short term passage in the digestive tract, lethality of 37 C and anaerobic environments, and sensitivity to feces makes gastrointestinal pseudoparasitism unlikely in these organisms.


Ultracytochemical demonstration and probable localization of 3beta-hydroxysteroid dehydrogenase activity with a ferricyanide technique.

In order to localize 3beta-hydroxysteriod dehydrogenase activity on the ultrastructural level, sections of Newt and Rat adrenocortical tissues, fixed in a mixture of glutaraldehyde (0.25%) and formaldehyde (1%), were incubated in a medium containing namely a 3beta-hydroxysteroid as substrate, NAD, potassium ferricyanide as final electron acceptor and copper sulfate. In some experiments, phenazine methosulfate (PMS), an electron carrier which can substitute for the activity of the endogenous NADH-diaphorase, is added at various concentrations to the incubation medium. A final precipitate of copper ferrocyanide is observed in the immediate vicinity of the tubules of the smooth endoplasmic reticulum, or in contact with their external faces. The reaction product can also be seen in mitochondrial cristae. The reaction does not take place in incubation media lacking substrate or containing cyanoketone, a specific inhibitor of 3beta-hydroxysteroid dehydrogenase. the addition of PMS to the incubation medium increases the intensity of the reaction, but does not modify the localization of the precipitate.


Combined visualization of central catecholamine- and acetylcholinesterase-containing neurons: application of the glyoxylic acid and thiocholine histochemical methods to the same Vibratome section.

This paper describes a procedure for demonstration of catecholamine- and acetylcholinesterase-containing neurons in the same section of central nervous tissue. The brains are first processed according to the glyoxylic acid (GA) fluorescence method for catecholamine neurons, i.e. perfused with an ice-cold GA solution, sectioned on a Vibratome instrument, immersed in a GA solution and dried under a stream of warm air. The unmounted sections are examined and photographed in the fluorescence microscope, and then stained for acetylcholinesterse according to Holmstedt's modification of the Koelle thiocholine method (incubation for 4-6 h with acetylthiocholine as substrate and Mipafox as inhibitor of non-specific cholinesterases). the sections are then examined in the light microscope, rephotographed, and the picture compared with that following the GA reaction. The present technique makes possible, for the first time, detailed light microscopical studies of themorphological relations between central catecholamine-and acetylcholinesterase-containing neurons in the same section.


Critical analysis of the use of the acrolein-Schiff method as a possible DNA reaction.

Histophotometric examination was carried out on nuclei of lymphocytes in human peripheral blood, which were subjected to various tests in order to assess the acrolein-Schiff method as a possible DNA specific reaction, in comparison with the traditional Feulgen reaction. Special attention was paid to the degree of difference between responses attributable to a direct Schiff reaction obtained in the fraction of nuclear proteins after treatment with acrolein. From the results obtained it appears that an acrolein-Schiff reaction, following extraction of proteins, may be considered a qualitative reaction for DNA. Our findings also show that there is no relationship between the degree of response to the acrolein-Schiff reaction and that the Feulgen reaction, which is to be expected in view of the different mechanisms of the two reactions.


Temporal relationship between glucose 6-phosphate dehydrogenase activity and DNA-synthesis.

Wounds have been inflicted in the skin of guinea-pigs. Measurements were made on the basal cells 39-54 h later, at different times of the day. It has been shown that there can be two peaks of mitosis, one about mid-day and the other about 22 h. Synthesis of DNA, measured by Feulgen microdensitometry, preceded mitotic activity. Marked changes were found in glucose 6-phosphate dehydrogenase activity, measured by quantitative cytochemistry and microdensitometry. The greatest activity preceded DNA-synthesis, indicating that pentose-shunt metabolic activity is involved in biosynthetic processes required for cell proliferation.


An autoradiographic study of macromolecular syntheses in the epithelium of the ductus epididymidis in the mouse. II. Incorporation of L-fucose-1-3H.

Glycoprotein dynamism in the mouse epididymis was studied by means ofhistoautoradiography after injection of L-fucose-1-3H. The label was detected, at thirty minutes p.i., in the area occupied by Golgi apparatus in the epithelial cells. At 4 h p.i. the label was already present inthe lumen of ductus epididymidis. At this time interval, the luminal labelling was highest in the initial segment of the epididymis and decreased against the more distal segments considerably. At ten days p.i. very high labelling was detected in the luminal contents in the terminal segment of the ductus epididymidis and in ductus deferens, the labelling in the proximal segments of the epididymis being much lower. These observations suggested a wave of labelled glycoprotein in epididymal plasma passing through the epididymis after a fucose pulse. Higher labelling was detected in so-called "clrial was seen in epididymal and uterine spermatozoa, mostly in sperm tail region.


Intranuclear synthesized and native glycogen particles in human gastric cancer: ultrastructure and histochemistry.

Ultrastructural and histochemical studies on human gastric cancer cells disclosed the presence of native and synthesized glycogen particles. The glycogen particles were investigated in the histochemical synthesis of glycogen particles from glucose 1-phosphate by the phosphorylase-branching glycosyltransferase system and non-incubated native glycogen in human gastric adenocarcinoma tubulare. It was observed that focal synthesis localized inthe intracytoplasmic matrix and intranucleus. Intranuclear synthesized glycogen appeared as a rosette form ranging from 1100 to 1300 A in diameter and free particles ranging from 325 to 900 A in diagmeter. The synthesis of glycogen appeared in the nucleus as well as in the cytoplasm of the human gastric cancer cells, and the synthesized glycogen was observed as a group of particles. Newly formed glycogen particles appeared occasionally in the interchromatin area as a large macromolecular structure of rosette form. Native glycogen appeared as a free-particle (250-333 A, medium =300 A) and aggregated rosette from (694-1050 A, medium=917 A) in the autophagosome of gastric cancer cells. There was not, however, a native glycogen particle in the nuclei of gastric cancer cells. Under certain conditons the nuclei of gastric cancer cells can acquire the capacity to synthesize glycogen.


Bone alkaline phosphatase kinetics studied by a new method.

Studies of enzyme kinetics by histochemical methods has been seriously impaired by available methods. This study combines two newer methods, i.e., sectioning undecalcified bone from glycol methacrylate and the use of atomic absorpton spectrophotometry for photographic densitometry. The results indicate that the substrate concentration for zero order kinetics of the alkaline phosphatase reaction in bone is 0.5 mg/ml of substrate; and the Km of the same reaction is estimated to be 0.25 mg/ml or 0.56 mM of substrate.


[Investigations on the glycocalyx with toluidin blue staining (author's transl)].

The study was concerned with the molecular structure of the erythrocyte membrane and its anisotropic staining with toluidine blue. Enzymatic or chemical degradation impairs the topo-optical staining. Decreased anisotropy results also from digitonin treatment of glutaraldehyde fixed cells. Incubation in a mixture of chloroform and methanol abolishes the anisotropic staining with toluidine blue, but it has been restored by the aldehyde bisulfite-procedure. The efficacy of a treatment with chloroform-methanol is greatly reduced int eh case of agglutinated erythrocytes. The reversibly collapsed glycocalyx is devoid of topo-optical staining. The findings refer to the spatial orientaiton of glycoproteins at the cell surface. Degradation or loss and rearrangement, respectively, change the glycocalyx structure and likewise deteriorate the condition for the anisotropic staining. Alterations of the lipid layer of the membrane may result in similar effects. There was, however, no indication of an intercalation into the lipid layer of dyestuff molecules. In conclusion, the topo-optical toluidine blue staining is considered a powerful method aiding studies of the glycocalyx of erythrocytes (and presumably of other types of cells too).


Consecutive demonstration of nerves containing catecholamine and acetylcholinesterase in the rat cornea.

The innervation of the cornea of newborn (two day old) and adult rats was investigated using glyoxylic-acid-induced fluorescence (GIF) for catacholamines and subsequent acetylcholinesterase reaction. Fluorescent nerve were observed around the limbal vessels and in the pericorneal nerve plexus, from which they branched towards the central parts of the cornea. The fluorescent corneal nerves were either nonvaricose or had varicosities at intervals of 10 micra. When the animals had been pretreated with nialamide, noradrenaline and propranolol, some fluorescent branching nerve terminals with numerous varicosities also appeared. All fluorescent nerves disappeared two days after ipsilateral superior cervical sympathectomy. When the acetylcholinesterase (AChE) reaction was performed subsequently to the GIF reaction the following nerve types could be identified: 1. nerves containing both catecholamine (CA) fluorescence and AChE, 2. Nerves containing only AChE.


A comparison between the one-step and the two-step copper thiocholine procedure for the cytochemical localization of cholinesterases.

A comparison between the one-step and the two step copper thiocholine procedure for the subcellular localization of cholinesterases was undertaken. The results indicate that only under experimental conditions with short incubation times and precise control of the conversion into sulphide is the localization of the primary precipitate and that of the secondary precipitate identical. It was concluded that the conversion of the primary precipitate into Cu-sulphide is not necessary and can lead to artefacts.


Corticosteroid-induced changes in glucose metabolism of chondrocytes.

Immature mice were treated for up to 12 weeks with daily doses of triamcinolone diacetate. Using quantitative histochemical methods, the proximal epiphyseal plate of the humerus was studied at regular intervals. By the tenth injection significant decrease was noted in the acid glycosaminoglycans content (25%) and in the neutral mucopolysaccharides (30%). Concomitantly, a marked increase was noted in the intracellular depots of glycogen (70%). It is suggested that the hormone's antiglycolytic effect in cartilage caused the glucose metabolic pathway to divert in the direction of glycogen synthesis, and thereby interfered with the normal synthetic pathway of the chondrocytes. The hormone's primary effect on the cells' hexose metabolism could be responsible, at least in part, for its inhibitory influence on bone growth.


Cholinesterases of the gall bladder.

Cholinesterase histochemistry of the human gall bladder was studied using two specific methods. Distribution of acetylcholinesterase: In the mucosa, nerve fascicles consisting of densely packed parallel single nerve fibres, small ganglia and "spot"- and "glomerule"- like concentrations of acetylcholinesterase activity were observed. In the muscle layer, a wide-meshed network of delicate nerves, with occational areas of very dense innervation, and small ganglia were seen. In the serosa, "glomerule"- like structures surrounded by dense "baskets" of delicate nerves were observed.-- The general scheme of distribution of non-specific cholinesterases was similar to that of acetylcholinesterase. It seems that the cholinergic innervation of the gall bladder is related to both secretion and absorption and contractility. Some cholinergic nerves are probably sensory, especially because acetylcholinesterase-positive structures, possibly pressure of stretch receptors, supplied with nerves were observed in the mucosa and the serosa. The cholinergic innervation of the gall bladder muscle was scarce except occasional areas of very dense innervation. It may thus be concluded that the intermuscle spread of excitation plays an important role, the majority of the smooth muscle cells receiving their nervous influence via electrotonic coupling.


Qualitative electron probe analysis of secretory ameloblasts and odontoblasts in the rat incisor.

Rapidly frozen growing rat incisors were freeze fractured and freeze dried in preparation for energy dispersive X-ray emission microanalysis in a scanning electron microscope. Ca levels were found to be elevated in the distal cell body of odontoblasts, whereas Ca was uniformly low over all parts of the cell body of secretory ameloblasts. The results suggest fundamental differences in the mechanisms by which these two cell types process Ca, and that Ca possibly diffuses through the secretory ameloblast layer on its way to the enamel.


[A case report of an unusually long uvula (author's transl)].

An unusually long uvula as a cause of chronic throat irritation with the sensation of a foreign body in a 35-year old patient is reported, with symptoms relieved by partial resection of the uvula.


[The investigation of different types of vocal disorder by statistical frequency analysis (author's transl)].

Common disorders of the vocal cords were assessed by indirect and direct laryngoscopy and by stroboscopy, and they were compared over the frequency range of "a". Amplitude and frequency variations from the normal are illustrated in recurrent laryngeal nerve paralysis, intubation granuloma, chronic oedema, the hyperkeratosis of chronic laryngitis, hypokinesia and hypokinetic dysphonia. In several cases, the effects of exercise or previous surgery are demonstrated. The described technique gives a useful aid to the management of vocal cord disease.


[Reconstructive surgery of the orbit and adjacent paranasal structures (author's transl)].

In reconstruction of the orbital floor, homograft lyophilised dura or cialit-stord rib cartilage are suitable, but the best materials are autologous cartilage or silastic or teflon. Autograft bone from the maxilla or rib is rarely used. The surgery of traumatic hypertelorism and the reconstruction of the medial angle of the eye after orbito-nasal fractures are described and illustrated. With complete destruction of the floor of the orbit, a fronto-temporal pedicled flap combined with auricular cartilage is recommended. In this way, the orbital floor and the lower eyelid can be reconstructed. The epithelial lining of the orbit can be developed from a pedicled flap of maxillary sinus mucus membrane.


[Applied nystagmometry in differentiating vesitbular diseases (author's transl)].

Nystagmus as a reaction on vestibular stimulation is influenced by many factors which are difficult to control. One of the most important parameters correlating best with the excitability of the peripheral vestibular apparatus is the speed of the slow phase of the nystagmus. This can be registered directly by use of the nystagmometer (or Blauert System), together with the speed of the fast phase. All parameters of the nystagmus can be easily described when recorded. However, an exact description of the nystagmic reaction should not be considered as a complete diagnosis by itself alone; the diagnosis can only be the result of combining nystagmometry, audiometry and other otoneurological or neurological findings with the patient's presenting complaints (or history of the disease involved).


[Surgical correction of the paralyzed vocal cord in the intermediate position].

The present report describes the favorable use of fascia lata in the treatment of vocal cord paralysis as compared to other methods frequently used (such as, injection of artificial substances, implantation of cartilage or silicone, and stretching of the paralyzed cord).


[Magnifying Larynxstroboscopie (author's transl)].

A procedure for stroboscopic observation of vocal cord vibrations by means of a magnifying laryngoscope is reported. In addition, the clinical problems which can be managed successfully by this procedure are discussed.


[Intracranial arteriovenous malformation in one family -- oto- and neurological aspects (author's transl)].

Intracranial arteriovenous malformations in a father and daughter are described. The pathology involved in one of the patients was localized in the left dura, whereas that of the other was located in the left parietal lobe. Although clinical symptoms were different in each patient, possible hereditary factors in causing the malformations are discussed.


Evaluation of less than recommended dosages of levamisole phosphate for the treatment of gastrointestinal nematodes of cattle.

The anthelmintic activity of 3 dosages of injectable levamisole phosphate was evaluated in 84- to 145-kg calves from a herd of cattle with a history of heavy gastrointestinal nematode infections. Trichostrongylid egg counts in the calves varied from 450 to 700/g of feces. The anthelmintic was administered subcutaneously to 3 groups of 10 calves each, at the rate of 8 mg/kg of body weight (current manufacturer's recommendation), 6 mg/kg, and 4 mg/kg. A 4th group of 10 calves was utilized as untreated control calves. At necropsy, comparison of worm burdens between treated and untreated calves indicated apparent reductions (at 8 mg/kg, 6 mg/kg, and 4 mg/kg, respectively) for the various nematodes to be: Haemonchus placei adults-99.9, 100, and 98.3%; H placei L4-91.0, 94.0, 98.0%; O ostertagia late L4-93.8, 86.7, and 96.3%; Trichostrongylus axei adults-99.1, 100, and 100%; Cooperia spp adults-99.8, 99.5, and 99.5%; and Oesophagostomum radiatum adults-100, 100, and 100%. Statistical evaluation, by one-way analysis of variance, of the mean number of each species recovered showed significant (P less than 0.05) differences in the worm burdens between treated and untreated calves, but differences in efficacy between any 2 of the 3 drug dosages were not significant.


Distribution of paratuberculosis in Wisconsin, by soil regions.

A study was undertaken to determine the relationship between concentration of paratuberculosis-infected herds and soil types in Wisconsin. Locations of farms on which paratuberculosis had occurred between 1971 and 1975 were obtained from the Wisconsin Department of Agriculture. The disease occurred mainly in the rolling and undulating areas. Fifty percent of the infection herds were in the southwestern "driftless area" and the southeast uplands; 43% occurred in the western part of the northern silty and loamy uplands; the other 7% were scattered in the east and east-central part of the state. The disease did not necessarily occur in the areas of high cattle concentration. It was concluded that the disease persisted in regions with acid soils but not in regions with alkaline, calcereous soils.


Bovine immunoglobulins following induced parturition.

Immunoglobulins in colostrum that are absorbed into the calf's blood were studied in cows in which parturition was induced by corticosteroids 3 to 22 days before expected full-term calving. The colostral and calf serum concentrations of IgG were not different from those in cows and their calves at full-term calving. Colostral IgG content decreased precipitously between 2 and 12 hours postpartum in both groups of cows.


Evaluation of free-roaming mule deer as carriers of anaplasmosis in an area of Idaho where bovine anaplasmosis is enzootic.

Samples of blood from 87 Rocky Mountain mule deer (Odocoileus hemionus hemionus) were inoculated into 3 susceptible splenectomized calves to determine the anaplasmosis carrier status of the deer. The deer were trapped along the Idaho-Utah state boundary, near Stone, Id. Acute anaplasmosis was induced in 2 of the 3 inoculated calves, and blood from the 3 calves caused anaplasmosis when inoculated into adult non-splenectomized cattle. Serum rapid card agglutination testing revealed 13 (14.9%) positive reactions among the 87 mule deer. When these seropositive samples were evaluated with the complement-fixation test, positive reactions were not found and only 3 (3.5%) serums gave suspect reactions. A serologic survey for anaplasmosis in 1,852 cattle that cohabit spring and summer rangeland areas with mule deer revealed 14.5% reactors by the serum rapid card agglutination test. The study area consisted of an ecosystem that supports cattle, free-roaming mule deer, and Dermacentor andersoni, and thus contained the elements necessary to effect interspecies transmission of Anaplasma marginale. The significance of wildlife reservoirs and their bearing on anaplasmosis control and eradication programs needs further investigation.


Malignant melanomas in a Duroc boar.

A Duroc boar had 2 malignant melanomas of the skin, with metastases into several lymph nodes, lungs, liver, and spleen. All tumors had these characteristics: invasion of lymph and blood vessels, necrosis, numerous giant cells containing granules, heavily pigmented as well as lightly pigmented and unpigmented melanocytes, few anaplastic features, and few mitotic figures. In the skin tumors, there was neither intraepithelial growth nor junctional activity.


Cryptosporidiosis in three pigs.

Coccidia of the genus Cryptosporidium were found at necropsy in 3 pigs. The organisms were embedded in the microvillous border of crypt epithelial cells of the large intestine. Mild inflammation was associated with the infection but without clinical signs of enteritis.


Portal vein anomaly and hepatic encephalopathy in a horse.

Periodic episodes of diffuse central nervous system disease occurred in a yearling Thoroughbred gelding that had a history of frequent respiratory tract disease and stunted growth. Hepatic encephalopathy was diagnosed on the basis of history, clinical signs, prolonged bromsulphalein clearance, and increased blood ammonia content. Because of the poor prognosis and recurrent clinical signs the horse was euthanatized. Necropsy revealed an arteriovenous anomaly and thrombosis of the portal vein. Histologically, there was diffuse primary astrocytosis of the brain.


Navicular disease in the horse: risk factors, radiographic changes, and response to therapy.

In a retrospective study, 74 horses met defined historical and clinical features indicative of navicular disease. Most of the affected horses were 4 to 9 years old. Males had a greater risk of navicular disease than females, geldings had a greater risk than stallions, and Quarter Horses had a greater risk than other breeds. Diagnostic radiographic changes were found in 42 of 70 horses examined. The distribution of diagnostic radiographic changes between the right and left fron feet was equal. There was no correlation between the finding of diagnostic radiographic changes and the horse's response to therapy or the type of work for which the horse had been used. A questionnaire regarding the current status of the horses in the study was mailed, and 51 replies were received. Of the 38 horses that were alive at least 6 months after treatment and for which the current status was known, 9 were sound at the time of follow-up (from 7 to 91 months after treatment). Three of these horses had been treated medically, 4 surgically, 1 by corrective shoeing, and 1 not treated. No advantage for medical or surgical therapy was demonstrated. The poor response to therapy in this group of horses suggests that the prognosis for horses with navicular disease should be guarded, and that the probability of a return to a prelameness capacity for work is slight.