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Biomedical subjects

D Stewart

Publications and source records attributed to D Stewart.

At least 145 records · Page 8Linked to original sources
PubMed1998

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Antiemetics↗
PubMed1998

A double-blind, multicenter clinical trial comparing efficacy of once-daily metronidazole 1 percent cream to vehicle in patients with rosacea.

The efficacy and safety of a new formulation of metronidazole 1 percent cream applied once daily was compared to vehicle cream in a double-blind, randomized, parallel group, ten-week clinical study. The results showed that metronidazole 1 percent cream was significantly better than vehicle in reducing the lesions of rosacea, improving erythema, and physician's global rosacea scores. The incidence of adverse events related to the skin was low.

Administration, Topical↗
PubMed1998

Preparation, attitudes and behaviour in nonhospital cardiac emergencies: evaluating a community's readiness to act.

OBJECTIVE: To determine how people in a moderately sized Ontario city believe they will react if they witness someone colapsing. DESIGN: Telephone survey. SETTING: The cities of Kitchener and Waterloo, part of the Regional Municipality of Waterloo, Ontario, with a combined population of 378,000. PARTICIPANTS: Households were randomly contacted and a questionnaire was administered, provided the respondent was over 44 years of age and agreed to be interviewed. Of 2479 households with eligible respondents, 811 (33%) completed the questionnaire. OUTCOMES: Age, sex, educational level, cardiac risk factors and cardiopulmonary resuscitation (CPR) training of respondents were determined, as well as actions they would take if cardiac arrest occurred in a family member at home or in stranger in the street, and associated emotions and barriers to implementing actions. RESULTS: Among the first three actions that respondents who were not prompted with possible responses said they would take, 311 (72%) witnessing a collapse at home, compared with 166 (44%) witnessing a collapse on the street, would call 911, the police or an ambulance. Other 'first three actions' in home collapse were checking for breathing (120 [28%]), checking for pulse (91 [21%]) and administering CPR (34 [8%]); these actions were less commonly selected in response to a strangers collapse and when respondents were not prompted. Respondents felt they would be more likely to perform CPR on a friend than on a stranger (OR 1.38, 95% CI 1.10 to 1.58). When asked how likely they would be to perform specific acts when witnessing a collapse, 254 (69%) of respondents thought they would call their family doctor and 179 (48%) thought they were likely to begin chest compressions. Barriers to performing CPR centred around legalities and disease transmission. CONCLUSION: Older people do not know how to act effectively in a cardiac emergency. Traditional CPR and public awareness programs have been ineffective in reaching this population; alternative means are required to help the public respond more effectively to cardiac emergencies.

Accidents↗
PubMed1998

Update on endothelin.

Endothelin is a very potent vasoconstrictor peptide produced by the vascular endothelium. Several studies have shown that the endothelin system is activated in various cardiovascular conditions, including myocardial infarction, heart failure and pulmonary hypertension. The known actions of the endothelin-1 isoform suggest that it may be an important mediator in several of the pathophysiological manifestations of heart failure. Data on the potential value of endothelin antagonists in heart failure are reviewed.

Endothelin-1↗
PubMed1998

[Treatment of cancer of the bladder in elderly patients with an intra-arterial chemotherapy and radiotherapy combination: 10-year experience].

PURPOSE: Analysis of the results obtained in elderly (75 years and older) included a phase II trial combining intra-arterial cisplatin and concurrent radiation into invasive bladder cancer. PATIENTS AND METHODS: Thirty-five patients (28 males and 7 females) were accrued from 1985 to 1996. There were 1 Ta, 4 T2, 11 T3A, 12 T3B, 3 T4A, and 4 T4B patients. Nine had unilateral hydronephrosis and two bilateral hydronephrosis. There were 28 transurethral resections which were incomplete in 23 patients. Intra-arterial cisplatin was given as 2-4 hours infusion (60-90 mg/m2) split through both internal iliac arteries on day 1, 14, 21, and 42. Irradiation to the pelvis was started on day 14 and consisted of 40 Gy/20 fractions followed by a boost of 20 Gy/10 fractions to the tumor with margins of 2 cm. RESULTS: Thirty (86%) completed fully the protocol. One patient died from sepsis secondary to the treatment. The tumor response was evaluable in 29 patients and complete response was observed for 27 of them. Five of these 27 patients had an isolated bladder relapse which was salvaged by cystectomy in two patients. There were 11 deaths from bladder cancer (31% of the patients): 9 from distant metastase, one from local failure, and one from treatment. CONCLUSION: This combined modality yields excellent results with high complete response rate and good tolerance. This approach may therefore be particularly appropriate for the elderly.

Aged↗
PubMed1998

Guidelines for the management of Parkinson's disease. The Parkinson's Disease Consensus Working Group.

Parkinson's disease is a chronic and disabling illness and there is currently wide variation in its management. This article presents the first UK-specific guidelines for the management of Parkinson's disease and it contains a treatment decision free to aid the physician in deciding when and how to treat patients. We hope this document will prove useful to all those involved in the planning and delivery of care to patients with Parkinson's disease.

Aged↗
PubMed1997

X-ray crystallographic studies of Candida albicans dihydrofolate reductase. High resolution structures of the holoenzyme and an inhibited ternary complex.

The recent rise in systemic fungal infections has created a need for the development of new antifungal agents. As part of an effort to provide therapeutically effective inhibitors of fungal dihydrofolate reductase (DHFR), we have cloned, expressed, purified, crystallized, and determined the three-dimensional structure of Candida albicans DHFR. The 192-residue enzyme, which was expressed in Escherichia coli and purified by methotrexate affinity and cation exchange chromatography, was 27% identical to human DHFR. Crystals of C. albicans DHFR were grown as the holoenzyme complex and as a ternary complex containing a pyrroloquinazoline inhibitor. Both complexes crystallized with two molecules in the asymmetric unit in space group P21. The final structures had R-factors of 0.199 at 1.85-A resolution and 0.155 at 1.60-A resolution, respectively. The enzyme fold was similar to that of bacterial and vertebrate DHFR, and the binding of a nonselective diaminopyrroloquinazoline inhibitor and the interactions of NADPH with protein were typical of ligand binding to other DHFRs. However, the width of the active site cleft of C. albicans DHFR was significantly larger than that of the human enzyme, providing a basis for the design of potentially selective inhibitors.

Amino Acid Sequence↗
PubMed1997

Acute and long-term effects of the angiotensin-converting enzyme inhibitor, enalapril, on adrenergic activity and sensitivity during exercise in patients with left ventricular systolic dysfunction.

Patients with heart failure and left ventricular systolic dysfunction exhibit increased adrenergic activity but blunted adrenergic responsiveness. We studied patients enrolled in the Studies of Left Ventricular Dysfunction, examining exercise responses of heart rate (HR) and plasma norepinephrine (PNE). Eighty-seven patients were studied before randomization; 65 of these were examined 1 year after randomization to placebo or enalapril. Compared with prevention trial (asymptomatic) patients, patients in the treatment trial (symptomatic) had higher resting HR and PNE levels and less increase in HR with a greater increase in PNE with exercise. Acute administration of enalapril increased the resting HR in patients in the prevention trial only but had no significant effect on PNE. After 1 year of therapy, patients in the prevention trial exhibited no change. Within the treatment trial, the placebo group displayed both a higher peak PNE and increase in PNE with exercise than did the enalapril group, whose HR response was maintained in spite of a reduction of exercise PNE. We conclude that (1) compared with asymptomatic patients, symptomatic patients with reduced left ventricular ejection fraction manifest greater resting and exercise adrenergic activity, with blunted HR response; and (2) in symptomatic patients, 1 year of enalapril treatment effected an augmented HR response to adrenergic stimulation, supporting an interaction between the renin/angiotensin and adrenergic nervous systems. Normalization of adrenergic tone and response likely contributes to the benefits of long-term angiotensin-converting enzyme inhibitor therapy.

Aged↗
PubMed1997

The feasibility of assessing women's perceptions of the risks and benefits of fertility drug therapy in relation to ovarian cancer risk.

OBJECTIVE: To determine the feasibility of asking women undergoing fertility treatment the maximum increased risk of ovarian cancer they would be willing to tolerate in order to take ovulation-induction drugs. DESIGN: A prospective pilot study of women attending fertility clinics over a 2-month period. SETTING: Two tertiary care fertility clinics in Toronto. PATIENT(S): Sixty-one English-speaking women were approached and 85% (n = 52) were enrolled. INTERVENTION(S): A self-administered questionnaire with fertility-specific questions. Thirty-eight women also were asked to complete standardized scales of anxiety and optimism. MAIN OUTCOME MEASURE(S): Women's report of the maximum level of lifetime risk of ovarian cancer they were willing to tolerate in order to undergo fertility treatment. RESULT(S): Seventy-nine percent were willing to accept an increased risk of ovarian cancer. Only 24% understood that treatment for ovarian cancer usually was not curative. CONCLUSION(S): A majority of patients were willing to tolerate a modest increase in their lifetime risk of ovarian cancer because of fertility treatment, most basing their estimate of acceptable risk on limited awareness of the issue.

Adult↗
PubMed1997

Effect of fluoxetine on menstrual cycle length in women with premenstrual dysphoria.

OBJECTIVE: To examine whether changes in menstrual cycle length occurred in women who received 20 mg of fluoxetine per day and women who received 60 mg of fluoxetine per day as compared with women who received placebo. METHODS: A two-cycle, single-blind placebo phase was followed by a six-cycle double-blind phase. Only placebo nonresponders were randomized to one of three treatment arms: placebo, fluoxetine 20 mg/day, or fluoxetine 60 mg/day. Cycle length was established using a prospective daily calendar. Cycle-length data from women who completed at least three treatment cycles were used in this analysis. Cycle-length change was defined a priori as cycle lengthening or shortening of 4 days or more (1 or more standard deviations from the mean change between baseline cycles). RESULTS: Eleven of the 62 women receiving 60 mg of fluoxetine per day and seven of the 70 women receiving 20 mg of fluoxetine per day but only one of the 61 women in the placebo group demonstrated cycle-length change at the end of the first treatment cycle (P = .011). In total, 15% of the women in the fluoxetine 60 mg/day group demonstrated a cycle-length change during two of the three observed cycles compared with 6% of the women in the fluoxetine 20 mg/day group and 3% of the women in the placebo group (P = .048). Women with cycle-length changes demonstrated either shortening or lengthening only. There were no differences between the number of women with changes in either direction. CONCLUSION: Cycle-length change occurred more frequently in the fluoxetine 60 mg/day group than in the fluoxetine 20 mg/day or placebo groups. The effects of selective serotonin reuptake inhibitors on menstrual cycle length are mostly unknown and warrant careful monitoring in women of reproductive age, who are the prime consumers of these medications.

Adult↗
PubMed1997

One-week therapy with twice-daily butenafine 1% cream versus vehicle in the treatment of tinea pedis: a multicenter, double-blind trial.

BACKGROUND: Butenafine hydrochloride, a benzylamine derivative with potent antifungal activity, has been used in Japan to treat superficial fungal diseases. OBJECTIVE: We evaluated the safety and efficacy of twice-daily butenafine versus its vehicle in the treatment of interdigital tinea pedis in a multicenter, randomized, double-blind, parallel-group trial. METHODS: A total of 402 patients with interdigital tinea pedis and a positive potassium hydroxide examination were enrolled. Of the 271 patients who had culture-confirmed tinea pedis and were assessed for efficacy, 132 applied butenafine and 139 applied vehicle twice daily for 1 week. Patients were assessed for mycologic cure, effective treatment, overall cure, and mycologic/clinical cure. RESULTS: The rates of all four end points were significantly higher with butenafine than with vehicle 5 weeks after treatment ended. Rates of mycologic cure and effective treatment with butenafine were significantly higher than with vehicle at cessation of treatment. Adverse events to treatment occurred in less than 1% of patients treated with butenafine and 2% of patients who applied vehicle. CONCLUSION: Butenafine applied twice daily for 1 week is highly effective in treating interdigital tinea pedis.

Administration, Topical↗
PubMed1997

Partially mismatched blood cell transplants for high-risk hematologic malignancy.

Eleven patients with high-risk hematologic malignancy received cryopreserved but otherwise unmanipulated blood cell transplants (BCT) from partially mismatched family members in whom progenitor cells had been mobilized by G-CSF. Donors were mismatched by up to one antigen in the GVH direction and up to three antigens in the rejection direction. Outcomes were compared with those of 22 patients receiving BCT from fully matched donors. Two mismatched patients died without engraftment on day 21 and 32. One had rejected bone marrow from the same donor, the other was mismatched by two antigens in the rejection direction and received the lowest dose of CD34+ cells. Median time to granulocyte engraftment was 21.5 (range 16-33) days for the mismatched group compared with 16 (11-28) days for the matched group (P = 0.01). No correlation was found between CD34+ cell dose and time to granulocyte or platelet recovery. In the mismatched and matched BCT groups respectively, the risk of grade II-IV acute graft-versus-host disease (GVHD) was 73% vs 28% (P = 0.001) and of chronic GVHD 100% vs 78% at 18 months (P = 0.01). The relationship of T cell dose to acute GVHD could only be evaluated in the matched group and no correlation was found. One of 11 mismatched patients and eight of 22 matched patients had relapse or persistent disease. Disease-free survival at 1 year was similar at 55% for mismatched and 50% for matched BCT. These results indicate that allogeneic BCT from partially mismatched family members is accompanied by a high incidence of GVHD but may result in comparable survival to BCT from fully matched donors.

Adolescent↗
PubMed1997

Factors influencing yields of progenitor cells for allogeneic transplantation: optimization of G-CSF dose, day of collection, and duration of leukapheresis.

Mobilization of hematopoietic progenitor cells by G-CSF was attempted on 89 occasions in 85 healthy donors. Three dose ranges of G-CSF were chosen for analysis: low (4-7.4 micrograms/kg), intermediate (7.5-10 micrograms/kg) and high (> 10 micrograms/kg). A target blood level for apheresis of 20 x 10(6)/L CD34+ cells was reached by day 3 in 75 patients (84%) and by day 4 in all but 1 (99%). Target yields above 2.5 x 10(6)/kg for 75 unmanipulated transplants were exceeded in a single collection in 73 donors (97%). Correlation of CD34+ cell yields to blood CD34+ cell level before leukapheresis was moderate only (r2 = 0.32). There was close linear correlation between processed volume and cumulative CD34+ cell yield, with a median r2 value of 0.98 (range 0.74-1.00). Yields of CD34+ cells achieved on day 3 were significantly lower after the high dose than after the intermediate G-CSF dose (21 +/- 3 versus 29 +/- 6 x 10(6)/L blood processed, p = 0.03). After the low dose of G-CSF, yields on day 4 were higher than on day 3 (48 +/- 10 versus 22 +/- 4 x 10(6)/L blood processed, p = 0.01). There was no difference between day 3 and day 4 yields with the intermediate G-CSF dose. In 73 of 93 (78%) leukaphereses, the CD34+ cell yield was more than 100% of the estimated intravascular CD34+ cells at the beginning of collection and ranged up to 342%. These data indicate that a daily dose of 7.5-10 micrograms/kg G-CSF, given as a multiple of 300 and 480 micrograms ampoules, is a convenient regimen giving adequate yields from a single collection on day 3 or 4 in most donors. Measuring blood CD34+ cell levels is of limited value in predicting yields, but monitoring CD34+ cell yields during leukapheresis may help to minimize unnecessary or inefficient collection.

Antigens, CD34↗
PubMed1997

HLA class I genotyping by cDNA sequence of a Vietnamese family expressing a weak B46 antigen.

Serological heterogeneity in HLA-B46 antigens has been described. Previous studies have identified B*4601 as the allele encoding the "strong" B46 antigen found in Chinese populations. Serological characterization of a Vietnamese family revealed a "weak" B46 antigen. Complementary DNA for the HLA-A, B and C alleles of three family members were cloned and the coding regions sequenced. The allele encoding the weak B46 antigen has the same coding sequence as B*4601, demonstrating that the antigenic differences are not due to polymorphism in the amino acid sequence of the HLA-B heavy chain. The recently described HLA-B*1525 and HLA-Cw*0403 alleles were also found to segregate in this Vietnamese family.

Alleles↗
PubMed1997

Bacteraemia caused by periodontal probing.

Bacteraemia of oral origin may result in infective endocarditis in susceptible individuals. The aim of this pilot study was to investigate the occurrence of bacteraemia due to periodontal probing. Thirty patients (15 male, 15 female; mean age 42.7 years) with untreated periodontitis were investigated. All were free of significant medical disorders and none had taken antibiotics in the previous month. Prior to and immediately following periodontal probing, 20 mL of venous blood were obtained from each patient and inoculated into aerobic and anaerobic blood culture bottles and incubated. Negative bottles were monitored continuously for three weeks before being discarded. Periodontal probing consisted of measuring pockets at six points around each tooth and recording the presence or absence of bleeding. A positive bacteraemia was recorded for three of the patients prior to probing. One patient exhibited Prevotella species whilst two exhibited skin commensals. Following probing, 13 patients (43 per cent) exhibited bacteraemia of oral origin. Viridans streptococci were the most common isolates (45 per cent). No significant correlations were found between bacteraemia and the severity of periodontitis or extent of bleeding on probing. The results indicate that periodontal probing can cause bacteraemia in patients with periodontitis. It would be advisable for patients considered at risk of developing infective endocarditis to receive antibiotic prophylaxis for periodontal probing if they have radiographic evidence of periodontitis.

Adult↗