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Biomedical subjects

S R Smith

Publications and source records attributed to S R Smith.

At least 19 recordsLinked to original sources
PubMed1992

Analysis of the genotoxicity of municipal solid waste incinerator ash.

Combined bottom and fly ash obtained from a Chicago, IL, municipal solid waste incinerator (MSWI) was extracted with organic solvents, water or acidified water. The mean amounts of organic material isolated from each extraction procedure were 688.2, 91.8 and 167.7 micrograms/g MSWI ash. These extracts were evaluated for toxicity and mutagenicity in Salmonella typhimurium strains TA98 and TA100. We developed and calibrated a micropreincubation assay to evaluate small concentrations of the organic extracts. No direct-acting mutagens were found, however the acid-treated aqueous extracts were toxic. Materials isolated with methylene chloride methanol were mutagenic after hepatic microsomal activation (S9). The mutagenic potencies of the organic extract normalized to a per gram ash basis was the induction of 103.46 revertants in TA98 and 247.5 revertants in TA100. The aqueous extracts were neither toxic nor mutagenic. However, the acid-treated aqueous extract was mutagenic to TA100. The organic material isolated from the acidic extract had an induced mutagenic potency of 44.2 revertants/mg extract. Normalizing these data indicate a mutagenic potency of 7.4 revertants/g MSWI ash leached.

Animals↗
PubMed1992

Detection of bone marrow abnormalities in patients with Hodgkin's disease by T1 mapping of MR images of lumbar vertebral bone marrow.

Pixel by pixel T1 mapping of MR images has been used in conjunction with image analysis techniques to study the lumbar vertebral bone marrow of 20 patients with refractory or relapsed Hodgkin's disease prior to salvage chemotherapy, or high dose chemotherapy with autologous bone marrow rescue. Compared to 18 age matched controls, seven patients had significantly abnormal lumbar vertebral marrow T1 histograms with median, 5% and 95% centile T1 values that lay outside a three dimensional 95% probability region obtained for the normals. Six of these patients had increased areas of high T1 consistent with bone marrow involvement with lymphoma; although, only in two of them had Hodgkin's disease been detected by bilateral iliac crest bone marrow biopsy. Post-treatment studies were performed in four patients who had abnormal areas of high T1 in the lumbar vertebral bone marrow. All showed normalisation of the T1 histogram, with a reduction of T1 values to within the normal range as defined by the studies of age matched controls. T1 mapping of bone marrow offers potential for detecting bone marrow infiltrates in patients with lymphoma, and also for the assessment of treatment response.

Adult↗
PubMed1992

Diabetes-induced glomerular dysfunction: links to a more reduced cytosolic ratio of NADH/NAD+.

These studies were undertaken to examine effects of elevated glucose levels on glycolysis, sorbitol pathway activity, and the cytosolic redox state of NADH/NAD+ in isolated glomeruli. Blood-free glomeruli were isolated from kidneys of male, Sprague-Dawley rats using standard sieving techniques, then incubated for one hour at 37 degrees C, pH 7.4, pO2 approximately 500 torr, in Krebs bicarbonate/Hepes buffer containing 5 or 30 mM glucose. Elevated glucose levels increased glucose 6-phosphate, fructose 6-phosphate, total triose phosphates, lactate, the lactate/pyruvate ratio, sorbitol, and fructose, but did not affect sn-glycerol 3-phosphate, pyruvate, or myo-inositol levels. The more reduced glomerular cytosolic redox state (manifested by the tissue lactate/pyruvate ratio) induced by 30 mM glucose was completely abrogated by aldose reductase inhibitors added to the diet two to seven days prior to glomerular isolation. These observations, coupled with evidence linking glucose- and diabetes-induced glomerular dysfunction to increased sorbitol pathway metabolism, support the hypothesis that metabolic imbalances associated with a more reduced ratio of cytosolic NADH/NAD+ (resulting from increased glucose metabolism via the sorbitol pathway) play an important role in mediating glucose- and diabetes-induced glomerular dysfunction.

Aldehyde Reductase↗
PubMed1992

Effects of thromboxane synthase inhibition with CGS 13080 in human cyclosporine nephrotoxicity.

Cyclosporine is a potent immunosuppressive agent, however, its use is limited by nephrotoxicity. Increased production of the potent vasoconstrictor thromboxane A2 contributes to cyclosporine nephrotoxicity in animal models, but the role of thromboxane in human cyclosporine nephrotoxicity has not been established. We therefore studied cyclosporine-treated renal allograft recipients who had evidence of toxicity manifested by decreased renal function. We measured GFR and PAH clearance (CPAH) before, during, and one week after a 48-hour intravenous infusion of the thromboxane synthase inhibitor CGS 13080. At baseline, the urinary excretion of TXB2 and 2,3-dinor-TXB2 was elevated in the study patients compared to healthy subjects. CGS 13080 infusion caused selective and nearly complete inhibition of thromboxane metabolite excretion in all patients. Mean CPAH improved 33% from 223 +/- 45 to 298 +/- 59 ml/min/m2 (P = 0.055) during infusion, while mean GFR improved 9% from 50.1 +/- 3.9 at baseline to 54.6 +/- 4.5 ml/min/1.73 m2 (P = 0.111). The effect on GFR occurred primarily in those patients taking calcium channel blockers. The mean increase in GFR in these 5 patients was 10.0 +/- 2.8 versus -1.0 +/- 2.8 ml/min/m2 in the remainder. We conclude that thromboxane synthase inhibitors may be useful in attenuating the nephrotoxic effects of cyclosporine following renal transplantation.

Adult↗
PubMed1992

A behavioral study of bilateral middle cerebral artery hemorrhagic ischemia in rats.

The middle cerebral artery was severed bilaterally (bMCA) in adult rats, and controls experienced sham operations. Tactile sensorimotor and gross locomotor functions, measured by the tape test and a rod walking test, were initially impaired in the injured animals. However, these deficits had resolved within 9 and 30 days respectively. The animals were trained in a multiple T water maze task to find the location of a hidden escape platform at the rate of one trial per day for 30 days. Analyses of the number of errors committed and latency to find the escape platform revealed that the bMCA injured rats suffered deficient reference memory, but no decline in working memory. These data support further the use of the bMCA preparation as a model of stroke.

Animals↗
PubMed1992

External fixation of lower limb fractures in children.

Thirty-four tibial and femoral shaft fractures in 32 children between the ages of 3 and 15 years were treated by external fixation over a 5-year period. The indications were fractures occurring in association with other major injuries and failure of conservative treatment to maintain satisfactory reduction. There was one case of delayed union and one early refracture. The overall pin track infection rate was 6%, but the rate for the tibial pins (2.1%) was much lower than for the femoral pins (10.3%). Union was achieved at an average of 11.7 weeks in the femoral fractures and 10.0 weeks in the tibial fractures. The use of external fixation is recommended for childhood femoral and tibial fractures, particularly in children with multiple injuries.

Adolescent↗
PubMed1992

The effect of using a pre-brushing mouthwash (Plax) on oral hygiene in man.

The aim of this study was to investigate whether the use of a pre-brushing mouthwash (Plax) improved subjects' oral hygiene over a 2-week period. In a double-blind placebo controlled cross-over study, 33 adult subjects (mean age 35.3 years) used either Plax or a placebo mouthwash for 30 s prior to toothbrushing during a 2-week period. After a washout period of 4 weeks, the subjects used the other mouthwash in the same way. The modified plaque index of Quigley and Hein (QHI) was recorded for 16 teeth (16, 14, 13, 11, 21, 23, 24, 26, 36, 34, 33, 31, 41, 43, 44, 46) at each visit. The bleeding index (BI) was recorded at the beginning and end of the study. Results were analysed using a paired one-tailed t-test. Neither plax nor placebo mouthwashes reduced plaque scores significantly (p > 0.05) below baseline. There was no statistically significant difference between the mean BI at the beginning of the trial (0.42) and at the end (0.44). These results suggest that the routine use of Plax is not a useful adjunct to toothbrushing.

Aged↗
PubMed1992

Severe haemolysis and renal failure in a patient with paroxysmal nocturnal haemoglobinuria.

Transfusion of about 60 ml of ABO incompatible plasma in 4 units of pooled platelets precipitated severe haemolysis, unmasking the emergence of paroxysmal nocturnal haemoglobinuria (PNH), in a patient with aplastic anaemia. In vitro tests showed that her red cells were lysed by both ABO compatible and incompatible plasma from normal donors. The behaviour of this case and the in vitro results suggest that it might be hazardous to relax the longstanding recommendation on transfusing patients with PNH by restricting the washing of blood components to those containing ABO incompatible plasma.

ABO Blood-Group System↗
PubMed1992

Privatization in health and human services: a critique.

Privatization currently enjoys wide appeal as a solution to public problems. Supporters of privatization hope that shifting responsibility for the funding, administration, and delivery of services to private organizations and individuals will spur market competition and thus lower costs, improve service effectiveness, and enhance program quality. An increasingly common form of privatization in health and human services is contracting with nonprofit organizations. Such contracting, in practice, does not follow market principles but is, instead, fraught with politics and inadequate information and built on long-term relationships between government and contract agencies. The operations and practices of contracting have important implications for the ongoing debate on the desirability of vouchers for health care insurance and for reform in the contracting process.

Contract Services↗
PubMed1992

Potassium chloride lowers blood pressure and causes natriuresis in older patients with hypertension.

Epidemiologic surveys, experimental studies in animals, and clinical trials in young and middle-aged patients with hypertension indicate that dietary potassium lowers blood pressure. The mechanism of the antihypertensive effect is not well defined. Variations in serum potassium within the physiologic range may directly affect vascular smooth muscle tone. Potassium may also influence the regulation of blood pressure through effects on sodium handling, aldosterone secretion, the renin/angiotensin system, renal kallikrein, eicosanoids, and atrial natriuretic peptide. This study was undertaken to confirm the blood pressure-lowering effect of potassium in older patients and to determine the mechanism of the antihypertensive effect. Twenty-two patients greater than or equal to 60 yr of age were admitted to a Clinical Research Unit for 8 days after a 2-wk period free of antihypertensive medication. Patients were placed on an isocaloric diet containing 200 mmol/day of Na+, 70 mmol/day of K+, and 500 mg/day of Ca2+ and were treated in a randomized, double-blinded manner with either potassium chloride (120 mmol/day) or placebo. After 4 days, patients were crossed over to the alternate treatment. Systolic blood pressure decreased 8.6 mm Hg (95% confidence interval -14.6, -2.6), and diastolic blood pressure decreased 4.0 mm Hg (-6.9, -1.0) during potassium chloride supplementation. There was no significant change in blood pressure during treatment with placebo. Serum K+ was 3.9 +/- 0.1 mmol/L after 3 days of placebo and 4.3 +/- 0.1 after 4 days of potassium chloride (P less than 0.002). Urinary sodium excretion averaged 192 +/- 11 mmol/day after placebo and 221 +/- 8 after potassium treatment (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Actions of a 5-lipoxygenase inhibitor, Sch 40120, on acute inflammatory responses.

Sch 40120 (10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b] [1,8]naphthyridin-5(7H)-one) is an inhibitor of the 5-lipoxygenase enzyme in rat neutrophils, human neutrophils and the the MC9 murine mast cell clone with IC50 values of 8, 4 and 7 microM, respectively. The drug was examined for its effects on acute inflammatory responses in the paw and pleural cavity of rats. The drug suppressed paw inflammation triggered by a reverse passive Arthus reaction or a subplantar injection of the polysaccharide carrageenan with p.o. ED50 values of 0.2 and 1.5 mg/kg, respectively. In reverse passive Arthus reaction and carrageenan pleurisy models, Sch 40120 was found to suppress both the cellular and fluid components of the acute inflammation. The p.o. ED50 values for inhibition of cells and fluid in pleurisy models were in the range of 0.1 to 0.7 mg/kg. When applied locally to the ears of mice, the drug blocked an arachidonic acid-induced and leukotriene-mediated ear inflammation with an ED50 of 0.072 mg/ear. These findings suggest that Sch 40120 is a potent anti-inflammatory agent that may be particularly useful in the treatment of inflammatory diseases such as psoriasis in which leukotrienes appear to be major mediators of the pathological symptoms that characterize the disease state.

Acute Disease↗
PubMed1992

Detection of in vivo-induced IL-1 mRNA in murine cells by flow cytometry (FC) and fluorescent in situ hybridization (FISH).

Flow cytometry (FC) and fluorescent in situ hybridization (FISH) were used to detect in vivo induced IL-1 alpha (a) messenger RNA. Spleen cells and thioglycollate-induced peritoneal exudate cells (PEC) were harvested from Balb/C mice three hours after intraperitoneal injection of 20 micrograms LPS. Cells from each population were phenotyped for MAC or IAd, fixed in 4% paraformaldehyde and then permeabilized with 70% ETOH. RNA-RNA FISH was performed by incubating suspended cells at 37 degrees C for 17 hours with biotinylated sense IL-1a, antisense IL-1a or antisense IL-2 probes in 50% formamide. Hybridized cells were washed in 2X SSC, treated with RNAse, stained with avidin conjugated to fluorescein (FITC) or allophycocyanin (APC) and analyzed immediately by FC. Initially, avidin-FITC was used to detect hybridized probe. Dual fluorescent FC analysis of IL-1a mRNA expression in LPS stimulated IAd+ cells showed an increase in mean fluorescent intensity (MFI) of 51 log channels (0.25 logs) when compared to unstimulated cells. Additionally, induction of specific IL-1a mRNA expression in cells from LPS treated animals was illustrated by increases in percent positive cells (24%) and in equivalent soluble fluorescein molecules (ESFM) bound (47%) when compared to cells from vehicle treated mice. Unhybridized cells and cells hybridized with control antisense IL-2 probe did not exhibit increases in MFI or ESFM. In subsequent experiments on MAC+ PEC, the use of avidin-APC to detect bound probe resulted in a greater separation between the FISH signals of antisense IL-1a and control sense probe (121 log channels, 0.6 logs) than that seen with FITC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗