Protein-free diets do not protect high-incidence diabetes-prone BioBreeding rats from diabetes

Dietary factors have been reported to affect the development of spontaneous diabetes in various colonies of inbred and outbred diabetes-prone (DP) BioBreeding (BB) rats. Several studies have attributed a protective effect to a diet omitting crude protein mixtures in favor of purified casein, hydrolyzed casein, or free amino acids. We have used inbred BB rats, all of which become diabetic in specific pathogen-free (SPF) conditions when fed ordinary rat chow, to test the capacity of 2 different protein-free diets to modulate BB rat diabetes in 2 distinct pathogen-free environments. BB rats known to all develop diabetes by 100 days of age were fed from birth with 1 of 3 diets. By 120 days of age, 100% of the animals on a standard diabetogenic chow diet, 83% of animals on an amino acid-based protein-free diet, and 100% of animals on a hydrolyzed casein-based diet had developed diabetes (P >.05). A slight delay in the age of onset was observed among rats fed the amino acid-based diet, but this delay coincided with a reduction in weight gain among these animals compared with the rats on a standard diet. Histology showed insulitis in all rats at either diabetes onset or 120 days of age. We conclude that our unique strain of specific pathogen-free BB rats are not protected from diabetes when fed an amino acid-based diet and suggest that their insensitivity to dietary manipulation may be due to an as yet unknown factor present in the diabetes-resistant (DR), but not the DP BB rat genetic background.     

The Swedish coeliac disease epidemic with a prevailing twofold higher risk in girls compared to boys may reflect gender specific risk factors

In the mid 1980s the incidence of coeliac disease in Swedish children below 2 years of age increased threefold within a few years, and after a 10-year high incidence period returned equally rapidly to the previous level. Analysing the epidemic with respect to any change in female to male ratio over time, or shift in age at diagnosis, may increase the understanding of coeliac disease aetiology. In a population-based incidence study of childhood coeliac disease, 2151 cases (811 boys/1340 girls) were diagnosed from 1973 to 1997. Incidence rates and relative risks (RRs) were calculated by gender, age at diagnosis and calendar time. Cumulative incidences by age and gender were calculated for different birth cohorts. A twofold higher risk (RR: 1.9, 95% confidence interval (CI) 1.7–2.1) for coeliac disease in girls as compared to boys prevailed throughout the epidemic. Further, during the post-epidemic period there was an upward shift in age at diagnosis. So far, however, a majority of the cases diagnosed at older ages belong to birth cohorts of the epidemic period, i.e. cohorts that already had a high coeliac disease risk before 2 years of age. Our results suggest that girls as compared to boys may be genetically more vulnerable to environmental exposures influencing the immunological processes towards coeliac disease. Further, an increased risk for coeliac disease during the first years of life due to, for example, unfavourable infant dietary habits, may result in an increased total childhood risk for coeliac disease. A longer follow-up, even into adulthood, is needed to determine whether or not the lifetime risk has changed.     

Violence against women increases the risk of infant and child mortality: a case-referent study in Nicaragua

OBJECTIVE: To investigate the impact of violence against mothers on mortality risks for their offspring before 5 years of age in Nicaragua. METHODS: From a demographic database covering a random sample of urban and rural households in Le n, Nicaragua, we identified all live births among women aged 15-49 years. Cases were defined as those who had died before the age of 5 years, between January 1993 and June 1996. For each case, two referents, matched for sex and age at death, were selected from the database. A total of 110 mothers of the cases and 203 mothers of the referents were interviewed using a standard questionnaire covering mothers' experience of physical and sexual violence. The data were analysed for the risk associated with maternal experience of violence of infant and under-5 mortality. FINDINGS: A total of 61% of mothers of cases had a lifetime experience of physical and/or sexual violence compared with 37% of mothers of referents, with a significant association being found between such experiences and mortality among their offspring. Other factors associated with higher infant and under-5 mortality were mother's education (no formal education), age (older), and parity (multiparity). CONCLUSIONS: The results suggest an association between physical and sexual violence against mothers, either before or during pregnancy, and an increased risk of under-5 mortality of their offspring. The type and severity of violence was probably more relevant to the risk than the timing, and violence may impact child health through maternal stress or care-giving behaviours rather than through direct trauma itself.     

Costs of internal fixation and arthroplasty for displaced femoral neck fractures: a randomized study of 68 patients

We included in a prospective, randomized study 68 patients aged 70 years or older, with displaced cervical hip fractures. The patients were randomized to internal fixation with hook-pins (36) or primary arthroplasty (32) (total or hemiarthroplasty due to their prefracture status) and followed for 2 years. Patients with rheumatoid arthritis, mental confusion and/or residence in an institution were excluded. The postoperative stay in hospital, rehabilitation wards or nursing homes were recorded as well as complications and the costs of surgery. The aim of this study was to compare the accumulated costs of each method, during the first 2 years after the fracture. In the internal fixation group, 15/36 were considered failures, as compared to 1/32 in the arthroplasty group. As regards primary treatment of the fracture, the durations of surgery and hospital stay were shorter after internal fixation, but the total need for hospitalization/institutionalization was somewhat longer in these patients. The mean 2-year cost for a patient with internal fixation was USD 21,000 and of one with primary arthroplasty USD 15,000. We conclude that primary arthroplasty is a cost-efficient treatment. Considering the very much higher failure rate after internal fixation--leading to increased suffering for these patients--primary arthroplasty stands out as the best method for displaced fractures of the femoral neck.     

Estrogen receptor expression in lumbosacral dorsal root ganglion cells innervating the female rat urinary bladder

We have investigated whether bladder afferent neurons are likely to be targets for circulating estrogens by mapping estrogen receptor (ER) distribution in lumbosacral dorsal root ganglia (DRG) of adult female rats. Sensory neurons innervating either the detrusor or trigone regions were identified by application of fluorescent retrograde tracer dyes to the bladder wall. Labelled neurons were classified by their immunoreactivity for either type of ER (ERalpha or ERbeta) and further compared with subpopulations of neurons containing substance P, calcitonin gene-related peptide and vanilloid receptor (a marker of polymodal nociceptors). Both ER types were expressed in numerous sensory neurons of either upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost complete coexpression of ERalpha and ERbeta. ER-positive neurons were mainly small-medium size (18-25-microm diameter), indicating that they may be nociceptors and/or supply visceral targets. Most bladder-projecting neurons expressed ERs and the majority of these also expressed neuropeptides or vanilloid receptor. Afferent neurons supplying detrusor and trigone regions had similar immunohistochemical features. About a third of the bladder-projecting neurons expressed both ER and vanilloid receptor, suggesting a mechanism by which estrogens could influence bladder pain. The prevalence of different chemical classes of ER-positive bladder-projecting neurons was reflected throughout the entire population of neurons in dorsal root ganglia of these spinal levels, suggesting that neurons supplying other pelvic visceral targets may have similar chemical profiles. These results suggest that many functional classes of sensory neurons innervating the lower urinary tract are likely to be targets for circulating estrogens, including many nociceptor neurons. The coexistence of ERalpha and ERbeta suggests a broad range of potential mechanisms by which estrogens may exert their genomic effects in this system.     

Occupant- and crash-related factors associated with the risk of whiplash injury

PURPOSE: Given that a motor vehicle crash (MVC) had occurred, to evaluate whether occupant- and crash-related factors, such as age, gender, seating position and type of MVC are associated with the risk of whiplash injury. METHODS: A study of occupants in cars covered by motor insurance at one of the largest insurance companies in Sweden, was undertaken during a one-year period. The study population comprised all occupants in cars exposed to an MVC in which at least one occupant was injured (n = 7120). Adjusted estimates of the relative risk of whiplash injury, associated with the different factors, were calculated by means of binomial regression analysis. RESULTS: Considering different MVCs, rear-end collisions were associated with the highest relative risk of whiplash injury when compared with side impacts (1.82; 95% CI 1.68-1.96), while drivers showed the strongest association with respect to seating position when compared with passengers in the rear seat (1.78; 95% CI 1.60-1.97). Females had a somewhat higher relative risk of whiplash injury than males (1.20; 95% CI 1.16-1.25). Regarding age, the relative risk was moderately increased across the different age groups when compared with the oldest age group. No interaction was observed on the additive scale. CONCLUSIONS: Given that an MVC had occurred, subjects exposed to a rear-end collision and drivers had a substantial increased risk of whiplash injury, while age and gender were of minor importance.     

K-ATP channel independent effects of pinacidil on ATP production in isolated cardiomyocyte or pancreatic beta-cell mitochondria

Evidence has been presented that mitochondria contain ATP sensitive potassium channels (mK-ATP channels), which may confer tissue protection upon activation. It is, however, not known whether activation of mK-ATP channels has a direct effect on mitochondrial ATP production. This study was performed to define the effect of pinacidil (PIN) on ATP production by oxidative phosphorylation in isolated cardiomyocyte or pancreatic beta-cell mitochondria. Cardiomyocyte mitochondria produced seven times more ATP than beta-cell mitochondria in the presence of pyruvate/malate. PIN inhibited pyruvate/malate-induced mitochondrial ATP production with half maximal effect at 360 microM in both cell types. The inclusion of 5-hydroxydecanoate (5-HD) did not prevent this inhibition. Succinate induced a similar ATP production in cardiomyocyte or beta-cell mitochondria. In beta-cell mitochondria succinate-induced ATP production was inhibited by PIN with half maximal effects at 500 microM PIN. However, in cardiomyocyte mitochondria PIN stimulated succinate-induced ATP production 3-fold with half maximal effect at 100 microM and maximal effect at 200 microM. This PIN-dependent stimulation was mimicked by rotenone. The inclusion of 5-HD could not prevent these PIN effects. In conclusion, PIN may inhibit complex 1 of the respiratory chain without indications of opening mK-ATP channels. In cardiomyocytes with metabolically inhibited succinate dehydrogenase this results in a stimulation of ATP production conferring tissue protection. In beta-cells without a metabolically inhibited succinate dehydrogenase, there is no stimulation by PIN and tissue protection by PIN is not to be expected.     

Expression profiling to predict outcome in breast cancer: the influence of sample selection

Gene expression profiling of tumors using DNA microarrays is a promising method for predicting prognosis and treatment response in cancer patients. It was recently reported that expression profiles of sporadic breast cancers could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors. Having observed an overlap in those data between the genes that predict outcome and those that predict estrogen receptor-alpha status, we examined their predictive power in an independent data set. We conclude that it may be important to define prognostic expression profiles separately for estrogen receptor-alpha-positive and estrogen receptor-alpha-negative tumors.     

Objective assessment of the degree of dementia by means of EEG

The aim of the study was to elaborate a method to estimate the degree of cognitive impairment in Alzheimer's disease from the EEG quantitative indicators. We examined 38 unmedicated patients with a diagnosis of Alzheimer's disease, with various stages (mild, moderate, and severe) of dementia. The EEG recordings were evaluated both visually and by means of computer analysis. The EEG spectra and coherences in 6 frequency bands were calculated in 16 EEG derivations. Among various EEG indicators, a decrease in the alpha coherence and an increase in the delta coherence was found to be most significantly correlated to the degree of dementia. Combining 6 variables from the spectrum and coherence analysis by means of the multiple regression model, a high correlation (r = 0.87) between a set of EEG variables and the Mini-Mental State Examination score could be obtained. The results suggest that the EEG can supplement the clinical examination by providing an independent assessment of the degree of dementia. The results also suggest that the EEG coherences are of particular interest in dementia, being an indicator of the signal transfer between various parts of the brain cortex.