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Biomedical subjects

F E Smith

Publications and source records attributed to F E Smith.

At least 19 recordsLinked to original sources

Characteristics of HIV infected patients cared for at "academic model for the prevention and treatment of HIV/AIDS" clinics in western Kenya.

BACKGROUND: With the new initiatives to treat large numbers of HIV infected individuals in sub-Saharan Africa, policy makers require accurate estimates of the numbers and characteristics of patients likely to seek treatment in these countries. OBJECTIVE: To describe characteristics of adults receiving care in two Kenyan public HIV clinics. DESIGN: Cross-sectional cohort analysis of data extracted from an electronic medical records system. SETTING: Academic Model for the Prevention and Treatment of HIV/AIDS (AMPATH) HIV clinics in Kenya's second national referral (urban) hospital and a nearby rural health center. SUBJECTS: Adult patients presenting for care at HIV clinics. MAIN OUTCOME MEASURES: Gender and inter-clinic stratified comparisons of demographic, clinical, and treatment data. RESULTS: In the first nineteen months, 790 adults visited the urban clinic and 294 the rural clinic. Mean age was 36 +/- 9 (SD) years. Two-thirds were women; a quarter had spouses who had died of acquired immune deficiency syndrome (AIDS). HIV/AIDS behavioural risk factors (multiple sexual partners, rare condom use) and constitutional symptoms (fatigue, weight loss, cough, fever, chills) were common. Rural patients had more symptoms and less prior and current tuberculosis. Men more commonly presented with symptoms than women. The cohort CD4 count was low (223 +/- 197 mm3), with men having significantly lower CD4 count than women (185 +/- 175 vs. 242 +/- 205 p = 0.0007). Eighteen percent had an infiltrate on chest radiograph. Five percent (most often men) had received prior antiretroviral drug therapy, (7% in urban and 1% in rural patients, p = 0.0006). Overall, 393 (36%) received antiretroviral drugs, 89% the combination of lamivudine, stavudine, and nevirapine. Half received prophylaxis for tuberculosis and Pneumocystis jirovecii. Men were sicker and more often received antiretroviral drugs. CONCLUSIONS: Patients presenting to two Kenyan HIV clinics were predominantly female, ill and naive to retroviral therapy with substantial differences by clinic site and gender. Behavioural risk factors for HIV/AIDS were common. A thorough understanding of clinical and behavioural characteristics can help target prevention and treatment strategies.

Acquired Immunodeficiency Syndrome↗

Open-label randomized trial of torsemide compared with furosemide therapy for patients with heart failure.

PURPOSE: Because the bioavailability of oral furosemide is erratic and often incomplete, we tested the hypothesis that patients with heart failure who were treated with torsemide, a predictably absorbed diuretic, would have more favorable clinical outcomes than would those treated with furosemide. PATIENTS AND METHODS: We conducted an open-label trial of 234 patients with chronic heart failure (mean [+/- SD] age, 64 +/- 11 years) from an urban public health care system. Patients received oral torsemide (n = 113) or furosemide (n = 121) for 1 year. The primary endpoint was readmission to the hospital for heart failure. Secondary endpoints included readmission for all cardiovascular causes and for all causes, numbers of hospital days, and health-related quality of life. RESULTS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to need readmission for heart failure (39 [32%] vs. 19 [17%], P <0.01) or for all cardiovascular causes (71 [59%] vs. 50 [44%], P = 0.03). There was no difference in the rate of admissions for all causes (92 [76%] vs. 80 [71%], P = 0.36). Patients treated with torsemide had significantly fewer hospital days for heart failure (106 vs. 296 days, P = 0.02). Improvements in dyspnea and fatigue scores from baseline were greater among patients treated with torsemide, but the differences were statistically significant only for fatigue scores at months 2, 8, and 12. CONCLUSIONS: Compared with furosemide-treated patients, torsemide-treated patients were less likely to be readmitted for heart failure and for all cardiovascular causes, and were less fatigued. If our results are confirmed by blinded trials, torsemide may be the preferred loop diuretic for patients with chronic heart failure.

Aged↗

Malignant chondroblastoma presenting as a recurrent pelvic tumor with DNA aneuploidy and p53 mutation as supportive evidence of malignancy.

We report a rare case of malignant chondroblastoma, which presented in a 47-year-old man as a recurrent tumor, 18 years following wide excision of a typical pelvic chondroblastoma. Radiologic studies of the recurrent tumor showed a large, lytic, destructive lesion of the right pelvic bones and femur, with a pathologic fracture of the latter, a large pelvic soft tissue mass, and multiple pulmonary metastases. Biopsy tissue showed typical features of chondroblastoma, but also increased nuclear atypia, hyperchromasia, and pleomorphism, compared to the original tumor, and, most significantly, abnormal mitotic figures. Immunohistochemical studies of the recurrent tumor revealed p53 mutation and extensive proliferative activity, and flow cytometric studies showed DNA aneuploidy, none of which was present in the original tumor. The patient received chemotherapy and radiation, but died of disease eight months after presentation. We also review chondroblastoma in general, to assign this unusual lesion to a tumor subtype.

Aneuploidy↗

Laboratory evaluation of tissue heart valves. A comparative assessment.

Tissue of commercially prepared tissue heart valves were evaluated and compared with aluminium treated, fixed porcine valve tissue in vitro (tensile strength, scanning and transmission electron microscopy) and in vivo (calcification potential after subcutaneous implantation in the rat model). Valve leaflets (n = 40) were divided into four groups according to the method of treatment: Group I (fixed in 0.652% glutaraldehyde, control), Group II (fixed and treated with aluminium), Group III (fixed and treated with Toluidine blue) and Group IV (fixed and treated with watersoluble alkyl sulphate). Tensile strength was not influenced in Group II and III (p > 0.05). Group IV indicated a significant (p < 0.05) reduction in tensile strength. Scanning electron microscopy revealed damage and loss of surface endothelium in Group III and IV respectively. Transmission electron microscopy indicated damage to underlying matricial cells in Group III and IV. Calcification potential was significantly (p < 0.001) reduced in Group II to IV. We conclude that damage ultrastructure could contribute to the reduced tensile strength in Group IV and that reduced tensile strength might have an influence on the long-term durability of tissue heart valves. Antimineralization treatment of tissue heart valves does retard calcification but is yet unable to inhibit the process completely.

Animals↗

Apoptosis contributes to the involution of beta cell mass in the post partum rat pancreas.

A significant reduction of beta cell mass has been described during the post partum period in the endocrine rat pancreas. We examined the mechanisms of this involution in Sprague Dawley rats by analyzing beta cell mass, beta cell replication, and beta cell size at end of pregnancy and 4 and 10 days after delivery. beta cell replication was significantly decreased at 4 days post partum but had returned back to nonpregnant levels by 10 days post partum. Similarly, beta cell size was significantly decreased at 4 and 10 days post partum as compared with the end of pregnancy, and at 10 days post partum was significantly decreased as compared with controls. At 4-6 days post partum, DNA fragmentation characteristic of apoptosis (programmed cell death) was detected in pancreatic islets, as assessed by in situ terminal deoxynucleotidyl transferase and nick translation assay. Only occasional cells were labeled with this assay in nonpregnant rats and at other time points after delivery. Condensed chromatin and apoptotic bodies, the morphological characteristics of apoptosis, were detected in beta cells of pancreatic islet at 3 and 4 days after delivery by electron microscopic analysis, confirming the occurrence of apoptosis in involuting islets. The expression of TRPM 2 and TGF beta 1, often enhanced in models of apoptosis, were studied during the post partum period by Northern blot analysis and immunohistochemistry. Levels of TRPM 2 gene and its protein, clusterin, were not different from controls; however, the TGF beta 1 gene and its protein expression were enhanced at 3 days post partum. Our study confirms the capability of beta cells to down-regulate their mass using the mechanisms of changes in rates of beta cell replication and of beta cell death, and changes in beta cell size to achieve homeostasis of the functional endocrine tissue.

Animals↗

The Frank Stinchfield Award. Pulmonary fat embolism in revision hip arthroplasty.

Unilateral cemented hip hemiarthroplasty was done on 16 dogs who subsequently had revision arthroplasty and who were divided into 1 control and 3 experimental groups: The first group had cement extraction using osteotomes; the second, using a high speed burr; the third, an ultrasonic tool. Hemodynamic and transesophageal echocardiographic monitoring were done. Postmortem pulmonary specimens were examined for differences in the quantity of fat emboli. There was a significant increase in emboli with the ultrasonic tool as compared with osteotomes and high speed burr. There was no significant difference in emboli between the osteotomes and high speed burr. Fat emboli syndrome is related to mechanical compression of the femoral canal. The ultrasonic instrument was unique in its tendency to cause large embolic showers, especially during extraction of the distal cement plug. In these young dogs, minimal hemodynamic changes and no cardiac dysrhythmias occurred, which in part may be attributed to their good health. These changes may remain subclinical for patients with good cardiorespiratory reserve, or may become life threatening for those with poor reserve. By outlining the mechanisms of fat embolism in revision total hip arthroplasty, it may be possible to decrease future morbidity, especially in patients who frequently have cardiopulmonary disease.

Animals↗

Pancreatic Reg/pancreatic stone protein (PSP) gene expression does not correlate with beta-cell growth and regeneration in rats.

The Reg/pancreatic stone protein (PSP) gene is postulated to be an important regulator of pancreatic beta-cell growth. To investigate this hypothesis, we analysed the expression of the Reg/PSP gene following a 90% pancreatectomy and after chronic glucose infusion, two well-defined models of pancreatic beta-cell growth. There was a rapid induction of the Reg/PSP gene in the remnant pancreas after a 90% pancreatectomy in rats during the period of marked growth of the exocrine and islet tissue. However, a similar rapid, but smaller, induction of the Reg/PSP gene was observed in sham-operated rats and in non-surgical control rats in which there was no enhanced pancreatic growth. Furthermore, there was no pancreatic Reg/PSP gene induction in a model of selective beta-cell growth, the chronic glucose-infused rat. Thus, it is unlikely that Reg/PSP is a beta-cell specific growth factor, even though the function of this important pancreatic gene is still unknown.

Animals↗

Subtypes of psychosocial adjustment to breast cancer.

By means of cluster analytic techniques, four subtypes of psychosocial adjustment were identified in a sample of 122 breast cancer patients who completed the Psychosocial Adjustment to Illness Scale. Internal consistency and internal validity of the derived typology were suggested by the finding that two different hierarchical agglomerative clustering methods (average linkage between groups, Ward's) produced similar solutions. Three of the derived subtypes reported normal affect levels but different patterns of relative strengths and dysfunctions, while the fourth subtype appeared to be highly distressed and globally maladjusted. External validation was demonstrated by differentiating the subtypes on variables of negative affect, avoidance coping, and fighting spirit. The clinical and heuristic implications of these findings are discussed. The findings highlight the need for comprehensive assessment of psychosocial functioning of cancer patients. They demonstrate that even non-emotionally distressed patients can have very different profiles of adjustment and may benefit from correspondingly individually tailored psychosocial interventions.

Adaptation, Psychological↗

Effects of feeding high-concentrate diets at restricted intakes on digestibility and nitrogen metabolism in growing lambs.

In Trial 1, 12 wether lambs (34.2 +/- .8 kg BW) were used to determine the effects of restricting intake of diets increasing in percentage of concentrate, to achieve isoenergetic intakes, on digestibility and N metabolism. The trial consisted of two 14-d periods, 9 d for adaptation and 5 d for total collection of urine and feces. Treatments were 22, 39, 61, and 92% concentrate diets fed at ad libitum intake and 90, 80, and 70% of ad libitum intake, respectively. Diets were formulated to provide equal daily intakes of ME. Feeding diets increasing in proportion of concentrate at restricted intakes resulted in linear increases (P < .001) in DM, OM, ADF, and NDF digestibilities. Starch digestibility was not affected (P > .10) by intake. Apparent N digestion was improved (P < .001) with restricted feeding of diets containing greater proportions of concentrate. Nitrogen retention was increased (P < .005) for lambs receiving diets containing a greater proportion of concentrate at reduced intakes. In Trial 2, 12 wether lambs (30.6 +/- .6 kg BW) were used to determine the effects of feeding high-concentrate (92%) diets at reduced intakes on digestibility and N metabolism. Diets were fed at ad libitum intake and 90, 80, and 70% of ad libitum intake. The trial consisted of two 14-d periods, similar to Trial 1. Restricting the intake of high-concentrate diets improved (P < .001) digestibility of DM, OM, ADF, starch, and CP. Digestibility of DM, ADF, CP, and starch increased .142, .423, .497, and .046 percentage units, respectively, for each 1% reduction in DM intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Effects of energy density and protein source on diet digestibility and performance of calves after arrival at the feedlot.

Sixty Angus crossbred steers (initial BW, 237 kg) were used in a 2 x 2 factorial experiment to determine the effects of energy density and protein source in receiving diets on steers performance and total tract nutrient digestion. The factors compared were energy density (1.80 vs 1.48 Mcal/kg of NEm, referred to as high-energy and low-energy, respectively) and protein source (ring-dried blood meal [BM] vs soybean meal [SBM]). Diets containing BM resulted in a 10.6% greater (P < .09) ADG and a 7.6% improvement (P < .05) in efficiency of feed utilization compared with those containing SBM. High-energy diets resulted in an 8.7% improvement (P < .05) in feed efficiency vs low-energy diets. Dry matter digestibility (DMD), NDF digestibility (NDFD), and CP digestibility (CPD) were exceptionally high during wk 1, when DMI was approximately 1.5 kg/d. Nutrient digestibility declined during wk 2 and 3, as intake increased, before stabilizing between wk 4 and 6. Additionally, NDFD was not consistently lower (P > .10) during this study for high-energy diets than for low-energy diets. The results of the overall performance data indicate that, compared to SBM, feeding BM may improve ADG and feed efficiency during the receiving period when dietary CP is approximately 13%. Additionally, DMD, NDFD, and CPD were higher on d 7 than at any other time, indicating that by d 7 ruminal function was not adversely affected. Therefore, it seems that the reduced feed intake and growth rate normally seen during the first 2 wk in the feedlot is not caused by a reduction in diet digestibility.

Animal Feed↗

Characterization of type I IGF receptor and IGF-I mRNA expression in cultured human and bovine glomerular cells.

Glomerular hypertrophy is reported in several endocrine disorders such as acromegaly and diabetes mellitus, where abnormalities of growth hormone and insulin-like growth factor (IGF-I) have been reported. In the present report, we have cultured bovine and human glomerular endothelial cells, and bovine glomerular epithelial and mesangial cells, and characterized the expression of IGF-I mRNA and its receptor in these cells. High affinity, specific receptors for IGF-I were identified in all three types of cells by radioreceptor assays. Receptor number (Ro) derived by Scatchard analysis revealed an unusually high number of Type I IGF receptors, approx. 1.2 x 10(5) receptors/cell in glomerular endothelial cells. Affinity crosslinking studies and immunoprecipitation with antibodies against the Type I IGF receptor identified the alpha-subunit of the IGF-I receptor as having a molecular mass of 140 kDa. Biologically, IGF-I was more potent than insulin or IGF-II in stimulating DNA synthesis in glomerular endothelial cells. Northern blot analysis showed that glomerular and aortic endothelial cells expressed IGF-1 mRNA of 1.7 kb. In contrast, renal glomeruli showed several IGF-1 mRNAs of 7.5, 1.7 and 1.2 kb. Thus, the demonstration of both a prepondence of Type I IGF receptors coupled with the growth promoting effects of IGF-I in glomerular endothelial and epithelial cells, as well as the local production of IGF-I mRNA suggests that IGF-I serves an important role as an autocrine or paracrine regulator of the growth of renal glomeruli.

Animals↗

The hypotriglyceridemic effect of fish oil in adult-onset diabetes without adverse glucose control.

Diabetic control as judged by five criteria did not deteriorate after 6 months of fish oil compared to 6 months of olive oil supplementation in 16 patients with NIDDM who were eating a low fat, high complex carbohydrate diet. Plasma total and VLDL triglyceride and cholesterol decreased significantly after fish oil supplementation; plasma total and HDL cholesterol concentrations did not change. The LDL cholesterol level was significantly increased with fish oil supplementation, suggesting that patients with NIDDM who are given a fish oil supplement to decrease the plasma total and VLDL triglyceride levels may also need further dietary and/or pharmaceutical therapy to maintain an LDL cholesterol level compatible with a low risk of coronary disease. The study emphasizes the safe use of fish oil over a 6-month period in diabetic patients.

Aged↗

A second pathway for regeneration of adult exocrine and endocrine pancreas. A possible recapitulation of embryonic development.

Substantial regeneration of both the endocrine and exocrine pancreas occurs after a 90% partial pancreatectomy in the young adult rat. We have reported previously that replication of preexisting islet and exocrine cells is enhanced 3- to 4-fold. Here, we report a second pathway of regeneration, that of proliferation and differentiation of precursor cells in the ductal epithelium. As shown with in vivo pulse labeling using 5-bromo-2'-deoxyuridine, an expansion of the ductal epithelium occurs. Proliferation is seen first in the common pancreatic duct and sequentially in smaller ducts of the ductal tree as focal areas of proliferation small ductules form. By 60 h after pancreatectomy, only these focal areas show heavy 5-bromo-2'-deoxyuridine staining. These proliferating ductules comprise 12.8% of the pancreatic volume at 3 days after pancreatectomy but are uncommon at 7 days after pancreatectomy. Coincident with the appearance and disappearance of these regions was a 3.5-fold increased growth of the pancreatic remnant compared with its equivalent of sham animals. These small ductules differentiate into new pancreatic islets and exocrine tissue, forming new lobules of pancreas that are indistinguishable from the preexisting ones. This second pathway of rapid regeneration recapitulates embryonic development in its pattern of ductal proliferation and subsequent differentiation. Furthermore, these studies provide evidence of the presence of precursor/stem cells in the adult pancreas.

Animals↗

The relationship of dispositional optimism, daily life stress, and domestic environment to coping methods used by cancer patients.

The relationship of dispositional optimism, daily life stress, and domestic environment to two types of coping methods was examined in a group of 94 cancer patients. As expected, dispositional optimism and domestic environment made significant contributions to the prediction of avoidance coping. Dispositional optimism contributed significantly to the prediction of active-behavioral coping. Specifically, a significant positive relationship was obtained between active-behavioral coping and optimism. A significant positive relationship also was found between avoidance coping and both daily stress and domestic environment. Avoidance coping was negatively related to dispositional optimism. In multivariate analyses, gender and disease-related variables did not make significant contributions to the prediction of coping method. Suggestions for future research were made.

Adaptation, Psychological↗

Enhanced insulin-like growth factor I gene expression in regenerating rat pancreas.

Insulin-like growth factor I (IGF-I) mRNA expression was studied after 90% partial pancreatectomy in the rat to determine whether IGF-I was associated with pancreatic regeneration. The level of IGF-I mRNA was maximally increased (4-fold above control value) 3 days after pancreatectomy, but thereafter gradually decreased, returning to control levels by 14 days after surgery. By in situ hybridization, IGF-I mRNA in both pancreatectomized and sham-operated rats was localized to capillary endothelial cells, indicating that this is the site of IGF-I expression in the normal rat pancreas. However, enhanced IGF-I mRNA expression was localized to focal areas of regeneration unique to pancreatectomized rats. In these areas, epithelial cells of proliferating ductules and individual connective tissue cells expressed IGF-I, suggesting that IGF-I may play an important role in the growth or differentiation of pancreatic tissue.

Animals↗

The influence of simvastatin on adrenal corticosteroid production and urinary mevalonate during adrenocorticotropin stimulation in patients with heterozygous familial hypercholesterolemia.

The adrenal gland requires a continuous supply of cholesterol for the biosynthesis of adrenal corticosteroids, which can be supplied by low density lipoprotein receptor-mediated uptake or local synthesis. The present study examined whether hypolipidemic therapy with a potent HMG CoA reductase inhibitor, simvastatin, compromises the adrenal response to ACTH stimulation in adult patients with heterozygous familial hypercholesterolemia. The adrenal response to a 36-h continuous ACTH infusion was determined at baseline and after 2 months of simvastatin treatment (40 mg, twice daily) in eight patients. Simvastatin reduced total and low density lipoprotein cholesterol levels by 36% and 45%, respectively. The time course of the increase in serum cortisol concentrations with continuous ACTH infusion was the same before and during simvastatin therapy, as were the rates of urinary excretion of free cortisol, 17-hydroxycorticosteroids, and 17-ketosteroids. Urinary excretion of mevalonate, which correlates with rates of whole body cholesterol synthesis, decreased from 3.8 +/- 0.42 (+/- SEM) mu,ol/24 h at baseline to 2.75 +/- 0.56 on simvastatin; no significant changes were seen in the urinary mevalonate levels before and after simvastatin therapy during ACTH stimulation. We conclude that the hypolipidemic effects of simvastatin in patients with heterozygous familial hypercholesterolemia are paralleled by a decrease in urinary mevalonate, but that the drug does not adversely affect ACTH-stimulated adrenal corticosteroid production.

Adrenal Cortex↗