Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study.

The aim of this study was to study the influence of hormone replacement therapy (HRT) on weight changes, body composition, and bone mass in early postmenopausal women in a partly randomized comprehensive cohort study design. A total of 2016 women ages 45-58 years from 3 months to 2 years past last menstrual bleeding were included. One thousand were randomly assigned to HRT or no HRT in an open trial, whereas the others were allocated according to their preferences. All were followed for 5 years for body weight, bone mass, and body composition measurements. Body weight increased less over the 5 years in women randomized to HRT (1.94 +/- 4.86 kg) than in women randomized to no HRT (2.57 +/- 4.63, p = 0.046). A similar pattern was seen in the group receiving HRT or not by their own choice. The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat. The main determinant of the weight gain was a decline in physical fitness. Women opting for HRT had a significantly lower body weight at inclusion than the other participants, but the results in the self-selected part of the study followed the pattern found in the randomized part. The change in fat mass was the strongest predictor of bone changes in untreated women, whereas the change in lean body mass was the strongest predictor when HRT was given. Body weight increases after the menopause. The gain in weight is related to a decrease in working capacity. HRT is associated with a smaller increase in fat mass after menopause. Fat gain protects against bone loss in untreated women but not in HRT-treated women. The data suggest that women's attitudes to HRT are more positive if they have low body weight, but there is no evidence that the conclusions in this study are skewed by selection bias.     

Who benefits from endoscopic sclerotherapy of bleeding oesophageal varices? Proposal for differential indications. The Copenhagen Esophageal Varices Sclerotherapy Project.

The value of early sclerotherapy for variceal haemorrhage remains unsettled, possibly because the treatment may be beneficial to some patients and harmful to others. On the basis of a randomized clinical trial of sclerotherapy in 187 patients presenting with their first variceal haemorrhage, we examined the relationship between clinical, endoscopic and biochemical characteristics at admission and the treatment effect on mortality. As previously published, sclerotherapy had no overall effect on the very high mortality during the first 6 weeks (47%), but thereafter the mortality and risk of rebleeding were reduced. The analysis showed that in the 48% of the patients with disturbed consciousness and/or elevated plasma creatinine, sclerotherapy considerably increased short-term mortality, and this was not compensated for by increased long-term survival. Among patients without these characteristics, sclerotherapy reduced mortality in the 25% with ascites, but did not affect short-term mortality in the 27% without. Sclerotherapy significantly improved the long-term survival of these patients. The results suggest that sclerotherapy should not be used in patients with disturbed cerebral or renal function, whereas it may be beneficial in patients without these characteristics.     

Mortality in major affective disorder: relationship to subtype of depression

A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3–10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of ≥ 18 and/or a Hamilton subscale score of ≥ 9. Diagnostic classification according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years of observation.     

Concordance between symptom screening and diagnostic procedure: the Hopkins Symptom Checklist-25 and the Composite International Diagnostic Interview I

The definition of case is a core issue in psychiatric epidemiology. Psychiatric symptom screening scales have been extensively used in population studies for many decades. Structured diagnostic interviews have become available during recent years to give exact diagnoses through carefully undertaken procedures. The aim of this article was to assess how well the Hopkins Symptom Checklist-25 (HSCL-25) predicted cases by the Composite International Diagnostic Interview (CIDI), and find the optimal cut-offs on the HSCL-25 for each diagnosis and gender. Characteristics of concordant and discordant cases were explored. In a Norwegian two-stage survey mental health problems were measured by the HSCL-25 and the CIDI. Only 46% of the present CIDI diagnoses were predicted by the HSCL-25. Comorbidity between CIDI diagnoses was found more than four times as often in the concordant cases (cases agreed upon by both instruments) than in the discordant CIDI cases. Concordant cases had more depression and panic/generalized anxiety disorders. Neither the anxiety nor the depression subscales improved the prediction of anxiety or depression. The receiver operating characteristic (ROC) curves confirmed that the HSCL-25 gave best information about depression. Except for phobia it predicted best for men. Optimal HSCL-25 cut-off was 1.67 for men and 1.75 for women. Of the discordant HSCL-25 cases, one -third reported no symptoms in the CIDI, one-third reported symptoms in the CIDI anxiety module, and the rest had symptoms spread across the modules. With the exception of depression, the HSCL-25 was insufficient to select individuals for further investigation of diagnosis. The two instruments to a large extent identified different cases. Either the HSCL-25 is a very imperfect indicator of the chosen CIDI diagnoses, or the dimensions of mental illness measured by each of the instruments are different and clearly only partly overlapping. Accepted: 11 November 1997     

Sequential expression of carbohydrate antigens with precursor-product relation characterizes cellular maturation in stratified squamous epithelium

Cell surface carbohydrates are excellent markers for cellular differentiation and maturation due to great structural and antigenic diversity and to known precursor/product relations. Several blood group related carbohydrate antigens were analyzed in human labial stratified non-keratinized epithelium from 16 healthy individuals by immunohistology using monoclonal antibodies. The expression of these antigens was correlated with erythrocyte phenotype and saliva secretor status. Three distinct compartments of the epithelium were found and defined by the sequential expression of derivatives of Type 2 chain structures: lower, confined to basal cell layers (N-acetyllactosamine), middle, to parabasal cell layers (H) and upper, to spinous cell layers (Le(y)/Le(x)). Although the antigens are related to blood group antigens they are largely expressed independently of the ABO, Lewis and secretor types, and may therefore serve as "universal" markers in differentiation studies of normal and pathological epithelium.     

Do concentrations of neurotransmitters measured in lumbar cerebrospinal fluid reflect the concentrations at brain level?

Summary CSF concentrations of vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK), noradrenaline (NA) and dopamine (DA) were measured in the lateral ventricles and at the lumbar level in patients with normal pressure hydrocephalus (NPH). The concentrations of VIP (n=15), NA (n=10) and DA (n=10) were significantly higher at the lumbar level than at the ventricular level, whereas the concentrations of CCK (n=9) were similar at the two sites. A signifikant positive correlation between the concentrations measured at the two levels was found for VIP (r_s=0.65; p0.01) and DA (r_s=0.94; p0.001). The results indicate that the concentrations of transmitter substances measured in CSF at the lumbar level not necessarily are indicative for concentrations measured more centrally. The negative correlations between Evans ratio and L-CSF VIP (r_s=-0.76; p 0.001), and between resistance to outflow and V-CSF as well as L-CSF CCK (r_s=-0.75); p 0.05) might be explained by a reduction in number of cortical neurons or by disturbances in CSF dynamics in patients with NPH.     

Risk indicators for low back trouble

A general population of 928 men and women aged 30, 40, 50 and 60 years participated in a health survey with emphasis on low back trouble (LBT). In all 135 variables were analysed to identify possible indicators for first-time experience and recurrence or persistence of LBT during a one-year follow-up. Stepwise logistic regression analyses were carried out to identify the most informative combinations of indicators for prediction of LBT. For men, a high risk for recurrence or persistence of LBT was associated with frequent LBT in the past, worsening of the LBT since its onset, sciatica and living alone. For women corresponding risk indicators were: recency of the last LBT episode, waking up during night because of LBT, aggravation of LBT when standing, rumbling of "the stomach" and smoking. The strongest risk indicators for first-time experience of LBT were epigastric pain, daily smoking and low isometric endurance of the back muscles. In addition, hospitalisations for whatever cause and a long distance from home to work showed predictive power for first-time LBT among gainfully employed participants. The results indicate that persons with either recurring or first-time LBT had more health problems and probably lived under a higher psycho-social pressure than those without LBT in the follow-up year.     

Real-time PCR methods for independent quantitation of TTV and TLMV

There is considerable interest in the possible clinical effects of the human circoviruses TT virus (TTV) and TTV-like mini virus (TLMV). Most people appear to have at least one of these viruses replicating actively in their bodies, thus mere correlation of the presence of virus and disease states are probably less informative than a quantitative analysis of viraemia. Real-time PCR based methods, with either SYBR Green or TaqMan probe, designed to quantitate selectively TTV and TLMV are described. The suggested TaqMan-based protocols were suitable for quantitation of viruses in the range of 10(2)-10(9) copies/ml of sample; and proved, by sequencing of PCR products, to be specific for each of the two viruses.     

On the isolation of mast cells from human adenoids and tonsils

Human adenoids and tonsils were disintegrated mechanically and the cells dispersed by passage through a stainless-steel screen in EDTA-containing buffer. Collagenase digestion did not increase the yield of adenoidal cells. The mast cell content of the cell suspensions was in the range of 1–10 mast cells/10⁴ cells with an estimated mean of 1–2 mast cells/10⁴ cells, a value considerably below previous reports on adenoidal cell suspensions. The mast cell content was determined by staining with toluidine blue at low pH (to prevent interference by phagocytes). The mast cell count as assessed by alcian blue staining and by fluorescence microscopy after FITC-anti-human IgE binding was similar. Various attempts to enrich the cell suspension (i.e. by differential centrifugation, by gradient centrifugation on Ficoll or Ficoll-Hypaque and by velocity sedimentation at unit gravity) all gave negative results.