Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP)

BACKGROUND: The association of serum lipids with coronary heart disease has been studied extensively in middle-aged men and, to a lesser extent, in similar women. Less well defined are lipid variables predictive of CHD in individuals of age > or = 60 years. METHODS AND RESULTS: The Systolic Hypertension in the Elderly Program recruited 4736 persons (mean age, 72 years; 14% were black; and 43% were men). Mean systolic and diastolic blood pressures were 170 and 77 mm Hg, respectively. Baseline mean total cholesterol was 6.11 mmol/L (236 mg/dL); HDL cholesterol, 1.39 mmol/L (54 mg/dL); and non-HDL cholesterol, 4.72 mmol/L (182 mg/dL). Triglyceride levels were 1.62 mmol/L (144 mg/dL) for fasting participants and 1.78 mmol/L for the total group. LDL cholesterol, estimated in fasting samples with triglycerides of < 4.52 mmol/L, averaged 3.98 mmol/L (154 mg/dL). Mean follow-up was 4.5 years. In multivariate Cox regression analyses, baseline total, non-HDL, and LDL cholesterol levels and the ratios of total, non-HDL, and LDL to HDL cholesterol were significantly related to CHD incidence. HDL cholesterol and triglycerides were not significant in these analyses. In fasting participants with triglyceride levels of < 4.52 mmol/L, a 1.03 mmol/L (40 mg/dL) higher baseline total, non-HDL, or LDL cholesterol was associated with a 30% to 35% higher CHD event rate. CONCLUSIONS: The results of this study support the concept that serum lipids are CHD risk factors in older Americans.     

Does the gender of a patient or the gender of a therapist affect the treatment of patients with major depression?

The role of gender was examined in the process and outcome of therapy in the treatment of depressed outpatients seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Patients received either interpersonal therapy, cognitive-behavioral therapy, imipramine plus clinical management, or placebo plus clinical management. None of the therapist-patient by gender groupings (i.e., therapist gender, therapist-patient gender matching vs. mismatching, or patients' beliefs about whether a male or female therapist would be more helpful) were significantly related to measures of treatment process and outcome, controlling for type of treatment and severity of pretreatment depressive symptoms. Findings were duplicated when examining the effects of gender within only the psychotherapeutic modes of treatment for the groupings of therapist gender and therapist-patient gender matching versus mismatching.     

Replication of O6-methylguanine-containing DNA by repair and replicative DNA polymerases

The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion.     

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.     

Time-dependent differential changes of immune function in rats exposed to chronic intermittent noise

Noise is a highly relevant environmental and clinical stressor. Compared to most other experimental stressors, noise is a modest activator of neuroendocrine pathways that mimic the situation in human health where neuroendocrine activation by environmental stressors is often absent or difficult to establish. Little is known about the effects of noise exposure on the immune system. In the present work, the effects of a low-intensity chronic intermittent unpredictable noise regimen on various parameters of immune function was studied. Male wistar rats were exposed to a randomized noise protocol (white noise, 85 dB, 2-20 kHz) for 10 h per day, 15 min per h over a total period of 3 weeks. Control animals were exposed to ambient sound only. Immune function was monitored after 24 h, 7 days, and 21 days of noise exposure. Noise induced several significant changes in immune function in a time-dependent differential pattern involving both immunosuppression and immunoenhancement. After 24 h, serum IgM levels were increased and peripheral phagocytic activity was decreased. Splenic lymphocytic proliferation to mitogens was significantly decreased after 7 days, but slightly elevated after 3 weeks. The activity of splenic NK cells was increased significantly after 24 h and 7 days, but suppressed after 3 weeks. These results show that various parameters of immune function are affected differentially over time in a period of chronic mild noise stress, possibly due to sequential activation of different physiological mechanisms.     

Effect of polyethylene on osteocalcin, alkaline phosphatase and procollagen secretion by human osteoblastic cells

BACKGROUND AND STUDY AIMS: Anastomotic leakage is a severe complication in gastric surgery and it is associated with a high rate of mortality. Conservative treatment sometimes is not sufficient to stem the leakages and, even when it is sufficient, it takes a long time. The present study describes the first experience in the treatment of anastomotic leakages with endoscopic clipping. PATIENTS AND METHODS: From May 1995 to December 1996, seven patients with postoperative anastomotic leakages after gastric surgery were prospectively treated in our Endoscopy Service. Metallic endoclips (MD 850, Olympus Corp., Tokyo, Japan) with prongs 12 mm long and 6 mm wide were applied, controlling the closure of the leakage by endoscopy, using radiographs to confirm the closure 24 hours later. RESULTS: Complete closure of the leakage was obtained in all seven cases. A single session of endoscopic clipping was needed for five patients while two other required, respectively, two and three sessions. The median time of leakage closure after endoscopic clipping was 2.3 days (range 1-5 days). The clips spontaneously dislodged within 1 month in five patients and within the second month in the other two patients. CONCLUSION: Endoscopic treatment of anastomotic leakages by metallic clips represents a safe and easily repeated method and, compared to conservative treatment, it seems to offer several time and cost advantages. Further studies involving a larger number of patients are needed to verify this finding.     

Time-dependent optical spectroscopy and imaging for biomedicalapplications

The application of optical spectroscopy and imaging in living tissue is complicated by multiple scattering of light. In spectroscopy, this scattering causes uncertainty in the pathlength traveled by photons in the tissue, while images suffer reduced resolution and contrast. Picosecond light sources and fast detectors have made it possible to address these problems by direct measurement of the photon time-of-flight. Diffusion models of light propagation can be used to relate the measured distribution of photon transit times to the scattering and absorption coefficients of the tissue. The advantages of absolute absorption measurement are demonstrated for two problems: determination of hemoglobin oxygenation in tissue and in vivo measurement of the uptake of an exogenous chromosphere such as photosensitizer. Optical imaging may also be improved by the elimination of multiply scattered photons or by selective detection of photons arriving from a given region of the tissue. The potential advantages of these techniques are discussed and illustrated with experimental data     

SPECT, CT, and MRI in head injury: acute abnormalities followed up at six months

We report a case of cervicofacial necrotizing fasciitis that developed after blepharoplasty, an occurrence that, to our knowledge, has not previously been reported in the medical literature. A patient who presented to our institution 3 days after undergoing blepharoplasty of the upper eyelid was diagnosed as having fulminant fasciitis involving extensive areas of the face, scalp, and neck. We review the case in detail and discuss clinical and radiological clues to diagnosis, surgical and medical management, wound care, and subsequent scar contracture. This case emphasizes the need for individualized, appropriate postoperative care and for an awareness of this rare, potentially fatal complication. Early recognition and aggressive treatment of cervicofacial fasciitis can arrest its rapid progression and prevent devastating sequelae.