Quantitation of urinary hydroxypyridinium cross-links from collagen by high-performance liquid chromatography.

Pyridinoline and deoxypyridinoline are intermolecular cross-links in mature collagen in bone and cartilage. The urinary excretion of the two compounds correlates well to bone turnover. A fast, sensitive, and accurate isocratic ion-pairing reverse-phase high-performance liquid chromatography method for measurement of pyridinoline and deoxypyridinoline in urine has been established. Intra- and inter-assay precision were 5-7% and 12-14%, respectively. Recovery for pyridinoline was 97.4% and for deoxypyridinoline 94.3%. The detection limit was 0.4 pmol. Pyridinoline:creatinine and deoxypyridinoline: creatinine ratios in healthy subjects, were 38.8 nmol:mmol and 13.0 nmol:mmol, respectively. Increased values of both cross-links were observed in children, in the age group 20-29 in both sexes, and in post-menopausal women.


Sensitive enzyme-linked immunosorbent assay for measurement of autoantibodies to human thyroid peroxidase.

The development of a sensitive assay for detection of autoantibodies against one of the major thyroid antigens, thyroid peroxidase (TPO), is described. TPO was purified from human thyroid tissue by: (1) isolation of thyroid microsomes using homogenization and differential centrifugation, (2) solubilization of membrane proteins by Zwittergent 3-14, and (3) anion exchange liquid chromatography on a FPLC Mono Q column. Autoantibodies against TPO (TPO-Ab) were measured using an enzyme-linked immunosorbent assay (ELISA) with serum samples diluted 1:100. Standards containing 70, 7, 0.7, 0.02 and 0 U ml-1 TPO-Ab were employed (reference standard code 66/387 NIBSC, London, UK). The detection limit was 0.02 U ml-1 corresponding to 2 U ml-1 in undiluted serum. The inter- and intra-assay coefficients of variation were 8.6% and 5.3%. In 109 healthy control subjects TPO-Ab was found in 9 (8.3%), while 43 (97.7%) out of 44 patients with newly diagnosed untreated Graves' disease had detectable TPO-Ab in serum. All of 16 patients with newly diagnosed spontaneously developing primary hypothyroidism had circulating TPO-Ab (range 16-7000 U ml-1). The new assay is a valuable tool for evaluation of thyroid autoimmunity in individual patients and for studying the epidemiology of thyroid autoimmunity.


Effect of lovastatin on lipoprotein fluidity in patients with hypercholesterolaemia.

Lovastatin was administered to six hypercholesterolaemic patients (mean plasma cholesterol 450 mg dl-1). Plasma lipoproteins (VLDL, LDL, and HDL) were separated before and following 7 and 12 weeks treatment with lovastatin. Fluidity was quantified by fluorescence polarization measurements using 1,6-diphenyl 1,3,5 hexatriene (DPH) as the fluorescent probe. Lovastatin treatment resulted in a significant reduction of total plasma cholesterol, LDL cholesterol and VLDL cholesterol (-41%, -44%, -68%, respectively). Fluidity measurements showed significant (p < 0.01) increase in LDL fluidity by 11% and 21% after 7 and 12 weeks of lovastatin treatment, whereas, VLDL fluidity was increased by 27% after 12 weeks of therapy. HDL fluidity was not altered. These alterations in the fluidity of the atherogenic lipoproteins (LDL and VLDL) in hypercholesterolaemic patients may prove to be of significance in reducing the risk of atherosclerosis.


Transferability of clinical laboratory data within a health care region.

Analytical data for S-Creatinine and S-Urate are presented from seventeen laboratories in the Swedish Uppsala-Orebro regional quality assessment program. The bias and imprecision as well as the instability of the measurement procedures in the participating laboratories were estimated over three 14-week periods. Bias was estimated by a linear least squares fit of the difference between measured and assigned values vs. assigned values, and expressed in absolute and relative terms. Instability of the measurement procedures was estimated by comparing slope and intercept of regression lines of measured vs. assigned values from three fourteen week periods. According to our experiences we recommend regression analysis to describe the performance of the analytical methods of a laboratory over time. The results show that most laboratories fell within the limits of +/- 15% bias for S-Creatinine above 100 mumol l-1 and +/- 17% for S-Urate at concentrations above 250 mumol l-1. Various steps to reduce the inter-laboratory variability are suggested, including numerical correction of individual laboratory results using correction functions. In a few laboratories, instability was too high to allow for numerical corrections of analytical results.


Renal function in patients with untreated acute myocardial infarction.

This study provides data on plasma volume (PV), extracellular volume (ECV) and renal function in 8 untreated patients with acute myocardial infarction (AMI). At day 2 and day 10 after AMI, glomerular filtration rate (GFR), urinary excretion rate of water (Vu), sodium clearance (CNa) and lithium clearance (CLi) were used for assessing reabsorption rates of sodium and water in proximal and distal nephron segments. PV and blood pressure at day 2 were not significantly different from values at day 10. Heart rate (HR), weight and ECV at day 2 were significantly increased when compared with values at day 10 (78 vs. 62 pr. min and 17.0 vs. 16.2 1, respectively). Plasma norepinephrine values were slightly elevated at day 2 and day 10. GFR was initially high and decreased from day 2 to day 10 (118 vs. 104 ml min-1) together with CLi and Ck. However, Vu, CNa and fractional excretion rate of sodium increased markedly from day 2 to day 10. The results suggest that sodium and water retention in the initial phase of AMI without left ventricular failure is due to an increase in tubular reabsorption in distal nephron segments mediated by mechanisms other than the sympathetic nervous system.


DNA synthesis and related enzymes altered in compensatory lung growth in rats.

Left pneumonectomy was performed on 4 week-old male Fischer-344 rats. Changes in DNA biosynthesis and the activities of related enzymes were studied in the contralateral lungs of the pneumonectomized animals (n = 55) and compared with sham-operated (n = 55) and untreated control animals (n = 40) The wet weight of the contralateral lung of the pneumonectomized rats reached that of both lungs of the untreated and sham-operated rats 14 days after the operation. The activities of thymidine kinase and DNA polymerase from the regenerating lungs were elevated on Days 1 and 7. To determine the molecular forms of DNA polymerase in the crude extract, phosphocellulose column chromatography was performed. The type of DNA polymerase with the highest activity was alpha in regenerating lung on Days 1, 3, and 7. These results suggest that DNA replication for cellular proliferation was elevated in the remaining lung after pneumonectomy. In addition, an interlobar difference in DNA biosynthesis was observed in the remaining lung. The increase was especially marked in the cardiac lobe, followed by increases in the DNA content of the remaining lobes on Day 7. From these observations we conclude (1) that increased activity of DNA polymerase alpha is likely to be an initial change in compensatory lung growth, and may be caused by some unknown stimulator in lung tissue, and (2) that DNA biosynthesis may differ among the lobes of the lung, at least until 3 days post-pneumonectomy.


Enzymatic microdetermination of plasma and serum free fatty acids.

A simple and sensitive enzymatic method for determination of plasma and serum fatty acids (FAs) is described. The method is based on acylation of long chain FAs by a bacterial acyl-CoA synthetase (ACS) producing equivalent amounts of acyl-CoA and AMP. AMP production was measured using the coupled reaction of myokinase (MK), pyruvate kinase (PK) and lactate dehydrogenase (LDH) allowing fluorinate detection of NADH. Two moles of NAD were produced per mole of FA acylated. Concentrations of substrates and enzymes were kept as low as possible maintaining the ACS reaction as rate limiting. Addition of fat-free human serum albumin (HSA) to standards reduced initial reaction rates but did not affect end-point fluorescence levels. Triton X-100 partly counteracted the inhibition by HSA. To keep albumin concentration low, plasma or serum samples were diluted by 1:400. Duplicate measurements of plasma or serum FA concentrations between 0 and 2 mmol l-1 can then be performed on 5 microliters samples with intra- and inter-assay variation coefficients of 1.7 and 4% respectively.


Taurine content and distribution in equine skeletal muscle.

Taurine (TAU) is found in large but variable amounts in the skeletal muscles of many species. It has been reported that slow twitch muscles in the rat exhibit higher TAU levels than fast twitch muscles. Variation in muscle taurine content may be attributable to differences in the fibre type composition of different muscles. TAU content (mmol kg-1 dry muscle) and percentage type-1, type-2A, and type-2B fibre section area (f.s.a.) were measured in muscle samples taken from up to six sites in the middle gluteal muscle of four horses and one pony at post mortem and in biopsy samples taken from twenty Thoroughbred horses in race training. TAU was positively correlated to type-1 f.s.a. (r = 0.94, p < 0.001) in both post mortem samples and biopsies from horses in race-training. Multiple linear regression analysis was used to estimate the TAU content of individual fibre types when present at 100%. TAU is almost exclusively localized in type-1 fibres. The TAU content of type-1 and type-2A fibres was estimated to be 45.4 mmol kg-1 d.m. and 4.5 mmol kg-1 d.m. respectively in the post mortem horses, and 32.4 mmol kg-1 d.m. and 7.9 mmol kg-1 d.m. respectively in the horses in training. TAU was estimated to be absent from type-2B fibres in both horse groups.


Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat.

The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism.


Phorbol myristate acetate-induced lung injury: involvement of reactive oxygen species.

Using lucigenin-enhanced chemiluminescence, isolated rat lungs perfused with physiological salt-Ficoll solution were studied to test whether phorbol myristate acetate (PMA)-induced lung injury was mediated by reactive oxygen species (ROS). PMA (0.03 micrograms ml-1) caused small but significant increases in lung ROS levels and pulmonary arterial perfusion pressure (Ppa) but did not induce lung oedema. PMA (0.15 micrograms ml-1) induced lung oedema with large increases in ROS production and Ppa. Superoxide dismutase (SOD) inhibited the increases in ROS, Ppa, and lung oedema. Catalase and dimethylthiourea inhibited lung oedema but did not attenuate the increases in ROS and Ppa entirely. Indomethacin attenuated lung oedema partially but did not inhibit the increases in ROS and Ppa. These data indicate that PMA-induced lung injury is dependent on PMA concentration and ROS are responsible for such lung injury. Thromboxane plays a minor role for PMA-induced lung injury. The different effects of oxygen radical scavengers suggest that different radical species contribute to the increased pulmonary vascular response and lung injury.


Mononuclear cell magnesium and retention of magnesium after intravenous loading in patients with acute myocardial infarction.

A magnesium (Mg++) retention test was performed in 19 patients with acute myocardial infarction (AMI) 4-11 days after admission to the coronary care unit. The retention of Mg++ was 45 +/- 23% of the 30 mmol given intravenously. It has been proposed that a retention of more than 20% represents Mg++ deficiency. The mononuclear cell Mg++ concentration before the retention test was on an average slightly higher in the AMI patients than in 25 healthy volunteers (72.5 +/- 24.2 vs. 62.9 +/- 9.2 mumol g-1 protein) indicating no Mg++ depletion in the first group. The reason why patients during the phase of AMI show an increased retention of Mg++ is unknown, but changes in concentrations of several hormones and a reduction in blood glucose could be of importance. Serum concentrations of Mg++ were lower on admission than after 4-11 days. These initial reductions are probably due to increased concentrations of circulating catecholamines during the early hours of AMI.


Genetic variation of human aspartic proteinases.

The human aspartic proteinases include pepsinogen A, pepsinogen C, cathepsin D, cathepsin E and renin. Comparative analysis of the proteinase genes reveals a high degree of similarity with regard to their respective coding sequences and the location of exon-intron junctions. Despite strong conservation of the regions containing the active site aspartyl groups, genetic polymorphisms have been identified for each of the proteinase genes with the exception of cathepsin D. These genetic polymorphisms are useful for localization of genes on linkage maps as well as determination of gene copy number. The chromosomal location of each aspartyl proteinase has been determined by a variety of gene mapping methods employing recombinant DNA probes including; analysis of somatic cell hybrid mapping panels, in situ hybridization to metaphase chromosome preparations and family linkage analysis with polymorphic markers. Pepsinogen A exhibits the most extensive polymorphism among aspartic proteinases which can be detected by either by protein electrophoresis or by DNA analysis. Southern blot hybridization with respective DNA probes and polymerase chain reaction (PCR) amplification have revealed nucleotide differences located within the coding and noncoding portions of the aspartic proteinase genes. These polymorphisms can be used to investigate potential roles of each proteinase in genetically influenced clinical conditions. The development of additional highly polymorphic markers detected by PCR amplification of divergent nucleotide sequence repeats will greatly assist with documentation of the effect of genetic variation of the aspartic proteinases may have in specific clinical diseases such as ulcer and hypertension.


Chicken pepsin and the other avian aspartic proteinases.

The results of studies on chicken pepsinogen and pepsin from the adult animals and from chicken embryos are presented and some of the problems are discussed. A brief summary of other investigations on aspartic and acid proteinases of birds is given and the possible future trends of research in this field are outlined.


Understanding HIV protease: can it be translated into effective therapy against AIDS?

The protease of human immunodeficiency virus (HIV) has been extensively studied. The structure and function relationships of this protease and its role in HIV life cycle is well known. We have use recombinant HIV protease and mutagenesis technology to study HIV protease and compare it to the eukaryotic aspartic proteases. When putative active-site hydrogen bonds are placed in the HIV protease, the pKa values of two active-site groups are only slightly downshifted. Corresponding removal of these H-bonds from the active sites of pepsin and rhizopuspepsin do not appreciably alter the active-site pKa values. The Kcat values are strongly decreased by these mutations. These observations suggest that the active-site H-bonds in HIV protease and other aspartic proteases control the rigidity of the catalytic apparatus but not the ionization of the active-site groups. A mechanism of catalysis by the HIV protease has been suggested based on kinetic and mutagenesis studies. The strategies involved in the development of HIV protease inhibitors are discussed. In spite of the pitfalls in each approach, it appears probable that a battery of inhibitors can be developed for the treatment of AIDS.


Substrate specificity and inhibitors of aspartic proteinases.

Aspartic proteinases of vertebrate, fungal and retroviral origin have been characterised by utilisation of chromogenic peptide substrates and synthetic inhibitors as probes. By this means, the molecular topography of sub-sites within the active site cleft of individual enzymes has been elucidated. With suitable selection of residues to occupy each sub-site, the design of effective inhibitors specifically targetted against individual aspartic proteinases has become feasible.


Some aspects of structural studies on aspartic proteinases.

This paper gives a brief overview over the differences and similarities in the structure of aspartic proteinases presently available. Comparison of the three-dimentional structure of different aspartic proteinases by a common intramolecular coordinate system have been performed. The intramolecular movable subdomains have been localized and the role of motion in substrate binding and zymogen activation is discussed.


Multidisciplinary cycles for protein engineering: site-directed mutagenesis and X-ray structural studies of aspartic proteinases.

The specificity and pH profile of aspartic proteinases have evolved to include not only pepsin with a broad specificity and an optimal activity in acid media, but also renin, with high specificity for angiotensinogen and activity close to neutral pH. Comparisons of the structures and catalytic activities of aspartic proteinases provide helpful clues for engineering new activity profiles. We illustrate an approach that involves recombinant DNA techniques, biochemistry, structure determination and biocomputing. We use the 3-D structures of inhibitor complexes of several aspartic proteinases to define likely intermediates and specificity sub-sites. The multidisciplinary research is organised as cycles, in which each cycle tests a design hypothesis proposed in the previous cycle. We use one member of the aspartic proteinase family, chymosin, to illustrate these ideas in engineering enzymes with altered pH optima and specificities.


The aspartic proteases.

The Aspartic proteases (EC 3.4.23) are a group of proteolytic enzymes that share the same catalytic apparatus. Members of the aspartic protease family can be found in different organisms, ranging from humans to plants and retroviruses. The best known sources of aspartic proteases are the stomach of mammals, yeast and fungi, with porcine pepsin as the proto type. The aim of this review is to summarize some of the characteristics of the aspartic protease family.


Protein engineering of the milk-clotting aspartic proteinases.

Calf Chymosin and a fungal protease from Mucor pusillus (Mucor rennin) are members of the aspartic proteinases used as milk-coagulants in cheese industry. A system for production of recombinant chymosin as inclusion bodies in Escherichia coli cells and its refolding into the active form was established. Another expression system for production of Mucor rennin in Saccharomyces cerevisiae was also established. Mucor rennin was efficiently excreted from the yeast host as a heavily glycosylated form. Glycosylation affected both the secretion and the enzyme properties. Site-directed mutagenesis of the Tyr residue at position 75 in chymosin and Mucor rennin revealed its crucial role in catalytic function of the aspartic proteinases. The results also suggested possibility to improve practical properties of the milk-clotting enzymes by site-directed mutagenesis.


Production of prochymosin, pepsinogen and progastricsin, and their cellular and intracellular localization in bovine abomasal mucosa.

A brief overview of research is presented on the production, cellular and intracellular localization of prochymosin, pepsinogen and progastricsin in bovine abomasal mucosa from fetus to adult. Prochymosin is produced early during gestation (10th week) and is significantly related to milk-feeding. Pepsinogen and progastricsin start to be produced later during gestation (20th week) and are produced in low amounts as long as the calf is fed milk. With age, pepsinogen becomes the dominating zymogen in the abomasal mucosa. Most of the cell types in the fundic gland have the ability to produce all three zymogens and are also found in the same individual secretory granules of these cells.


Chymosin: a short review on foetal and neonatal gastric proteases.

All vertebrates in which the age dependent expression of gastric proteases has been investigated show a characteristic developmental pattern. Neonatal proteases which show partial immunochemical identity with calf chymosin have been observed in several species. The amino acid sequence of lamb chymosin shows 94% of identity with that of calf chymosin. Chymosins from pig and cat show about 85% and 75% of identity with calf chymosin. Chicken embryonic pepsinogen appears to be more related to calf chymosin than to other gastric proteases. A pseudo-gene for a chymosin-like protease from man has been identified. But a functional, human chymosin-like neonatal protease has not been identified. The possible physiological significance of chymosin and the clotting of milk are discussed.


Clinical implications of serum pepsinogen and progastricsin in man.

The serum pepsinogens in man have been reviewed with respect to clinical and physiological significance. The many places of synthesis of pepsinogen (PG A) and progastricsin (PG C) are described. The major part of serum pepsinogen and progastricsin is synthezized in the stomach, and the findings after antrectomy indicate that the majority of the pepsinogens in serum originates from the corpus of the stomach. The concentrations of pepsinogen and progastricsin in serum in relation to stomach diseases, e.g. ulcer disease, gastritis, and cancer of the stomach, are described. Despite typical findings, i.e. hyperpepsinogenemia in duodenal ulcer disease, or hypopepsinogenemia in atrophic gastritis or stomach cancer, there is a big overlap in serum concentrations between the groups reducing the clinical value of routine measurements of pepsinogens. Most promising are the findings in stomach cancer disease, where the combined measurement of pepsinogen levels and the isozymogen Pg5 is found to be highly indicative for the presence of a gastric carcinoma. Reports state that pepsinogens are excellent markers of recurrence of gastric cancer somewhere in the body after total gastrectomy. Genetical studies have--concerning pepsinogen--proved the multiple gene/multiple loci model. There is only a single progastricsin gene in humans and no genetic heterogenity has been found. Finally, the relationship between gastric infection with the bacterium Helicobacter pylori, and elevated pepsinogen and progastricsin levels in the blood, and the search for serologic markers of gastric diseases is discussed.


Gene structures of pepsinogens A and C.

Pepsinogen is an inactive precursor of pepsin, a typical aspartic proteinases, synthesized in the chief cells of gastric glands. There are two major groups of pepsinogen, namely pepsinogen A (PGA) and pepsinogen C (PGC) (or progastricsin), and each frequently has isozymogens. The relative extents of expression of the two pepsinogens vary among animal species and, moreover, their biosynthesis is known to be affected by such bioactive peptides as gastrin and secretin; however, the regulation mechanism of pepsinogen biosynthesis, hence pepsinogen gene expression is not yet clear. Therefore, it is thought to be of fundamental importance to elucidate the primary structures of the pepsinogen gene for such studies. This report describes the primary structures of human PGA and PGC genes and rat PGC gene. The organization of the genes is essentially the same; each gene was found to be separated into nine exons by eight introns of various lengths, encoding the amino acid sequence of the corresponding prepepsinogen. These results show that these genes are all derived from a common ancestral gene. The 5'-flanking region of human PGA gene, however, was different from those of human and rat PGC genes, whereas those of human and rat PGC genes were similar to each other. Thus, it is suggested that the expression of the PGA and PGC genes are somewhat differently regulated.


Effects of interferon-gamma and tumour necrosis factor-alpha on epithelial HLA class-II expression on jejunal mucosal biopsy specimens cultured in vitro.

HLA class-II molecules present antigen to the immune system and are expressed by normal villous enterocytes. Increased expression occurs in inflammatory bowel and coeliac disease, and it is suggested that cytokines may mediate such increased expression. The effects of the cytokines IFN-gamma and TNF-alpha on epithelial HLA class-II expressions have been studied in adult human jejunal mucosal biopsy specimens cultured in vitro. Specimens from nine patients with normal jejunal histology were cultured for 24 h with IFN-gamma, TNF-alpha, or both. Six of nine patients showed increased HLA-DR and HLA-DP expression after culture with the cytokines. We have demonstrated that these cytokines induce increased epithelial HLA class-II expression in adult jejunal mucosal specimens cultured in vitro, a model that most closely resembles the in vivo state. This provides further evidence that such increased expression occurs secondarily to the products of immunologic activation.


Gastric changes in coronary-operated patients with low-dose aspirin.

Low-dose aspirin is widely used in patients operated on for coronary disease as secondary prevention of coronary artery occlusion. The changes caused by aspirin in therapeutic doses to gastric mucosa are well documented, but the effect of long-term low-dose aspirin is not so well known. Forty-six volunteer coronary-operated patients with daily low-dose aspirin were interviewed postoperatively, and an upper gastrointestinal tract endoscopy was performed and biopsy specimens taken 3 months after the operation. The findings were compared with a normal population sample of 358 persons from a study previously published. There were significantly more erosions and ulcers or fresh scars in the study group than in the control population--11 of 46 patients and 24 of 358 patients, respectively. The presence of superficial gastritis was similar. Mostly, the lesions were asymptomatic. History of peptic ulcer disease, use of other ulcerogenic drugs, smoking, and alcohol consumption had no predictive value for acute lesions. In contrast, the lesions were associated with chronic superficial gastritis and Helicobacter pylori infection.


Influence of stress on the healing and relapse of duodenal ulcers. A prospective, multicenter trial of 2109 patients with recurrent duodenal ulceration treated with ranitidine. RUDER Study Group.

The influence of psychologic factors on the healing and relapse of duodenal ulcers under treatment with ranitidine was studied in a prospective, multicenter trial in 2109 patients with an endoscopically proven duodenal ulcer (DU) and a history of recurrent duodenal ulceration. All patient received ranitidine (300 mg daily), and, after healing, 1899 patients continued maintenance treatment (ranitidine, 150 mg daily) for 2 years. A physician's assessment of stress (stress or no stress) was made at every consultation. In the healing phase an overall classification of stress as absent, intermittent, or continuous was made, and in the maintenance phase patients were classified dichotomously as having stress (stress on at least half of the follow-up consultations) or no stress. In addition, at the start of the healing phase stress was measured by means of a standardized questionnaire. Continuous stress, as assessed by the physicians, was associated with a lower 14-day healing rate (35.7%) than intermittent or absent stress (42.4%; relative risk (RR) for delayed healing in patients with continuous stress, 1.19; 95% confidence interval (CI), 1.06-1.33; P < 0.02). Differences in the 14-day healing rate for patients with low and moderate stress scores (43.1%) compared with those with high and very high stress scores (37.9%) just failed to reach statistical significance (RR for patients with stress, 1.14; 95% CI, 0.998-1.29; P = 0.051). During the 1st year of maintenance treatment 18.3% of patients with stress, but 10.9% of patients without stress, had a DU relapse (RR of stress for DU relapse during the first year, 1.73; 95 CI, 1.44-2.09; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Can pH recordings suggest defective esophageal peristalsis in patients with gastroesophageal reflux?

The data provided by 24-h pH monitoring in 40 patients with gastroesophageal reflux, divided in three groups in accordance with esophageal motor pattern, were compared. Patients with hypomotility had significantly greater reflux rates than those with normal motility or hypermotility, if we consider both total time with pH < 4 and time with pH < 4 corresponding to episodes of > 5 min duration. We conclude that when 24-h pH monitoring shows very high reflux rates, basically corresponding to episodes lasting > 5 min, we should suspect the presence of defective esophageal peristalsis, which must be confirmed with a manometric study.


Observer homogeneity in the histologic diagnosis of Helicobacter pylori. Latent class analysis, kappa coefficient, and repeat frequency.

Four pathologists independently examined 82 antral mucosal biopsy specimens for the presence of Helicobacter pylori and indicated whether their assessments were certain. The pathologists made a positive diagnosis in from 56% to 84% of the specimens (significant heterogeneity, p < 0.01). The frequency of uncertain diagnoses was from 4% to 20% (p < 0.01). Uncertain statements occurred more frequently among negative than among positive diagnoses. For the six pairs of observers the kappa coefficients were between 0.39 and 0.82. By a latent class analysis measures of diagnostic accuracy were calculated comparing the observers' assessments with an estimated consensus diagnosis. The predictive values of a positive diagnosis ranged from 0.70 to 1.00. By calculation of repeat frequencies--that is, the probability that an observer's statement was confirmed by another observer--it became evident that uncertain statements were less frequently (61%) confirmed than were certain ones (85%). It is concluded that observer homogeneity is only moderate with regard to the histologic diagnosis of H. pylori, which should be considered both in daily clinical routine and in scientific studies. Disagreement between observers was associated with negative diagnoses, presumably because the pathologists felt more uncertain in these cases.


Symptom provocation in irritable bowel syndrome. Effects of differing doses of fructose-sorbitol.

The role of fructose and sorbitol, when ingested together, in the aetiology of irritable bowel syndrome (IBS) is controversial. The aims of this study in IBS patients, therefore, were to compare differences in symptom provocation with various doses of fructose-sorbitol and to relate differences in the extent of colonic hydrogen production after each dose to such symptom provocation. Two different mixtures of fructose and sorbitol--20 g fructose plus 3.5 g sorbitol ('lower' dose) and 25 g fructose plus 5 g sorbitol ('higher' dose)--were administered to 15 patients with IBS and to 24 healthy controls. Breath hydrogen concentrations were determined at 10-min intervals for 3 h after ingestion of each mixture, and the presence and severity of a range of gastrointestinal symptoms were recorded on a standard form before, during, and after the study. Total symptom score in IBS patients, but not controls, was greater (p < 0.05) after the higher than after the lower dose of fructose-sorbitol mixture, and, for the higher dose, symptoms were significantly greater in IBS patients than in controls (p < 0.05). Moreover, the increase in total symptom score between the higher and lower dose mixtures was of a greater magnitude (p = 0.01) in IBS patients than in controls. No significant correlation was observed between the increase in symptom score and the increase in peak hydrogen concentration or the increase in integrated hydrogen response between lower and higher dose mixtures, although these latter increases were at times substantial.(ABSTRACT TRUNCATED AT 250 WORDS)


Ulcerative proctocolitis in Orebro, Sweden. A retrospective epidemiologic study, 1963-1987.

In a retrospective epidemiologic study of the period 1963 to 1987 the annual incidence of definite ulcerative proctocolitis increased from 3.3 to 14.9/10(5), and during the last 10 years the mean incidence was 13.1/10(5) population. The incidence of extensive and total colitis was fairly stable, whereas an increase of ulcerative proctitis and distal colitis was seen. The increase in incidence is probably an artefact caused by better retrieval of cases in the latter part of the study. The prevalence on 31 December 1987 was 234/10(5) inhabitants. The male to female ratio was 1.59:1, compared with 0.96:1 in the general population. The median age at diagnosis was 33 years and increased almost 7 years by the end of the study, probably caused by an increased proportion of ex-smokers, who at diagnosis were, on average, 9 years older than lifetime non-smokers. The highest age- and sex-specific incidence was found in middle-aged men, who were ex-smokers to a significantly higher extent than women. No specific birth cohort was at an increased risk, and no second incidence peak in older age groups was seen.


No significant correlation between histologic changes of the papilla of Vater and juxtapapillary diverticulum. Special reference to the pathogenesis of gallstones.

The aim of this study was to investigate the significance of histologic changes of the papilla of Vater in cases with a juxtapapillary diverticulum, with special reference to the pathogenesis of gallstones. Three hundred and sixty-two autopsy cases, mainly of aged people, were analyzed. The incidence of both diverticulum and gallstone increased with age. The presence of diverticulum was associated with a significant increase of gallstones (49% versus 20%; P < 0.01). Analysis by the type of gallstones showed a significantly higher incidence of bilirubinate in cases with juxtapapillary diverticula. Stones both in the gallbladder and in the extrahepatic bile ducts were more prevalent in cases with diverticula as compared with the cases without diverticula. No significant relationship was found between juxtapapillary diverticula and the degree of histologic changes in the papilla of Vater, such as inflammatory cellular infiltration, fibrous proliferation, glandular proliferation, or muscular hypertrophy and proliferation of the sphincter of Oddi. These facts imply that juxtapapillary diverticula are not involved in the formation of gallstones via histologic changes of the papilla of Vater, whereas diverticula may play an important role in the pathogenesis of gallstones, especially of bilirubin stones.


Free protein S deficiency in patients with chronic inflammatory bowel disease.

Free protein S, protein C, and C4b-binding protein (C4b-BP) were measured in randomly selected outpatients: 22 with Crohn's disease (CD) and 16 with ulcerative colitis (UC). Active disease was recorded in 10 patients with CD and 4 with UC. Fourteen patients (63.6%) with CD and 4 (25%) with UC had free protein S values below the normal range, with mean values of 62% and 78% of that found in healthy control subjects (p < 0.01). The C4b-BP level was 127% in patients with CD as compared with 89% in both healthy subjects and UC patients (p < 0.01). The protein C levels were similar in the three groups. The present results add to the factors already known favouring thromboembolic complications in inflammatory bowel disease and which might play a major role both for the pathogenesis and for the increased tendency to venous thromboembolism in these diseases.


Cyclosporin pharmacokinetics after intravenous and oral administration in patients with Crohn's disease.

Cyclosporin kinetics were estimated after single-dose intravenous and oral administration in 12 patients with Crohn's disease in accordance with a three-compartment model with zero-order inputs. Cyclosporin was measured in whole blood with a specific monoclonal radioimmunoassay. The median bioavailability (f) was 23.7% (range, 0-49.1%); the distribution volume at steady state, 2.3 l/kg (range, 1.0-3.5 l/kg); clearance (CL), 7.6 ml/min/kg (range, 4.8-10.8 ml/min/kg); and t1/2(z) 7.9 h (range, 3.2-13.9 h). Both the extent and rate of bioavailability were significantly lower in six of the patients, who had low or undetectable cyclosporin levels during a preceding therapeutic trial. After repeated oral administration significant correlations were found between the single-dose f/CL ratios and the steady-state blood concentrations, indicating that the kinetics did not change markedly with time. We conclude that the disposition kinetics of cyclosporin in patients with Crohn's disease are comparable to those of other groups, whereas the bioavailability may be decreased. It is suggested that cyclosporin levels should be monitored closely, and intravenous treatment should be considered in patients with a rapid gut transit time, because cyclosporin absorption seems to follow zero-order kinetics.


Effect of drugs on colonic eicosanoid accumulation in active ulcerative colitis.

The effect of immunosuppressive drugs, 4-aminosalicylic acid (4-ASA), acetyl 5-aminosalicylic acid (5-ASA), and ketotifen on human colonic eicosanoid accumulation was evaluated in view of enhanced accumulation in patients with active ulcerative colitis. Azathioprine (100 micrograms/ml), cyclosporin (100 micrograms/ml), and methotrexate (100 micrograms/ml) significantly inhibited, by 25-35%, prostaglandin E2 (PGE2) accumulation by organ-cultured colonic mucosa of ulcerative colitis patients. Methotrexate was the only immunosuppressive drug that inhibited leukotriene B4 (LTB4) accumulation (50%), whereas azathioprine inhibited the accumulation of leukotriene C4 (LTC4) (25%). 5-ASA and its metabolite, acetyl 5-ASA, inhibited by 20-70% PGE2, LTB4, and LTC4 accumulation in the culture, supporting the contention that acetyl 5-ASA is as active as 5-ASA in these respects. 4-ASA had no effect on any of the eicosanoids. Ketotifen, a mast cell stabilizer, significantly inhibited the accumulation of PGE2, LTB4, and LTC4 by 33-60%. These results suggest a potential, new, unrecognized mode by which the immunomodulators induce part of their therapeutic effects in inflammatory bowel disease and support the contention that acetyl 5-ASA is as active as 5-ASA. The results obtained also indicate that ketotifen, used effectively in the prevention of bronchial asthma, inhibits the accumulation of colonic eicosanoids and, thus, may be of value in the treatment of inflammatory bowel disease.


Triple therapy of Helicobacter pylori infection in peptic ulcer. A 12-month follow-up study of 93 patients.

This study was undertaken to evaluate the success of triple therapy in peptic ulcer patients and ulcer relapses. One hundred and one consecutive Helicobacter pylori-positive peptic ulcer patients were assigned to an open trial with 2 weeks of treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. At the 6-week follow-up only 1 duodenal ulcer was unhealed of 57 active ulcers, and H. pylori was found to be eradicated in 84% of the 100 subjects. The sensitivity to metronidazole was determined from 71 pretreatment strains of H. pylori. Eradication of H. pylori succeeded in 89% of the patients with metronidazole-susceptible strains and in 61% of patients with metronidazole-resistant strains (p < 0.03). All 16 patients in whom the treatment failed to eradicate the organism had metronidazole-resistant strains after treatment. The ulcer relapse rate was low. At the 12-month follow-up of 93 patients only 1 of the 84 H. pylori-negative patients (including 4 patients after new successful therapy) had relapsing ulcers (2 asymptomatic episodes), and 1 had H. pylori reinfection, whereas 3 of the 9 bacteria-positive patients relapsed (p = 0.002); at the 2-year control 2 more patients had ulcer relapses. The eradication of H. pylori infection clearly prevents relapses of peptide ulcer, but the success of triple therapy depends on the frequency of pretreatment metronidazole-resistant H. pylori strains.


Biometric evaluation of gastric urease activity in man.

The 14C-urea breath test is claimed to be the best test for detection of Helicobacter pylori infection. We present a procedure for estimating its cutoff value on the basis of biometric evaluation only, without involving other diagnostic methods. Cumulative gastric urease activity (CA) was determined during the first 30 min after oral administration of 14C-urea (92.5 kBq) in 56 random volunteers and 49 consecutive patients with peptic ulcer disease. The distribution of CA in random volunteers was positively skewed. Logarithmic transformation yielded two separate populations, each normally distributed. Their normal probability density functions intercepted at log cutoff value. A bimodal distribution of log CA was confirmed in patients with peptic ulcer disease before and after treatment aimed at H. pylori eradication. Cutoff values were determined for both random volunteers and patients with peptic ulcer disease. By application of the present procedure for determination of cutoff value, the 14C-urea breath test distinguishes between individuals who have an increased gastric urease activity and individuals who do not, with the smallest possible arbitrariness.


Prediction of major pathologic conditions in dyspeptic patients referred for endoscopy. A prospective validation study of a scoring system.

This study aimed to validate the use of a decision support system previously developed on answers to a structured interview of dyspeptic outpatients and designed to identify patients at low risk of organic dyspepsia. We evaluated the performance of the scoring system in two cohorts of dyspeptic outpatients: 878 consecutive Danish patients (study group) referred for upper endoscopy and 1279 British patients whose results had previously been reported (validation group). Performance of the scoring system was analysed by receiver-operating characteristic (ROC) curves and comparison of loss in detection rate of organic dyspepsia, defined as cancer, ulcer, and complicated oesophagitis. The performance of the scoring system in the study group was less favourable over the entire span of cut-off points evaluated. This was reflected by a significant decrease in area under the ROC curve (65.1% versus 75.0%). The only cut-off point with an acceptable loss in detection rate (3.1%) led to a reduction in endoscopic activity of only 7.5%. Despite optimal working conditions the scoring system could not be used as a safe method of extracting dyspeptic patients with a low probability of organic dyspepsia. Before adopting a predictive scoring system, clinicians must evaluate its applicability in their own setting.


[The basic ideas for evaluating diagnostic tests in medicine and periodontics].

In the medical literature, and in particular in the field of periodontology, one could observe since several years an increasing interest in diagnostic tests. However, these are often difficult to comprehend. Indeed, understanding the value of these tests implies mastering the meaning of certain basic notions such as sensitivity, specificity and predictive value. The aim of this paper is to present these essential theoretical notions in a simple way and to illustrate them using clinical examples. Finally, several applications of these tests in the field of periodontology will be discussed.


[The late results with a fixed denture in less well-off adults. A retrospective study].

In this retrospective study 141 patients were re-examined after having been treated with at least two crowns or one fixed bridge each at the Cantonal Public Dental Clinic of Zurich (Volkszahnklinik) between 1974 and 1984. After an average "wearing time" of more than 9 years, 88% of the crowns and 92% of the bridges were still in function. 4 patients had already lost all their reconstructions incorporated in the "Volkszahnklinik" and were not examined clinically. 115 (84%) of the remaining 137 patients were satisfied with their reconstructions. The mean papillary bleeding index (PBI) was significantly higher on crowned teeth compared to the untreated teeth. The mean probing depth of the crowned premolars and incisors was also significantly higher compared to that of the natural teeth. The results of the study show that the success rate of fixed reconstructions fitted at the Cantonal Public Dental Clinic of Zurich are within the ranges reported by other similar institutions.


Treatment of Class II, div. 1 malocclusion with the activator and with the Begg technique.

The effect of treatment of Angle Class II, division 1 malocclusion with an Andresen activator or with the Begg technique with or without premolar extraction was studied retrospectively with X-ray cephalometry. The treatment with the Begg technique was followed by a phase of retention with an activator. Three groups of 25 children who had been treated with one of the methods were compared regarding facial morphology and soft tissue profile before and after the treatment and changes during the period of treatment. The treatment effect (correction of the distal occlusion and normalisation of the overjet and overbite) was similar with the three methods. The overjet was mainly corrected through skeletal changes, which accounted for 70%, 77% and 62% of the overjet correction produced by the activator, Begg extraction and Begg non-extraction treatment, respectively. Thus, all three methods of treatment had a skeletal (orthopedic) effect. The dental component of the overjet correction was with all three methods of treatment a retroclination of the upper incisors. This was to some extent offset by a retrusion of the lower incisors, which also occurred in all groups. The facial morphology and the soft tissue profile after the treatment were similar in the three groups. There were no differences in the soft tissue profile and only marginal differences in facial morphology as a result of the three methods of treatment.


[The microstructure of leucite-reinforced glass ceramics].

The dentine materials of the metal ceramic systems VMK 68 and Biodent as well as the ceramics of all ceramic systems Duceram, Cosmotech, Optec, IPS-Empress and Corum were tested for their leucite content. The structure analysed in the scanning electron microscope showed leucite in the dendritic and idiomorphic form. X-ray diffraction analyses verified the leucite content in metal ceramic systems and ceramics of the nonbonded systems. Comparing the metal ceramic systems with the nonbonded systems, an increase in leucite content was observed in the nonbonded systems.


[Causes of prenatal foal loss in Switzerland].

In Switzerland during the foaling season 1988 and 1989 the cause of abortion in 60 foals was investigated. Special attention was paid to infections with equine herpesvirus 1 (EHV 1). Diagnosis were based on post-mortem, histopathological, bacteriological and immunofluorescence investigation. The results confirm data from other countries, that EHV 1 is the most prevalent viral (20%) cause of abortion, followed by various bacterial agents (12%). Other causes were umbilical torsion, twin pregnancy and malformations. In 18% of the cases the investigation of fetuses did not give any results as to the cause of abortion, suggesting maternal factors as only cause of abortion.


[Kinetic study of the lumbar vertebrae and the lumbosacral passage in German shepherd dogs. 1. Functional anatomy and kinetic foundation].

In the dog congenital or acquired stenosis of the lumbosacral region is commonly encountered. In humans the lumbosacral junction is the most often affected part of the vertebral column. Lumbosacral instability, one possible etiology for stenosis of the vertebral canal plays an important role in man. This study summarizes the functional anatomy and some important geometric and kinematic considerations necessary for the understanding of the motion (flexion-extension) between two adjacent vertebra.


[Serious reactions after the TSH-stimulation test in the dog].

The thyrotropin response test is the most common test for the diagnosis of hypothyroidism. Here we report serious adverse effects in two dogs after intravenous administration of bovine TSH. The clinical signs were consistent with an anaphylactoid or anaphylactic reaction. In both cases a previous sensibilization with bovine TSH can be excluded. We discuss the etiology and emphasize the most probable cause to be an anaphylactoid reaction. Preventive measures are discussed.


[Oscillating potentials on the B-wave of the ERG in the dog].

The oscillatory potentials (OP) on the b-wave of the canine ERG are characterized. Normal values for an OP-index, implicit times and periodicity are given. The OP-index increases during dark adaptation as well as with increasing stimulus intensities for white light flashes. Scotopic blue and red stimuli, although balanced for the maximum b-wave amplitude, surprisingly result in higher OP-indices for red flashes. Implicit times decrease for all OP with increasing stimulus intensities. Scotopic balanced red light results in OP with markedly reduced implicit times compared to blue light stimulation. The intervals between two OPs remain constant during dark adaptation, however, intervals between OPs with longer implicit times tend to be shorter. In contrast, the b-waves for scotopic balanced stimuli show rhythmic oscillations with constant intervals between them, the intervals being shorter for blue light than for red light. The intervals between OPs tend to become shorter with increasing stimulus intensities. This investigation indicates that OPs are influenced but not generated by photoreceptors. The examination of a dog with optic nerve hypoplasia indicates that the ganglion cells do not contribute to the biogenesis of OPs. The prognostic value of OPs in the early diagnosis for hereditary retinal degenerations in the dog is discussed.


Evidence from 12S ribosomal RNA sequences that onychophorans are modified arthropods.

The evolutionary relationships of the onychophorans (velvet worms) and the monophyly of the arthropods have generated considerable debate. Cladistic analyses of 12S ribosomal RNA sequences indicate that arthropods are monophyletic and include the onychophorans. Maximum parsimony analyses and monophyly testing within arthropods indicate that myriapods (millipedes and centipedes) form a sister group to all other assemblages, whereas crustaceans (shrimps and lobsters) plus hexapods (insects and allied groups) form a well-supported monophyletic group. Parsimony analysis further suggests that onychophorans form a sister group to chelicerates (spiders and scorpions) and crustaceans plus hexapods, but this relationship is not well supported by monophyly testing. These relationships conflict with current hypotheses of evolutionary pathways within arthropods.


Activation of a plant gene by T-DNA tagging: auxin-independent growth in vitro.

A transferred DNA (T-DNA) tagging vector with the potential to produce dominant mutations was used with cocultured Agrobacterium tumefaciens and protoplasts to tag genes involved in the action of the plant growth substance auxin. Transgenic calli were selected for their ability to grow in the absence of auxin in the culture media. From one experiment, 12 calli that displayed this phenotype were recovered, of which 11 were able to regenerate into plants. In one plant studied in detail, protoplast division in the absence of auxin genetically cosegregated with a single T-DNA insert. A messenger RNA encoded by a 6.4-kilobase sequence of plant genomic DNA rescued from the mutant is overexpressed relative to untransformed plants. The genomic DNA, as well as a cognate complementary DNA, once transfected into protoplasts promote growth and cell division in vitro in the absence of exogenously added auxin.


Map-based cloning of a gene controlling omega-3 fatty acid desaturation in Arabidopsis.

A gene from the flowering plant Arabidopsis thaliana that encodes an omega-3 desaturase was cloned on the basis of the genetic map position of a mutation affecting membrane and storage lipid fatty acid composition. Yeast artificial chromosomes covering the genetic locus were identified and used to probe a seed complementary DNA library. A complementary DNA clone for the desaturase was identified and introduced into roots of both wild-type and mutant plants by Ti plasmid-mediated transformation. Transgenic tissues of both mutant and wild-type plants had significantly increased amounts of the fatty acid produced by this desaturase.


Dynamics of ribozyme binding of substrate revealed by fluorescence-detected stopped-flow methods.

Fluorescence-detected stopped-flow and equilibrium methods have been used to study the mechanism for binding of pyrene (pyr)-labeled RNA oligomer substrates to the ribozyme (catalytic RNA) from Tetrahymena thermophila. The fluorescence of these substrates increases up to 25-fold on binding to the ribozyme. Stopped-flow experiments provide evidence that pyr experiences at least three different microenvironments during the binding process. A minimal mechanism is presented in which substrate initially base pairs to ribozyme and subsequently forms tertiary contacts in an RNA folding step. All four microscopic rate constants are measured for ribozyme binding of pyrCCUCU.


Three-dimensional structure of dimeric human recombinant macrophage colony-stimulating factor.

Macrophage colony-stimulating factor (M-CSF) triggers the development of cells of the monocyte-macrophage lineage and has a variety of stimulatory effects on mature cells of this class. The biologically active form of M-CSF is a disulfide-linked dimer that activates an intrinsic tyrosine kinase activity on the M-CSF receptor by inducing dimerization of the receptor molecules. The structure of a recombinant human M-CSF dimer, determined at 2.5 angstroms by x-ray crystallography, contains two bundles of four alpha helices laid end-to-end, with an interchain disulfide bond. Individual monomers of M-CSF show a close structural similarity to the cytokines granulocyte-macrophage colony-stimulating factor and human growth hormone. Both of these cytokines are monomeric in their active form, and their specific receptors lack intrinsic tyrosine kinase activity. The similarity of these structures suggests that the receptor binding determinants for all three cytokines may be similar.


Consequences of replication fork movement through transcription units in vivo.

To examine the basis for the evolutionary selection for codirectionality of replication and transcription in Escherichia coli, electron microscopy was used to visualize replication from an inducible ColE1 replication origin inserted into the Escherichia coli chromosome upstream (5') or downstream (3') of rrnB, a ribosomal RNA operon. Active rrnB operons were replicated either in the same direction in which they were transcribed or in the opposite direction. In either direction, RNA polymerases were dislodged during replication. When replication and transcription were codirectional, the rate of replication fork movement was similar to that observed in nontranscribed regions. When replication and transcription occurred in opposite directions, replication fork movement was reduced.


Encoding of a homolog of the IFN-gamma receptor by myxoma virus.

Many poxvirus-encoded virulence factors have been identified as proteins that are secreted from infected cells. The major secreted protein (37 kilodaltons) from cells infected with myxoma virus is encoded by the M-T7 open reading frame. This protein has significant sequence similarity to the human and mouse receptors for interferon-gamma (IFN-gamma). Furthermore, the myxoma M-T7 protein specifically binds rabbit IFN-gamma and inhibits the biological activity of extracellular IFN-gamma, one of the key regulatory cytokines in the host immune response against viral infections.


Regulation of the differentiation of teratocarcinoma cells into primitive endoderm by G alpha i2.

The amount of the heterotrimeric G protein subunit G alpha i2 decreases after the induction of F9 teratocarcinoma cells to become primitive endoderm in the presence of retinoic acid (RA). The reduction of the G alpha i2 protein in F9 cells by antisense RNA expression was associated with (i) loss of receptor-mediated inhibition of adenylyl cyclase; (ii) decreased cell doubling time; (iii) induction of a primitive, endoderm-like phenotype in the absence of RA; and (iv) production of the differentiation marker tissue-type plasminogen activator. Expression of a constitutively active, mutant G alpha i2 blocked RA-induced differentiation. These data suggest the involvement of G alpha i2 in the control of stem cell differentiation and provide insight into the involvement of G proteins in growth regulation.


Production and initial characterization of bionites: materials formed on a bacterial backbone.

The addition of soluble metal salts of calcium, iron, or copper to cultures of Bacillus subtilis grown in web form nucleated precipitation at the surface of the bacterial cell walls. The mineralized cell filaments can be drawn into a fiber that when dried consists of a bacterial thread backbone carrying an inorganic solid. The ratios of organic to inorganic components (by weight) in the stiff brittle materials, called bionites, were: 1.08 for fe(2)bactonite, 1.8 for calbactonite, 2.3 for fe(3)bactonite, and 5 for cu(2)bactonite. X-ray photoelectron spectra suggest that the fe(3)bactonite contains Fe2O3, that calbactonite contains calcium carbonate, and that cu(2)bactonite contains CuCl (Cu I). Acid-base reactions of the bionites are compatible with these identifications. Burning out the organic phase of the febactonites yields a black magnetic material, presumably magnetite. The burnt cubactonite appears to yield elemental Cu(s). Calbactonite upon hydration was able to retain a genetically engineered enzymatic activity.


Behavioral lifetime of human auditory sensory memory predicted by physiological measures.

Noninvasive magnetoencephalography makes it possible to identify the cortical area in the human brain whose activity reflects the decay of passive sensory storage of information about auditory stimuli (echoic memory). The lifetime for decay of the neuronal activation trace in primary auditory cortex was found to predict the psychophysically determined duration of memory for the loudness of a tone. Although memory for the loudness of a specific tone is lost, the remembered loudness decays toward the global mean of all of the loudnesses to which a subject is exposed in a series of trials.


[Role of the hypophysis in the renal responses upon stimulation of the brain osmoreceptor].

The experiments were performed in rats anaesthetized with alpha-chloralose and urethane. Intracerebroventricular administration of hypertonic saline (icv. HS) resulted in an increase in renal plasma flow rate, glomerular filtration rate, urine flow rate, urinary sodium excretion, urinary potassium excretion, and osmolar clearance, and a decrease in free water clearance. These responses were abolished in hypophysectomized rats, but were not significantly affected by intravenous injection of vasopressin (VP) receptor (V1 and V2) antagonist. The urinary dopamine (DA) excretion did not change significantly after icv. HS. Moreover, administration of benserazide, an inhibitor of the enzyme L-aromatic amino acid decarboxylase that converts L-dopa to DA, did not attenuate the diuresis and natriuresis induced by icv. HS. These results suggest that the renal responses upon stimulation of the brain osmoreceptor are dependent on the integrity of the hypophysis, while the VP and DA are not essential to these renal responses. The hypophysial factors responsible for the icv. HS-induced renal responses remain to be explored.


[The effects of stimulation of the brain osmoreceptor on the tubular reabsorption of sodium, chloride and potassium in rats].

The tubular reabsorption of sodium, chloride and potassium was studied with micropuncture technique and electron probe X-ray microanalysis before and following intracerebroventricular administration of hypertonic saline (icv. HS) in rats. At the late proximal convoluted tubules, the fractional delivery of sodium increased from 53.0 +/- 2.1% to 66.0 +/- 2.9% (P < 0.01), the fractional delivery of chloride increased from 65.4 +/- 3.4% to 78.2 +/- 3.9% (P < 0.05), but the fractional delivery of potassium and tubular fluid osmolarity were unaltered. At the early distal convoluted tubules, the fractional delivery of sodium increased from 8.2 +/- 0.9% to 13.6 +/- 1.8% (P < 0.05), the fractional delivery of chloride increased from 5.4 +/- 0.8% to 9.5 +/- 1.4% (P < 0.05), the tubular fluid osmolality increased from 139.8 +/- 6.9 mOsm/kg H2O to 181.3 +/- 15.6 mOsm/kg H2O2 whereas fractional delivery of potassium did not show significant change. Under the condition of diuresis provoked by the intravenous administration of furosemide the kaliuresis induced by icv. HS was abolished, while the icv. HS-elicited diuresis and natriuresis remained unaffected. These results indicate that stimulation of the brain osmoreceptor inhibits the proximal tubular reabsorption of sodium chloride which in turn enhances sodium-potassium exchange in the distal tubules and collecting ducts.


[Effects of calcium blockers on the performance of left and right ventricles during acute hypoxia].

In anesthetized and thoracotomized 20 adult dogs under artificial respiration, the effects of calcium blockers (nifedipine, diltiazem and verapamil) on the mechanics of the left and right cardiac pumps under acute hypoxia were observed. The left and right ventricular pressure (LVP and RVP) and their dp/dt (+/- dp/dtmax), aortic flow (Fa), pulmonary pressure (Ppa) and heart rate (HR) were recorded. After treatment with calcium blockers, LVP and L +/- dp/dtmax decreased, and Fa increased, while RVP, R +/- dp/dtmax and Ppa all tended to increase. These results showed that the effects of calcium blockers on the performance of the left and right ventricles were different, suggesting that the dependence of left and right myocardium on calcium was different in degree. The mechanics of the left and right ventricles responded differently to calcium blockers under acute hypoxia. After treatment with calcium blockers, pressor responses on LVP by acute hypoxia disappeared. There was a great increase in Fa. Decrease in pressor response of RVP and Ppa was also observed in acute hypoxic dogs receiving verapamil and diltiazem. Comparing the effects of nifedipine, diltiazem and verapamil on the mechanics of the left and right cardiac pumps under acute hypoxia, it appears that diltiazem exerts beneficial effect on the performance of cardiac pump under acute hypoxia.


[Microinjection of 5-HT into the rostral ventrolateral medulla reduced the hyperviscosity and elevation of blood pressure induced by stress].

Experiments were carried out on 62 wistar rats. The hyperviscosity and elevation of blood pressure were induced by hanging and restraining the rats with their four limbs tied on a frame. It was found that microinjection of 5-HT (25 micrograms/10 microliters) into the 4th ventricle of the brain or bilateral microinjection of 5-HT (4 micrograms/0.5 microliters/site) into rostral ventrolateral medulla (rVLM) reduced stress-induced hyperviscosity (p < 0.01) and elevation of blood pressure (p < 0.01). The effect of 5-HT injected into the 4th ventricle or rVLM was blocked by bilateral microinjection of cinanserine (4 micrograms/0.5 microliter/site) into rVLM. These results suggest that microinjection of 5-HT into 4th ventricle and rVLM could reduce stress-induced hyperviscosity and elevation of blood pressure and these effects were probably mediated via 5-HT receptors in the rVLM.


[Role of endothelium-derived relaxing factor in the contractions of intrapulmonary artery induced by oxygen-derived free radicals in chronic hypoxic rat].

The role of endothelium-derived relaxing factor (EDRF) on the effect of oxygen-derived free radicals (generated by xanthine-xanthine oxidase system) on intrapulmonary arterial in chronic hypoxic rats was studied by a microbioassay method. Intrapulmonary artery rings with intact or denuded endothelium of hypoxic (5,000 m, 10 days) and normoxic rats were prepared for observation of oxygen-derived free radicals induced contraction. It was shown that oxygen-derived free radicals induced contractions of intrapulmonary arterial rings with intact endothelium were obviously augmented in hypoxic rats than in normoxic controls. The augmented responses could be further potentiated by the addition of EDRF inactivator reduced hemoglobin (RHb), but diminished or even abolished by applying superoxide dismutase (Cu-Zn SOD). However, no effect on denuded rings was observed when RHb or SOD was added. It is concluded that chronic hypoxia may attenuate the action of EDRF in the enhancement of the reactivity of intrapulmonary artery to oxygen-derived free radicals.


[Effect of intraventricular administration of histamine and its receptor agonists on pentagastrin-induced gastric acid secretion in rats].

The present study shows the dual effects of intraventricularly injected histamine (0.25-2.0 micrograms/5 microliters) on pentagastrin-induced gastric acid secretion. Male Wistar rats weighing 200-300 g were anesthetized with intraperitoneal sodium pentobarbital. Gastric acid was continuously washed out with 37 degrees C saline solution by means of a perfusion pump. On the background of continuous intravenous infusion of pentagastrin [7.5 micrograms/(kg.h),] histamine (0.25 microgram/5 microliters) or 2-pyridylethylamine (PEA, 10 micrograms/5 microliters), a H1-receptor agonist, was injected into the third ventricle through a chronically implanted canula. The acid output decreased 10 min after injection and did not recover at 90 min. When the dose of histamine was increased to 1.0 micrograms or 2.0 micrograms, dual effects appeared. The acid output decreased respectively in 73% or 50% of the animals, while in the rest 27% and 50% of the animals, the acid output increased. H2-receptor agonist dimaprit (10 micrograms/5 microliters, i.c.v.) or impromidine (0.1 micrograms/5 microliters, i.c.v.) had no pronounced effect on pentagastrin-induced acid secretion. Pretreatment with diphenhydramine (16 micrograms/0.2 ml or 32 micrograms/0.2 ml, i.m.) abolished the inhibitory effect of histamine and PEA on acid secretion. These results suggest that histamine may be involved in the central regulation of gastric acid secretion, and the inhibitory effect may be mediated by H1-receptors in the brain. The mechanism underlying the production of the dual effects of histamine is unknown.


[Effects of castration and testosterone-replacement on hypothalamic and plasma luteinizing hormone-releasing hormone levels in the aged male rat].

Hypothalamic and plasma luteinizing hormone-releasing hormone (LHRH) levels following orchidectomy (ORDX) and testosterone (T)-replacement were compared between young (2-3 months old) and aged (24-26 months old) male rats by radioimmunoassay. Plasma T level and hypothalamic LHRH content are markedly decreased in the aged rat as compared to those of the young rat, whereas plasma LHRH levels are similar in the two groups. Following ORDX and ORDX plus T-replacement, plasma T levels in both groups are about the same, whereas the rates of variation of hypothalamic and plasma LHRH levels in the aged rat are significantly lower than those in the young rat. These results suggest that the negative feedback mechanism of the hypothalamic LHRHergic system is impaired in the aged rat, which may be one of the important reasons causing age-dependent deterioration of the functional control of hypothalamic-pituitary-testicular axis.


[Hormonal regulation of PAI-1 secretion by cultured rat ovarian cells].

Rat ovarian cells produce not only plasminogen activator (tPA) but also plasminogen activator inhibitor type 1 (PAI-1), and their coordinated geneexpression induced by gonadotropins are thought to be responsible for follicular rupture. In this study, it was demonstrated that (1) theca-interstitial compartment synthesizes the majority of PAI-1 activity in the ovary before ovulation, the follicular wall may therefore serve as a specific barrier to prevent the secretion of PA into the extrafollicular compartment; (2) Granulosa cells contribute only small amount of ovarian PAI-1 activity, but synthesize most of tissue-type plasminogen activator activity involved in the process leading to ovulation: (3) Since only matured cumulus-oocyte complexes secrete high level of tPA and PAI-1, both tPA and PAI-1 activity in the conditioned medium may be used as reliable markers for evaluating oocyte quality for in vitro fertilization.


[Role of endothelin in the pathogenesis of rat experimental hypertension produced by aorta narrowing and saline uptake].

Endothelin is a bioactive polypeptide released from vascular endothelium, which has a strong action promoting vascular contraction, proliferation and hypertrophy of vascular smooth muscle cells. The present investigation was performed on the hypertensive rat produced by narrowing abdominal aorta and drinking saline. It was observed that the level of plasma endothelin in the hypertensive rats was doubled (9.70 +/- 0.68 vs. sham group 4.11 +/- 0.33 pg/ml, P < 0.01), and administration of specific endothelin-antiserum into hypertensive rats significantly attenuated the increase in the blood pressure (18.97 + 1.32 vs. 27.33 + 0.09 kPa in untreated hypertensive rats, P < 0.01), and dramatically ameliorated malfunction resulting from myocardial hypertrophy. The results suggest that endothelin is an important factor in the pathogenesis of hypertension, and that inhibition of endothelin action may be a new effective way in prevention and therapy of hypertension.


[Alterations of pulmonary arterial pressure following intraventricular injection of histamine in rabbits].

The changes of the pulmonary arterial pressure (PAP) following microinjection of histamine (HA) into the lateral ventricle in the rabbit were investigated. It was found that (1) Intraventricular injection of HA (50 micrograms) induced either an increase (in the majority) or a decrease in PAP and cardiac output (CO), or a biphasic response characterized by a decrease followed by an increase. Slowing down of heart rate (HR) and elevation of carotid arterial pressure (CAP) were observed accordingly. (2) After bilateral cervical vagotomy or fixing the heart rate by cardiac pacing, drop in CO and PAP in response to HA was no longer observed. Instead, they even showed some constant increase. The pressor response of PAP and CAP to HA could be partially blocked by phentolamine applied intravenously without affecting the increment of CO. On the other hand, intravenous injection of propranolol could totally block the HA-induced increment of CO, but not affect the pressor responses of PAP and CAP. Intravenous injection of hexamethonium or combined application of phentolamine and propranolol could completely abolish all the increment responses in CO, PAP and CAP to HA. (3) The cardiovascular responses to HA could be blocked by the H1 receptor blocker-chlorpheniramine, but not by H2 receptor blocker-cimetidine. It is thus assumed that HA applied intraventricularly can activate the central H1 receptor, thus inducing an increase in the cardiac output and vasoconstriction of pulmonary and peripheral vessels giving rise to an elevation of both PAP and CAP by way of sympathetic nerve. Central application of HA also induces bradycardia by activating vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS)


[The respiratory facilitating effects by electrical and chemical stimulation of central nucleus amygdala].

Experiments were performed on fifty urethan anesthetized (1 g/kg) rabbits of both sexes, vagotomized and spontaneously breathing. The respiratory responses to electrical and chemical stimulation of ACE were observed. The results were as follows: 1. Long train electrical stimulation of ACE caused significant respiratory facilitating effects: inspiratory prolongation and increase of respiratory rate and depth. 2. Short brust of electrical stimulation administered in ACE during the mid inspiratory and expiratory phases elicited the prolongation of inspiratory phase and the expiratory off-switch (EO-S) effect, respectively. 3. Microinjection of monosodium L-glutamate (MSG) (1 mol/L, 1 microliter) into ACE produced the similar respiratory effects as that of electrical stimulation. 4. Control experiments had no significant effect on respiration. The results showed that the activation of neurons in ACE caused facilitation of respiration. It is suggested that ACE region may take an important part in facilitating the basic respiratory rhythm.


Comparison of the quantitative buffy coat technique with the conventional thick blood film technique for malaria case detection in the field.

The quantitative buffy coat (QBC) technique was compared with the conventional thick blood film technique in a malaria survey carried out in a mesoendemic area of malaria in Betau, Pahang, Malaysia. The QBC technique was found to be a rapid technique but had a sensitivity of about 56% and a specificity of 95%, using the thick blood film method as the "gold standard". Malaria species identification was unsatisfactory with the QBC technique as it could identify parasites correctly in only about 60% of specimens. It was unable to detect as positive about 58% of specimens which had parasite counts < or = 500 per ul but could detect about 94% of those with counts > 500 per ul. This difference in positive detection rate was significantly different (p < 0.05). It cannot quantify parasitemia easily and the specimens cannot be stored for future reference and for quality control purposes. It is therefore concluded that the QBC technique cannot replace the classical thick blood film technique for use in malaria control programmes. Its use may be appropriate in situations like busy blood banks and outpatient clinics where rapid screening of malaria infection is needed but where experienced malaria microscopists may not be available.


A review of patients with a 'normal' coronary angiogram over a 3-year period.

Over a period of 36 months, we detected 54 patients with normal coronary arteries or non-critical coronary artery stenosis within our study series of coronary angiography. We studied these patients to determine their clinical, electrocardiographic, stress testing and angiocardiographic characteristics. We detected among them a preponderance of female sex and a higher incidence of ethnic Indians. The majority of the patients studied had one or more coronary risk factors. 52% had a normal resting ECG. In those with a positive stress test and reports available for review, there is a near equal distribution of horizontal and J-type ST depression. Those patients with a positive treadmill tend to have a higher left ventricular end diastolic pressure (LVEDP) at cardiac catheterization. We also noted in this group of patients a higher proportion with a small distal left anterior descending artery. These patients also tend to have higher LVEDP even in the presence of normal left ventriculogram. Our current series suggests the possibility of raised left ventricular end-diastolic pressure and the presence of a "small distal left anterior descending artery" syndrome in association with patients with a 'false positive' treadmill test.


The profile of ICU admissions for acute severe asthma in a general hospital.

The clinical profile of 22 patients admitted to the Intensive Care Unit of Alexandra Hospital over a 2-year period was studied. The mean age was 48.8 years with a majority in the older age group. The attacks leading to admission were generally rapid in evolution with 59% having symptoms for less than 12 hours and 84% for less than 24 hours. Most had a history of severe asthma, and of long duration. The pre-admission therapy had been suboptimal in the majority. Severe respiratory acidosis was a predominant feature. 68% were transferred to the ICU within one hour of arrival at hospital. Mechanical ventilation was required in 86.4% of cases, but the duration of ventilation was usually short. There was no serious complication due to barotrauma. Overall mortality was 23% (5/22). Problems in patient education remain a major hurdle in our attempt to reduce asthma mortality.


Nontuberculous mycobacterial disease of the lungs in Singapore.

Information on lung disease due to nontuberculous mycobacteria (NTM) is lacking in Singapore. A review of the records at the Central Tuberculosis Laboratory up to the end of 1988 showed that 23 patients seen between 1976 to 1988 inclusive had cultures which were repeatedly positive for NTM. Of the 23 cases analyzed, 15 were found to have lung disease which could be attributed to NTM. There were 9 males and 6 females with a male to female ratio of 1.5:1. The patients were either middle aged or elderly. The 2 main infective agents were M avium-intracellulare and M kansasii. Ten (67%) patients had moderately advanced and 5 (33%) had far advanced disease. Concurrent disease of the lung was present in 10 patients (67%). Seven (47%) patients had bronchiectasis, 1 (7%) had both bronchiectasis and chronic obstructive pulmonary disease (COPD) and 2 (13%) had COPD. A past history of pulmonary tuberculosis was present in 10 patients (67%). Lung disease due to NTM is uncommon in Singapore. Treatment failure was attributed to poor compliance, a possibility which could not be excluded in those patients who had adverse reactions.


Some observations on the epidemiology of peptic ulcer disease in Singapore.

Several lines of evidence suggest that, of the three main races of Singapore, peptic ulcers are more common among the Chinese and Indians when compared to the Malays. These include studies on hospital series of patients with or without appropriate control groups, studies on the incidence of surgery for perforated ulcer as well as mortality statistics. A reduction in the Chinese:Malay difference in the incidence of perforated ulcer over three decades suggests that environmental factors are involved in producing these racial differences. However, we have to date been unable to determine the factor(s) responsible. The incidence of perforated ulcer in Singapore is increasing while ulcer mortality is declining. This is similar to the situation in Hong Kong but different from that in the western countries.


Blood pressure tracking as an indicator of hypertension risk.

The significance of high blood pressure to cardio- and cerebrovascular disease is well recognized. The associated mortality and morbidity risks call for multiple approaches to control the development of high blood pressure. Recent studies have shown that precursors of cardiovascular disorders may be apparent from a young age, and that these can persist and contribute to disease in later life. With regard to blood pressure, the phenomenon of persisting at the same rank has been referred to as tracking. This allows for the possible identification of high-risk groups, for whom early intervention can be initiated. In this paper, some of the findings of studies on blood pressure tracking are reviewed.


Intravenous sedation for upper gastrointestinal endoscopy: Midazolam versus propofol.

Propofol was compared with Midazolam for sedation during upper gastrointestinal endoscopy in a randomised, double blind study. Both drugs were equally acceptable to endoscopists and patients. There was significant oxygen desaturation after sedation and during endoscopy (p < 10(-6)). Significantly more patients in the propofol group could remember the diagnosis which was revealed to them immediately after the gastroscopy (p < 0.001).


Effects of radiation on hearing in patients with malignancies of head and neck.

Patients with normal hearing at the start of radiation were tested for hearing during (30 GY) and at the end of radiation therapy (45-60 GY) in order to determine if there was any alteration in their pure tone hearing thresholds. A significant increase in the hearing threshold was found at high frequencies at the end of therapy. At the end of the course of radiation, clinical findings suggestive of middle ear changes due to radiation were seen in 33% of the ears. Patients whose ears are included in the field of radiation may have to be forewarned to expect a loss in their acuity of hearing, especially those whose professional life may depend on it.


Myopia produced in young chicks by intermittent minimal form visual deprivation--can spectacles cause myopia?

Spectacle use has been postulated to aggravate or cause human myopia. Form visual deprivation, by complete full-time occlusion or refractive lenses, has been demonstrated to cause axial myopia in animals. We raised young chicks in conditions which closely approximate plano spectacle wear in humans. In addition, we sought to achieve more physiological conditions of form deprivation. Nine newborn chicks were raised with intermittent monocular visual deprivation and their eye growth and refraction monitored by retinoscopy, ultrasonic A-scan biometry and with a travelling microscope. After hatching, the nictitating membranes were sutured for 3-4 days. This was followed by a transparent plano plastic cover over the same eye for 3-4 days per week. After 3 weeks, the manipulated eyes were more myopic (mean refraction -0.72 D, axial length 13.11 mm) than fellow eyes (+0.83 D, 11.99 mm) (p < 0.05 and p < 0.01 respectively). These results suggest that the chick eye is exquisitely sensitive to disturbances in the visual environment; intermittent minimal manipulation by conditions simulating spectacle wear in man was myopiagenic. It is postulated that spectacles can cause form visual deprivation of foveal and nonfoveal neurons (and hence myopia) by reducing luminance and contrast, chromatic and spherical aberration (in nonfoveal neurons) and restriction and distortion from the frame.


The rotary influence of articular contours during passive glenohumeral abduction.

Automatic external rotation at the glenohumeral joint is an essential component of active as well as passive elevation of the arm through abduction. Recent studies have demonstrated this automatic rotation to be present during passive abduction using cadaveric glenohumeral joints even in the absence of extra-articular influences like the coraco-acromial arch and glenohumeral muscles. In the present study, simulated abduction in disarticulated cadaveric joints was shown to be associated with automatic external rotation suggesting a role in this mechanism for the articular contours.


The role of computed tomography in the evaluation of retinoblastoma.

To assess the importance of Computed Tomography(CT) in the evaluation of retinoblastoma, we reviewed thirteen cases of retinoblastoma which presented at Hospital University Sains Malaysia, Kelantan, Malaysia, from August 1986 to June 1991. High resolution computed tomography of the orbits was performed in all patients prior to therapy. Nine patients (69%) had unilateral and four (31%) had bilateral retinoblastoma. The interesting features were the remarkably high incidence in the right eye (89%) as compared to the left eye (11%) in unilateral retinoblastoma, and overall predominance of the male population (male to female ratio was 2:1). Computed tomography detected intraocular calcification in 82% of the tumourous eyes. All patients presented at late stages when tumours were of large size. The presence of calcification was not related to the size of the tumour. CT detected calcification in a suspected retinoblastoma with a high degree of accuracy. Computed tomographic evidence of intraocular calcification in children under 3 years of age is highly suggestive of retinoblastoma.


The mental diseases hospital, Singapore (1st 100 years)--a short history (Part II).

This article (in four parts) traces the history of the first four Mental Hospitals built in Singapore, which were occupied in 1840, 1861, 1887 and 1928. The management of the patients is described; also their lives and deaths. Mention is also made of the doctors and others who looked after them.


Non-steroidal anti-inflammatory drugs--uses and complications.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are important in the management of any inflammatory arthritis. However, all NSAIDs have side effects--NSAID related gastropathy (the most common serious side-effect), reversible NSAID nephropathy, dermal complications, hematologic complications, hepatic complications, central nervous system complications, pulmonary complications etc. Patients who have more severe forms of rheumatic disease, take higher doses of NSAIDs with steroids and suffer concomitant medical illness are at higher risk for these toxicities. In all cases, the benefits from the use of NSAIDs must outweigh the risk. When managing a high risk patient, consider alternate therapy and if an NSAID must be used, always monitor the patient carefully.


The antiphospholipid syndrome.

The antiphospholipid syndrome (APS) describes an entity characterised by recurrent thrombosis, recurrent spontaneous abortions, thrombocytopenia, and elevated levels of antiphospholipid antibodies (IgG or IgM). The clinical features of APS include manifestations of thrombosis and/or cell damage. There is usually an associated underlying connective tissue disorder. The primary antiphospholipid syndrome refers to the presence of these clinical features without evidence of an associated autoimmune disorder. Detection of these antibodies include the lupus anticoagulant test, VDRL test and assays for anticardiolipin antibodies. Overlapping populations of these antibodies are detected by various immunologic tests. Management is based on the use of immunosuppressives, platelet inhibitors and anticoagulants.


A case report on gangrene following simultaneous traumatic open metatarsophalangeal and interphalangeal dislocations of the left big toe.

Simultaneous metatarsophalangeal and interphalangeal dislocations of the big toe are rare injuries. Gangrene of the big toe following open dislocations was reported in a 20-year-old man.


Medical treatment of Cushing's syndrome with aminoglutethimide and ketoconazole.

We report a 54-year-old Chinese man with Cushing's syndrome from bilateral adrenal adenomata in whom surgery was contraindicated because of his intercurrent medical conditions. Instead, he was successfully treated with aminoglutethimide 0.75 gm/day (which reduced his 24-hour urinary free cortisol from 628 nmol/day to 177 nmol/day in 4 weeks), followed by ketoconazole 0.6 gm/day which continued to suppress the urinary free cortisol level. We conclude that aminoglutethimide or ketoconazole offers a viable non-surgical alternative to the treatment of Cushing's syndrome.


Mumps encephalomyelitis.

A 7-year-old Indian girl developed complete paralysis of her lower limbs and acute urinary retention 10 days after suffering from mumps. Encephalomyelitis due to mumps was not suspected initially since it is a rare complication of mumps, although relatively well-documented. However, the preceding history of parotitis and the presence of mumps-specific IgM in both blood and cerebrospinal fluid led to the diagnosis. The initially severe acute neurological deficits resolved completely three months after onset of her illness. Serological investigations were helpful in diagnosing neurological complications of mumps in this case, and especially where there is no preceding parotitis.


Nasal positive pressure ventilation in the treatment of chronic hypercapnic respiratory failure: a case report.

This paper describes the use of a nasal mask to deliver intermittent positive pressure ventilation to treat chronic respiratory failure in one patient with severe kyphoscoliosis. After two months of overnight nasal ventilation at home the patient achieved normal blood gases, showed improved inspiratory muscle strength, effort tolerance and was able to return to work. Intermittent nasal ventilation is a safe and effective ventilatory support modality for some patients with hypercapnic respiratory failure.


Overestimation of severity of mitral stenosis during cardiac catheterization due to a large left atrial thrombus.

We report a case of mitral stenosis with a large left atrial thrombus which was obstructing pulmonary venous inflow where the conventional use of the pulmonary capillary wedge pressure as an approximation of the left atrial pressure during diagnostic cardiac catheterisation led to the over-estimation of the severity of mitral stenosis.


Phase I/II study of high-dose rate interstitial radiotherapy for head and neck cancer.

From July 1991 through December 1991, a phase I/II study of high-dose rate interstitial radiotherapy for head and neck cancer was performed to determine any acute adverse effects and mucosal reaction as well as the feasibility of this therapy. A total of seven patients with head and neck cancer (tongue: four cases; mouth floor: one case; buccal mucosa: one case; oral mucosa of lower lip: one case) were entered into this study. The dose schedule of high-dose rate interstitial radiotherapy ranged from 35 Gy/ten fractions (bid)/week to 60 Gy/ten fractions/week. No major or minor early complication was observed. Spotted mucositis appeared starting three days after the end of high-dose rate interstitial radiotherapy while confluent mucositis developed and approached a peak at ten days but disappeared by the fourth to eighth week. Early tumor responses of all patients were complete.


[Cancer rehabilitation in the Federal Republic of Germany--a critical review from the perspective of rehabilitation psychology].

Against the background of a common criticism of the rehabilitation system, the situation of rehabilitation research and practice in oncology is reviewed. A lack of efforts aimed at vocational rehabilitation as well as the main emphasis in inpatient services is criticized. Till now, outpatient services as well as psychosocial rehabilitation care are not as well established, as they should be with regard to provide assistance in coping with the disease and in adapting to the various disabilities may be followed by cancer. As rehabilitation research in oncology is still at its very beginning, we know little about the acceptance of rehabilitation measures as well as the rehabilitation process in its correlation between outcome criteria. Our own pilot study provides first results concerning vocational rehabilitation and acceptance of medical rehabilitation services. As conclusion, we need more elaborated research in oncological rehabilitation for optimizing and further developing rehabilitation care system especially with respect to outpatient and psychosocial services.


Water-filtered infrared-A radiation: a novel technique to heat superficial tumors.

A novel device consisting of an infrared-A (= ultrared-A) radiation source equipped with a water filter in the radiation path is described which allows for the therapeutic heating of superficial experimental and human tumors. Preliminary studies with agar phantoms showed that heating in the presence of the water-cuvette avoids intolerable overheating in the very superficial layers. This effect can be further enhanced by surface cooling with room air such that a stratification of the temperature distribution can be achieved. In subsequent experiments, temperature distributions were recorded in the x-, y- and z-axis of superficial rodent tumors. The results obtained confirm those from the phantom experiments, showing that therapeutically relevant temperatures (T > or = 42 degrees C) could be achieved through the tumor mass to a depth of approximately 1.2 cm. Temperature homogeneity is comparable to that seen in superficial tumors undergoing water-bath hyperthermia. This novel technique has proved to be reliable, is well-tolerated, is easy to apply, and is easily accessible to a larger number of potential users for the local heating of superficial malignancies.


[How tolerant are partial dose values? Some additional remarks on the concept of a tolerance dose].

By means of the NSD formula and its modifications (CRE, TDF) evaluated from radiotherapy experience by Ellis, it is possible to estimate the acceptance of applied radiotherapy and fractionation scheme. Because the parameters of the Ellis formula are calculated from patients data, they show a dispersion as usually in biological systems. These dispersions are considered as entrance error. In mathematical transformations errors are multiplied according to the principle of superposition of errors. Especially when judging tolerance values of organs of risk the dispersion is quite important. The problem of dispersion of resulting partial tolerance values is demonstrated by some examples of clinical cases.


Elevated intraocular pressure, pigment dispersion and dark hypopyon in endogenous endophthalmitis from Listeria monocytogenes.

Listeria monocytogenes endophthalmitis occurred in an immunologically competent patient with no identifiable extraocular septic focus. The patient presented with a dark hypopyon and markedly elevated intraocular pressure, and the diagnosis was established by culture and histopathologic examination of ocular fluid. Four of the fourteen reported cases of Listeria monocytogenes endophthalmitis also presented with a dark hypopyon, and all cases had markedly elevated intraocular pressure. The presence of a dark hypopyon and elevated intraocular pressure may indicate endogenous intraocular infection with Listeria monocytogenes, even in an apparently healthy host.


Multiple cranial neuropathies: presenting signs of systemic lymphoma.

A 58-year-old man four years after orthototic liver transplantation presented with a mental neuropathy, multiple ocular motor nerve palsies, and an upper extremity motor neuropathy. Serial neuroimaging, cerebrospinal fluid analysis, total body computerized tomography and paraesophageal needle biopsy failed to reveal the underlying etiology. Sural nerve biopsy showed endoneurial perivascular infiltration with lymphoid cells, and bone marrow biopsy confirmed the diagnosis of a Burkitt's-type lymphoma. Systemic lymphoma with neural infiltration should be suspected in the immunosuppressed patient who presents with cranial or peripheral neuropathies.


Disc swelling: a tall tail?

A 30-year-old man presented with monocular visual loss secondary to chronic papilledema, due to an ependymoma involving the spinal cord. No other neurological symptoms were present at the time. Initial neuroradiologic tests as well as laboratory investigations were negative, except for elevated pressure and protein concentration of his cerebrospinal fluid. In spite of intensive investigation, the diagnosis of a spinal cord tumor was delayed for approximately 12 months until he presented with neurologic symptoms attributable to a spinal cord lesion. This is only the fourth case reported of a spinal cord tumor associated with papilledema presenting with visual loss, without any other manifestations of either elevated intracranial pressure, or spinal disease. Possible mechanisms for elevated intracranial pressure in cases of spinal cord tumors are reviewed.


Remembrance of Hans Goldmann, 1899-1991.

Professor Hans Goldmann died in Bern on November 19th, 1991 at the age of 92 years. His outstanding intellectual capacity was discovered at an early age and demonstrated throughout his life. He was appointed as teaching assistant of the famous A. Cermak von Seysenegg, Chairman of the Institute of Physiology of the German Charles University in Prague. During his stay at the University of Prague, he was influenced by the famous people of his time, such as Einstein (physicist), Mach (physicist and psychophysicist), Lorenz (behavioral scientist), Popper (philosopher), Schlick (physicist and philosopher), Hering (physiologist), and others. Goldmann absorbed the essence of these disciplines to a very large extent. This, together with his remarkable intellect, enabled him to produce outstanding research work within a large spectrum of sciences more or less directly related to ophthalmology. Goldmann became known in particular for his exceptional and fundamental work on perimetry and glaucoma and he managed to cast his basic insight into practical, easy-to-operate, high-precision diagnostic instruments which, several decades after their invention, are still used by every ophthalmologist. He will enter history as one of the very great pioneers in ophthalmology.