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Biomedical subjects

M Hamilton

Publications and source records attributed to M Hamilton.

At least 91 records · Page 5Linked to original sources
PubMed1996

Outcomes of patients undergoing transplantation with older donor hearts.

BACKGROUND: The limited number of donor hearts relative to the number of waiting recipients is the major determinate of a growing inequity. Although a number of potential options are being vigorously pursued, the most effective immediate solution is to expand acceptance criteria for donor age and medical condition. This report is a review of our early and late results with the use of older donors, including simultaneously "bypassed" donor hearts. METHODS: Between April 1987 and September 1994, 52 patients received older donor hearts (older than 45 years) with a mean donor age of 51 years. Ten patients in this group received hearts simultaneously bypassed with from 1 to 4 grafts per patient. Donor and recipient age, diagnosis, and HLA match were compared between the older donor group and a contemporaneous younger (younger than 45) donor group (N = 324). Also compared was actuarial survival at up to 5 years of follow-up in addition to graft function, bypass graft patency, infection and rejection incidence at 1 year, and the prevalence of transplant-associated coronary artery disease in the two groups. Echocardiography, coronary angiography, and intravascular coronary ultrasonography were used for this assessment. RESULTS: One-year actuarial survival was 84% for the older donor group, which included 19 status 1 patients (survival 76%) and 23 status II patients (survival 90%). In the bypassed donor subgroup there was a 60% 1-year actuarial survival with 5 status 1 patients (survival 80%) and 5 status II patients (survival 40%). At 1 year, left ventricular function and the incidence of infection and rejection were equal between these two donor groups. Five-year actuarial survivals were the same between the overall older and younger donor groups. Finally, the development of transplant-associated coronary disease was similar in both groups up to 5 years after transplantation. CONCLUSIONS: This initial review of heart transplantation with older donor hearts, including bypassed hearts, demonstrates similar early and late survival outcomes as compared with those of a contemporaneous younger donor group. Significantly, there appears to be no difference in the development of transplant-associated coronary artery disease during the follow-up period. The older donor represents a potential immediate increase in the number of suitable hearts for transplantation. Bypassed donor hearts represent a small but potentially significant subgroup that may be safely and effectively used when appropriately matched to the recipient by age and medical condition. Greater experience, particularly with this bypassed group, will help determine optimal donor-to-recipient matching for the future.

Adult↗
PubMed1996

Chlorhexidine spray effects on plaque accumulation in developmentally disabled patients.

Chlorhexidine gluconate has been studied as an adjunct to standard oral hygiene techniques in developmentally disabled patients in reducing plaque accumulation. The purpose of this double blind crossover study was to determine the efficacy of two concentrations of chlorhexidine spray (0.12% and 0.06%) on plaque accumulation in developmentally disabled patients. Informed consent was obtained for 8 developmentally disabled patients 12 to 33 years of age. Patients were randomly assigned to one of two groups of four each. One group received twice daily 0.12% chlorhexidine spray while the other received the 0.06% chlorhexidine spray for 30 days, followed by twice daily chlorhexidine spray (0.12% and 0.06%) alternating groups, for a period of 30 days. Final plaque indices were determined. Normal oral hygiene practices continued throughout the study. Significant plaque reduction occurred with the 0.12% and 0.06% spray solutions. No significant differences occurred between the two concentrations. The results of this study suggest that twice daily chlorhexidine spray at a concentration of 0.06% is as effective in reducing plaque accumulation as a 0.12% chlorhexidine concentration.

Adolescent↗
PubMed1995

Validated assays for the determination of gemcitabine in human plasma and urine using high-performance liquid chromatography with ultraviolet detection.

Procedures are described for the determination of gemcitabine, a new anti-tumor agent, and its uridine metabolite in human plasma and in human urine. The sample preparation for the plasma assay involves precipitation of plasma proteins with isopropanol and ethyl acetate. Following this, the solids are discarded and the supernatant is evaporated to dryness. For the urine assay, the sample is diluted with methanol and evaporated to dryness. For both procedures, the residue is reconstituted in mobile phase prior to injection into a normal-phase (amino column) liquid chromatographic system followed by UV detection at 272 nm. The limits of quantitation for both compounds are 50 ng/ml in plasma and 20 micrograms/ml in urine. The procedures were used to provide pharmacokinetic data for both compounds in man following the intravenous administration of a 1000 mg/m2 dose of gemcitabine.

Antimetabolites, Antineoplastic↗
PubMed1995

Assessing Impact of Weight on Quality of Life.

This paper is a preliminary report on the development of a new instrument, the Impact of Weight on Quality of Life (IWQOL) questionnaire, that assesses the effects of weight on various areas of life. We conducted two studies utilizing subjects in treatment for obesity at Duke University Diet and Fitness Center. The first study describes item development, assesses reliability, and compares pre- and post-treatment scores on the IWQOL. In the second study we examined the effects of body mass index (BMI), gender, and age on subjects' perceptions of impact of weight on quality of life. Results indicate adequate psychometric properties with test-retest reliabilities averaging .75 for single items, and .89 for scales. Scale internal consistency averaged .87. Post-treatment scores differed significantly from pre-treatment scores on all scales, indicating that treatment produced positive changes in impact of weight on quality of life. The results of the second study indicate that the impact of weight generally worsened as the patients' size increased. However for women there was no association between BMI and impact of weight on Self-Esteem and Sexual Life. Even at the lowest BMI tertile studied, women reported that weight had a substantial impact in these areas. There were also significant gender differences, with women showing greater impact of weight on Self-Esteem and Sexual Life compared with men. The impact of age was a bit surprising, with some areas showing positive changes and others showing no change.

Adult↗
PubMed1995

The metabolites of nitric oxide in sickle-cell disease.

Plasma NOx concentrations were raised in 22 acute painful crises in SCD. We have measured blood concentrations of nitric oxide metabolites (NOx) in sickle-cell disease (SCD), and shown that they are increased compared with healthy controls (P = 0.002), and haemoglobin E/beta-thalassaemic controls (P = 0.05). Concentrations in steady-state SCD were also higher than in healthy controls (P = 0.04) but not significantly different from the concentrations at the beginning of painful crises (P = 0.34). Importantly, in 12 regularly exchanged sicklers, the mean pre-transfusion NOx concentration did not differ significantly from the control population (P = 0.52), suggesting that the changes in NO metabolism can be reversed. It is unlikely that the increased concentrations of NOx in SCD result from anaemia or haemolysis as the untransfused haemoglobin E/beta-thalassaemics did not show increased levels.

Acute Disease↗
PubMed1995

A scale for the assessment of hedonic tone the Snaith-Hamilton Pleasure Scale.

BACKGROUND: Hedonic tone and its absence, anhedonia, are important in psychopathological research, but instruments for their assessment are lengthy and probably culturally biased. METHOD: A new scale was constructed from the responses of a large sample of the general population to a request to list six situations which afforded pleasure. The most frequent items were reviewed and those likely to be affected by cultural setting, age, or sex were removed. A pilot study led to an abbreviated scale of 14 items, covering four domains of pleasure response. This questionnaire was subjected to psychometric evaluation in new samples from the general population and psychiatric patients. RESULTS: The scale was found to have a score range that would distinguish a 'normal' from an 'abnormal' response. Validity and reliability were found to be satisfactory. CONCLUSIONS: The new scale, the Snaith-Hamilton Pleasure Scale (SHAPS), is an instrument which may be recommended for psychopathological research.

Adolescent↗
PubMed1994

Researching self help drug treatment: collaboration and conflict in the age of harm reduction.

While there is evidence supporting the effectiveness of drug treatment in self help groups there are many points of divergence between the philosophies traditionally espoused by these groups and those advocated within harm reduction policies. In this paper we examine some of the differences between self help and harm reduction approaches. We argue that (in common with other treatment modalities) self help groups have altered and developed in response to changing community expectations and that this process should be expected to continue. We report on our ongoing exploration of research partnerships with self help group members focusing particularly upon research conducted in collaboration with self help groups in Victoria. We argue that research partnerships have advantages for both parties. These partnerships have the potential to better inform researchers of developments in the self help community (including the practices of active drug users). Research partnerships also encourage better understanding among self help group members of some of the potential problems that, as research has indicated, may be associated with certain self help group practices. We advocate such understanding as a potentially effective means of encouraging the appropriate development and refinement of self help group practices in line with harm reduction principals.

Alcoholics Anonymous↗
PubMed1994

Fulminant ulcerative colitis in pregnancy.

Most pregnant women with a history of ulcerative colitis will have a normal pregnancy and deliver a healthy child. Medical therapy can usually control the disease in those patients who experience an exacerbation, and only a minority of women progress to severe colitis necessitating surgery in pregnancy. We describe a woman who developed colitis in the first weeks of pregnancy that initially responded to steroid enemas. She then relapsed and progressed to severe colitis requiring a sub-total colectomy in the 26th wk of pregnancy. This was complicated by intra-abdominal sepsis and an abscess that required drainage. She successfully completed pregnancy, to be delivered of a healthy daughter in the 32nd wk of pregnancy.

Adult↗
PubMed1993

Pharmacokinetics of the anticancer agent sulofenur in mice, rats, monkeys, and dogs.

The absorption and pharmacokinetics of sulofenur [N-(indan-5-sulfonyl)-N'-(4-chlorophenyl)urea, LY186641] and its major metabolites were examined in mice, rats, monkeys, and dogs. The compound is a diarylsulfonylurea currently being evaluated as an oncolytic agent in phase I and II trials. In all species, sulofenur was well absorbed after an oral dose, but over a prolonged period, and sulofenur exhibited a fairly long half-life of elimination from plasma. These values ranged from 6 h in rats up to 30, 110, and 200 h in mice, monkeys, and dogs, respectively, at doses (240-1000 mg/m2) within the range of those used in clinical trials. Experiments describing the high degree of binding of sulofenur to plasma proteins (consistently > 99%) help to explain these relatively long half-lives. There is, however, a large difference between these plasma half-lives in the species studied. Sulofenur was previously found to be extensively metabolized to products that are excreted primarily into the urine. In this study, its major metabolites, which are found mainly in the urine, were also minor components of the drug-related material (< 10% of the sulofenur concentrations) in the plasma of rats treated with sulofenur. The absorption, binding characteristics, and elimination of these major metabolites after their administration to rats were also compared with sulofenur.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Influence of dietary sodium restriction on lipid metabolism.

The possible increase in total and low-density lipoprotein cholesterol following severe restriction of dietary NaCl was reported in 1990 and and 1991 from three experiments, one in the United States and two in Germany. Each of these experiments lasted only 1 week. To evaluate the clinical side effects we analyzed data collected from patients who completed a course of NaCl-restricted weight reduction at the Duke Diet and Fitness Center. Observations of lipid changes are not available for periods of less than 3 weeks; however, we were able to collect data on lipid and lipoprotein changes from 556 participants 25 days after they were referred for weight reduction. Total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels returned to normal in the majority of obese patients. In our slightly longer observation period in patients on a 1000 mg NaCl restricted diet we found no evidence of hyperlipidemic side effects. We believe that the hyperlipidemia resulting from severe sodium restriction in non-hypertensive, normal-weight individuals is not relevant to the problem of nonpharmacological and diuretic treatment of obese hypertensive patients. In clinically healthy, normal-weight, normotensive individuals severe salt restriction serves no practical or therapeutic purpose.

Cholesterol↗
PubMed1993

Perceived client and program moderators of successful therapeutic community treatment for drug addiction.

Research examining moderators of therapeutic community treatment outcomes has tended to emphasize the importance of length of stay in programs. To this extent the research literature implies a causal role for treatment in the determination of treatment outcomes. Using the Delphi technique, a panel of residents, staff members, and other drug treatment agency staff involved with the Odyssey House therapeutic community in Melbourne were surveyed regarding their perceptions of factors moderating successful treatment in this program. Examination of the perceptions of those involved with the delivery of therapeutic community treatment suggested a strong respect for the importance of client motivational factors in the determination of treatment outcomes. It is suggested that future research in this area could profitably focus on attempts to quantify the separate contribution of treatment and nontreatment factors in explaining treatment outcomes.

Adolescent↗
PubMed1993

Neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma.

Gastric adenocarcinoma is typically diagnosed at an advanced stage, and even with "curative" gastrectomy, most patients die of recurrent disease. Neoadjuvant chemotherapy for locally advanced gastric cancer is an experimental treatment strategy that may increase resectability and improve survival for patients afflicted with an almost uniformly fatal neoplasm. At our institution, we are evaluating the efficacy of fluorouracil, leucovorin, and interferon alfa-2A administered for three cycles, followed by surgery and consolidation therapy for patients with T3-4, N1-2, M0 gastric adenocarcinoma. The rationale for the use of neoadjuvant therapy combined with radical extirpative surgery in this setting and related issues are discussed.

Adenocarcinoma↗
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↗