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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 19 recordsLinked to original sources
PubMed1992

Antitumor activity and clinical pharmacology of sulofenur in ovarian cancer.

BACKGROUND: Sulofenur is a diarylsulfonylurea with demonstrated antitumor activity in patients with advanced epithelial ovarian cancer refractory to standard chemotherapy. The dose-limiting toxic effects observed in phase I clinical trials have been anemia and methemoglobinemia, resulting in cyanosis. PURPOSE: The purposes of this study were to further define the response rate, toxic effects, and pharmacokinetics and pharmacodynamics of sulofenur in patients with advanced ovarian cancer. METHODS: We conducted a phase II trial of sulofenur at a dose of 800 mg/m2 per day in 35 patients with stage III or IV ovarian cancer refractory to standard chemotherapy. Pharmacokinetics and pharmacodynamics were analyzed by comparing sulofenur parent and metabolite plasma levels with methemoglobin levels. RESULTS: Partial responses lasting 6.5-18 weeks occurred in four (15%; 95% confidence interval = 4%-35%) of the 26 patients assessable for response. In addition, 42% (11) of the assessable patients had prolonged stable disease (median, 20 weeks). The first nine patients received sulofenur as a daily oral dose for 14 days, with a 21-day treatment cycle. However, they developed substantial anemia and methemoglobinemia. As a result, the next 26 patients received sulofenur daily for 5 days followed by 2 days of rest for 3 consecutive weeks, with a 28-day treatment cycle (5/2-day schedule). Preclinical models predicted that 2 days of rest would decrease toxicity while maintaining antitumor activity. Patients treated with the 5/2-day schedule had relatively less severe anemia and methemoglobinemia and needed fewer red blood cell transfusions (31% versus 78% of patients), but 31% still required dose reductions because of these toxic effects. The hydroxy and keto metabolites of sulofenur had prolonged plasma half-lives relative to the parent compound, and the difference was statistically significant. In addition, the correlations of metabolite concentrations with methemoglobin levels were higher than the correlation of sulofenur concentrations with methemoglobin levels, and those differences were statistically significant. CONCLUSION: We conclude that sulofenur has modest clinical activity in heavily pretreated patients with ovarian cancer. IMPLICATIONS: The toxic effects of anemia and methemoglobinemia may limit the ultimate clinical utility of diarylsulfonylureas until less toxic derivatives with alternate metabolic pathways can be identified.

Adult↗
PubMed1992

Sensitive method for the quantitation of nortriptyline and 10-hydroxynortriptyline in human plasma by capillary gas chromatography with electron-capture detection.

A method for the determination of nortriptyline and 10-hydroxynortriptyline concentrations in human plasma by capillary gas chromatography with electron-capture detection is described. The procedure requires 1.0 ml of plasma and uses maprotiline as an internal standard. The compounds are extracted from alkalinized plasma with hexane-2-butanol (98:2) and back-extracted into hydrochloric acid. The acid solution is then made basic and the compounds are re-extracted into n-butyl chloride. The extract is evaporated to dryness, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography on a fused-silica capillary column coated with phenylmethyl silicone. The calibration curves for nortriptyline and 10-hydroxynortriptyline are linear in the ranges 3-40 and 7-90 micrograms/l, respectively, with coefficients of variation for within-day and between-day precision of less than 12%. The quantitation limits for nortriptyline and 10-hydroxynortriptyline are 1 and 3 micrograms/l, respectively. This procedure was used to analyze more than 1400 samples following sub-therapeutic doses of nortriptyline in human subjects. The assay was sufficiently sensitive for use in pharmacokinetic analysis.

Chromatography, Gas↗
PubMed1992

Prospective study of short and long regimens of gonadotropin-releasing hormone agonist in in vitro fertilization program.

OBJECTIVE: To assess the usefulness of a short regimen in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial was set up to compare long and short regimens of gonadotropin-releasing hormone agonist administration for ovulation induction in IVF. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Eighty-seven patients undergoing IVF were randomized between the two protocols. Stimulation regimen was the only variable being tested. MAIN OUTCOME MEASURES: Stimulation response and occurrence of luteinizing hormone (LH) surges. RESULTS: There was no difference in the stimulation requirements, response to stimulation, number of follicles aspirated, or the number of oocytes obtained. The fertilization rates, number of embryos transferred, and pregnancy rates were also similar in both groups. Like the long regimen, it prevents the occurrence of a premature LH surge. CONCLUSION: The short regimen is a useful and cheaper alternative in ovarian stimulation of patients undergoing IVF.

Adult↗
PubMed1992

Prospective study of short and ultrashort regimens of gonadotropin-releasing hormone agonist in an in vitro fertilization program.

OBJECTIVE: To assess the usefulness of the ultrashort regimen of gonadotropin-releasing hormone agonist (GnRH-a) in ovulation induction in an in vitro fertilization (IVF) program. DESIGN: A prospective randomized trial comparing short and ultrashort regimens of GnRH-a. SETTING: Aberdeen Assisted Reproduction Unit. PATIENTS: Forty-eight patients having IVF for the first time were randomized between the two protocols. MAIN OUTCOME MEASURES: Response to ovarian stimulation and occurrence of spontaneous luteinizing hormone (LH) surges. RESULTS: In ovulation induction, fertilization, and pregnancy rates the ultrashort regimen produces results that were no different to the short regimen but it did not always prevent an LH surge. CONCLUSION: The ultrashort regimen can be a useful alternative for ovarian stimulation of patients undergoing IVF.

Adult↗
PubMed1992

Physical examination of swine.

Swine may be examined to evaluate a disease state or a lowered economic performance or as a herd health consultation. As much of the examination as possible should be performed without handling the animal. A thorough history, evaluation of herd records, environmental examination, and herd examination should be performed prior to the evaluation of an individual animal. All necessary equipment should be available when starting the individual examination. The animals is then restrained and examined, and necessary samples are taken. Post-mortem examinations or slaughter house evaluations are a very frequent part of a health examination on swine. All samples taken should be in accordance with the standards of the laboratory that you use. You should work closely with the laboratory to obtain the best results. Physical examination of swine can be rewarding for the veterinarian as well as the producer. The most important aspect to remember is to have enough information and the proper equipment available to handle the animals for the minimal amount of time to gain the maximum benefits. Vietnamese pot-bellied pigs are similar to domestic swine in terms of their diseases and health but are dissimilar in management; pot-bellied pigs are frequently brought to the veterinarian for individual examinations. History is the most valuable part of the examination, followed by observation. Pot-bellied pigs prefer to be held securely with a hand under the chin and rump. The examination is conducted similarly to the examination of any companion animal. Chemical restraint often is necessary for sampling or minor surgical procedures. Owners should be consulted prior to the use of any restraint. This will help win their approval and confidence when working on their pets. While performing the physical examination, look at the pig's overall health as well as specific breed characteristics. Try to stay abreast of swine vaccination recommendations; you may be consulted in this regard. Most importantly, never forget even though they are pigs, pot-bellied pigs are companion animals and should be handled as such.

Animals↗
PubMed1992

The consequences of a change in formulation of methadone prescribed in a drug clinic.

Methadone mixture DTF (1mg in 1ml) is a safe non-injectable alternative to methadone tablets (5mg). It also allows for a more gradual detoxification from opiate dependence. For these reasons it was decided to 'rationalise' our prescribing so that methadone in mixture form only would be dispensed. At the beginning of 1989, 66 opiate-dependent patients were receiving methadone tablets, 61 the methadone mixture. We report the consequences of instituting a policy change which was clearly very unpopular with patients. Of the 66 patients receiving methadone tablets prior to the change to mixture, 53 were represcribed tablets by the end of the 3-month follow-up period. In many cases this was because of an intense resistance to the change over, physical complications of methadone mixture occurred in very few. We were able to observe a decline in social stability and an increased use of non-prescribed drugs in some patients who changed to methadone mixture. More far-reaching consequences of the change included an increase in chemist break-ins, an increase in the street value of methadone tablets and greater hostility and threatening behaviour towards staff. These changes reflect psychological rather than pharmacological or pharmacokinetic effects.

Adult↗
PubMed1991

Utilization of dental services by older adults in four Ontario communities.

The elderly tend to use dental services less than most younger age groups. While the elderly's utilization rates may be rising, very low utilization by edentulous people depresses the overall rate for the group. We use data from the Ontario Study of the Oral Health of Older Adults to identify the variations in the use of dental services in the four study sites of Toronto, North York, Simcoe County and Sudbury and District. We reached 3,033 subjects by telephone and conducted dental examinations and a multi-item personal interview with 907 of them. The 907 subjects ranged in age from 50 to 87 years, 57 percent were female and two-thirds were born in Canada. Overall, 60.5 percent had seen a dentist or denturist in the previous year, but this was much lower among the edentulous (17 percent) when compared to the dentate (72 percent) (Chi-square test; p less than .0001). Of the 357 who did not visit a dentist or denturist in the previous year, nearly half (48 percent) felt they had nothing wrong and 20 percent reported they could not afford care. A high proportion (94 percent) of the edentulous reported visiting only for pain or trouble compared to 26 percent of the dentate (Chi-square test; p less than .0001). Using logistic regression, we found dental status (edentulous), community of residence (Sudbury), income (up to $20,000) and dental insurance coverage (none) were important factors in not making a dental visit in the last year. These same factors, plus education (elementary) were important where subjects reported visiting a dentist or denturist only when there was pain or trouble.

Aged↗
PubMed1979

A comparative trial of the decanoates of flupenthixol and fluphenazine.

A double-blind trial was carried out comparing the effects of decanoates of flupenthixol and fluphenazine on the symptoms, ward behaviour and functional capacity in occupational therapy in 51 chronic schizophrenic patients. The patients were carefully selected on the basis of rigid criteria for diagnoses. To exclude nonresponders to neuroleptics the patients were first taken off neuroleptic drugs and only those who appeared to show deterioration were included in the trial. The dosage of drugs was varied according to clinical indications. The length of the trial was initially 4 months and 31 patients were followed for an additional 4 months. To ensure reliability multiple assessments were made at the start and the end of the trial. Most of the statistical tests showed no differences between the treatments, but some of those relating to affective symptoms showed an advantage for flupenthixol as compared with fluphenazine. There were no differences in the incidence of extra-pyramidal side-effects which required treatment in only 32% of the patients on each drug.

Adult↗
PubMed1979

Post-ECT cognitive defect and elevation of blood pressure.

There is evidence that ECT causes a breakdown of the blood-brain barrier through the rise of blood pressure it induced. Using the Benton test of cognitive function the day before and three hours after ECT treatment in 27 depressed patients, impairment of function was highly correlated with the maximum rise of systolic BP during the treatment.

Adult↗
PubMed1979

[Rating of antidepressant activity (author's transl)].

In this brief review. I have mentioned recent developments and the possibility of new ones. I have referred to technical problems in the organisation of trials, the selection of patients, methods of assessment and their statistical anlaysis, the specific problems of side-effects of drugs and, finally, the social aspects of depressive illness.

Antidepressive Agents↗
PubMed1979

Effects of carbon monoxide on operant behavior of laboratory rats and baboons.

Carbon monoxide (CO) was evaluated for its effects on the operant behavior of laboratory rats and juvenile baboons. For the rat studies the procedures included a 2-min variable interval (2-min VI) or fixed interval (2-min FI) schedule of reinforcement, a 60:1 fixed ratio (FR) schedule and a multiple fixed ratio, fixed interval (FR:FI) schedule. Carbon monoxide concentrations of 50-200 ppm for 2-hr exposure periods produced minimal effects on VI rates. Response rates were increased for all animals somewhere in the concentration range of 25-200 ppm. Response rates were depressed at 500 ppm CO. Behavioral effects at 50 ppm CO were not correlated with blood CO levels. Data averaged for grops of three animals show FI rate increased slightly above controls at 50 and 100 ppm CO and decreased at 200 ppm. FR rate increased at 50 ppm and decreased at 100 and 200 ppm. For the baboon studies, a delayed match-to-sample discrimination task was used. The effects of CO (6 hr per day over a 5-day period) on the discrimination task was limited to an occasional mistake by an animal. CO did produce a slowing of the animals' response times as well as an increase of extra responses during the delay intervals. The changes in extra responses were dose related.

Animals↗