A scoring system to identify men at high risk of a heart attack.

A scoring system for identification of men at high risk of a heart attack within 5 years of screening is presented. The full scoring system includes an electrocardiogram and blood cholesterol measurement and the top fifth of the distribution of this full score yields 59% of the major ischaemic heart disease events occurring in the 5 years after screening. An intermediate scoring system, without an electrocardiogram but retaining blood cholesterol, yields 58% of cases from the top fifth of the score distribution. A basic (GP) score, without electrocardiogram or blood cholesterol measurement, yields 54% of cases and is recommended for use in opportunistic screening in general practice. This high risk strategy would increase public awareness of the size of the problem, help to prevent premature death and provide a useful complement to the population strategies of health education and government policy.     

Objectively measuring physical ability in elderly persons: the Physical Capacity Evaluation.

The Physical Capacity Evaluation, a performance measure of functional capabilities comprised of 13 tasks simulating those used in activities of daily living, was tested on 289 community-dwelling elderly people and compared against a widely used self-report measure of function, the Health Assessment Questionnaire. Factor analysis identified one dominant component in each instrument. Internal consistency reliability (Cronbach's alpha) was .90 for both instruments. Global disability (Health Assessment Questionnaire) and function (Physical Capacity Evaluation) scores were correlated -.74. One-week retest reliabilities on 58 subjects were .94 for the Physical Capacity Evaluation and .95 for the Health Assessment Questionnaire. The Physical Capacity Evaluation is a valid and reliable measure of physical performance for use with elderly people.     

The relationship between beta-2-microglobulin,CD4 lymphocyte count,AIDS and death in HIV-positive individuals.

The relationship, in 539 individuals infected with the human immunodeficiency virus (HIV), between two prognostic markers, the CD4 count and beta-2-microglobulin (B2M), and the development of the acquired immunodeficiency syndrome (AIDS) and death was investigated. Cox proportional hazards models were used to determine the risk of AIDS or death. In a multivariate model which adjusted for demographic factors and treatment, the most recent measurements of B2M (relative hazard (RH) 1.37 per g/l higher) and CD4 count (RH 2.17 per log-unit lower) were both significantly associated with the development of AIDS. Similarly, in a multivariate model which additionally adjusted for the development of AIDS as a time dependent covariate, there was a strong relationship with risk of death for the most recent measurements of B2M (RH 1.34 per g/l higher), and CD4 lymphocyte count (RH 1.91 per log-unit lower). A difference in the level of B2M could be used among patients with similar CD4 counts as an indicator of increased risk of progression to AIDS or death. Using the most recent values of these markers provides a better estimate of the risk of AIDS or death, compared to the more common method of analysis, where baseline values of the markers are used.     

Rewarming and cardiac surgery: a review

Patients undergoing cardiac surgery are mildly hypothermic by the completion of the surgical procedure. They need to return to a normothermic state if enzymatic functions are to proceed in their normal manner. The body can produce heat by elevating metabolic rate or by activating the shivering mechanism. Metabolic rate peaks shortly after separation of the patient from cardiopulmonary bypass, and therefore contributes to heat production. Because of the effects of neuromuscular blockage administered both during and after surgery; these patients may be unable to generate heat by shivering, and shivering is usually undesirable. This eliminates the major heat production mechanism available to the body. Therefore, heat must be transferred down its gradient by means of convection and conduction. External and internal methods accomplish these goals. External methods, which minimize additional heat loss, include the use of warming lights, elevation of room temperature, and the use of blankets. Internal methods, which transfer heat by convection, may be used to help actively reverse hypothermia. Such techniques include warmed inhalation gases and intravenous fluids, warmed nasogastric lavage fluid, and warmed peritoneal dialysis fluid for patients with end-stage renal failure with severe electrolyte disorders after surgery.     

Regulation of PTC phenotype and function by TGF-β1: implications for transdifferentiation

Introduction There is now increasing evidence that proximal tubular cells (PTCs) contribute to renal interstitial fibrosis by alteration of matrix turnover and by the generation of pro‐fibrotic cytokines such as TGF‐β1. Recent studies suggest that, through a process of transdifferentiation, the PTCs are one source of the interstitial myofibroblasts that directly drive the fibrotic process. The aim of this work was to examine the role and mechanism by which TGF‐β1 may regulate PTC phenotype and function. Methods Experiments were performed using both primary‐cultures of PTC and the human PTC cell line HK2. All experiments were performed on growth‐arrested cells in the absence of serum. Results TGF‐β1 altered cell phenotype, assessed by light microscopy, with cells appearing elongated and spindle‐shaped. This was associated with loss of cell–cell contact and rearrangement of the actin cytoskeleton, increased formation of stress fibres and focal adhesions. Disruption of the actin cytoskeleton with cytochalasin‐D prevented phenotypic alterations following addition of TGF‐β1. Transient transfection with Smad‐2/‐4 or Smad‐3/‐4 expression vectors did not alter cell phenotype. Previously, we have demonstrated β‐catenin translocation to PTC nuclei and its association with Smad proteins following addition of TGF‐β1, suggesting the possibility that TGF‐β1 may modulate Wnt signalling. Wnt‐responsive Xtwn‐reporter construct was, however, silent in response to TGF‐β1. Similarly, a second Wnt‐/LEF‐1‐regulated element Toplflash, which does not contain Smad‐binding sites, was insensitive to TGF‐β1 signalling. In contrast, phenotypic changes in response to TGF‐β1 were abrogated by inhibitors of the RhoA downstream target ROCK, which also prevented loss of cell–cell contact and adherens junction disassembly. Removal of TGF‐β1 and addition of 1% FCS, however, reverted cell phenotype to a typical cobblestone epitheliod appearance, suggesting that TGF‐β1 did not result in terminal PTC transdifferentiation. Cells grown on tissue culture dishes coated with either type‐I or type‐III collagen also acquired an elongated fibroblastic phenotype; this effect was exaggerated by the addition of TGF‐β1. In contrast to the cells stimulated with TGF‐β1 alone, following stimulation by both TGF‐β1 and exposure to interstitial collagens, cell phenotype was stable in that it was not reversed upon removal of TGF‐β1 and addition of FCS. Addition of TGF‐β1 to cells grown on type‐IV collagen had no greater effect than TGF‐β1 alone. Addition of TGF‐β1 alone had little effect on the expression of α‐SMA. In contrast, cells grown on either type‐I or type‐III collagen, following addition of TGF‐β1, demonstrated marked increased expression of α‐SMA, which appeared to be incorporated into the cell cytoskeleton. Similarly, the combination of interstitial collagen (either type‐I or type‐III) and TGF‐β1 had synergistic effect on the relocation and down‐regulation of the epithelial markers E‐cadherin and cytokeratin. Finally, the results demonstrated synergistic effects of coating with interstitial collagen (either type‐I or type‐III), on cell ‘fibroblastic’ cell function as assessed by cell migration and by the synthesis of type‐III and type‐IV collagen. Conclusion The results of these in vitro experiments suggest that terminal transdifferentiation of proximal tubular epithelial cells is the result of a combination of the effects of the pro‐fibrotic cytokine TGF‐β1 and exposure of the cells to components of the interstitial extra‐cellular matrix to which the cells are not exposed in the absence of damage to the tubular basement membrane.