Search

Abstract Objectives--Preliminary assessment of the adequacy of AIDS surveillance efforts in Europe by comparing data from two official sources--AIDS surveillance and mortality statistics. Methods--The study used ENAADS (European Non-Aggregate AIDS [...]

Aims.Whether the public stigma associated with mental illness negatively affects an individual, largely depends on whether the person has been labelled ‘mentally ill’. For labelled individuals concealing mental illness is a common strategy to cope with mental illness stigma, despite secrecy's potential negative consequences. In addition, initial evidence points to a link between stigma and suicidality, but quantitative data from community samples are lacking.Methods.Based on previous literature about mental illness stigma and suicidality, as well as about the potential influence of labelling processes and secrecy, a theory-driven model linking perceived mental illness stigma and suicidal ideation by a mediation of secrecy and hopelessness was established. This model was tested separately among labelled and unlabelled persons using data derived from a Swiss cross-sectional population-based study. A large community sample of people with elevated psychiatric symptoms was examined by interviews and self-report, collecting information on perceived stigma, secrecy, hopelessness and suicidal ideation. Participants who had ever used mental health services were considered as labelled ‘mentally ill’. A descriptive analysis, stratified logistic regression models and a path analysis testing a three-path mediation effect were conducted.Results.While no significant differences between labelled and unlabelled participants were observed regarding perceived stigma and secrecy, labelled individuals reported significantly higher frequencies of suicidal ideation and feelings of hopelessness. More perceived stigma was associated with suicidal ideation among labelled, but not among unlabelled individuals. In the path analysis, this link was mediated by increased secrecy and hopelessness.Conclusions.Results from this study indicate that among persons labelled ‘mentally ill’, mental illness stigma is a contributor to suicidal ideation. One explanation for this association is the relation perceived stigma has with secrecy, which introduces negative emotional consequences. If our findings are replicated, they would suggest that programmes empowering people in treatment for mental illness to cope with anticipated and experienced discrimination as well as interventions to reduce public stigma within society could improve suicide prevention.

Background:There are only a small number of prospective studies that have systematically evaluated standardised diagnostic criteria for mental disorder for more than a decade. The aim of this study is to present the approximated overall and sex-specific cumulative incidence of mental disorder in the Zurich cohort study, a prospective cohort study of 18–19 years olds from the canton of Zurich, Switzerland, who were followed through age 50.Method:A stratified sample of 591 participants were interviewed with the Structured Psychopathological Interview and Rating of the Social Consequences of Psychological Disturbances for Epidemiology, a semi-structured interview that uses a bottom-up approach to assess the past-year presence of 15 psychiatric syndromes. Seven interview waves took place between 1979 and 2008. Approximated cumulative incidence was estimated using Kaplan–Meier methods.Results:Rates of mental disorder were considerably higher than those generally reported in cross-sectional surveys. We found rates ranging from 32.5% for major depressive disorder to 1.2% for Bipolar I disorder. The cumulative probability of experiencing any of the mental disorders assessed by age 50 was 73.9%, the highest reported to date. We also found that rates differed by sex for most disorders, with females generally reporting higher rates of mood, anxiety and phobic disorder, and males reporting higher rates of substance- and alcohol-related disorders.Conclusions:These findings confirm those of other long-term prospective studies that indicate the nearly universal nature of disturbances of emotion and behaviour across the life span. Greater community awareness of the normative nature of these experiences is warranted. An important area of future research is study long-term course and stability to determine who among those with such disturbances suffer from chronic disabling mental disorders. Such longitudinal studies may aid in directing services and intervention efforts where they are most needed.

Background.Seasonal as well as weekly cycles in suicide have been described, replicated and poorly understood for a long time. In Western countries, suicides are typically least frequent on weekends and most frequent on Mondays and Tuesdays. To improve understanding of this phenomenon a strategy is required which focuses on anomalous findings beyond the regular patterns. Here, we focused on instances where the weekly suicide patterns disappear or are interrupted.Methods.We used data from Swiss and Austrian mortality statistics for the periods 1969–2010 and 1970–2010, respectively. First, the data were cross-tabulated by days of the week and the available socio-demographic information (sex, age, religious affiliation and region). Second, time series of cumulated daily frequencies of suicide were analysed by seasonal Autoregressive Integrated Moving Average (ARIMA) models which included intervention effects accounting for Easter and Pentecost (Whit) holidays.Results.First, the cross tabulations showed that weekly cycles may be smoothed above all in young persons and smoothed in drowning, jumping and car gas exhaustion suicides. Second, the ARIMA analyses displayed occasional preventive effects for holidays Saturdays and Sundays, and more systematic effects for holiday Mondays. There were no after effects on Tuesdays following holiday Mondays.Conclusions.In general, the weekend dip and the Monday backlog effect in suicide show striking similarities to the Advent season effect and are interpretable within the same template. The turning points between low and high frequencies possibly provide promising frames for the timing of prevention activities.

Aims.Prevalence and covariates of subclinical psychosis have gained increased interest in the context of early identification and treatment of persons at risk for psychosis.Methods.We analysed 9829 adults representative of the general population within the canton of Zurich, Switzerland. Two psychosis syndromes, derived from the SCL-90-R, were applied: ‘schizotypal signs’ and ‘schizophrenia nuclear symptoms’.Results.Only a few subjects (13.2%) reported no schizotypal signs. While 33.2% of subjects indicated mild signs, only a small proportion (3.7%) reported severe signs. A very common outcome was no ‘schizophrenia nuclear symptoms’ (70.6%). Although 13.5% of the participants reported mild symptoms, severe nuclear symptoms were very rare (0.5%). Because these two syndromes were only moderately correlated (r= 0.43), we were able to establish sufficiently distinct symptom clusters. Schizotypal signs were more closely connected to distress than was schizophrenia nuclear symptoms, even though their distribution types were similar. Both syndromes were associated with several covariates, such as alcohol and tobacco use, being unmarried, low education level, psychopathological distress and low subjective well-being.Conclusions.Subclinical psychosis symptoms are quite frequent in the general population but, for the most part, are not very pronounced. In particular, our data support the notion of a continuous Wald distribution of psychotic symptoms in the general population. Our findings have enabled us to confirm the usefulness of these syndromes as previously assessed in other independent community samples. Both can appropriately be associated with well-known risk factors of schizophrenia.

Aims.To examine stigma- and knowledge-related barriers to help-seeking among members of the general population.Methods.In a representative survey of young to middle-aged Swiss adults (n= 8875), shame about a potential own mental illness, perceived knowledge about and satisfaction with one's mental health, psychiatric symptoms and attitudes towards help-seeking were assessed.Results.A latent profile analysis of all participants yielded two groups with different attitudes towards help-seeking. Relative to the majority, a one-in-four subgroup endorsed more negative attitudes towards seeking professional help, including psychiatric medication, and was characterized by more shame, less perceived knowledge, higher satisfaction with their mental health, younger age, male gender and lower education. Among participants with high symptom levels (n= 855), a third subgroup was reluctant to seek help in their private environment and characterized by high symptoms as well as low satisfaction with their mental health.Conclusions.Shame as an emotional proxy of self-stigma as well as poor subjective mental health literacy may be independent barriers to help-seeking. Interventions to increase mental health service use could focus on both variables and on those individuals with more negative views about professional help, in the general public as well as among people with a current mental illness.

Glucocorticosteroids (GCS) are established in the treatment of active Crohn's ileitis and ileocolitis. Recently, the topical steroid budesonide was found to be effective in untreated patients with Crohn's disease (CD) causing less side effects than conventional GCS. No clinical data have been reported about the effects of switching from conventional GCS to budesonide in terms of side effects and disease activity. The primary aim of this study was to evaluate the development of side effects after switching from conventional GCS treatment to Eudragit L-coated budesonide (pH-modified release formulation) in patients taking 5–30 mg prednisolone equivalent per day for at least two weeks. In all, 178 patients with active CD (N= 88) or CD in remission during GCS treatment (N= 90) were included. Conventional GCS treatment was tapered down during a maximum of three weeks, with simultaneous intake of 3 × 3 mg budesonide. Thereafter, patients received 3 × 3 mg budesonide alone for six weeks. GCS-related side effects, disease activity and adverse events were documented at study entry and after 0, 2, 4, and 6 weeks of budesonide treatment. The percentage of patients with GCS-related side effects decreased from 65.2% (intention-to-treat-population) at entry to 43.3% (P< 0.0001) at the end of the trial. The total number of GCS-related side effects decreased significantly from 269 to 90. Of the patients who entered the study with active disease under conventional GCS therapy, 38.6% were in remission at the end of the study. Of the patients who entered the study with CD in remission, 78% stayed in remission after switching from conventinal GCS to budesonide. In conclusion, switching from conventional GCS treatment to budesonide leads to a significant reduction of GCS related side effects in patients with CD without causing rapid deterioration of the disease.

Auf der Basis des Canberra Interview for the Elderly wurde die depressive Verstimmung mittels der Psychogeriatric Assessment Scales (PAS) nach DSM-III-R-Kriterien bei 921 Probanden im Alter von 65 Jahren und mehr erfasst. Dabei wurden die Anzahl der depressiven Symptome (ADS) und die Prävalenzrate der Depression (PRD) allgemein, nach Alter und Geschlecht bestimmt. Die PAS-Skala ergab, dass 41,8% der Probanden keine depressiven Symptome aufweisen, 50,2% 1–3 und 8,0% 4 oder mehr depressive Symptome hatten. Die durchschnittliche ADS betrug 1,27. Frauen wiesen eine statistisch signifikant höhere ADS auf im Vergleich zu Männern (1,53 vs. 1,05). Die ADS stieg mit dem Alter an. Probanden mit niedriger Schulbildung sowie Geschiedene und Verwitwete wiesen eine statistisch signifikant höhere ADS auf verglichen mit Probanden mit hoher Schulbildung und Verheiraten bzw. Ledigen. Es bestand eine starke positive Assoziation der ADS mit Demenz und Behinderungen in den Aktivitäten des täglichen Lebens. In der multivariaten Regressionanalyse erwies sich das Geschlecht – jedoch nicht das Alter – als starker Risikofaktor für ADS. Die allgemeine Prävalenzrate der Depression betrug 8,0%. Frauen wiesen eine statistisch signifikant höhere PRD auf als Männer (10,4% vs. 3,9%). Die PRD stiegen mit dem Alter der Betagten an. Die multivariate logistische Regressionsanalyse bestätigte das Vorliegen einer positiven statistisch signifikanten Relation zwischen dem Alter sowie dem Geschlecht und der Depression, bereinigt für andere Risikofaktoren. Data for this analysis came from a cross-sectional study on dementia, depression, and disability conducted in Zurich and Geneva in 1995/96. The random sample stratified by age and gender consisted of 921 subjects aged 65 and more. Based on the Canberra Interview for the Elderly, depression was assessed by means of psychogeriatric assessment scales (PAS) according to DSM-III-R criteria. The number of depressive symptoms (NDS) and the prevalence rate of depression (PRD) were computed for the whole sample as well as according to age and gender. To evaluate the independent effects of age as well as gender with regard to the risk of being depressed, multivariate analyses were conducted. On average, 13% of females vs 8% of males reported having at least one depressive symptom. The PAS yielded 298 (41.8%) subjects without depressive symptoms, 341 (50.2%) with 1–3 symptoms, and 60 (8.0%) with four or more. The average NDS was 1.27 (95% CI 1.16–1.39). For females, NDS values statistically significantly higher than those for males were calculated (1.53, 95% CI 1.35–1.70 vs 1.05, 95% CI 0.90–1.20). The NDS increased significantly with age. Subjects with low education levels and being divorced or widowed had statistically significantly higher NDS values than highly educated, married, or single persons. There were strong positive associations between NDS, dementia, and activities of daily living. Multivariate regression analysis revealed gender – however, not age – as a strong risk factor for NDS. Overall PRD amounted to 8.0% (95% CI 5.7–10.2%). Females had statistically significantly higher PRD values than males (10.4%, 95% CI 7.0–13.9% vs 3.9, 95% CI 2.0–5.9%). The PRD increased substantially with age. After adjustment for other risk factors, multivariate logistic regression analysis confirmed the positive statistically significant association between age, gender, and depression.

In renal extracts, some renin is present as "high molecular weight renin," a heterodimeric complex of renin with the 46-kDa renin-binding protein (RnBP), also known as N-acyl-D-glucosamine 2-epimerase. Because RnBP specifically inhibits renin activity, the protein was proposed to play an important role in the regulation of the renin-angiotensin system (RAS). Using gene targeting, we have generated mice lacking RnBP and tested this hypothesis in vivo. In particular, we analyzed biosynthesis, secretion, and activity of renin and other components of the RAS in mice lacking RnBP. Despite extensive investigations, we were unable to detect any major effects of RnBP deficiency on the plasma and renal RAS or on blood pressure regulation. Contrary to previous hypotheses, we conclude that RnBP does not play a significant role in the regulation of renin activity in plasma or kidney. However, RnBP knockout mice excrete an abnormal pattern of carbohydrates in the urine, indicating a role of the protein in renal carbohydrate metabolism.

Background & Aims: This study investigated if long-term treatment with high-dose mesalamine reduces the risk of clinical relapse of Crohn's disease after surgical resection. Methods: In a prospective, randomized, double-blind, multicenter study, 4 g of mesalamine (Pentasa; Ferring A/S, Vanlose, Denmark) daily was compared with placebo in 318 patients. Treatment was started within 10 days after resective surgery and continued for 18 months. Primary outcome parameter was clinical relapse as defined by an increase in Crohn's Disease Activity Index, reoperation, septic complication, or newly developed fistula. Risk factors for recurrence were prospectively defined to be analyzed in a stepwise proportional hazards model. Results: Cumulative relapse rates (+/-SE) after 18 months were 24.5% +/- 3.6% and 31.4% +/- 3.7% in the mesalamine (n = 152) and placebo (n = 166) groups, respectively (P = 0.10, log-rank test, 1-sided). Retrospective analysis showed a significantly reduced relapse rate with mesalamine only in a subgroup of patients with isolated small bowel disease (n = 124; 21.8% +/- 5.6% vs. 39.7% +/- 6.1%; P = 0.02, log-rank test). Probability of relapse was predominantly influenced by the duration of disease (P = 0.0006) and steroid intake before surgery (additional risk, P = 0.0003). Conclusions: Eighteen months of mesalamine, 4 g daily, did not significantly affect the postoperative course of Crohn's disease. Some relapse-preventing effect was found in patients with isolated small bowel disease. GASTROENTEROLOGY 2000;118:264-273

Not Available

Rat liver synthesizes a glycoprotein with Mr of 80.000 (gp 80) which is partly inserted into the plasma membrane and partly secreted into the serum. The membrane‐integrated and the secretory form of this glycoprotein have an identical peptide pattern, but different N‐linked glycans. Whereas gp 80 from the serum is glycosylated with complex‐type oligosaccharides, gp 80 from the plasma membrane has high mannose glycans. Phase separation with Triton X‐114 showed that membrane‐integrated gp 80 contains hydrophobic portions, whereas secretory gp 80 has hydrophilic properties. Intracellular transport and oligosaccharide processing of gp 80 were studied in vivo in the endoplasmic reticulum, the Golgi apparatus and plasma membranes of rat liver and in serum using pulse‐chase labeling with L‐[35S]methionine and immunoprecipitation. Peak labeling of gp 80 was reached in the endoplasmic reticulum 10 min after the pulse, in the Golgi apparatus 20 min later, and in the plasma membrane after 2 h; in the serum the specific radioactivity was steadily increasing during the experiment. Gp 80 of the endoplasmic reticulum was completely sensitive to endo‐beta‐N‐glucosaminidase H (endo H), but simultaneously occurred in the Golgi apparatus in an endo H‐sensitive and endo H‐resistant form. The endo H‐sensitive form was transported to the plasma membrane, the endo H‐resistant species secreted into the serum. Conversion from the endo H‐sensitive to the endo H‐resistant form was completed within 10 min after transfer of gp 80 to the Golgi apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)

Paraprofessionals working in a residential alcoholism treatment program had significantly more "custodial" attitudes and attitudes of "humanism" toward alcoholics and beliefs concerning a psychological etiology of alcoholism than did paraprofessionals at a sobering-up station.

An experiment was conducted varying bicycle crank length as a ratio of cyclist's crotch height over a range from 0.17 to 0.23. A light and a heavy load were used with ten young male subjects. Heart rate, oxygen consumption and perceived exertion measures were taken during bicycle ergometer pedaling sessions. All measures showed the superiority of a crank length of about 0.20 of crotch height (0.10 of standing height). A change of crank length of three percentage points of crotch height increases energy expenditure by one kcal/minute. The standard crank is too long for 60% of adult males and almost 100% of females. Varied crank lengths or adjustable cranks should be made available.

Complexes of granulocyte elastase and a1-antitrypsin are markers for granulocyte activation. In 75 patients with acute pancreatitis these complexes were immunologically determined daily in plasma during the first week of hospitalization. Patients were classified into three groups: mild pancreatitis (I, =1 complication, N=34), severe pancreatitis (II, =2 complications, N= 29), lethal outcome (III, N=12). Initially, granulocyte elastase (mean±sem) was lower in group I (348±39 µg/liter) as compared to groups II (897±183 µg/l) and III (799±244 µg/liter), P<0.001 for I vs II + III. Initial elastase concentrations >400 µg/liter were consistent with a severe or fatal course of the disease but did not distinguish between severe and lethal pancreatitis. In patients with mild or severe disease, mean elastase concentrations decreased continuously during the following days (197±15 µg/liter in mild cases, 325±30 µg/liter in severe cases at day 7). In patients with lethal disease, however, mean elastase concentrations even increased at day 2 and remained higher than 700 µg/liter during the observation period. At days 1 and 2 the predictive value for severe or lethal disease of raised (>400 µg/liter) elastase concentrations [positive predictive value (PPV) 82%, negative predictive value (NPV) 81%] was better than that of elevated (>100 mg/liter) C-reactive protein (PPV 73%, NPV 73%), elevated (>4.0 g/liter) a1-antitrypsin (PPV 59%, NPV 50%), or decreased (<1.5 g/liter) a2-macroglobulin (PPV 82%, NPV 67%). When the time course of the concentrations of the acute-phase proteins was studied, it was found that rises of granulocyte elastase were followed by elevated C-reactive protein levels after one day, by elevated a1-antitrypsin levels after two days and by decreased a2-macroglobulin levels after three to four days. We conclude that granulocyte elastase is a good early marker for the severity of acute pancreatitis. Compared with elevated levels of C-reactive protein and a1-antitrypsin release of granulocyte elastase reflects an event that precedes acute-phase protein induction.

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.

The glucosidase inhibitors 1-deoxynojirimycin, N-methyl-1-deoxynojirimycin and castanospermine were used to inhibit oligosaccharide processing in primary cultures of rat hepatocytes. Their effect on the glycosylation of alpha 1-proteinase inhibitor (alpha 1PI) and alpha 1-acid glycoprotein (alpha 1AGP) was studied. Of the three glucosidase inhibitors examined, 1-deoxynojirimycin inhibited not only oligosaccharide trimming but also glycosylation de novo of newly synthesized proteins, resulting in the formation of alpha 1PI with two and three (normally carrying three) and alpha 1AGP with two to five (normally carrying six) oligosaccharide side chains. In the presence of the glucosidase inhibitors, glucosylated high-mannose-type oligosaccharides accumulated. Whereas most of the endoglucosaminidase-H-sensitive oligosaccharides formed in the presence of 1-deoxynojirimycin contained only one glucose residue, N-methyl-1-deoxynojirimycin and castanospermine led mainly to the formation of oligosaccharides with three glucose residues. None of the three glucosidase inhibitors completely prevented the formation of complex-type oligosaccharides. Thus, in their presence, alpha 1PI and alpha 1AGP with a mixture of both high-mannose and complex-type oligosaccharides were secreted.

Zusammenfassung: Glukokortikoide sind wirksame Medikamente zur Behandlung der Colitis ulcerosa. Das Auftreten von Nebenwirkungen ist von der Dosis und Dauer der Behandlung abhängig und kann bei langjähriger Einnahme bis zu 80% betragen. Eine seltene unerwünschte Wirkung der Glukokortikoidtherapie ist die steroidinduzierte Myopathie. Es existiert eine akute und eine chronische Form. Die chronische Steroidmyopathie betrifft vornehmlich die Muskulatur des Schulter- und Beckengürtels und äußert sich in einer proximalen Muskelschwäche. Histologisch findet sich eine Atrophie der Typ-IIb-Muskelfasern. Die chronische Steroidmyopathie entsteht nach längerer Einnahme einer mittleren bis höheren Dosis von Glukokortikoiden. Eigener Fall: In der vorgestellten Kasuistik, entwickelte ein 25jähriger Patient mit linksseitiger Colitis ulcerosa nach monatelanger Glukokortikoidbehandlung eine chronische Steroidmyopathie. Nach Umstellung von der oralen systemischen Steroidbehandlung auf Budesonid besserte sich die Myopathie. Die linksseitige Colitis ulcerosa blieb in Remission. Schlußfolgerung: Der Fall dokumentiert das Verschwinden einer bedeutsamen Steroidnebenwirkung nach Umstellung von einer systemischen Steroidtherapie auf Budesonid.

Experimental studies have shown that interleukin-6 induces all major acute-phase proteins in the liver, including C-reactive protein. In 50 patients with acute pancreatitis, the serum concentrations of interleukin-6 and C-reactive protein were determined daily during the first week of hospitalization. Patients were divided into three groups according to clinical criteria: mild pancreatitis (<- 1 complication; n = 25), severe pancreatitis (≥ 2 complications; n = 15), and lethal outcome (n = 10). Patients with mild disease showed initially slightly elevated levels of interleukin-6 (22.0 ± 9.8 U/mL) that decreased to low levels within 4 days (5.0 ± 1.0 U/mL). In patients with severe pancreatitis, serum concentrations of interleukin-6 were initially clearly elevated (35.0 ± 7.5 U/mL) and remained slightly elevated until day 7 (13.0 ± 2.0 U/mL). Patients with lethal outcome had markedly elevated initial interleukin-6 concentrations (61.0 ± 15.0 U/mL) that decreased but were still elevated at day 7 (26.0 ± 2.5 U/mL). In all three groups, C-reactive protein concentrations followed the course of interleukin-6 concentrations by 1 day. There was a positive correlation between maximal interleukin 6 concentrations and maximal increases in the serum concentrations of C-reactive protein (r= 0.66). At days 1 and 2, increased (>15 U/mL) interleukin-6 concentrations (positive predictive value, 91%; negative predictive value, 82%) predicted a severe or lethal course of the disease more accurately than elevated [>; 0.10 g/L (>10 mg/dL)] C-reactive protein concentrations (positive predictive value, 67%; negative predictive value, 79%). In conclusion, elevated serum concentrations of interleukin-6 followed by increased levels of C-reactive protein reflect the severity of acute pancreatitis.

Thyroid function has been evaluated in 6 prepubertal male and 9 female thalassemic patients. Four of the latter were sexually immature (Group I), with very low estradiol levels and the remainder had more advanced sexual development (Group II). Subjects were challenged with TRH and the response compared to adult controls and a group of 15 males aged 13–18 years with constitutional delayed adolescence. All patient groups and controls had normal levels of T4, T3and T3resin uptake. When compared to adult controls or males with constitutional delayed adolescence, the male thalassemic patients had increased basal TSH levels with an exaggerated response to TRH. Long term testosterone enanthate led to a decrease in integrated TSH secretion, showing that androgens may decrease the TSH response to TRH. The more sexually mature females of Group II also had increased basal and stimulated TSH levels; however, the sexually immature females of Group I had basal TSH and TSH responses to TRH equivalent to female controls. In Group I patients there were, moreover, no changes in TSH response during administration of estradiol valearate for 3 months and conjugated estrogens for 8 months. The high basal and stimulated TSH levels in the males and Group II females are most likely due to subclinical primary hypothyroidism. This has been previously described in thalassemia. On the other hand, failure of estrogens to increase the TSH response to TRH in Group I females is evidence of pituitary involvement, which is also well documented in this clinical condition. Finally the low testosterone levels in the male patients could also account for their enhanced TSH response.

The infiltration of leukocytes has been linked to the pathophysiology of complicated or severe pancreatitis. We have tested the ability of leukocyte scintigraphy using technetium-99m-hexamethyl propylene amine oxine (HM-PAO) as label to demonstrate the localization of leukocytes in the pancreas during acute pancreatitis. Twenty-eight patients with acute pancreatitis (eight with biliary, 13 with alcoholic, and seven with unknown origin) were studied with leukocyte scintigraphy using planar imaging and single photon emission computed tomography (SPECT). Fourteen patients had a mild (group I), 11 a severe (group II), and three a lethal outcome (group III) of pancreatitis. All patients of group III, six of group II, and two of group I had a positive leukocyte scan. Thus, the sensitivity of leukocyte scintigraphy for the detection of a lethal course, of acute pancreatitis was 100%, of a severe course 54%, and of a severe or lethal course 64%. The specificity of a negative scan for a mild pancreatitis was 86%. Comparison of the results of leukocyte scintigraphy with those of contrast enhanced CT showed that six of eight patients with pancreatic necrosis in CT had a positive leukocyte scan, but only five of 20 patients without detectable pancreatic necrosis in CT. In summary, leukocyte infiltration into the pancreas during pancreatitis can be demonstrated by noninvasive leukocyte scintigraphy using technetium-99m-HM-PAO as label. A correlation between the severity of the disease and leukocyte infiltration exists.

The effects of 2-deoxy-2-fluoro-D-galactose (dGalF) on N- and O-glycosylation of proteins was studied in rat hepatocyte primary cultures and in human monocytes. In hepatocytes, dGalF at concentrations of 1 mM or higher completely inhibited N-glycosylation of alpha 1-antitrypsin and alpha 1-acid glycoprotein, whereas 4 mM-2-deoxy-D-galactose (dGal) only slightly impaired N-glycosylation. In monocytes, 1 mM- or 4 mM-dGalF blocked N-glycosylation of alpha 1-antitrypsin and of interleukin-6, while O-glycosylation of interleukin-6 remained unaffected. In monocytes, dGal had no effect on protein N-glycosylation. Addition of uridine effectively prevented the UTP deficiency induced by dGalF, but had no effect on the inhibition of protein N-glycosylation by dGalF. Using 19F-n.m.r. spectroscopy, 2-deoxy-2-fluoro-D-galactose 1-phosphate (dGalF-1-P), UDP-dGalF and UDP-dGlcF could be identified as the major metabolites of dGalF in hepatocytes as well as in monocytes. In conclusion, compared with dGal, dGalF is a more efficient inhibitor of protein N-glycosylation. The effect is not caused by the depletion of UTP induced by dGalF, but rather by metabolites of dGalF. dGalF is metabolized not only in hepatocytes but also in peripheral blood monocytes, which can be used for ex vivo studies of disturbances in D-galactose metabolism.

Remanit 4565 S is a newly developed austenitic stainless steel with high nitrogen content. Its characteristic features include better mechanical strength and toughness values, delayed precipitation of carbides and inter-metallic phases, as well as improved corrosion resistance. This material can be used for fabrication by welding without risk of pore formation. Using the filler metals SG-NiCr 20 Mo 15 (Thermanit Nimo C) or SG-NiCr 28 Mo (Thermanit 30/40 E) according to the field of application, joints produced by the TIG process are as corrosion resistant as the base metal.

By two exemplary clinical situations — acute viral hepatitis, acute-phase reaction of the liver — the significance of basic research for the understanding of clinical phenomena and for the development of new diagnostic and therapeutic procedures is demonstrated. The very different phenomena following infection with the hepatitis-B-virus can be explained by the variation in the interactions of virus and liver cell, by the immune reaction of the host, and by mutants of the virus. The reaction of the liver to an extrahepatic infection is mediated by interleukin-6, and characterized by an alteration in protein metabolism. The synthesis of acute-phase proteins is increased. The proteins confine the local injury and establish the homeostasis of the organism.

The biosynthesis of the proteinase inhibitor alpha 1-antitrypsin has been studied in rat hepatocyte primary cultures. Newly synthesized alpha 1-antitrypsin was found in hepatocytes as a glycoprotein of an apparent molecular weight of 49,000 carrying oligosaccharide side chains of the high mannose type. In the hepatocyte medium a secreted alpha 1-antitrypsin of an apparent molecular weight of 54,000 could be identified as a glycoprotein with carbohydrate chains of the complex type. Pulse-chase experiments revealed a precursor-product relationship for the two forms of alpha 1-antitrypsin. When the hepatocytes were treated with swainsonine, an intracellular form of alpha 1-antitrypsin with an apparent molecular weight of 49,000 indistinguishable from that of control cells was found. However, the alpha 1-antitrypsin secreted from swainsonine-treated hepatocytes was different from that present in control media. It was characterized by a lower apparent molecular weight (51,000), a higher amount of [3H]mannose incorporation, half as much incorporation of [3H]galactose, and the same amount of [3H]fucose incorporation compared to alpha 1-antitrypsin of control media. In contrast to the 54,000 complex type alpha 1-antitrypsin from control media the 51,000 alpha 1-antitrypsin from the medium of swainsonine-treated cells was found to be susceptible to the action of endoglucosaminidase H, even when fucose was attached to the proximal GlcNAc residue. alpha 1-Antitrypsin secreted from swainsonine-treated cells combines features usually associated with either high mannose or complex type oligosaccharides and therefore represents a hybrid structure. In spite of its effect on the carbohydrate part of alpha 1-antitrypsin swainsonine did not impair the secretion of the incompletely processed glycoprotein.

Summary Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) of unknown etiology. They are characterized by an activation of intestinal mononuclear cells. Cytokines play a crucial role in the regulation of the functions of these cells. An increased synthesis of the cytokines interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factora (TNFa), which are primarily synthesized by activated monocytes/macrophages has been described in patients with IBD. The synthesis of interleukin-2 (IL-2) and of interferon? (IFN?), which are produced by lymphocytes, on the other hand, has been found to be decreased. The published data are, however, not quite consistent. In patients with IBD there is not only a stimulation of the local cytokine production in the gut. The blood levels and the synthesis of the cytokines IL-1, IL-6 and TNFa by peripheral blood mononuclear cells are also increased, in particular in patients with Crohn's disease. Drugs, which are commonly used for the treatment of IBD impair the synthesis of these cytokines in monocytes/macrophages.

The regulation of interleukin-6 (IL-6) expression by IL-1 and retinoic acid (RA) was studied in the human epidermoid carcinoma cell line, HEp-2.

1-Deoxynojirimycin was found to inhibit oligosaccharide processing of rat alpha 1-proteinase inhibitor. In normal hepatocytes alpha 1-proteinase inhibitor was present in the cells as a 49,000 Mr high mannose type glycoprotein with oligosaccharide side chains having the composition Man9GlcNAc and Man8GlcNAc with the former in a higher proportion. Hepatocytes treated with 5 mM 1-deoxynojirimycin accumulated alpha 1-proteinase inhibitor as a 51,000 Mr glycoprotein with carbohydrate side chains of the high mannose type, containing glucose as measured by their sensitivity against alpha-glucosidase, the largest species being Glc3Man9GlcNAc. Conversion to complex oligosaccharides was inhibited by the drug. In addition, increasing concentrations of 1-deoxynojirimycin inhibited glycosylation resulting in the formation of some alpha 1-proteinase inhibitor with two instead of three oligosaccharide side chains. 5 mM 1-deoxynojirimycin inhibited the secretion of alpha 1-proteinase inhibitor by about 50%, whereas secretion of albumin was unaffected. The oligosaccharides of alpha 1-proteinase inhibitor secreted from 1-deoxynojirimycin-treated cells were characterized by their susceptibility to endoglucosaminidase H, incorporation of [3H]galactose, and [3H]fucose and concanavalin A-Sepharose chromatography. It was found that 1-deoxynojirimycin did not completely block oligosaccharide processing, resulting in the formation of alpha 1-proteinase inhibitor molecules carrying one or two complex type oligosaccharides. Only these alpha 1-proteinase inhibitor molecules processed to the complex type in one or two of their oligosaccharide chains were nearly exclusively secreted. This finding demonstrates the importance of oligosaccharide processing for the secretion of alpha 1-proteinase inhibitor.

GASTROENTEROLOGY 1998;115:1306-1307

We studied 28 patients with Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI). Twenty-two developed symptomatic hypoglycemia within 2 days of life (15 of these required surgery) while 5 developed first symptoms at age 2-7 months (1 required surgery). Twelve patients belonged to 5 families indicating a genetic basis for the disease (autosomal recessive). Non-pancreatectomized patients received frequent high carbohydrate feedings, raw cornstarch, diazoxide and/or somatostatin analogue (Sandostatin™, Sandoz, Switzerland, n=5). All 85-90% pancreatectomized patients (n=15) required some medical treatment for hypoglycemia post-operatively. Three patients died (2 of sepsis and 1 of acute gastric perforation). Diabetes developed only in the 1 patient who had a total pancreatecomy. Of 25 living patients, 16 entered remission between 0.3 & 8 years of age (follow-up 0.3-12 years, mean 5.5 years). Of the 22 living patients who were not retarded at diagnosis, 21 developed normally while 1 is retarded (IQ 65). Pathologic examination of 16 pancreata showed focal findings in 3, the rest being histologically normal for age. Beta-cells from 3 histologicaly normal pancreata were cultured on extra-cellular matrix and showed significant & unchanged insulin secretion at all levels of glucose tested (0-16.7 mmol), which suppressed with epinephrine or somatostatin and stimulated with IBMX or forskolin.In conclusion: PHHI appears to be caused by a functional β-cell defect, presumably genetic in origin, manifested by a lack of suppression of insulin secretion by low glucose, and which may resolve spontaneously with time. Intensive conservative treatment, with 85-90% pancreatectomy only when absolutely necessary, resulted in a good long-term prognosis in 95% of our patients in whom the diagnosis was made before the onset of neurologic damage.