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Biomedical subjects

T Steele

Publications and source records attributed to T Steele.

12 recordsLinked to original sources
PubMed2001

Phase I clinical and pharmacokinetic trial of irofulven.

PURPOSE: To evaluate the clinical tolerability of a new schedule of 6-hydroxymethylacylfulvene (irofulven, MGI 114, HMAF, NSC 683863), a semisynthetic sesquiterpene derived from the cytotoxic mushroom metabolite illudin S. Irofulven has been shown to induce DNA damage and apoptosis in vitro and has shown activity in a number of human tumor xenograft models. A number of drug-resistant cell lines including those that express the mdr phenotype, retain sensitivity to irofulven. METHODS: We conducted a phase I trial of irofulven given as an intravenous infusion (30 min) on a daily x5 schedule every 28 days. A total of ten patients were enrolled and treated at three dose levels, 6, 8, and 11 mg/m2 per day. RESULTS: Irofulven reached steady-state concentrations during the 30-min infusions with biexponential kinetics. Irofulven disappeared rapidly from plasma and was detectable for only 15-30 min after the end of the infusion. The mean half-life was 4.91 min and the mean clearance was 4.57 l/mm per m2. Peak plasma concentrations of irofulven of approximately 300 ng/ml were achieved. Pharmacokinetic parameters did not differ significantly from day 1 to day 5. Irofulven was highly emetogenic. Other prominent toxicities included anorexia and fatigue. One case of delayed-onset metabolic acidosis possibly secondary to irofulven was observed. No other renal or metabolic toxicity was encountered. One patient experienced a late-onset grade 3 extravasation skin injury thought to be secondary to extravasation of irofulven. Minimal marrow suppression was observed. No objective tumor responses were observed. CONCLUSIONS: The recommended phase II dose on this schedule is 6 mg/m2.

Acidosis↗
PubMed1997

The effect of N-methylation on fenfluramine's neurotoxic and pharmacologic actions.

N-Methylation separates methamphetamine's neurotoxic and pharmacologic effects. In particular, N-methylation eliminates methamphetamine's neurotoxic activity while preserving its behavioral pharmacologic activity. The purpose of the present studies was to determine whether N-methylation could also be used to separate fenfluramine's neurotoxic and pharmacologic effects. Fenfluramine-induced serotonin neurotoxicity was assessed by measuring serotonin axonal markers 2 weeks after fenfluramine administration. Pharmacologic effects of fenfluramine were assessed by measuring fenfluramine-induced anorexia and fenfluramine discrimination. Both fenfluramine and its N-methylated analog, N-methylfenfluramine, produced dose-related effects in food intake, drug-discrimination and neurotoxicity studies. Although N-methylation reduced the neurotoxic potency of fenfluramine, it also reduced its pharmacologic activity. Neurotoxic potency was reduced 4- to 8-fold (depending on brain region), while pharmacologic potency was reduced 4- to 10-fold (depending on paradigm). Notably, N-methylation did not change the efficacy of fenfluramine as a serotonin neurotoxin, anorectic agent or discrimination stimulus. These results indicate that fenfluramine's behavioral and neurotoxic effects, unlike those of methamphetamine, are not dissociated by N-methylation. Further, the present results suggest that the effectiveness of side-chain nitrogen substitution in separating the behavioral and neurotoxic effects of amphetamine derivatives is strongly influenced by ring substitutions.

Animals↗
PubMed1996

Characterizing cochlear mechano-electric transduction using a nonlinear systems identification procedure.

A nonlinear systems identification technique [J. S. Bendat, Nonlinear System Analysis and Identification from Random Data (Wiley, New York, 1990)] provided the frequency-domain parameters of a third-order system polynomial equation describing cochlear mechano-electric transduction (MET) in Mongolian gerbils. The magnitude of the linear system term was the largest followed by the cubic and quadratic terms. The phase of the linear and cubic system terms differed by approximately 180 deg and the phase of the quadratic term lay between. Between-animal and within-animal variability was smallest for the linear and cubic terms, and largest for the quadratic term. Summing linear and nonlinear coherence functions revealed that the third-order system polynomial equation characterized approximately 83% of MET for low frequencies and 92% for high frequencies. Animals exposed to a 4-kHz pure tone at 100 dB SPL for 20 min showed changes in the magnitude and phase of the parameters of the third-order polynomial equation. An increase in linear coherence and a decrease in nonlinear coherence occurred at frequencies centered at the exposure frequency. Below the exposure frequency, linear coherence decreased and nonlinear coherence increased. Summation of the coherence functions showed that the third-order polynomial equation characterized MET better after exposure to the pure tone.

Animals↗
PubMed1996

The experience of being a male student nurse.

Although schools of nursing market their programs to all segments of society, men are underrepresented in schools of nursing. The purpose of this study was to identify male students' perceptions of the motivational factors, barriers and frustrations encountered in becoming a nurse. Eighteen students attended one of four focus groups representing one associate program, two baccalaureate programs and one diploma program. The students' belief that society perceived nursing as a feminine profession was an underlying thread that related to many of their perceptions and feelings. The most influential support people noted were immediate family, especially wives. The participants also believed that high school counselors were of no assistance in choosing nursing as a career. Even though the schools of nursing were perceived as supportive, the participants had feelings of isolation and self-doubt.

Adult↗
PubMed1993

Role of colposcopy in the diagnosis and outpatient treatment of cervical intraepithelial neoplasia.

One hundred and seventy nine women with abnormal smears referred for colposcopy to the Samaritan Hospital were studied. After confirming CIN on repeat smear, colposcopy and histology, cone biopsy was carried out. One hundred and twenty one patients (68%) had treatment either with electrical loop diathermy under local anaesthesia (105 patients, 59%) or laser excision of transformation zone under general anaesthesia as a day case (16 patients, 9%). Cone biopsy was done in 121 patients (32%). We conclude that colposcopy is a valuable tool in combination with cytology and histology for diagnosis and delineating the extent of CIN, thus avoiding unnecessary cone biopsies particularly in women of child bearing age. The majority of patients were treated by an outpatient procedure, which is easy to learn, safe, effective and inexpensive.

Adolescent↗
PubMed1992

Comparison of the efficacy and adverse effect profile of cefotaxime and ceftriaxone in ICU patients with susceptible infections.

In a prospective randomized double-blind trial, the efficacy and safety of cefotaxime and ceftriaxone were compared in intensive care unit (ICU) patients with serious infections requiring systemic antimicrobial therapy. Patients were randomly assigned to receive either cefotaxime 1 g i.v. t.i.d. or ceftriaxone 2 g every 24 hr. Clinical and bacteriologic assessments were made before treatment, at 48 hr and 5 days during treatment, and 48 hr after treatment. At the time of reporting, a total of 34 patients had been entered into the trial, 27 of whom were evaluable; 23 patients (85%) completed a minimum of 5 days antibiotic treatment. At the end of treatment, using current statistics 67% of cefotaxime and ceftriaxone patients demonstrated clinical cure or improvement. Bacteriologic responses appeared greater in the cefotaxime group (55% vs 42%). The incidence of adverse effects, which were usually minor, was similar in each group. From these preliminary results, it would appear that at the doses used in this study, cefotaxime and ceftriaxone are equally effective in the treatment of infections in the ICU.

Adolescent↗
PubMed1977

A case of coccidioidomycosis in Australia.

We report what we believe to be the first case of coccidioidomycosis to be diagnosed within Australia, and emphasize the dangers of handling Coccidioides immitis in the laboratory.

Animals↗
PubMedDate not supplied

Synthesis and neurotoxicological evaluation of putative metabolites of the serotonergic neurotoxin 2-(methylamino)-1-[3,4-(methylenedioxy)phenyl] propane [(methylenedioxy)methamphetamine].

Theoretical considerations and recent experimental data have prompted an investigation of the neurotoxicological properties of the 6-hydroxydopamine analogue 2-(methylamino)-1-(2,4,5-trihydroxyphenyl)propane (5) and its possible precursor 1-[2-hydroxy-4,5-(methylenedioxy)phenyl]-2- (methylamino)propane (4), potential metabolites of the serotonergic neurotoxin MDMA. Systemic, intracerebroventricular, and intraparenchymal (intrastriatal and intracortical) administration of 4 led to no detectable alterations of hippocampal or cortical serotonin or striatal dopamine levels in the rat under conditions that caused significant biogenic amine depletions by established neurotoxins. By contrast, intraparenchymal administration of 5 caused profound depletions of dopamine and serotonin, with the former being more severely depleted than the latter. Although not conclusive, these data suggest a possible role for 5 in the mediation of MDMA's neurotoxic actions.

3,4-Methylenedioxyamphetamine↗