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Biomedical subjects

R Townsend

Publications and source records attributed to R Townsend.

At least 19 recordsLinked to original sources
PubMed2001

Differential recognition of obligate anaerobic bacteria by human mannose-binding lectin.

Deficiency of the innate, humoral immune component mannose-binding lectin (MBL) predisposes individuals to a variety of infections, but the importance of MBL in infection by anaerobes has not been addressed. The attachment of MBL to a wide range of anaerobic bacteria associated with human disease and colonization was surveyed. The results suggest that for the species we examined, resistance to MBL binding may be associated with organisms that are more commonly pathogenic and that MBL binding to some bacteria may be phase variable.

Bacteria, Anaerobic↗
PubMed2001

Contribution of age and gender to outcome of blunt splenic injury in adults: multicenter study of the eastern association for the surgery of trauma.

BACKGROUND: The purpose of this study was to examine the contribution of age and gender to outcome after treatment of blunt splenic injury in adults. METHODS: Through the Multi-Institutional Trials Committee of the Eastern Association for the Surgery of Trauma (EAST), 1488 adult patients from 27 trauma centers who suffered blunt splenic injury in 1997 were examined retrospectively. RESULTS: Fifteen percent of patients were 55 years of age or older. A similar proportion of patients > or = 55 went directly to the operating room compared with patients < 55 (41% vs. 38%) but the mortality for patients > or = 55 was significantly greater than patients < 55 (43% vs. 23%). Patients > or = 55 failed nonoperative management (NOM) more frequently than patients < 55 (19% vs. 10%) and had increased mortality for both successful NOM (8% vs. 4%, p < 0.05) and failed NOM (29% vs. 12%, p = 0.054). There were no differences in immediate operative treatment, successful NOM, and failed NOM between men and women. However, women > or = 55 failed NOM more frequently than women < 55 (20% vs. 7%) and this was associated with increased mortality (36% vs. 5%) (both p < 0.05). CONCLUSION: Patients > or = 55 had a greater mortality for all forms of treatment of their blunt splenic injury and failed NOM more frequently than patients < 55. Women > or = 55 had significantly greater mortality and failure of NOM than women < 55.

Adult↗
PubMed2000

Anatomic and metabolic risk factors for nephrolithiasis in patients with autosomal dominant polycystic kidney disease.

The prevalence of nephrolithiasis is considerably greater in patients with autosomal dominant polycystic kidney disease (ADPKD) than in the general population. We evaluated anatomic and metabolic factors that may be associated with an increased prevalence of nephrolithiasis in patients with ADPKD. We compared anatomic parameters among ADPKD patients with or without nephrolithiasis as diagnosed by ultrasonography, whereas metabolic factors were determined by 24-hour urinary chemical analysis. Patients with ADPKD and nephrolithiasis had more renal cysts (P < 0.05) and a larger predominant renal cyst size (P < 0.005) than patients without nephrolithiasis. Concurrently, individual stone-forming kidneys had a greater cyst number (P < 0.05) and a significantly larger predominant cyst size (P < 0.01) compared with kidneys without stones. Patients with ADPKD and nephrolithiasis had a significantly lower creatinine clearance than those without nephrolithiasis (68.7 +/- 8.6 versus 94.8 +/- 5.4 mL/min, respectively; P < 0.05). Twenty-four-hour urinary analysis showed that patients with ADPKD and nephrolithiasis had significantly lower urinary volumes (P < 0. 05), and levels of urinary phosphate (P < 0.05), magnesium (P < 0. 005), and potassium (P < 0.05). Although not statistically significant, patients with ADPKD with stones tended to have lower levels of urinary citrate, and both groups showed a high percentage (range, 49% to 60%) of patients with hypocitraturia. Our data are consistent with the hypothesis that patients with ADPKD who develop nephrolithiasis do so because of increased intrarenal anatomic obstruction, as well as lower levels of such urinary inhibitors of stones as magnesium and citrate.

Adult↗
PubMed2000

Blunt splenic injury in adults: Multi-institutional Study of the Eastern Association for the Surgery of Trauma.

BACKGROUND: Nonoperative management of blunt injury to the spleen in adults has been applied with increasing frequency. However, the criteria for nonoperative management are controversial. The purpose of this multi-institutional study was to determine which factors predict successful observation of blunt splenic injury in adults. METHODS: A total of 1,488 adults (>15 years of age) with blunt splenic injury from 27 trauma centers in 1997 were studied through the Multi-institutional Trials Committee of the Eastern Association for the Surgery of Trauma. Statistical analysis was performed with analysis of variance and extended chi2 test. Data are expressed as mean +/- SD; a value of p < 0.05 was considered significant. RESULTS: A total of 38.5 % of patients went directly to the operating room (group I); 61.5% of patients were admitted with planned nonoperative management. Of the patients admitted with planned observation, 10.8% failed and required laparotomy; 82.1% of patients with an Injury Severity Score (ISS) < 15 and 46.6% of patients with ISS > 15 were successfully observed. Frequency of immediate operation correlated with American Association for the Surgery of Trauma (AAST) grades of splenic injury: I (23.9%), II (22.4%), III (38.1%), IV (73.7%), and V (94.9%) (p < 0.05). Of patients initially managed nonoperatively, the failure rate increased significantly by AAST grade of splenic injury: I (4.8%), II (9.5%), III (19.6%), IV (33.3%), and V (75.0%) (p < 0.05). A total of 60.9% of the patients failed nonoperative management within 24 hours of admission; 8% failed 9 days or later after injury. Laparotomy was ultimately performed in 19.9% of patients with small hemoperitoneum, 49.4% of patients with moderate hemoperitoneum, and 72.6% of patients with large hemoperitoneum. CONCLUSION: In this multicenter study, 38.5% of adults with blunt splenic injury went directly to laparotomy. Ultimately, 54.8% of patients were successfully managed nonoperatively; the failure rate of planned observation was 10.8%, with 60.9% of failures occurring in the first 24 hours. Successful nonoperative management was associated with higher blood pressure and hematocrit, and less severe injury based on ISS, Glasgow Coma Scale, grade of splenic injury, and quantity of hemoperitoneum.

Adult↗
PubMed1999

Safety and pharmacokinetic profile of gadobenate dimeglumine in subjects with renal impairment.

RATIONALE AND OBJECTIVES: To determine the safety and pharmacokinetics of gadobenate dimeglumine in a group of subjects with moderate or severe renal impairment. METHODS: The safety and pharmacokinetic profile of gadobenate dimeglumine, a gadolinium (Gd3+) chelate complex in development as a contrast agent for MRI, were evaluated in a placebo-controlled, double-blind, multicenter trial. Subjects with moderate or severe renal impairment (creatinine clearances of 31 to 60 or 10 to 30 mL/min, respectively) received a 0.2-mmol/kg intravenous bolus of Gd3+ or saline placebo. Blood samples (up to 72 hours) and urine and fecal samples (up to 216 hours) were assayed for total Gd3+ content by inductively coupled plasma atomic emission spectroscopy. Gd3+ blood concentration/time data were analyzed nonparametrically and parametrically using the software program WinNonlin VI.1. RESULTS: Mean (SD) values for Gd3+ area under the curve, blood clearance, steady-state volume of distribution, renal clearance, and creatinine clearance for the moderate group were 862 (392) micrograms.h/mL, 56 (25) mL/min, 21 (5) L, 47 (23) mL/min, and 46 (16) mL/min. Values for the severe group were 1347 (366) micrograms.h/mL, 31 (7) mL/min, 19 (6) L, 22 (7) mL/min, and 21 (8) mL/min. No Gd(3+)-related adverse events occurred. Mean values for Gd3+ recovery in urine and feces for moderate and severe groups were 74% and 6%, and 69% and 8% of the dose, respectively. Linear regression analysis demonstrated a significant relation between the level of renal function and blood clearance of Gd3+. CONCLUSIONS: Although mean blood clearance and renal clearance values progressively declined with increasing degree of renal impairment, based on the safety profile and the fact that the administered dose was double the standard dose used for MRI purposes, there appears to be no need for dose reduction in this population.

Adult↗
PubMed1999

High-fat meals reduce 24-h circulating leptin concentrations in women.

Leptin induces weight loss in rodents via its effects on food intake and energy expenditure. High-fat diets induce weight gain, but the mechanism is not well understood. Previous studies have not found an effect of dietary fat content on fasting leptin. There is a nocturnal increase of leptin, however, which is related to insulin responses to meals. We have reported that adipocyte glucose utilization is involved in insulin-induced leptin secretion in vitro. Accordingly, high-fat, low-carbohydrate (HF/LC) meals, which induce smaller insulin and glucose responses, would produce lower leptin concentrations than low-fat, high-carbohydrate (LF/HC) meals. Blood samples were collected every 30-60 min for 24 h from 19 normal-weight (BMI, 24.2 +/- 0.7 kg/m2; percent body fat = 31 +/- 1%) women on 2 days (10 days apart) during which the subjects were randomized to consume three isocaloric 730-kcal meals containing either 60/20 or 20/60% of energy as fat/carbohydrate. Overall insulin and glycemic responses (24-h area under the curve [AUC]) were reduced by 55 and 61%, respectively, on the HF/LC day (P < 0.0001). During LF/HC feeding, there were larger increases of leptin 4-6 h after breakfast (38 +/- 7%, P < 0.001) and lunch (78 +/- 14%, P < 0.001) than after HF/LC meals (both P < 0.02). During LF/HC feeding, leptin increased from a morning baseline of 10.7 +/- 1.6 ng/ml to a nocturnal peak of 21.3 +/- 1.3 ng/ml (change, 10.6 +/- 1.3 ng/ml; percent change, 123 +/- 16%; P < 0.0001). The amplitudes of the nocturnal rise of leptin and the 24-h leptin AUC were 21 +/- 8% (P < 0.005) and 38 +/- 12% (P < 0.0025) larger, respectively, on the LF/HC day. In summary, consumption of HF/LC meals results in lowered 24-h circulating leptin concentrations. This result may be a consequence of decreased adipocyte glucose metabolism. Decreases of 24-h circulating leptin could contribute to the weight gain during consumption of high-fat diets.

Adipose Tissue↗
PubMed1997

Bioactive peptide design based on protein surface epitopes. A cyclic heptapeptide mimics CD4 domain 1 CC' loop and inhibits CD4 biological function.

The interaction between CD4 and major histocompatibility complex class II proteins provides a critical co-receptor function for the activation of CD4(+) T cells implicated in the pathogenesis of a number of autoimmune diseases and transplantation responses. A small synthetic cyclic heptapeptide was designed and shown by high resolution NMR spectroscopy to closely mimic the CD4 domain 1 CC' surface loop. This peptide effectively blocked stable CD4-major histocompatibility complex class II interaction, possessed significant immunosuppressive activity in vitro and in vivo, and strongly resisted proteolytic degradation. These results demonstrate the therapeutic potential of this peptide as a novel immunosuppressive agent and suggest a general strategy of drug design by using small conformationally constrained peptide mimics of protein surface epitopes to inhibit protein interactions and biological functions.

Amino Acid Sequence↗
PubMed1996

Assessment of the allergenic potential of foods derived from genetically engineered crop plants.

This article provides a science-based, decision tree approach to assess the allergenic concerns associated with the introduction of gene products into new plant varieties. The assessment focuses on the source from which the transferred gene was derived. Sources fall into three general categories: common allergenic food proteins; less common allergenic foods or other known allergen sources; and sources with no history of allergenicity. Information concerning the amino acid sequence identity to known allergenic proteins, in vitro and/or in vivo immunologic assays, and assessment of key physiochemical properties are included in reaching a recommendation on whether food derived from the genetically modified plant variety should be labeled as to the source of the transferred gene. In the end, a balanced judgement of all the available data generated during allergenicity assessment will assure the safety of foods derived from genetically engineered crops. Using the approaches described here, new plant varieties generated by genetic modification should be introduced into the marketplace with the same confidence that new plant varieties developed by traditional breeding have been introduced for decades.

Allergens↗
PubMed1996

Ethical issues in organ donation and transplantation: are we helping a few at the-expense of many?

Ethical issues have always been apparent in the transplantation process and are becoming more evident as the demand for organs increases. The basic question is how just and ethical are the new policies enacted to encourage organ donation, considering that they affect the total public and benefit the small percentage of patients who require transplantation? Pros and cons of several of these policies will be discussed as will several clinical situations that raise ethical questions.

Adult↗
PubMed1995

Endovascular stent placement and magnetic resonance angiography for management of hypertension and renal artery occlusion during pregnancy.

BACKGROUND: Severe renovascular hypertension carries serious maternal and fetal risk. In patients failing medical therapy, therapeutic options include surgical revascularization, nephrectomy, and percutaneous angioplasty. CASE: A pregnant woman with long-standing hypertension developed accelerated hypertension despite multiple drug therapy. Magnetic resonance angiography diagnosed an atrophic kidney with a critical proximal right renal artery lesion. At 17 weeks' gestation, this renal artery occlusion was treated with percutaneous angioplasty and endovascular stent placement; hypertension has improved markedly, allowing discontinuation and tapering of her antihypertensive medications. Total fetal radiation dose was 0.002 Gy. CONCLUSION: Magnetic resonance angiography is a promising, noninvasive diagnostic method of evaluating renovascular hypertension during pregnancy. Transluminal angioplasty and endovascular stent placement can be performed safely and effectively with nominal fetal radiation exposure.

Adult↗