Alcohol use is associated with thinner cerebral cortex and larger ventricles in schizophrenia, bipolar disorder and healthy controls.

BACKGROUND: Excessive alcohol use is associated with brain damage but less is known about brain effects from moderate alcohol use. Previous findings indicate that patients with severe mental illness, particularly schizophrenia, are vulnerable to alcohol-related brain damage. We investigated the association between levels of alcohol consumption and cortical and subcortical brain structures in schizophrenia and bipolar disorder patients and healthy controls, and investigated for group differences for this association. METHOD: 1.5 T structural magnetic resonance images were acquired of 609 alcohol-using participants (165 schizophrenia patients, 172 bipolar disorder patients, 272 healthy controls), mean (s.d.) age 34.2 (9.9) years, 52% men. Past year alcohol use was assessed with the Alcohol Use Disorder Identification Test - Consumption part (AUDIT-C). General linear models were used to investigate associations between AUDIT-C score and cortical thickness, surface area, and total brain and subcortical volumes. RESULTS: Increasing AUDIT-C score was linearly associated with thinner cortex in medial and dorsolateral frontal and parieto-occipital regions, and with larger left lateral ventricle volume. There was no significant interaction between AUDIT-C score and diagnostic group. The findings remained significant after controlling for substance use disorders, antipsychotic medication and illness severity. CONCLUSION: The results show a dose-dependent relationship between alcohol use and thinner cortex and ventricular expansion. The findings are present also at lower levels of alcohol consumption and do not differ between schizophrenia or bipolar disorder patients compared to healthy controls. Our results do not support previous findings of increased vulnerability for alcohol-related brain damage in severe mental illness.

CD4+ and CD8+ lymphocytes and HIV RNA in HIV infection: high baseline counts and in particular rapid decrease of CD8+ lymphocytes predict AIDS.

OBJECTIVE: To study the progression of HIV infection in relation to immunological and virological variables with emphasis on the role of CD8+ lymphocytes. DESIGN: Prospective follow-up from October 1991 of patients observed for at least 18 months allowing nucleoside analogue monotherapy. Peripheral CD4+ and CD8+ lymphocyte counts, HIV RNA, and soluble CD8 were analysed by statistics allowing the evaluation of serial data, avoiding time points with concurrent infections. SETTING: Tertiary university clinic. PATIENTS: Forty-nine patients were followed for 52.6 months, baseline CD4+ count of 300 x 10(6)/l, sample interval of 5.9 months (medians). MAIN OUTCOME MEASURES: AIDS, death, and CDC groups B- or C-related events. RESULTS: AIDS developed in 28% of patients. Baseline CD8+ counts above the median were significantly associated with AIDS development; the best Cox model included CD8+ cells and the log10RNA/CD4 ratio. A decline in CD8+ counts relative to baseline most significantly predicted AIDS, along with higher baseline RNA and actual CD4+ counts of less than 200 x 10(6)/l. Levels of soluble CD8 in the blood relative to total CD8+ cells significantly increased in patients developing AIDS. Death occurred in 16% of the patients, and was only predicted by high CD8+ cell counts at baseline. CDC B- and C-related events occurred in 35% of the patients and were best predicted by high baseline CD8+ counts and high RNA levels. CONCLUSIONS: The serial quantitation of CD8+ lymphocytes gave highly significant predictive information on the natural progression of HIV infection in patients with moderate to severe immune deficiency. Our data suggest that the hyperactivation of CD8+ lymphocytes is an important factor leading to a numerical decrease of CD8+ lymphocytes in progressive HIV infection.

A prospective study of the natural course of cytomegalovirus infection and disease in renal allograft recipients.

BACKGROUND: Cytomegalovirus (CMV) infection is the single most frequent infectious complication in renal transplant recipients. Because no CMV-prophylaxis is given and ganciclovir is used only as deferred therapy for CMV disease at our center, we have been able to study the natural course of CMV infections. The aim was to assess risk factors for CMV infection and disease and thus identify subgroups of patients likely to benefit from CMV prophylaxis or preemptive therapy. METHODS: Between October 1994 and July 1997, 477 consecutive renal transplant recipients (397 first transplants and 80 retransplants) were included in the study. The patients were followed prospectively for 3 months with serial measurements of CMV pp65 antigen for monitoring activity of CMV infections. RESULTS: The incidence of CMV infections in first transplants was 68% in D+R- and D+/-R+ serostatus groups, whereas the incidence of CMV disease was higher in D+R- (56%) than in D+/-R+ (20%, P<0.001). No difference in severity of CMV disease in D+R- and D+/-R+ was seen except for an increased incidence of hepatitis in primary infections. One of 14 deaths could be associated with CMV disease in a seropositive recipient. Cox regression analysis showed that rejection (RR 2.5, P<0.01) and serostatus group D+R- (RR 3.9, P<0.001) were significant risk factors for development of CMV disease. The maximum CMV pp65 antigen count had significant correlation to disease only in CMV seropositive recipients, P<0.001. Conclusion. Renal transplant recipients can safely be given deferred ganciclovir therapy for CMV disease if they are intensively monitored for CMV infection. Patients with primary CMV infection (D+R-), CMV infected patients undergoing anti-rejection therapy and R+ patients with high CMV pp65 counts seem to have a particular potential for benefit from preemptive anti-CMV-therapy.

A randomized placebo-controlled trial of an omega-3 fatty acid and vitamins E+C in schizophrenia.

Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia. We examined the clinical effect of adding an omega-3 fatty acid and/or vitamins E+C to antipsychotics. It was hypothesized that lower baseline levels of polyunsaturated fatty acids (PUFAs) would predict more benefit from the add-on treatment. The trial had a multicenter, randomized, double-blind, placebo-controlled 2 × 2 factorial design. Patients aged 18-39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway. They received active or placebo ethyl-eicosapentaenoate (EPA) 2 g day⁻¹ and active or placebo vitamin E 364 mg day⁻¹+vitamin C 1000 mg day⁻¹ (vitamins) for 16 weeks. The main outcome measures were Positive and Negative Syndrome Scale (PANSS) total and subscales scores, analyzed by linear mixed models. Ninety-nine patients were included. At baseline, erythrocyte PUFA were measured in 97 subjects. Given separately, EPA and vitamins increased drop-out rates, whereas when combined they did not differ from placebo. In low PUFA patients, EPA alone impaired the course of total PANSS (Cohen's d=0.29; P=0.03) and psychotic symptoms (d=0.40; P=0.003), especially persecutory delusions (d=0.48; P=0.0004). Vitamins alone impaired the course of psychotic symptoms (d= 0.37; P=0.005), especially persecutory delusions (d=0.47; P=0.0005). Adding vitamins to EPA neutralized the detrimental effect on psychosis (interaction d=0.31; P=0.02). In high PUFA patients, there were no significant effects of trial drugs on PANSS scales. In conclusion, given separately during an acute episode, EPA and vitamins E+C induce psychotic symptoms in patients with low levels of PUFA. Combined, these agents seem safe.

Comparing methods for estimating the variation of risks of cancer between small areas.

BACKGROUND: Analysing the geographical variation of cancer incidence is an important issue in epidemiological research. It might suggest new aetiologic hypotheses, provide guidelines for the design of new surveys and give ideas for preventive campaigns. METHODS: Four different methods for estimating the variation of cancer risks between small areas and three homogeneity tests were evaluated by simulation. In three of the methods the systematic variation of the relative risks (RR) was estimated by subtracting the expected Poisson variation from the total variation. The last method assumes that RR are gamma distributed and the maximum likelihood estimate (MLH) of the systematic variation parameter is calculated. A likelihood ratio test (LRT) of heterogeneity of RR based on this method is also evaluated, and compared with an ordinary chi2 test and the Potthoff and Whittinghill test (P&W). RESULTS: For most of the simulated data-sets, the estimates obtained by MLH are most precise, even if the assumption of gamma distribution of RR is violated. The LRT and P&W tests of homogeneity are also shown to perform better than the chi2 test. Most of the real cancer data-sets exhibited at least some geographical variation. Cancer of the lung, melanoma and other skin cancers, and cancers of the urinary bladder, pancreas and stomach, have the highest systematic variation. DISCUSSION: The study suggests that likelihood-based approaches are suitable, both for estimating the variation between small areas and for testing the null hypothesis of equal RR. Such geographical analyses might suggest new aetiological hypothesis.

Iterative random aggregation of small units using regional measures of spatial autocorrelation for cluster localization.

A method for localization of spatial disease clusters which uses a regional measure of spatial autocorrelation (RSAC) was recently developed by Munasinghe and Morris. They found this method to be an effective tool for the identification of regional disease clusters. In order to reduce the spurious variability of the estimated relative risks, the smallest geographic units were aggregated into analytic areas, consisting of a predefined minimum number of persons at risk (PAR). We found RSAC to be a valuable method and will propose some improvements. The present study illustrates that RSAC is quite sensitive both to the choice of PAR and the aggregation algorithm. Moreover, it does not utilize all the geographic details provided by the data sets, for instance the disease rates of the geographic units within the analytic areas. In order to overcome, at least to some extent, these problems, a modified version of the RSAC, called IRARSAC, is proposed. This method uses information, provided by the RSAC, from many different levels of aggregation. The performance of IRARSAC was shown to be more stable as compared to the RSAC, and it also seems to localize a greater proportion of the true clustering areas.

Spatial smoothing of cancer survival: a Bayesian approach.

A major aim of this paper is to propose and evaluate a method for describing the geographical variation in cancer survival. A fully hierarchical Bayesian approach (FB) which incorporates spatial autocorrelation of the hazard ratios is presented. The method was tried out on data sets of breast cancer and malignant melanoma patients from a population-based cancer registry. The performance of FB was compared with an ordinary Cox proportional hazard method. For both cancers both methods localized some areas of increased and some areas of decreased cancer-specific survival. The estimates provided by the Cox and the FB approach resembled each other, but the FB approach gave more geographical details. In particular, the boundaries of the clusters of high or low survival provided by the FB are more realistic.

[Survival and morbidity among children with low birth weight]. / Overlevelse og sykelighet blant barn med lav fødselsvekt.

Stillbirth and the mortality rate in low birthweight infants (less than 2,500 g) have been greatly reduced since 1967. 95% of all infants born in 1991-93 whose birthweight was between 500 and 999 g, and who survived to one year of age, would have died under the same circumstances in 1967-69. This improved survival is not, to any appreciable extent, related to an increase in demand at seven years of age for a basic grant or attendance benefit because of cerebral palsy or mental retardation. The number of basic grant and attendance benefits because of eye diseases has been reduced by about half for 7-year olds whose birthweight was low. On the whole, however, the number of basic grant and attendance benefits increased from about 1% in 1974-85 to 2.2% in 1986-94. This increase can be particularly attributed to skin and lung diseases. These results have been obtained by coordinating the record of the Medical Birth Registry of Norway and the records of the Social Security offices for all births (1,566,763) registered during the years 1967-93.