Probiotic bacteria in the management of atopic disease: underscoring the importance of viability

OBJECTIVES: The aim of this study was to assess the efficacy of oral supplementation of viable and heat-inactivated probiotic bacteria in the management of atopic disease and to observe their effects on the composition of the gut microbiota. METHODS: The study population included 35 infants with atopic eczema and allergy to cow's milk. At a mean age of 5.5 months, they were assigned in a randomized double-blind manner to receive either extensively hydrolyzed whey formula (placebo group) or the same formula supplemented with viable (viable LGG group) or heat-inactivated Lactobacillus GG (heat-inactivated LGG group), respectively. The changes in symptoms were assessed by the SCORAD method and the presence of some predominant bacterial genera in the feces detected with 16S rRNA-specific probes. RESULTS: The treatment with heat-inactivated LGG was associated with adverse gastrointestinal symptoms and diarrhea. Consequently, the recruitment of patients was stopped after the pilot phase. Within the study population, atopic eczema and subjective symptoms were significantly alleviated in all the groups; the SCORAD scores (interquartile range) decreased from 13 (range, 4-29) to 8 (range, 0-29) units in the placebo group, from 19 (range, 4-47) to 5 (range, 0-18) units in the viable LGG group, and from 15 (range, 0-29) to 7 (range, 0-26) units in the heat-inactivated LGG group. The decrease in the SCORAD scores within the viable LGG group tended to be greater than within the placebo group. The treatments did not appear to affect the bacterial numbers within the genera enumerated. CONCLUSIONS: Supplementation of infant formulas with viable but not heat-inactivated LGG is a potential approach for the management of atopic eczema and cow's milk allergy.     

A prognostic model and staging for metastatic uveal melanoma

BACKGROUND: To identify factors that independently contribute to overall survival in Stage IVB uveal melanoma and to subcategorize by prognosis. METHODS: Data of 91 consecutive patients who died of metastatic uveal melanoma in 1985-2000 were analyzed by Kaplan-Meier and Cox regression analysis. Main covariates were participation in annual review, symptoms, Karnofsky index, metastatic burden, liver function tests, and age. Time on chemotherapy was modeled as a confounder. A working formulation for staging patients according to predicted survival was designed. RESULTS: Of the 91 patients, 85% underwent annual liver imaging and function tests, 63% were asymptomatic, and 73% received chemotherapy. The median survival period was 8.4 months (95% confidence interval [CI], 6.3-11.8). Karnofsky index, largest dimension of the largest metastasis, metastatic burden, serum transaminase, lactate dehydrogenase, and alkaline phosphatase (AP) levels, and time on chemotherapy were strongly (P < 0.001) associated with survival. Symptoms (P = 0.031) and regular review (P = 0.081) were weakly associated with survival. Karnofsky index (P = 0.013), the largest dimension of the largest metastasis (P = 0.003), and serum AP level (P = 0.042) retained independent significance, adjusting for time on chemotherapy. Predicted median survival calculated for relevant covariate combinations was divided into three periods (> or =12 months vs. 6-11 months vs. < 6 months). Observed median survival for Stage IVBa was 14.9 months (95% CI, 11.7-21.3), for Stage IVBb 8.9 months (95% CI, 2.7-13.7), and for Stage IVBc 2.0 months (95% CI, 1.0-3.7). CONCLUSION: The model and working formulation for categorization can be tested as an aid in patient counseling and as a tool in design and analysis of clinical trials.     

Versican in epithelial ovarian cancer: relation to hyaluronan, clinicopathologic factors and prognosis

Versican, a proteoglycan previously reported to increase in other malignant tumours, was studied immunohistochemically in 299 primary epithelial ovarian cancers, their 43 metastases and 6 normal ovaries to evaluate its prognostic value and relation to hyaluronan, another extracellular matrix molecule increased in cancer and a binding partner of versican. The stainings were scored according to the area percentage of strong versican signal of total peri- and intratumoural stroma as low (<15%) or high (>or=15%). Epithelial staining of the tumours was scored as positive or negative. Low and high area percentage of strong stromal versican staining were observed in 133 and 166 carcinomas, respectively. A low area percentage of strong stromal versican staining correlated with mucinous histology (p = 0.019) and early International Federation of Gynecologists and Obstetritians (FIGO) stage (p < 0.0005), whereas a high percentage was associated with reduced 5-year survival rate of the patients (44% vs. 32%; p = 0.032). Versican was associated with the cancer cells in 151 tumours and correlated with clear cell histology (p < 0.0005), early FIGO stage (p = 0.049) and increased recurrence-free survival (63% vs. 47%; p = 0.032). However, in Cox's multivariate analyses with the conventional prognostic factors included, neither stromal nor cancer cell-associated versican reached a significant prognostic value. Versican is thus enriched in the malignant stroma surrounding and promoting the growth of ovarian cancer, probably acting with hyaluronan, and associates with unfavourable prognosis but does not constitute an independent indicator of patient survival.     

Human platelets express hemochromatosis protein (HFE) and transferrin receptor 2

OBJECTIVES: While body iron status may influence platelets, little information is available about platelet expression of proteins regulating iron homeostasis. HFE, the protein defective in hereditary hemochromatosis, and transferrin receptor 2 (TfR2) are two novel protein candidates that could be involved in mechanisms of iron transport across the platelet plasma membrane. METHODS: The expression and localization of HFE, TfR1 and TfR2 proteins in human platelets were examined using Western blotting and immunocytochemistry. RESULTS: Human platelets expressed HFE and TfR2, whereas no signal for TfR1 was found. The positive reactions for HFE and TfR2 were mainly confined to the platelet plasma membrane. CONCLUSIONS: Expression of HFE and TfR2 proteins in human platelets may indicate that the mutations in the corresponding genes could influence platelet count, size and/or activation. The presence of TfR2 and absence of TfR1 suggests that HFE may serve a different function in platelets compared with the other HFE-positive cell types, e.g. enterocytes, macrophages and syncytiotrophoblasts.     

Altered cardiovascular responses to nitrosorbide in alcohol withdrawal

The cardiovascular effects and pharmacokinetics of a single dose (20 mg sublingually) of isosorbide dinitrate (ISDN) were studied in 9 alcohol-dependent men during alcohol withdrawal syndrome (AW) on day 1 and after the resolution of AW on day 10. At the onset of AW, ISDN and its metabolites caused a hypotensive effect, which was increased on day 10, while no differences in ISDN-induced decrease in stroke volume were observed. Tachycardiac response to ISDN was more pronounced at onset of AW. On day 10, the AUC(0-1.5 h), C(max) and t((1/2)) of ISDN were increased compared with day 1. The results of this study suggest that nitric oxide may modulate the cardiovascular system in AW.     

Effects of an acute D2-dopaminergic blockade on the somatosensory cortical responses in healthy humans: evidence from evoked magnetic fields

We tested the possible role of dopaminergic activity in the processing of somatosensory afferent information in healthy humans. Somatosensory evoked magnetic fields (SEFs) were recorded in seven subjects in response to left median nerve stimulation. SEFs were obtained in all subjects after oral administration of 2 mg haloperidol, an antagonist to dopaminergic D2 receptors, and placebo, which were given in a randomized, double-blind cross-over design. SEFs were analyzed using a multiple equivalent current dipole (ECD) model, with one dipole at the right primary somatosensory cortex (SI) and at both left and right secondary somatosensory cortices (SII). The earliest responses from SI, peaking at about 20 ms (N20m) and 35 ms (P35m), were not affected by haloperidol. A later deflection peaking at about 75 ms (P60m), however, was slightly reduced (p < 0.05). Responses arising from SII were not significantly changed. The results suggest that dopaminergic activity may be involved in modulating somatosensory processing after the initial stages of cortical activation.     

Novel magnetic resonance imaging contrasts for monitoring response to gene therapy in rat glioma

Magnetic resonance imaging relaxation times, T(1rho) and Carr-Purcell T(2) (CP-T(2)), were measured in a glioma herpes simplex virus-thymidine kinase gene therapy model. In treated tumors with >50% cell death by histology, T(1rho) and CP-T(2) measured with short spacing (tau(CP)) between centers of adiabatic refocusing pulses showed similar enhanced sensitivity to cytotoxic cell damage over CP-T(2) measured with long tau(CP) (long-tau(CP) T(2): 54.3 +/- 0.7 and 55.4 +/- 1.2 ms, P = 0.30; short-tau(CP) T(2): 61.3 +/- 1.0 and 64.2 +/- 1.1 ms, P < 0.05 before and day 2 of treatment, respectively). Without treatment, long-tau(CP) T(2) provided the most pronounced contrast between tumor and normal cerebral tissue. These data demonstrate that endogenous T(2) contrast can be modulated and extended in a manner likely to be clinically important.     

Anaemia in the first but not in the second or third trimester is a risk factor for low birth weight

OBJECTIVE: To assess pregnancy outcome in women with anaemia during pregnancy. METHODS: The study design involved a retrospective chart review of all women registering for prenatal care in the area of Kuopio University Hospital between 1990 and 2000. A haemoglobin concentration below 100g/l was used as a cutoff for anaemia and affected women (N=597) were stratified by the trimester at which anaemia was diagnosed. Multiple regression analysis was used to compare obstetric outcomes in the study groups and in non-anaemic women (N=22,202). RESULTS: The frequency of anaemia was 2.6%, with 0.3% occurring in the first trimester. After controlling for confounding factors, anaemia detected in the first trimester was associated with low-birth-weight infants (OR=3.14, 95% CI: 1.35-7.28) whereas the mid- and third-trimester anaemia groups showed no significantly different outcomes when compared with the non-anaemic women. First trimester anaemia was not significantly associated with small birth weight for gestational age (OR=0.98, 95% CI: 0.41-2.17) or with premature delivery <37 weeks (OR=1.80, 95% CI: 0.72-4.49). CONCLUSIONS: Maternal anaemia detected in the first trimester is associated with low birth weight.     

Widening socioeconomic mortality disparity among diabetic people in Finland

BACKGROUND: A clear social class gradient in mortality has been consistently reported among western populations. However, in the early 1980s in Finland, no major socioeconomic differences in mortality were found among people with diabetes. The present study examines whether this exceptional finding persisted in the 1990s. METHODS: All residents of Finland aged 30 to 74 in the 1980 and 1990 population censuses were classified as diabetic or non-diabetic according to entitlement to reimbursement for diabetes medication. The patient's age at onset of the disease was used as a proxy for diabetes type. All diabetic and non-diabetic persons were followed up for mortality in 1981-1985 and 1991-1996. Age-adjusted relative death rates were obtained from Poisson regression models. RESULTS: From the early 1980s to the early 1990s marked socioeconomic mortality disparities favouring the better-off emerged among diabetic people. The increase in socioeconomic mortality differences from 1981-1985 to 1991-1996 was mainly due to divergence in deaths from diabetes, which contributed 52% of the increase in mortality disparity among women and 35% among men, and from cardiovascular diseases, whose contribution was 21% for women and 25% for men. CONCLUSIONS: From the early 1980s to the 1990s in Finland a clear socioeconomic gradient in mortality emerged in every age group of diabetic people. This was largely due to a much worse development among blue-collar than white-collar workers in deaths from diabetes and cardiovascular diseases.