ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension

The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure (SBP) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy. Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits. Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each. The study was a balanced, randomized crossover design with five periods: placebo; angiotensin converting enzyme inhibitors; beta-blocking drugs; calcium-blocking drugs; and thiazide diuretics. Blood pressure (BP) was measured 24 to 26 h after the previous dose. A questionnaire for side effects was administered at each visit. Seventy-four patients entered the study. beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods. There were 9 of 66 patients on P, 9 of 46 on beta-blockers, 4 of 65 on calcium-blocking drugs, 4 of 65 on diuretic, and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects. Decreases in SBP compared to randomized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg. Blood pressure decrease correlated with placebo BP (P < .0005, r = 0.53 to 0.70). When corrected for placebo, target SBP (<140 mm Hg) was reached in between 6% to 15% of patients on monotherapy. Sequential monotherapy achieved target in 29%. Angiotensin converting enzyme inhibitors, calcium-blocking drugs, and diuretics had no more side effects than placebo. Patients on beta-blockers had more side effects and the well-being score was reduced. Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure. beta-Blockers were relatively ineffective, were frequently contraindicated, and had more side effects. Monotherapy achieved control in only a small number of patients. In elderly people with essential hypertension, therapy should be instituted with diuretics or calcium-blocking drugs, but combination therapy will usually be required to achieve goal.     

Transformed T lymphocytes infected by a novel isolate of human T cell leukemia virus type II

Human T cell leukemia virus type II (HTLV-II) has been isolated from a patient (Mo) with features of leukemic reticuloendotheliosis (LRE) and from a patient with acquired immunodeficiency syndrome (AIDS). We have obtained another isolate of HTLV-II from a patient (CM) with severe hemophilia A, pancytopenia, and a 14-year history of staphylococcal and candidal infections but no evidence of T cell leukemia/lymphoma, AIDS, or LRE. Fresh mononuclear cells and cultured lymphocytes from CM express retroviral antigens indistinguishable by molecular criteria from HTLV-IIMo. Leukocyte cultures from CM yield hyperdiploid (48,XY, +2, +19) continuous lymphoid lines; human fetal cord blood lymphocytes (CBL) are transformed by cocultivation with these CM cell cultures but retain normal cytogenetic constitution. Electron microscopic examination of the CM cultures and transformed CBL reveals budding of extracellular viral particles, intracellular tubuloreticular structures, and viral particles contained within intracellular vesicles. CM cell cultures and the transformed CBL do not require exogenous interleukin 2, have T cell cytochemical features and mature T helper phenotypes, and exhibit minimal T helper and profound T suppressor activity on pokeweed mitogen-stimulated differentiation of normal B cells. These characteristics, which are similar to those observed with the first HTLV-II isolate, may represent properties of all HTLV-II-infected T cells.     

Tumor necrosis factor-alpha downregulates protein S secretion in human microvascular and umbilical vein endothelial cells but not in the HepG- 2 hepatoma cell line

Protein S deficiency, which is associated with thrombosis, can either be inherited or acquired. Recently, we reported that a decrease in free protein S was observed in 19 of 25 persons with HIV/AIDS. The proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), has been reported to be elevated in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients and has been shown to induce a procoagulant state on the surface of endothelial cells. We report here that recombinant TNF-alpha (rTNF-alpha) downregulated protein S synthesis in the SV-40T transfected human microvascular endothelial cell line (HMEC-1) model system by approximately 70% and in primary human umbilical vein and dermal microvascular endothelial cell cultures by approximately 50%. Using the HMEC-1 model, Northern blot analysis showed a decrease in protein S RNA at 24 hours that was corroborated by Western blot analysis and enzyme- linked immunosorbent assay (ELISA) quantification. Evidence supporting the specificity of the TNF-alpha effect included the following: (1) TNF- alpha down-regulation of protein S was completely blocked by TNF neutralizing antibody; (2) the effect was transient, and protein S was restored to near normal levels after TNF was removed from cell cultures; (3) an antibody directed to the TNF RI (55-kD receptor) was shown to mimic the action of TNF-alpha on HMEC-1 cells; and (4) other proinflammatory cytokines, interleukin (IL)-1, IL-6, and TGF-beta, had no effect on protein S secretion. However, TNF-alpha showed no regulatory control over protein S synthesis in the human hepatocellular carcinoma cell line HepG-2. We suggest that TNF-alpha downregulation of protein S may be a mechanism for localized procoagulant activity and thrombosis recently reported in some AIDS patients with associated protein S deficiency.     

Suppression of B-cell development as a result of selective expansion of donor T cells during the minor H antigen graft-versus-host reaction

A murine model of bone marrow (BM) transplantation in which donor (B10.D2) and recipient (BALB/c) mice were major histocompatibility complex (MHC) (H-2d) and Mls-1 identical, but incompatible at multiple non-MHC minor histocompatibility (H) antigens, and at Mls-2,3 was used to examine regeneration of B-cell development during the minor H antigen graft-versus-host reaction (GVHR). Mice that received T-cell- depleted allogeneic BM regained significant pre-B cells (sIg- 14.8+) in their BM. Mice undergoing GVHR after transplantation with allogeneic BM + T cells had less than 2% pre-B cells in their BM at day 7 and only 12% to 14% pre-B cells at days 21 and 28 compared with greater than 20% pre-B cells in the allogeneic controls. After partial recovery, the pre- B cells in the BM of GVH mice again decreased to less than 3% by day 42. This abnormal pattern of pre-B cell development in mice undergoing GVHR was associated with a reduced response to interleukin-7 (IL-7) in vitro. The delay in B-lineage cell reconstitution in mice with GVHR correlated with the expansion of donor V beta 3+ T cells in both the spleen and BM. BM T cells from mice with GVHR as well as isolated V beta 3+ T cells inhibited IL-7 colony-forming units from normal BM in co-culture assays. This inhibition could be reversed with anti- interferon gamma (IFN gamma) antibody. These data suggest that the delay in appearance and the reduction in proportion and number of pre-B cells observed early during the GVH reaction in this model is caused, in part, by the inhibitory actions of IFN gamma derived from donor V beta 3+ T cells on B-lineage cell development.     

Metabolic and energy balance in small- and appropriate-for-gestational-age, very low-birth-weight infants

This study compared nutrient utilization and postnatal weight gain composition in eight appropriate for gestational age (AGA: birth weight 1293 ± 107 g; gestational age 28.8 ± 1.4 weeks) and eight symmetrically growth-retarded (SGA: birth weight 1110 ± 230 g; gestational age 32.7 ± 1.9 weeks), very low-birth-weight (VLBW) infants. There was no significant difference in protein, mineral and energy intake between AGA and SGA infants. Nitrogen absorption (84 ± 3 and 83 ± 4%) and nitrogen retention (356 ± 48 and 352 ± 43 mg/kg/day) were similar in both groups. Fat absorption tended to be lower in AGA (78 ± 15%) than in SGA (87 ± 4%) infants. Calcium, phosphorus and magnesium absorptions were similar in AGA and SGA infants. Metabolizable energy utilization was similar in both groups; about 55% was expended and 45% stored in new tissues. Energy expenditure was 58 ± 4 kcal/kg/day in SGA infants and 61 ± 9 kcal/kg/day in AGA infants. Weight gain and its composition were similar in both groups. We conclude that nutrient and energy utilization are similar in AGA and symmetrically growth-retarded, VLBW infants.     

Body size and composition and the risk of gastric and oesophageal adenocarcinoma

Although evidence has been mounting that obesity may be related to the increased incidence of oesophageal and gastric cardia malignancies, these reports (mainly case-control studies) have relied on imperfect measures of obesity such as body mass index (BMI), and generally have not clearly distinguished between anatomical subsites within the oesophagus and stomach. In a prospective study of people aged 27-75 years, we directly measured fat mass and fat-free mass (using bioelectrical impedance analysis), height, weight and waist and hip circumferences. Among 41,295 people followed on average for 11.3 years, 30 cases with cancers in the gastric cardia or lower third of the oesophagus and 68 cases with noncardia gastric adenocarcinomas were ascertained via the population cancer registry. The risk of adenocarcinoma of the lower oesophagus and gastric cardia was positively associated with BMI with a hazards ratio (HR) and (95% confidence interval) for people with BMI>or=30 kg/m2 compared with those<25 kg/m2, of 3.7 (1.1-12.4), an HR per 10 cm increase in waist circumference of 1.46 (1.05-2.04), and a HR per 10 kg increase on fat-free mass of 2.06 (1.15-3.69). Noncardia gastric adenocarcinoma showed little relationship with body size. We observed an increased risk of adenocarcinoma of the lower oesophagus and gastric cardia associated with increased BMI, central adiposity and the nonfat component of weight, but found no association with noncardia gastric adenocarcinoma. An increasing prevalence of obesity may be associated with the increasing incidence of gastro-oesophageal cancer observed in many populations.     

Characteristics of diffuse muscular coactivation (DMC) in persons with fibromyalgia -- part 2

This study examined the electrical characteristics (Root Mean Square -- RMS and median frequency) of Diffuse Muscular Coactivation (DMC) associated with the tender points of fibromyalgia. DMC is defined as an increase from resting levels (tonus) in the electrical activity of any muscle during a movement which does not involve that muscle and is not part of the agonist -- antagonist unit. The results show an increase in RMS in fibromyalgia sufferers as compared to controls. Coactivation was stronger proximal to the neck and decreased in intensity as the area recorded moved distally. Median frequency changed over time but not significantly between groups. Possible neurological mechanisms are discussed.     

Body size and composition and prostate cancer risk.

Reported associations between body measurements and the risk of prostate cancer are weak and inconsistent, possibly because some measures used do not differentiate between adipose and nonadipose tissue, body components that would theoretically have different associations with prostate cancer. Some studies have addressed this problem by estimating lean body mass from subjects' age, height, and weight. In a prospective cohort study of men 27-75 years of age at recruitment in 1990-1994, body measurements were taken by trained interviewers. Nonadipose and adipose mass were calculated from bioelectric impedance analysis. Incident prostate cancers were ascertained by use of the population cancer registry. Altogether 16,336 men contributed 113,535 person-years and 477 cancers, of which 79 were "aggressive," to the analysis. We found no overall association between prostate cancer and any anthropometric measurement. Analysis stratified by cancer aggressiveness revealed modest associations between measures of adiposity and the risk of aggressive disease. On the basis of the WHO cut points and compared with men in the normal range of body mass index, the risk ratio for obese men was 2.2 (95% confidence interval, 1.2-4.1). For each 10-kg increase in fat mass, the risk ratio was 1.4 (95% confidence interval, 1.0-1.8). Energy imbalance may play a role in the development of aggressive prostate cancer.     

Whole body bone mineral content in healthy children and adolescents

Data from healthy children are needed to evaluate bone mineralisation during childhood. Whole body bone mineral content (BMC) and bone area were examined by dual energy x ray absorptiometry (Hologic 1000/W) in healthy girls (n = 201) and boys (n = 142) aged 5-19 years. Centile curves for bone area for age, BMC for age, bone area for height, and BMC for bone area were constructed using the LMS method. Bone mineral density calculated as BMC/bone area is not useful in children as it is significantly influenced by bone size. Instead, it is proposed that bone mineralisation is assessed in three steps: height for age, bone area for height, and BMC for bone area. These three steps correspond to three different causes of reduced bone mass: short bones, narrow bones, and light bones.