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Biomedical subjects

S Hunt

Publications and source records attributed to S Hunt.

At least 73 records · Page 4Linked to original sources

Familial history of stroke and stroke risk. The Family Heart Study.

BACKGROUND AND PURPOSE: Although familial history of stroke is generally perceived to be an important marker of stroke risk, very few epidemiological studies have been published to address this hypothesis. We sought to examine whether familial history of stroke is associated with the prevalence of stroke in the Family Heart Study, a National Heart, Lung, and Blood Institute-supported multicenter study of the familial, genetic, and nongenetic determinants of cardiovascular disease in populations. METHODS: The personal and familial histories of stroke were assessed in 3168 individuals (probands) who were at least 45 years old and 29,325 of their first-degree relatives with the use of a standardized questionnaire. RESULTS: The age-, ethnicity-, and sex-adjusted stroke prevalences were 4.8%, 4.9%, and 3.9% in probands with a positive familial, paternal, and maternal history of stroke, respectively, in comparison with 2.0% in probands without any positive familial history (P < .01). The age-, ethnicity-, and sex-adjusted odds ratios (95% confidence interval) of stroke were 2.00 (1.13, 3.54) for a positive paternal and 1.41 (0.80, 2.50) for a positive maternal history of stroke. Additional statistical adjustment for the proband's history of elevated cholesterol level, cigarette smoking status, history of coronary heart disease, hypertension, and diabetes did not alter the associations. A similar pattern was seen for African Americans and European Americans. CONCLUSIONS: The increased risk of stroke among persons with a positive familial history of stroke compared with those without a familial history of stroke is consistent with the expression of genetic susceptibility, a shared environment, or both in the etiology of stroke.

Black or African American↗

The concept of outcome.

The Enuresis Resource and Information Centre in the UK has recently launched a second edition of Guidelines on Minimum Standards of Practice in the Treatment of Enuresis. The purpose of the Guidelines is to provide a blueprint for service delivery in the UK, leading to enuresis services that offer effective, accessible and dependable treatment. In particular, these Guidelines propose minimum and target standards that enuresis services should aim to achieve, relating to referral, assessment and treatment, as well as catchment area appointments, research and referral. In addition, the Guidelines may be used to provide a framework within which enuresis services can be audited and evaluated. Successive cycles of observation, appraisal and action should encourage a continual improvement process in each clinic, resulting in a progressive development of the service offered.

Adult↗

Importance of decreased heart rate in predicting transplant coronary artery disease.

Studies in animals and humans have demonstrated that an increased heart rate is a predictor for the development of coronary atherosclerosis and overall cardiovascular mortality. In contrast, we have previously reported that the need for pacemaker implantation because of bradycardia in heart transplant recipients is associated with an increased prevalence of transplant coronary artery disease (TxCAD). Hence, the relevance of changes in heart rate to the development of TxCAD remains unclear. Intra-coronary ultrasound examinations (ICUS) were therefore analyzed in 130 heart transplant recipients (age 50 +/- 11 yr) studied at annual evaluations (3.7 +/- 3.0 yr after transplantation). Quantitative ultrasound measurements were obtained by calculating mean coronary artery intimal thickness (MIT) obtained by examination of the left anterior descending artery. The presence of TxCAD was defined as MIT > 0.3 mm. Resting heart rates (HR) were recorded with the patients in the supine position during routine echocardiography. Based on HR recordings, two groups were defined: group 1, HR below; or group 2, HR above the median. TxCAD was detected in 40% of the ICUS studies overall. The prevalence of TxCAD was higher in group 1 (49%) compared with group 2 (33%), p < 0.05. There was no significant difference in donor ischemic time or donor gender, recipient age, gender, body weight, CMV status, creatinine, total cholesterol, use of lipid lowering drugs or diltiazem. Donor age and use of beta-blockers were higher in group 1 compared with group 2 (29 +/- 10 vs. 25 +/- 9 yr, and 15% vs. 5%, for donor age and beta-blocker use, respectively). By multivariate regression analysis only donor age and years after transplantation were independently correlated with TxCAD. After excluding patients taking beta-blockers and diltiazem, the prevalence of CAD was still higher in group 1 (50%) vs. group 2 (34%). In conclusion, transplant coronary artery disease is more prevalent in patients with lower, rather than higher, heart rates. The reason for this is unclear, but may reflect impaired blood flow to the sinoatrial node.

Adult↗

Organ culture of human main and accessory lacrimal glands and their secretory behaviour.

The purpose of this study was to investigate the in vitro viability and secretory behaviour of human main and accessory lacrimal glands using an organ culture technique. We evaluated the influence of the second messengers cAMP and cGMP on secretion. Fragments less than 1 mm3 of main and accessory lacrimal glands as well as conjunctiva were cultured for 2-72 hr at 37 degrees C in an atmosphere consisting of 50% O2, 45% N2 and 5% CO2, using a specially devised culture medium (+/- cAMP or cGMP). The conjunctival tissue served as negative control. Supernatants were assayed for secretory-component-bound IgA, lactoferrin and lysozyme using ELISA. Cultured tissue pieces were embedded in paraffin, serially sectioned, stained and their volumes calculated using an image-analysis system. This enabled us to differentiate between secretory, connective and fatty tissue. Secreted exudate was correlated to the volume of secretory tissue. Viability of cultured organ pieces was determined by electron microscopic examination. Suitable organ culture conditions for human lacrimal glands were successfully established. Electron microscopic examinations proved that the structural characteristics of the organ and the polarity of the individual cells were well preserved up to 22 days of culture. Culture supernatants were assayed for secretory-component-bound IgA, lactoferrin, and lysozyme and showed that the amount of protein secreted increased with time. Upon addition of cAMP (1 x 10(-3) M) and cGMP (4 x 10(-3) M), secretion was elevated in both main and accessory lacrimal glands. An organ culture system for lacrimal glands was developed that maintains their structural and cellular characteristics as well as their secretory function for up to 22 days. We believe that this system mimics the in vitro state of the organ better than monolayer cultures and thus proves to be a valuable tool when examining lacrimal function in vitro. The fact that both cAMP and cGMP enhance secretion may help to shed some light on the cellular pathways human main and accessory lacrimal glands use for signal transduction.

Animals↗

Repeated administration of escalating high doses of dexfenfluramine does not produce morphological evidence for neurotoxicity in the cortex of rats.

Rats were treated for 28 days with increasing doses of dexfenfluramine (0.5, 1, 1.5, 2, 3, 4 and 5 mg/kg bid ip, each dose given for 4 days before being increased) and subsequently studied at intervals between 1 and 60 days following the cessation of treatment. Control rats received vehicle and were allowed food ad libitum or were pair fed with dexfenfluramine-treated animals. Immediately following drug treatment 5-HT immunoreactivity was increased in cortical areas compared to control animals. Subsequently, there was a persistent decrease in fine fibre density and the appearance of coarse truncated fibres. 5-HT levels in cortex were decreased 1 day following dexfenfluramine treatment but recovered to control values by 15 days. GFAP and GAP 43 immunoreactivity was unaffected by dexfenfluramine treatment compared to control animals, indicating a lack of evidence for neuronal degeneration and regeneration. Dexfenfluramine treatment decreased the density of 5-HT uptake sites in the cortex, labelled with [3H]-citalopram, but this partially recovered towards control values at 60 days. These alterations in 5-HT terminal networks conflict with the return of 5-HT levels to normal and the lack of evidence for degenerative changes or neuronal regrowth. On the basis of these results, it cannot be concluded that dexfenfluramine is neurotoxic.

Animals↗

Influence of oxygen free radicals and free radical scavengers on the growth behaviour and oxidative tissue damage of bovine retinal pigment epithelium cells in vitro.

PURPOSE: This investigation was carried out to ascertain whether oxygen free radicals can influence the growth behaviour and consecutive lipid peroxidation of retinal pigment epithelium (RPE) cells in vitro and whether scavengers can counteract these effects. METHODS: The experimental model was based on calf RPE cells. Hypoxanthine/xanthine oxidase (HX/XO) and superoxide dismutase/ catalase (SOD/CAT) served as the radical generating system and scavengers, respectively. The components were tested alone and in combination. Lipid peroxides were determined in culture supernatants by a thiobarbituric acid assay. RESULTS: Concentrations of up to 100 mumol/l of HX alone and 500/ 1000 microU of XO alone, as well as the application of the scavengers without the radical generating system (HX/XO), had no effect. Dose-related reduction of cell growth and increase of lipid peroxidation were found with HX/XO treatment (single dose of 500 and 1000 microU/ml 24 h after seeding). After application of 500 or 1000 microU/ml of XO, CAT, when given alone (1200 U/ ml), counteracted the effect of the radicals on cell growth and lipid peroxidation; SOD (300 U/ml) had no effect. A combination of SOD and CAT was no better than the effect of CAT alone. CONCLUSION: The prevention of radical-induced reduction of cell growth and lipid peroxidation by scavengers supports trials of therapy using antioxidants and/or free radical scavengers for various ocular syndromes with RPE involvement.

Animals↗

The 8.5-kb PstI allele of the stress protein gene, Hsp70-2: an independent risk factor for systemic lupus erythematosus in African Americans?

SLE is dramatically more prevalent in persons of African descent than in other populations. Several genes in the class III region of the MHC have been considered as potential susceptibility loci for this disorder, but the primary association(s) remains unknown. The stress protein gene, hsp70-2, is of special interest in this regard because it encodes a protein functionally relevant to antigen processing and presentation and has itself been identified as a putative susceptibility locus in organ-specific autoimmune diseases in Caucasians. To clarify the relationship of the hsp70-2 gene to SLE in African Americans, genomic DNA from 46 patients and 42 appropriately matched control subjects was analyzed for an RFLP of the hsp70-2 gene using the probe pH2.3 and the restriction endonuclease PstI, which identifies alleles of 8.5 and 9.0 kb. The 8.5-kb hsp70-2 allele was associated with SLE in this population (X2 = 8.2473, p = 0.0044). This association was not due to linkage disequilibrium with the C4A deletion or with HLA-DR3, as has been reported in Caucasians with IDDM. These data suggest that the 8.5-kb hsp70-2 allele may be an independent susceptibility marker for SLE in African Americans.

Alleles↗

Short contact 70% glycolic acid peels as a treatment for photodamaged skin. A pilot study.

BACKGROUND: Glycolic acid has been one of the more commonly used alpha hydroxy acids for the treatment of photodamaged skin. Its value as a quick "skin refreshing" peeling agent has been widely touted. This type of peel differs from a conventional therapeutic peel (eg, phenol, trichloroacetic acid, or a longer time exposure alpha hydroxy acid peel) in that there is little skin reaction and patients can go about their daily routine without concern. OBJECTIVE: To assess the potential value of glycolic acid-based refresher peels as a cosmetic procedure. METHODS: Twelve healthy subjects with at least a moderate degree of photodamage were treated with monthly serial 70% glycolic acid peels over a period of 4 months. In addition to the "peels," six subjects were randomized to a 10% glycolic acid-based moisturizer twice daily. Patients were evaluated monthly and graded on a clinical scale using objective measures. RESULTS: No conclusive differences were noted on histologic evaluation. Ninety percent (9/10) of patients felt that overall they noticed significant improvement, however, there was no distinction between the two treatment options. The improvement in fine wrinkling and pigmentation was primarily seen in the patients who additionally received 10% glycolic emollient twice daily. CONCLUSION: In this limited pilot study, no specific benefit could be assigned to the concomitant use of monthly glycolic acid refresher "peels" in the treatment of photodamaged skin.

Adult↗

Risk adjustment: the missing piece of market competition.

This DataWatch describes the process adopted by The Health Insurance Plan of California (The HIPC) for assessing and adjusting for health risk differences among participating health plans. We also report on the results of the 1996 risk assessment/adjustment calculations. A risk assessment value is calculated for each health plan based on the plan's enrollee mix as compared with the mix of enrollees in The HIPC as a whole. The results indicated that approximately 1 percent of total premium dollars needs to be transferred to bring all health plan scores within the acceptable level (+/- 5 percent) of risk distribution.

California↗

Prophylactic ganciclovir treatment reduces fungal as well as cytomegalovirus infections after heart transplantation.

Cytomegalovirus (CMV) infection is associated with an increased incidence of other opportunistic infections in organ transplant recipients. Whether this is related to immunomodulating effects of CMV or independent of CMV but associated with a host risk factor common to both infections is unclear. The purpose of this study was to determine whether the reduction in CMV infections seen with prophylactic ganciclovir treatment after heart transplantation is associated with a reduced incidence of other opportunistic infections. Of 149 patients prospectively enrolled in a multicenter, randomized, double-blind, placebo-controlled trial of ganciclovir to prevent CMV disease, 74 patients enrolled at this center (33 control and 41 ganciclovir-treated) were retrospectively identified. All received prophylactic OKT-3 and standard 3 drug maintenance immunosuppressive therapy. Actuarial survival and rejection rates and incidence of opportunistic infections (bacterial, fungal, and protozoal) for the 2 treatment groups were determined and compared using Cox-Mantel analysis. CMV disease occurred 2.5 times more frequently in the control group. There were no significant differences in survival or rejection rates nor in bacterial or protozoal infection incidence between the 2 groups. Bacterial infections occurred in 54% of control and 39% of ganciclovir-treated patients (P = 0.18). There were significantly fewer fungal infections in the ganciclovir-treated group (7% vs. 27%, P = 0.0071). CMV and fungal infections were both significantly reduced in patients who received ganciclovir prophylaxis. This suggests that active CMV disease may be causally associated with the development of opportunistic fungal infections.

Adult↗

Morphological and molecular response of the MOCH-1 oligodendrocyte cell line to serum and interferon-gamma: possible implications for demyelinating disorders.

The regional loss of oligodendrocytes is thought to be an important pathological event in a variety of demyelinating diseases of the central nervous system (CNS). Various components of serum, which are normally excluded from the CNS by the blood-brain barrier, have been implicated as mediators of demyelinating disorders. We have examined the effects of high concentrations of serum (10% fetal bovine serum, FBS), as well as the cytokine interferon-gamma (IFN-gamma), on an oligodendrocyte cell line, MOCH-1 cells. These cells changed from phase-bright, small round cells with multiple thin, branched processes in 1% FBS medium to flat, fibroblast-like cells with large cell bodies when cultured in 10% FBS medium or 1% FBS medium containing IFN-gamma. These morphological changes were accompanied by a large increase in expression of the astrocyte marker, glial fibrillary acidic protein (GFAP), as detected by Northern and Western blot analyses. In addition, Northern blot and fluorescence-activated cell sorting analyses revealed that IFN-gamma induced a very large increase in major histocompatibility complex (MHC) class I expression in MOCH-1 cells. MHC class II mRNA induction by IFN-gamma was also seen. In contrast, 10% FBS did not elevate either MHC class I or class II mRNA levels in MOCH-1 cells. The morphological and molecular effects of 10% FBS and IFN-gamma were reversible. We suggest that the response of MOCH-1 cells to high concentrations of serum and IFN-gamma may reflect an important in vivo response to oligodendrocytes to perturbations that occur in demyelinating disorders.

Animals↗

Characteristics of patients surviving more than ten years after cardiac transplantation.

The clinical status and quality of life of 40 patients who lived or are still alive more than 10 years after transplantation at our institution were reviewed with the use of our transplant database, prospective patient examinations, cardiac catheterization, and exercise testing. Patient-perceived health status was determined with use of the Nottingham Health Profile and General Well Being examinations. Factors associated with longevity were determined by a Cox proportional hazards model. Twenty-six patients are alive and 14 have died. The mean age at transplant was 32.4 +/- 12 years and the current age (or age at death) is 46.1 +/- 12.8 years. Actuarial freedom from rejection was similar to that of patients surviving less than 10 years (p = 0.8), but freedom from all types of infection was less (p = 0.005). Immunosuppressive drugs include cyclosporine (11/26 patients), azathioprine (24/26), and prednisone (26/26, mean dose 12.7 mg/day). Catheterization hemodynamic data show well-preserved graft function at a mean follow-up of 11.7 +/- 3.3 years. Graft coronary artery disease prevalence is 51.0% +/- 8%. Exercise test results are as follows: duration 8.7 +/- 3.5 minutes (range 2 to 16 minutes), maximum heart rate/expected rate 77.3% +/- 11% (50% to 92%), maximum systolic blood pressure 171 +/- 23 mm Hg (140 to 208 mm Hg), and metabolic equivalents 9.2 +/- 2.3 units (5.5 to 12.9 units), or about 84% of predicted. Mean score on the General Well Being examination was 75.3 +/- 21.6 (normal). Nottingham Health Profile scores were nearly normal, except for in the 50- to 64-year-old age group in categories of mobility, pain, sleep quality, and energy level. Causes of death were coronary artery disease in 7 of 14, infection in 4 of 14, lymphoma in 1 of 14, and nonlymphoid cancer in 2 of 14. In the Cox regression, variables most associated with survival (t > 2.0, multivariate p = 0.0005) were age at transplantation (t = 3.26), preoperative duration of illness (t = 3.57), postoperative cytomegalovirus infection (t = 2.16), and ejection fraction at 12 months after operation (t = -2.62). We conclude that cardiac transplantation can provide patients with end-stage cardiac failure an acceptable general medical condition, functional status, and perceived quality of life well into the second decade after operation.

Adult↗