Seasonality in schizophrenia-An analysis of a nationwide registry with 110,735 hospital admissions.

BACKGROUND: Seasonal patterns in hospitalizations have been observed in various psychiatric disorders, however, it is unclear whether they also exist in schizophrenia. Previous studies found mixed results and those reporting the presence of seasonality differ regarding the characteristics of these patterns. Further, they are inconclusive whether sex is an influencing factor. The aim of this study was therefore to examine if seasonal patterns in hospitalizations can be found in schizophrenia, with special regard to a possible influence of sex, by using a large national dataset. METHODS: Data on all hospital admissions within Austria due to schizophrenia (F20.0-F20.6) for the time period of 2003-2016 were included. Age standardized monthly variation of hospitalization for women and men was analyzed and the level of significance adjusted for multiple testing. RESULTS: The database comprised of 110,735 admissions (59.6% men). Significant seasonal variations were found in the total sample with hospitalization peaks in January and June and a trough in December (p < 0.0001). No significant difference in these patterns was found between women and men with schizophrenia (p < 0.0001). CONCLUSION: Our study shows that schizophrenia-related hospitalizations follow a seasonal pattern in both men and women. The distribution of peaks might be influenced by photoperiod changes which trigger worsening of symptoms and lead to exacerbations in schizophrenia. Further research is necessary to identify underlying factors influencing seasonal patterns and to assess whether a subgroup of patients with schizophrenia is especially vulnerable to the impact of seasonal variations.

Association of depression symptoms with receipt of healthcare provider advice on physical activity among US adults.

BACKGROUND: Given the high burden and prevalence of depression, various guidelines underscore the role of healthcare providers in supplying advice on physical activity (PA) as a potential modifying factor influencing the incidence and severity of depressive symptoms in adults. We aimed to investigate the extent to which healthcare providers provide PA advice to adults with depressive symptoms in the US. METHODS: Data on adults aged 20-64 years (n = 4971) in the National Health and Nutrition Examination Study between 2011 and 2016 were analysed. Depressive symptoms were assessed using the Patient Health Questionnaire and response options were categorised as "none or minimal", "mild", "moderate-severe". Receipt of PA advice from a healthcare provider was self-reported. We restricted our study sample to adults free from chronic diseases. RESULTS: Higher odds of receiving advice to exercise were reported among adults with mild (OR = 1.7, 95% CI: 1.3-2.3) and moderate-severe depressive symptoms (OR = 1.7, 95% CI: 1.0-2.8). Furthermore, exercise advice was more commonly reported among adults who were overweight, obese, Hispanic, Asian, being insured with private insurance, with education higher than high school, and had access to a routine place for health care. LIMITATIONS: Social and culutral aspects of overweight/obesity may prohibit generalizations. Cross sectional design does not allow for causal realtionships. CONCLUSIONS: In the US, fewer than one in three adults experiencing symptoms of depression report having received exercise advice from a healthcare provider. Providing such advice may be a sustainable clinical strategy in reducing the incidence and severity of depression symptoms.

Effect of increased opiate exposure on three years neurodevelopmental outcome in extremely preterm infants.

BACKGROUND: International guidelines recommend the use of item based scales for the assessment of pain and sedation. In our previous study, the implementation of the Neonatal Pain Agitation and Sedation Scale (N-PASS), and the associated systematic assessment and treatment of pain and sedation reduced pain and over-sedation in our intervention group, but lead to a significant increase of individual opiate exposure. This increased opiate exposure was not associated with impaired motor and mental development at one year of age. As one-year follow-up is not necessarily representative for future outcomes, we retested our sample at three years of age. METHODS: Fifty-three patients after (intervention group) and 61 before implementation (control group) of the N-PASS and the Vienna Protocol for the Management of Neonatal Pain and Sedation (VPNPS), were compared for motor, mental and behavioural development at three-years follow-up using the Bayley Scales of Infant Development. RESULTS: Cumulative opiate exposure was not associated with mental (p = .31) and motor (p = .20) problems when controlling for other important medical conditions, but was associated to lower behavioural scores (p = .007). No statistically significant differences were found with regard to mental (p = .65), psychomotor (p = .12) and behavioural (p = .61) development before and after the implementation of the N-PASS and the VPNPS. CONCLUSION: Implementing a neonatal pain and sedation protocol increased opiate exposure without affecting neurodevelopmental outcome at three-years of age.

The impact of altitude on birth weight depends on further mother- and infant-related factors: a population-based study in an altitude range up to 1600 m in Austria between 1984 and 2013.

OBJECTIVE: A negative impact of altitude on birth weight has been demonstrated for medium to high-altitude countries. STUDY DESIGN: The present study aims to show a similar effect for a lower altitude range up to 1600 m in the country of Austria and to adjust for several further risk factors related to mother and infant. In addition, we analyzed whether the effect of altitude influenced birth weight independently or interacted with other factors. For the purpose of this study, almost 1.9 million individual birth certificates of Austrian newborns born between 1984 and 2013 were analyzed. In a multivariate linear regression model, birth weight was associated with altitude of living address and following variables: sex, birth length, gestational age, level of education, maternal age, year of birth, parity, time to previous birth and marital status. RESULT: Birth weight decreased by 150 g/1000 m altitude, demonstrating a clear effect of altitude on birth weight also in a low to medium altitude level. Additionally, we could show that this effect also depends on other factors, namely gestational age, education of the mother, sex, birth length, year of birth and time to previous delivery. All variables interacted significantly (p<0.0001) with altitude. CONCLUSION: We observed a negative effect of altitude in an altitude range up to 1600 m. Furthermore, this effect also depends on other risk factors. Therefore, unadjusted estimates as described in many studies may be biased. This population-based study describes the effect of low-to-medium altitude on birth weight in central Europe over a period of 30 years.

Intravenous sildenafil i.v. as rescue treatment for refractory pulmonary hypertension in extremely preterm infants.

BACKGROUND: Intravenous sildenafil treatment has recently shown promising results and good tolerability in the treatment of refractory pulmonary hypertension (PH) in term and near-term neonates, while comparable data in preterm infants are still lacking. However, for critically ill preterm infants suffering from PH refractory to conventional treatment, sildenafil may represent a last treatment resort. PATIENTS AND METHODS: We reviewed the records of 6 critically ill extremely preterm infants who had suffered from PH refractory to conventional treatment and had obtained intravenous sildenafil after careful consideration as ultima ratio treatment. AIM: To describe the responses to sildenafil in terms of hemodynamic and respiratory changes during treatment and outcome. RESULTS: 4/6 patients showed resolution of severe PH with full reversal of ductal shunt direction into pure left-to-right shunt within 82 ± 35 h after sildenafil start. Remarkably, 2/6 patients developed pulmonary hemorrhage at a time point when significant improvement of PH had already taken place, both of them survived. Overall 4/6 patients died, two deaths were related to treatment-refractory PH. CONCLUSION: Intravenous sildenafil treatment seems effective in improving severe PH and hemodynamic instability in extremely preterm infants with refractory PH. Pulmonary hemorrhage may represent a distinct adverse effect of sildenafil treatment in these patients, presumably due to sudden reversal of ductal shunt. Accordingly, sildenafil should be restricted to most severe and refractory cases in this population.

Impact of low-grade intraventricular hemorrhage on long-term neurodevelopmental outcome in preterm infants.

PURPOSE: Despite a decreasing incidence, intraventricular hemorrhage (IVH) remains a point of major concern in neonatology due to its association to adverse neurodevelopmental outcome (NDO). Aim of this study was to compare outcome of preterm infants with different grades of IVH born below 32 weeks of gestational age (GA) with outcome of controls without IVH and to especially evaluate the influence of low grade IVH on NDO. METHODS: Four hundred seventy-one preterm infants with a GA below 32 weeks were admitted to our neonatal intensive care unit between 1994 and 2005 and included into analysis. RESULTS: IVH patients showed significantly lower mean psychomotor and mental developmental indices and a significantly higher percentage of cerebral palsy and visual impairment. Results of IVH patients born below 28 weeks of GA were significantly worse than results of IVH patients born at or above 28 weeks of GA. In all parameters, an increase of abnormal results with increasing grade of IVH could be observed; even patients with low-grade IVH (grades I and II) showed higher percentages of impairment compared to controls without any IVH. CONCLUSION: Even low-grade IVH has an significant impact on neurodevelopmental outcome of preterm patients and gestational age influences the impact of intraventricular hemorrhage on neurodevelopmental outcome.

Diabetic ketoacidosis at diagnosis in Austrian children in 1989-2008: a population-based analysis.

AIM: The aim of the study was to analyse the prevalence of diabetic onset ketoacidosis (DKA) during a period of 20 years (1989-2008) on a population basis in the whole of Austria. METHODS: A prospective population-based incidence study (1989-2008) was performed. The registered data set comprised blood glucose, pH, ketonuria and clinical symptoms of DKA at manifestation. DKA was defined as pH < 7.3 and severe DKA as pH < 7.1. Time trends were estimated using linear regression models. RESULTS: During the study period, 3331 children <15 years of age (1,797 boys and 1,534 girls) were registered with newly diagnosed type 1 diabetes. Of these, 1,238 (37.2%) presented with DKA, 855 (25.7%) had a mild and 383 (11.5%) a severe form, and one patient died at onset. DKA frequency was negatively associated with age at onset (p < 0.0001). In children <2 years the prevalence was 60%, with a higher risk for girls (70% vs 54% for boys, p < 0.05). Despite a significant increase in diabetes incidence in Austria during the observation period from 8.4 to 18.4/100,000 (p < 0.0001), no significant change in the prevalence of DKA at manifestation was observed. CONCLUSIONS: The overall frequency of DKA in children with newly diagnosed type 1 diabetes in Austria is high and has not changed during the last 20 years despite a clear increase in the manifestation rate. In particular, children less than 2 years of age have a high risk of DKA at onset.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Survival in a cohort of patients with haemophilia at the haemophilia care center in Vienna, Austria, from 1983 to 2006.

Survival of patients with haemophilia is still a relevant issue of great interest. A survival analysis was conducted among 226 patients with haemophilia A and B (128 severe haemophiliacs), who were treated at the haemophilia care centre in Vienna. Information on mortality in our patient cohort was obtained from the Austrian Central Death Register. Overall, 96 of a total of 226 patients (42.5%) died between 1983 and 2006; 37 patients (38.5%) died due to HIV-infection, 15 due to HCV infection, 15 due to bleeding (15.6%, respectively) and 29 (30.2%) due to various other causes. The mortality of HIV-positive patients was 74.3% (n = 55) and that of HCV-positive patients was 40.4% (n = 55) in the analysed period. The patient mortality rates were compared with those of the general Austrian male population following adjustment for age and calendar period. We found that the cumulative relative survival of all patients was 0.694 (95% CI 0.614-0.767). The cumulative relative survival of patients with severe haemophilia (FVIII or IX level < or =1%) was 0.489 (0.394-0.579), but was normal (0.986; 95% CI 0.858-1.082) for patients with mild or moderate haemophilia (FVIII or IX level 2-50%). The survival rate was lowest in HIV-positive patients (0.287; 95% CI 0.186-0.398), but was also decreased to 0.874 (0.776-0.951) in HIV-negative patients. It can, therefore, be concluded that the survival of patients with severe haemophilia is still decreased compared to those with non-severe haemophilia and the general male population, regardless of HIV-infection.

Homicide and major mental disorders: a 25-year study.

OBJECTIVE: This study was designed to investigate the association between major mental disorders (MMDs) and homicide. METHOD: The rates of exculpations because of MMDs among 1087 Austrian homicide offenders during 1975 and 1999 were compared with the rates of the respective disorders in the general population. RESULTS: MMDs were associated with an increased likelihood of homicide (two-fold in men and six-fold in women). This was exclusively because of schizophrenia (age-adjusted ORs in men 5.85, CI 4.29-8.01; in women 18.38, CI 11.24-31.55) and delusional disorder in men (OR 5.98, CI 1.91-16.51). Comorbid alcohol abuse/dependence (additionally) increased the odds in schizophrenia, major depression and bipolar disorder. CONCLUSION: The increased likelihood of homicide in subjects with MMDs cannot be fully explained by comorbid alcoholism. The results point to the special importance of sufficient treatment for a subgroup of mentally ill individuals being at higher risk of violence.

Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease.

BACKGROUND: Antibiotics and thiopurines have been employed in the management of fistulizing Crohn's disease, although evidence of their efficacy is rare. AIM: To evaluate, in a prospective, open-label study, the influence of antibiotics and azathioprine on the clinical outcome of perianal fistulas in patients with Crohn's disease. METHODS: Fifty-two patients entered the study, starting with an 8-week regimen of ciprofloxacin (500-1000 mg/day) and/or metronidazole (1000-1500 mg/day). Seventeen patients had already received daily azathioprine (2-2.5 mg/kg) at enrollment, whereas in 14 patients azathioprine was initiated after 8 weeks of antibiotic treatment. Outcome was evaluated by Fistula Drainage Assessment and the Perianal Disease Activity Index at weeks 8 and 20. RESULTS: Overall, 26 patients (50%) responded to antibiotic treatment, with complete healing in 25% of patients at week 8. The Perianal Disease Activity Index decreased significantly from 8.4 +/- 2.9 to 6.0 +/- 4.0 (P < 0.0001). At week 20, the outcome was assessed in 49 patients (94%), 29 of whom (59%) had received azathioprine. Response was noted in 17 of the 49 patients (35%), with complete healing in nine patients (18%). Patients who received azathioprine were more likely to achieve a response (48%) than those without immunosuppression (15%) (P = 0.03). The Perianal Disease Activity Index was closely associated with treatment response and perianal disease activity. CONCLUSION: Antibiotics are useful to induce a short-term response in perianal Crohn's disease, and may provide a bridging strategy to azathioprine, which seems to be essential for the maintenance of fistula improvement.

Rates of postmortem examination in Austria: the effect of distance between location of death and site of examination.

BACKGROUND AND OBJECTIVE: Despite the importance of autopsies for diagnosing disease and determining cause of death, autopsy rates are decreasing in many countries. Furthermore, autopsy rates are often not distributed randomly between different regions within countries. In this study we analyzed an apparent nonrandom spatial distribution of autopsy rates in Austria for the period 1991-2000. We tested the new hypothesis that the rate of autopsies performed on people who die at home depends on the distance from the residence to the hospital or forensic institute where autopsies are performed. METHODS: Data were extracted from the official mortality records for the years 1991-2000. Only persons who deceased in private residences were included. A logistic regression model was used. RESULTS: Even controlling for variability in sex, age, date of death, and family status, the effect of distance significantly implied lower autopsy rates in the alpine parts of Austria. CONCLUSIONS: This effect of distance may lead to artificially nonrandom mortality patterns in disease maps. As a consequence, the possibility of hypothesizing incorrect health risks to explain nonrandom mortality patterns increases.

An open-label trial of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, in inflammatory bowel disease-associated peripheral arthritis and arthralgia.

BACKGROUND: Conventional non-steroidal anti-inflammatory drugs have been associated with an increased risk of exacerbation of inflammatory bowel disease. AIM: To evaluate, in a prospective, open-label study, the safety and efficacy of a 20-day regimen of the selective cyclo-oxygenase-2 inhibitor, rofecoxib, 12.5-25 mg/day, in inflammatory bowel disease patients with associated peripheral arthropathy and/or arthritis. METHODS: Patients with clinically inactive to mild inflammatory bowel disease and a joint pain score of at least two points on a scale ranging from zero (none) to four (very poor) were eligible. Response was defined by a decrease of at least two points in the arthralgia score. RESULTS: Of the 32 patients included, 26 (81%) were treated with rofecoxib, 25 mg/day, and six (19%) with rofecoxib, 12.5 mg/day. In three patients (9%), rofecoxib had to be withdrawn after a few days due to gastrointestinal complaints which ceased immediately after drug discontinuation. No flare of inflammatory bowel disease occurred. Thirteen of the 32 patients (41%) were responders and, overall, the arthralgia score decreased from two to one (P = 0.0001). CONCLUSIONS: This is the first prospective study on the use of a selective cyclo-oxygenase-2 inhibitor in inflammatory bowel disease patients with peripheral arthropathy and/or arthralgia. The promising safety and efficacy profile warrants further evaluation in controlled trials.

The lunar cycle and the number of deliveries in Austria between 1970 and 1999.

The effect of the moon on the number of newborns has been investigated extensively with contradictory results but with few significant findings. In this paper, a possible lunar effect is analyzed by a nonlinear Poisson regression model similar to a Fourier analysis based on all children (n = 2,760,362) born in Austria between 1970 and 1999, i.e. 371 lunar cycles. We found no significant effect even when considering the influence of parity and gestation. Our study is in contrast to a French study using a similarly large data base which showed a weak but significant effect. Nevertheless, significant p values based on very large samples must be interpreted cautiously. Our study is in concordance with other studies which often use small and selected samples or rather inefficient statistical methods. We conclude that there is no significant effect of the lunar cycle on the number of deliveries in Austria.

Prostate cancer in Austria: impact of prostate-specific antigen test on incidence and mortality.

The aim of the study was to assess the impact of prostate-specific antigen (PSA) testing on prostate cancer mortality in Austria. A join-point regression model and permutation tests were used to identify changes in the slope of age-specific trends respectively calculating the annual percentage change (APC). Age-adjusted incidence increased (P < 0.01) between 1983 and 1997 by 79% from 52.2 to 93.6 cases per 100 000 men/year. Incidence in localized/regional stage disease increased in all ages by 143% from 25.7 to 62.4 cases per 100 000 men/year. Incidence in distant disease decreased (P < 0.01) between 1983 and 1997 in all ages by 38% from 9.5 to 5.9 cases per 100 000 men/year. Incidence in unstaged disease increased (P < 0.01) between 1983 and 1997 in all ages by 300% from 4.5 to 18 cases per 100 000 men/year. Age-adjusted mortality increased (P < 0.05) by 13% from 26.8 in 1983 to 30.3 deaths per 100 000 men/year in 1999. No significant changes of trends in mortality rates were detected in the age groups 50-59 years. In the age group 70-79 years the trend changed (P < 0.05) direction in 1991 and in 1994; 1983 through 1991 APC = 3.52 (95% CI 1.37, 5.72), 1991 through 1994 APC = -10.27 (95% CI -26.20, 9.1) and 1994 through 1999 APC = -0.25 (95% CI -4.55, 4.24). PSA testing increased incidence but no impact on mortality in the target population can be observed so far.

Azathioprine treatment and male fertility in inflammatory bowel disease.

BACKGROUND & AIMS: Long-term treatment with azathioprine (AZA) is well established in inflammatory bowel disease (IBD). AZA is metabolized to 6-mercaptopurine (6-MP), which interacts in purine metabolism and is therefore considered to have mutagenic potentials. This is the first study to examine the influence of AZA on semen quality. METHODS: Semen quality was examined and compared with World Health Organization (WHO) standards regarding sperm density, motility, morphology, ejaculate volume, and total sperm count in 23 IBD patients treated with AZA. In 10 of these patients, a semen sample was assessed before and during AZA treatment; in another 5, semen analysis was performed twice during at least 2 years of AZA therapy. RESULTS: In 18 patients treated with 1.5-2 mg/kg AZA daily for at least 3 months but without sulfasalazine, sperm density was 94 +/- 84 Mio/mL (94% within WHO standard), motility was 60% +/- 20% (67% within WHO standard), the proportion of sperm with normal morphology was 44% +/- 21% (67% within WHO standard), ejaculate volume was 3.4 +/- 1.5 mL (89% within WHO standard), and total sperm count was 297 +/- 272 Mio (94% within WHO standard). No changes in semen parameters were noted after 11 +/- 5 months of AZA administration or during long-term treatment (49 +/- 14 months). Sulfasalazine administration in 5 patients was associated with markedly reduced semen morphology. During the study period, 6 patients fathered 7 healthy children. CONCLUSIONS: Our data show that AZA does not reduce semen quality and thereby male fertility in IBD.

Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia.

OBJECTIVE: Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia. METHODS: One hundred three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity. RESULTS: Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L. CONCLUSIONS: Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.

Estrogen increases endothelial carbon monoxide, heme oxygenase 2, and carbon monoxide-derived cGMP by a receptor-mediated system.

Carbon monoxide, a gaseous activator of soluble guanylyl cyclase formed by a subtype of the enzyme heme oxygenase designated heme oxygenase-2 in vascular endothelium, has been found to dilate blood vessels independently from nitric oxide. Because of the parallels between nitric oxide and carbon monoxide, we speculated that estrogen might affect carbon monoxide production in vascular endothelium. Endothelial cells of human origin (umbilical vein and uterine artery) were incubated for 4 or 24 h with 10(-12)-10(-6) M 17beta-estradiol. 17beta-Estradiol, at a concentration such as that attained during the ovulatory phase of the menstrual cycle (10(-10) M), administrated for 4 h led to a 2-fold increase in intracellular carbon monoxide production and heme oxygenase-2 protein levels (P < 0.05). A reporter assay, measuring the formation of cGMP as the direct product of carbon monoxide-induced activation of soluble guanylyl cyclase in endothelial cells, also revealed a 56% increase in cellular cGMP after treatment with 10(-10) M E2 17beta-estradiol (P < 0.05). By contrast, higher 17beta-estradiol concentrations had no significant respective effects due to nitric oxide synthase inhibition of carbon monoxide release. This 17beta-estradiol effect appeared to be ER dependent, as preincubation with tamoxifen (10(-6) M) blocked the stimulatory effect of 17beta-estradiol in each instance. Our preliminary data indicate a potential role for carbon monoxide as a biological messenger molecule in estrogen-mediated regulation of vascular tone.

Normalization of pregnancy outcome in pregestational diabetes through functional insulin treatment and modular out-patient education adapted for pregnancy.

AIM: To investigate whether modular out-patient group education for flexible, Functional Insulin Treatment (FIT) adapted for pregnancy can eliminate diabetes-associated neonatal complications in pregestational diabetes. RESEARCH DESIGN AND METHODS: Outcome analysis of the modular out-patient group education and FIT based on separate insulin dosages for fasting, eating or correcting hyperglycaemia in 76 consecutive pregnancies (in 20 cases first after conception) of 59 patients with pregestational diabetes (Type 1 diabetes, n = 54). CONTROLS: (a) diabetic pregnancies: historical controls; (b) non-diabetic pregnancies: retrospective case-controlled study; (c) population-based data of all Austrian newborns registered within the respective time period. RESULTS: HbA1c of 113 +/- 18% of mean value (= 100%) of non-diabetic, non-pregnant population (103 +/- 14% during the last pregnancy trimester), and self-monitored blood glucose of 5.6 +/- 0.7 mmol/l (5.3 +/- 0.7 mmol/l during the last trimester) was achieved throughout all FIT pregnancies. Severe hypoglycaemia occurred in 14 pregnancies. The gestational age at delivery was 39.2 +/- 1.5 weeks (four cases (5.4%) < 37 weeks) with a birth weight of 3305 +/- 496 g. Four newborns (5.3%) were above the 90th, and nine (11.8%) below the 10th percentile for weight of reference population-based data. Hypoglycaemia was recorded in six newborns (8%). Malformations were found in two infants whose mothers booked for diabetes FIT education only after conception. The caesarean delivery rate was 25%. In comparison with historical diabetic pregnancy controls we demonstrated a reduction in major complications, and compared with non-diabetic women, a lowering of diabetes-related neonatal complication rates to general population levels. CONCLUSIONS: Structured, comprehensive, modular out-patient group education promoting self-choice of insulin dose for flexible, normal eating prior to conception normalizes pregnancy outcome in diabetes.

In vivo effects of recombinant human interleukin-10 on lymphocyte phenotypes and leukocyte activation markers in inflammatory bowel disease.

BACKGROUND: Interleukin-10 (IL-10) exhibits potent anti-inflammatory and immunosuppressive activities in vitro. Recent data indicate that treatment with recombinant human IL-10 (rHuIL-10) Crohn's disease is safe and may induce clinical and endoscopic remission. The present study investigates the in vivo immunomodulatory properties of rHuIL-10 in inflammatory bowel disease (IBD). METHODS: As part of two randomized, double-blinded, placebo-controlled trials, repeated flow cytometric analyses of lymphocyte phenotypes (CD3, CD4, CD8, CD16 + 56, CD19) and activity markers (human leukocyte antigen [HLA]-DR; intercellular adhesion molecule-1 [ICAM-1]; IL-2-receptor alpha [IL-2R alpha]; high affinity receptor for immunoglobulin G [IgG; Fc gamma RI]) on T cells, monocytes, and neutrophils were performed in 17 patients with IBD who received rHuIL-10 (5, 10, or 20 micrograms/kg) or placebo, administered subcutaneously, once daily for 28 days. RESULTS: Minor changes were noted in CD3+, CD8+, and CD3+/CD16 + 56+ lymphocyte phenotypes, whereas absolute numbers of CD4+ lymphocytes and CD19+ cells increased. T-cell activation markers HLA-DR and IL-2R alpha were downregulated. rHuIL-10 did not influence HLA-DR expression on monocytes. ICAM-1 modulation on monocytes and neutrophils was mild and inconsistent. Fc gamma RI expression was upregulated on both neutrophils and monocytes. CONCLUSIONS: These data indicate that the immunosuppressive effects of rHuIL-10 treatment are partly different from its in vitro observed actions. The increase of the cytotoxicity-mediating Fc gamma RI points to potential immunostimulating properties of this cytokine.