Comparison of Health and Safety Executive and Cumbrian birth cohort studies of risk of leukaemia/non-Hodgkin's lymphoma in relation to paternal preconceptional irradiation.

In 1993, a case-control study by the Health and Safety Executive (HSE) assessed the risk of leukaemia and non-Hodgkin's lymphoma (LNHL) among children of fathers employed at the Sellafield nuclear installation in relation to paternal preconceptional irradiation (PPI). It concluded that the statistical association between risk of LNHL and PPI was confined to children born in the village of Seascale, where the dose-response was extremely high and very significant. In contrast, in 2002, a Cumbrian birth cohort study, investigating largely the same cases, concluded that this statistical association was not significantly different among children born inside and outside Seascale and estimated the dose-response inside Seascale to be much lower. This review makes a detailed comparison of the two studies, considering their design, data and analyses. The differences between their findings are due to: (i) differences in the distribution of offspring-years which are differential with respect to dose category and Seascale birth status, (ii) a non-Seascale high-dose case included in the Cumbrian but not the HSE study, (iii) differences between analyses using categorical and continuous PPI dose and (iv) the presence of Seascale controls with PPI over 200 mSv in the Cumbrian but not the HSE study.     

Mother's education and perinatal problems in Finland.

This study using nationwide data expands a previous study from one area in Finland. The purpose was to study how perinatal problems (mortality, short gestation, low birthweight and low Apgar scores) vary by mother's social class, which is measured by level of education. Outcomes of all births in the 1987 Medical Birth Register were linked to the 1988 National Education Register with gives the estimated number of years of completed education. In unadjusted analyses, the lowest educational groups (less than 9 years) had the worst results for outcomes other than neonatal mortality. Results in the two highest educational groups (greater than or equal to 13 and 12 years of education) were similar and if anything, better in the second highest group. Excluding twins and adjusting for confounding variables (age, parity, county, urbanization of residence) by logistic regression analysis did not alter the results much. Adjustment for possible mechanisms correlated with social class (marital status, smoking, time of first antenatal visit) decreased the higher occurrence of low birthweight infants in the low educational groups. Reported previous miscarriages were more common in the higher educational groups. Based on the available background characteristics one would expect to have found the usual social gradient in perinatal problems to have persisted between the two highest educational groups. Further studies on factors causing the plateau in the gradient between these groups might be useful.     

Search for retrovirus in the chronic fatigue syndrome.

AIM: To examine peripheral blood and skeletal muscle from patients with chronic fatigue syndrome for exogenous retrovirus. METHODS: Blood samples from 30 patients and muscle biopsy specimens of 15 patients were examined for retroviral sequences by DNA extraction, polymerase chain reaction (PCR), and Southern blotting hybridisation. Sera were examined for human foamy virus by western immunoblotting and indirect immunofluorescence techniques. RESULTS: No differences between the patient and control populations was found for any of the PCR primer sets used (gag, pol, env, and tax regions of HTLV I/II). An endogenous gag band was observed in both the patient and control groups. All sera were negative for antibody to human foamy virus. CONCLUSION: The results indicate that there is no evidence of retroviral involvement in the chronic fatigue syndrome.     

Factors affecting renal allograft function in long-term recipients.

The natural history of renal allograft function in long-term recipients is not known. To characterize renal allograft function and the factors that affect it, we reviewed the records of all patients who received a renal allograft at the University of Wisconsin between 1965 and 1981 and selected those who had annual data on renal function for at least 10 years. We identified 155 patients--78 with living-related donors and 77 with cadaveric donors. All patients were adults receiving azathioprine and prednisone. Renal function was estimated by calculated creatinine clearances (Ccr), which correlated well with measured 24-hour creatinine clearances. The creatinine clearance data for each patient were plotted versus time. In 73% of patients, the creatinine clearance increased for several years before reaching a peak value. After the peak, the creatinine clearance declined in a linear manner. Stepwise regression analyses indicated that allografts from cadaveric donors had a greater increase in creatinine clearance from the value at year 1 to the peak than allografts from living-related donors (0.35 +/- 0.25 v 0.21 +/- 0.23 mL/s [21.4 +/- 15.0 v 12.7 +/- 13.8 mL/min]; P less than 0.001). The average time to reach the peak value of creatinine clearance was longer in cadaveric allografts (6.8 +/- 3.5 v 4.6 +/- 4.0 years; P less than 0.001). Postpeak, the rate of decline in creatinine clearance was faster in cadaveric allografts than in living-related ones (0.06 +/- 0.05 v 0.04 +/- 0.04 mL/s/yr [3.50 +/- 2.99 v 2.55 +/- 2.16 mL/min/yr]; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Review article: the dietary management of Crohn's disease

Enteral feeding has been shown to be as effective as primary therapy for Crohn's disease, but it requires high patient motivation, may be unpalatable and is expensive. However, in adolescents with growth failure and when corticosteroid therapy is contra-indicated or has failed, it may become the treatment of choice. Furthermore, dietary therapy allows circumvention of the adverse side-effects of repeated courses of steroids.
A number of different hypotheses have been proposed to explain the effect of enteral feeds but none has reached universal acceptance. Prospective trials suggest that the exclusion of whole protein is not necessary. Comparison of feeds with differing composition suggests that a low fat content increases efficacy and various explanations have been offered. The reduction of colonic bacterial load may also be important.
Because symptoms of Crohn's disease may be provoked by eating, there is a risk of falsely attributing symptoms to specific foodstuffs. However, in many individuals foods can be identified which affect disease activity, and their exclusion leads to prolongation of disease remission. Dietetic supervision during food testing is important to avoid detrimental effects on nutrient and micronutrient intake.     

Blood system responses in inflammation and mechanisms of their development]

A model of acute infectious peritonitis in mice demonstrated that the inflammation is attended by marked biphasic activation of bone-marrow granulomonocytopoiesis and that the activation is due in many respects to increased functional activity of elements forming the hemopoiesis-inducing microenvironment. This was suggested by increased colony-stimulating activity of the marrow mononuclear cells and the content of hemopoietic islets in the marrow. The colony-stimulating activity of peripheral blood also increased. It was established that inflammation is also characterized by activation of bone-marrow erythropoiesis, which is linked with increased erythropoietic activity of the hemopoiesis-inducing microenvironment and blood. There was a relation between the hemopoietic changes and the kinetics of leukocytes in the focus of inflammation.     

Interleukin-2 and granulocyte-macrophage colony-stimulating factor stimulate growth of a virulent strain of Escherichia coli.

The effect of human recombinant interleukin-2 (IL-2) and human recombinant granulocyte-macrophage colony-stimulating factor on the growth of a virulent strain of Escherichia coli in tissue culture medium and in untreated, normal mouse serum was investigated. Both of these cytokines enhanced the growth of the microorganism two- to threefold in tissue culture medium with or without additional fetal calf serum and in untreated mouse serum. IL-4 did not have any effect on the growth of this microbe under the conditions tested. That the enhancement of growth seen with recombinant IL-2 was due to the active cytokine was shown by the following data: (i) addition of an antibody to IL-2 abrogated the growth-promoting effect; (ii) the excipient buffer, which contained everything except the active cytokine, was inactive in modifying bacterial growth; and (iii) heat-inactivated recombinant IL-2 did not promote enhanced microbial growth. The enhancement of growth with IL-2 was significant with concentrations as low as 1 U/ml. Growth of an avirulent strain of E. coli was not stimulated by IL-2. Moreover, addition of IL-2 to growth virulent E. coli in tissue culture medium led to rapid removal of the cytokine from the medium. Collectively, these data suggest that cytokines may act as growth factors for some virulent bacteria.     

A method to differentiate between anti-C1q antibodies and C1q-binding immune complexes using collagenase-digested solid phase C1q.

A method for the detection of circulating immune complexes in the presence of autoantibodies to C1q is described. Solid phase C1q-digestion with bacterial collagenase results in the elimination of the collagen-like region of C1q. Binding of model immune complexes to this modified solid phase C1q is practically unaltered, while reactivity of anti-C1q antibodies is abolished by this procedure. In conjunction with an ELISA using the collagen-like region of C1q as antigen this modified C1q solid phase assay may be used to determine immune complexes and anti-C1q antibodies in the sera of patients with autoimmune rheumatic diseases.     

Effect of the aromatase inhibitor 4-hydroxyandrostene-3,17-dione progesterone synthesis by human luteal cells

The authors studied the effects of 4-hydroxyandrostene-3,17-dione (4-OHA) on progesterone (P), 17 beta-estradiol (E2), and 20 alpha-hydroxy-4-pregnen-3-one synthesis and pregnenolone accumulation in cultured human midluteal cells. A dose-dependent inhibition with and without human chorionic gonadotropin (hCG) of E2 and P production was observed. The accumulation of pregnenolone was significantly enhanced three to fourfold by 4-OHA in this culture system, as compared with control value. In addition, a sevenfold increase on pregnenolone accumulation was observed in the presence of 4-OHA plus 10 IU of hCG as compared with control values and 2.2-fold as compared with the 4-OHA treatments. These in vitro findings indicate a direct effect of 4-OHA on luteal steroidogenesis. Nevertheless, the suppressive effect of 4-OHA on P and E2 production is located at different sites of the steroidogenic pathway. In addition, the results demonstrate that hCG in the presence of 4-OHA stimulated pregnenolone accumulation, suggesting that the inhibition of P synthesis is in some steps after the formation of pregnenolone. These data indicate that the actions of 4-OHA on P or E2 formation have different inhibitory mechanisms.