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Biomedical subjects

W Anderson

Publications and source records attributed to W Anderson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Metabolism and excretion of the novel antipsychotic drug ziprasidone in rats after oral administration of a mixture of 14C- and 3H-labeled ziprasidone.

The metabolism and excretion of ziprasidone (5-[2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]ethyl]-6-++ +chloroindolin-2-one hydrochloride hydrate) were studied in Long Evans rats after oral administration of a single dose of a mixture of 14C- and 3H-labeled ziprasidone. The radioactive dose was quantitatively recovered over 7 days in both male and female rats. The percentage of the dose excreted in urine, bile, and feces of rats was 21.6, 19.2, and 55.6%, respectively. The total excretion in urine and bile suggested that at least 41% of the drug was absorbed. Absorption of ziprasidone was rapid, and the mean plasma concentrations of the unchanged drug and metabolites were slightly higher in the female rats than in the males. The maximal plasma concentrations for ziprasidone and metabolites were reached at 1 hr in both male and female rats. Based on AUC (0-12 hr) values, approximately 59 and 52% of the circulating radioactivity (average of 14C and 3H) was attributable to metabolites in male and female rats, respectively. Ziprasidone was extensively metabolized in rats, and only a small amount of ziprasidone was excreted as unchanged drug. Twelve metabolites were identified by ion spray LC/MS, using a combination of parent ion and product ion scanning techniques. The structures of eight metabolites were unambiguously confirmed by coelution on HPLC with synthetic standards, and four additional metabolites were partially identified. There was a gender-related difference in the excretion of urinary metabolites in Long Evans rats. The major route of metabolism in male rats involved N-dealkylation. In female rats the major metabolites were due to oxidation at the benzisothiazole ring. Based on the structures of these metabolites, four major and two minor routes of metabolism of ziprasidone were identified. The major routes included 1) N-dealkylation of the ethyl side chain attached to the piperazinyl nitrogen, 2) oxidation at the sulfur, resulting in the formation of sulfoxide and sulfone, 3) oxidation on the benzisothiazole moiety (other than sulfur), and 4) hydration of the C==N bond and subsequent oxidation at the sulfur of the benzisothiazole moiety. The minor routes involved N-oxidation on the piperazine ring and hydrolysis of the oxindole moiety.

Administration, Oral↗
PubMed1996

Chronic pulmonary hypertension in sheep: temporal progression of lesions.

Scant data exist on the evolution of the lesions of pulmonary hypertension. This study establishes a model in sheep in which the left upper lobe (LUL) was rendered hypertensive by a systemic-pulmonary shunt while the rest of the pulmonary circulation remained normotensive. By examining lung tissue at 2 months and 1 1/2 years after shunting, we sought the temporal progression of pulmonary hypertensive lesions. In the hypertensive LULs (n = 5), many vascular lesions were seen in contrast to the absence of lesions in both the contralateral normotensive lungs (n = 5) and the "control" lungs from sheep which underwent thoracotomy without shunting (n = 5). Vascular necrosis and vasculitis were present after 2 months (P < 0.01) but disappeared after 1 1/2 years. In contrast, intimal thickening was present after 1 1/2 years (n = 2, P < 0.01) but not significantly after 2 months. These intimal lesions often demonstrated increased cellularity staining positively for factor VIII. Plexiform lesions were present at 2 months (P < 0.05) but were more profuse after 1 1/2 years (P < 0.01). These findings are consistent with an early vascular injury and a later remodeling or reparative process in hemodynamic pulmonary hypertension.

Animals↗
PubMed1996

A prospective audit of wound infection rates after caesarean section in five West Yorkshire hospitals.

A three month prospective audit of wound infection following emergency and elective caesarean section was carried out in five West Yorkshire hospitals. Among 4076 women undergoing delivery in the five obstetric departments, the caesarean rate was 15.4%. The overall infection rate was 45/628 (7.2%) with a range of 2.5-17.2% between the five centres. The infection rate was 14/226 (6.2%) when antibiotics were used compared with 31/402 (7.7%) without antibiotics. The use of prophylactic antibiotics made no significant difference to the infection rate, which did not correlate with duration of labour or of ruptured membranes. The number of vaginal examinations correlated with the infection rate. In conclusion, the caesarean section rate observed was higher than that estimated for the UK as a whole, but was distorted by one centre with a high rate. For the other four hospitals the caesarean rate was unexceptional. The ratio of emergency to elective operations was comparable with recently reported values in the UK and the wound infection rate was within the widely varying limits found in previous studies. In view of the relatively low infection rate recorded without antibiotics, in the interests of cost effectiveness, prophylaxis may be limited in future to selected women at high risk. Because this was an audit rather than a randomized study we cannot exclude that this is already happening on an empirical basis.

Antibiotic Prophylaxis↗
PubMed1996

Effect of a patient's sex on the timing of thrombolytic therapy.

STUDY OBJECTIVE: We sought to determine whether a patient's sex independently influences the interval from emergency department arrival to the initiation of thrombolytic therapy in acute myocardial infarction (AMI). METHODS: We conducted a retrospective cohort study in two suburban EDs, one at a 929-bed tertiary care teaching hospital and the other at a 189-bed community hospital. Only patients found to be having an ST-segment-elevated AMI on their first ECG who were treated with a thrombolytic agent in the ED were eligible. We excluded patients who arrived at the ED after cardiac arrest or with a known AMI. We used as the main outcome measure the interval from ED arrival to initiation of thrombolytic therapy. Secondary outcome variables included time elapsed before ECG, interval between ECG and treatment, and 1-year mortality. RESULTS: Entry criteria were satisfied by 328 patients. The 88 women experienced a mean 23-minute delay to treatment initiation compared with men (P < .01). This observation is not accounted for by age, race, time of day, medical history, sex of the physician, type of thrombolytic agent, hospital, or triage category. The longest delays were found in women treated by female physicians, although female physicians also waited longer than male physicians to administer thrombolytic therapy to men. The mean time elapsed before the first ECG was also 6 minutes longer for women (P < .01) Women had an increased 1-year mortality rate that was fully explained by their advanced age at the time of AMI. CONCLUSION: We infer that a patient's sex may play a significant role in the observed delay in treatment for women. Our data, coupled with previously published work, strongly suggest a systematic negative effect for women in their interaction with the health care system during AMI. We suggest that variables other than systems issues affect the time elapsed before thrombolytic therapy.

Aged↗
PubMed1996

Mouse bone marrow-derived mast cells roll on P-selectin under conditions of flow in vivo.

Increased numbers of mast cells are noted at sites of wound healing and inflammation. These mast cells are either recruited from the bone marrow or proliferate locally under cytokine stimulation. However, the molecular mechanisms mediating initial adhesive interactions between mast cell precursors and vascular endothelial cells are not well understood. We have used a syngeneic dorsal skinfold chamber model of microcirculation to study early events of mast cell-endothelial cell interactions by intravital fluorescence microscopy. Because "rolling" represents the earliest step of granulocyte adhesion under conditions of flow, our objective was to determine whether vascular selectins promote rolling of immature mouse bone marrow-derived mast cells (MBMMC) on endothelial cells lining murine blood vessels in vivo. In this study, titanium window chambers were implanted on the dorsal skinfolds of BALB/c mice. The passage of injected fluorescently labeled MBMMC within blood vessels of the striated skin muscle was observed by stroboscopic epi-illumination. As previously determined for other leukocytes, MBMMC were observed to roll in venules but not in arterioles or capillaries. Mice were also treated with neutralizing anti-E-selectin (mAb 9A9) and anti-P-selectin (mAb 5H1) antibodies and tested for their ability to block MBMMC rolling on venular endothelial cells. Intravenous administration of mAb 5H1 resulted in a marked decrease in MBMMC rolling, whereas mAb 9A9 and isotype matched control antibodies had no effect on the rolling flux of MBMMC. These studies represent the first identification of P-selectin as a rolling receptor for MBMMC, and demonstrate the use of a dorsal skinfold technique to study MBMMC-endothelial cell interactions under conditions of physiologic flow. Further studies will determine whether vascular selectins participate in the rolling and tissue recruitment of true circulating immature mast cell precursors in vivo.

Animals↗
PubMed1995

Use of bioluminescence to model the thermal inactivation of Salmonella typhimurium in the presence of a competitive microflora.

The survival of Salmonella typhimurium was investigated by bioluminescence and standard plating techniques in pure cultures and in the presence of competitors after the cultures were heated to 55 degrees C for increasing lengths of time. Decimal reduction (D) values increased from 0.43 to 2.09 min in the presence of 10(8) CFU of competitors ml-1, indicating a significant protective effect.

Bacteriological Techniques↗
PubMed1994

Modelling the thermal inactivation of Salmonella typhimurium using bioluminescence data.

Inactivation of micro-organisms by heat is a traditional food processing technique used to reduce or eliminate the microbial load in foods thus preventing bacterial associated disease and food spoilage. Models of thermal death kinetics are routinely used to predict the amount of heat required but such models are limited by the acquisition of accurate thermal death data for bacteria in situ and in complex microflora. In vivo bioluminescence from lux recombinant bacteria is an important alternative to traditional plate counts for examining bacterial injury and stress but the thermal instability of luciferase has appeared to preclude its application in heating studies. We have developed a procedure which overcomes the thermal instability of luciferase and demonstrate that computer generated models of the thermal injury of Salmonella typhimurium show equivalence between bioluminescence and viable count data.

Hot Temperature↗
PubMed1993

Differential effects of diclofenac and aspirin on serum glutamic oxaloacetic transaminase elevations in patients with rheumatoid arthritis and osteoarthritis.

OBJECTIVE: To examine elevations in levels of serum glutamic oxaloacetic transaminase (SGOT) in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) taking placebo, aspirin, or diclofenac, and to seek possible explanations for the occurrence of these elevations. METHODS: We conducted a meta-analysis of individual case reports from 3 RA protocols and 5 OA protocols, encompassing 814 diclofenac-treated patients, 443 aspirin-treated patients, and 359 placebo-treated patients. All of the RA protocols had nearly identical inclusion and exclusion criteria, as well as safety studies and followup; the same was true for the OA protocols. Analysis included correlation analysis and multiple linear and logistic regression, accounting for numerous potential confounding variables, with the SGOT as the dependent variable. F tests were used for hypothesis testing. RESULTS: By several analytic approaches, the principal determinants of SGOT concentrations were found to be baseline SGOT value, the use of aspirin in RA patients, and the use of diclofenac in OA patients. Other significant factors contributing to an increase in SGOT concentrations were duration of therapy and, perhaps, daily dosage (mg/lb). Hypothesis testing supported these results. Given a statistically average patient, we predicted a 1-2% chance of a mildly elevated SGOT level occurring among placebo-treated patients, a 6-7% chance among diclofenac- or aspirin-treated patients with RA, a 12% chance among diclofenac-treated patients with OA, and a 2% chance among aspirin-treated patients with OA. CONCLUSION: This study demonstrates a powerful method for performing meta-analysis, using available individual patient data to examine numerous factors that may affect an outcome of interest. In this case, mild elevations of SGOT were examined and found to be related to baseline SGOT levels, diclofenac use (in OA), and aspirin use (in RA). Of numerous other potential factors examined, including age, sex, alcohol use, concomitant medications, and concomitant diagnoses, only duration of therapy and, to a small extent, daily dosage, were also consistent determinants of SGOT elevation. The SGOT elevations were minimal and were not related to the occurrence of clinical hepatitis: No clinical hepatitis occurred.

Arthritis, Rheumatoid↗