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Biomedical subjects

J M Hamilton

Publications and source records attributed to J M Hamilton.

At least 55 records · Page 3Linked to original sources
PubMed1994

Patronizing the old: how do younger and older adults respond to baby talk in the nursing home?

To test the implications of Communication Accommodation Theory for intergenerational talk to dependent older persons, eighty young adults and seventy-one older adults evaluated speakers in a brief taped conversation. Specifically, the study was conducted to determine whether the apparent nurturant quality of the baby talk tone of voice and parental style would compensate for the lack of respect associated with this type of patronizing talk to elders. The talk was either secondary baby talk or a neutral variant addressed to an elderly resident in a nursing home by either a nurse or a volunteer. The caregivers who used baby talk were rated as significantly less respectful and competent than their peers in the neutral condition, but no differences were observed for nurturance of the caregiver. The recipients of baby talk were perceived to be less satisfied with the interaction. These findings were true for both caregiver roles and both respondent age groups.

Adult↗
PubMed1993

A phase I study of continuous infusion 5-fluorouracil plus calcium leucovorin in combination with N-(phosphonacetyl)-L-aspartate in metastatic gastrointestinal adenocarcinoma.

Preclinical studies suggest that the biochemical effects of N-(phosphonacetyl)-L-aspartate (PALA), an inhibitor of aspartate carbamoyltransferase (ACTase), may increase the metabolic activation of 5-fluorouracil (5-FU) and enhance its cytotoxicity through both RNA- and DNA-directed mechanisms. In this Phase I trial, 22 evaluable patients with adenocarcinoma of the gastrointestinal tract were entered at escalating doses of 5-FU starting at 1150 mg/m2/day given as a concurrent 72-h i.v. infusion with a fixed dose of leucovorin (LCV), 500 mg/m2/day. The dose of 5-FU was escalated within patients according to individual tolerance, and then PALA at 250 mg/m2 was added 24 h prior to the initiation of the 5-FU/LCV infusion of the subsequent cycle. Dose-limiting mucositis and myelosuppression occurred during the initial cycle in 3 of 5 patients treated with 2300 mg/m2/day 5-FU; therefore, the recommended dose of 5-FU with concurrent LCV is 2000 mg/m2/day. Twenty-seven additional patients were then treated with escalating doses of PALA ranging from 375 to 2848 mg/m2, i.v., followed 24 h later by 2000 mg/m2/day 5-FU with high-dose LCV. Dose-limiting mucositis and myelosuppression occurred during the initial cycle in 2 of 3 patients entered at 2848 mg/m2 PALA. Dose-limiting mucositis and skin rash ultimately required both PALA and 5-FU dose reductions in 4 of 6 patients treated with 1899 mg/m2 PALA. Toxicity was similar, however, in patients receiving PALA at doses ranging from 375 to 1266 mg/m2. The mean steady-state plasma concentration of 5-FU at 2000 mg/m2/day was 6.5 +/- 0.9 microM; patients with 5-FU levels > 9 microM had a significantly higher incidence of serious gastrointestinal and hematological toxicity. Compared to each patient's own baseline, a significant trend for decreasing ACTase activity with increasing PALA dose was evident using cytosol isolated from peripheral blood mononuclear cells 24 h after PALA treatment (P2 = 0.01). PALA < or = 844 mg/m2 failed to appreciably inhibit ACTase activity at 24 h in most patients; furthermore, a decrease in ACTase activity by > 50% from baseline was seen in only 29% of cycles. More consistent inhibition of ACTase activity was seen with PALA > or = 1266 mg/m2. Even with the highest PALA doses, however, ACTase activity returned to baseline by 96 h in most patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1993

Phase II study of fluorouracil, leucovorin, and interferon alfa-2a in metastatic colorectal carcinoma.

PURPOSE: To test the activity of a regimen of interferon alfa-2a (IFN alpha-2a) 5 x 10(6) U/m2 subcutaneously (SC) days 1 through 7 combined with leucovorin 500 mg/m2/d intravenously (IV) over 30 minutes and fluorouracil (5-FU) 370 mg/m2/d through IV push 1 hour after leucovorin days 2 through 6 in a phase II study. PATIENTS AND METHODS: Forty-six patients with a good performance status (PS) with measurable colorectal cancer and no prior therapy for metastatic disease were entered. Cycles were repeated at 3-week intervals if toxicity had resolved. The 5-FU dose was increased by 15% if toxicity was mild, and decreased by 15% for grade 3 to 4 nonhematologic or grade 4 hematologic toxicity. RESULTS: Three complete responses (CRs) and 21 partial responses (PRs) were seen among 44 assessable patients (54%; 95% confidence interval, 39% to 70%). A moderately strong association was noted between PS and response: PS O (n = 26), two CRs and 15 PRs (65%); PS 1 (n = 13), one CR and six PRs (54%); PS 2 (n = 5), zero CRs and zero PRs (0%; two-tailed P = .026). With a median follow-up duration of 18.8 months, the median time to treatment failure (TTF) and survival were 7.8 months and 16.3 months, respectively. Doses were escalated to 425 mg/m2/d 5-FU in 10 patients, but only four tolerated the higher dose. When expressed as the most severe degree of toxicity experienced by each patient across all cycles, grade 3 to 4 toxicity of the following types was observed; mucositis, 37%; diarrhea, 40%; rash, 7%; fatigue, 14%; granulocytopenia, 13%. Dose-limiting toxicity at 370 mg/m2/d 5-FU eventually occurred in 28 patients (61%). Twelve patients (26%) required an IFN alpha-2a dose reduction for constitutional toxicity. CONCLUSION: This regimen has promising activity in advanced colorectal cancer, particularly in patients with an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1.

Adult↗
PubMed1993

Submental lipectomy with skin excision.

A new method of excision of submental skin and fat with modified Z-incision affords easy excision, wide exposure, and simple closure. Thirty-two patients over an 18-year period have had satisfactory results with inconspicuous scars. Modification of platysma muscles and subplatysmal fat excision are facilitated by the wide exposure. Use of this method has been limited to those cases in which a large submental fold is present in a patient who declines to have a regular rhytidectomy or in cases of residual submental redundancy after a complete rhytidectomy. Occasionally, a rhytidectomy is not sufficient.

Aged↗
PubMed1991

A pilot study of interferon alfa-2a in combination with fluorouracil plus high-dose leucovorin in metastatic gastrointestinal carcinoma.

Thirty-one assessable patients with metastatic adenocarcinoma of the gastrointestinal tract were entered onto a pilot study designed to assess the impact of recombinant interferon alpha-2a (rIFN alpha-2a) on the toxicity and pharmacokinetics of fluorouracil (5-FU) and leucovorin (LV). Patients received an initial cycle of 5-FU (370 or 425 mg/m2/d) with LV (500 mg/m2/d) for 5 days. If tolerated, the patient received the same dose of 5-FU/LV for the second cycle on days 2 to 6, with rIFN alpha-2a at 5 x 10(6) or 10 x 10(6) U/m2/d on days 1 to 7, or with 3 x 10(6) U/m2/d on days 1 to 14. In 26 matched cycles, rIFN alpha-2a administration was associated with an increased incidence of dose-limiting mucositis and diarrhea and a significantly lower median platelet nadir; rIFN alpha-2a did not significantly affect the median WBC or granulocyte nadir. Dose-limiting toxicity occurred in all six patients entered at 425 mg/m2/d of 5-FU/LV within two cycles. The majority of patients treated with 370 mg/m2/d of 5-FU/LV and 10 x 10(6) U/m2/d rIFN alpha-2a experienced grade 3 to 4 mucositis and diarrhea, whereas patients receiving 3 x 10(6) and 5 x 10(6) U/m2/d rIFN alpha-2a had acceptable toxicity. Administration of rIFN alpha-2a was associated with a dose-dependent decrease in 5-FU clearance. The increase in the area under the 5-FU concentration-time curve (AUC) was 1.3-fold and 1.5-fold in patients receiving 5 x 10(6) and 10 x 10(6) U/m2/d rIFN alpha-2a, respectively. Thus, the increase in 5-FU toxicity with rIFN alpha-2a may be explained by alterations in 5-FU pharmacokinetics. In 22 patients without prior 5-FU therapy, three complete (13.6%) and seven partial (31.8%) responses were seen, for an overall response rate of 45.4% (95% confidence interval, 24.4% to 67.8%). Since the 5 x 10(6) U/m2/d dose of rIFN alpha-2a increased the 5-FU drug exposure and was associated with acceptable toxicity, we recommend its further evaluation as given on days 1 to 7 in combination with 5-FU 370 mg/m2/d, with high-dose LV given on days 2 to 6.

Adenocarcinoma↗
PubMed1991

Levamisole: known effects on the immune system, clinical results, and future applications to the treatment of cancer.

Levamisole has been used in a wide array of clinical research and treatment settings over the past two decades, ranging from such diseases as helminthic infestations to various autoimmune diseases. Numerous preclinical evaluations and clinical trials with levamisole in the cancer arena have been sponsored by the National Cancer Institute and other agencies worldwide with the hopes of demonstrating anticancer activity. Trials in advanced breast cancer, lung cancer, colorectal cancer, melanoma, and lymphoproliferative diseases have generally been negative or inconclusive. However, there is some indication that levamisole may be useful by itself as an adjuvant therapy for resected melanoma; recently it has been shown to be effective in combination with fluorouracil (5-FU) as adjuvant therapy for tumor-node-metastasis (TNM) stage III (Dukes' C) colon carcinoma. In the aggregate, the past 20 years of clinical experience with levamisole has resulted in as many questions as answers. However, further testing of the anticancer activity of levamisole can be expected in clinical research trials over the next few years. Hopefully, these future trials will include studies of the mechanisms of action of this agent.

Animals↗
PubMed1991

Coping with stress.

Explore the source record for details and available documents.

Adaptation, Psychological↗
PubMed1989

Surrogate endpoints in clinical trials: cancer.

Investigators use a surrogate endpoint when the endpoint of interest is too difficult and/or expensive to measure routinely and when they can define some other, more readily measurable, endpoint, that is sufficiently well correlated with the first to justify its use as a substitute. A surrogate endpoint is usually proposed on the basis of a biologic rationale. In cancer studies with survival time as the primary endpoint, surrogate endpoints frequently employed are tumour response, time to progression, or time to reappearance of disease, since these events occur earlier and are unaffected by use of secondary therapies. In early drug development studies, tumour response is often the true primary endpoint. We discuss the investigation of the validity of carcinoembryonic antigen (a tumour marker present in the blood) as a surrogate for tumour response. In considering the validity of surrogate endpoints, one must distinguish between study endpoints that provide a basis for reliable comparisons of therapeutic effect, and clinical endpoints that are useful for patient management but have insufficient sensitivity and/or specificity to provide reproducible assessments of the effects of particular therapies.

Antineoplastic Agents↗
PubMed1989

Effects of norepinephrine and denervation on brown adipose tissue in Syrian hamsters.

Daily injections of either 0.8 or 3.2 mg norepinephrine (NE)/kg for 2 wk failed to stimulate brown adipose tissue (BAT) growth, GDP binding, or cytochrome-c oxidase activity (COA) in Syrian hamsters (Mesocricetus auratus). However, a single injection of 1.6 mg NE/kg produced a small (23%) but significant acute increase in BAT GDP binding without affecting COA. Thus there is some loss of sensitivity to NE with chronic treatment in Syrian hamsters. Unilateral sympathectomy by surgical denervation of the interscapular BAT (IBAT) resulted in decreased GDP binding and COA in the denervated pad. Chronic NE treatment in hamsters with denervated IBAT only partially reversed the denervation-induced decreases in GDP binding and COA. It therefore appears that NE is not solely responsible for the maintenance and stimulation of thermogenic activity and COA in Syrian hamster BAT. Denervation of IBAT also resulted in elevated levels of lipoprotein lipase (LPL) in this tissue, a surprising finding since brown and white adipose tissue LPL activity were both stimulated by chronic NE treatment. Therefore, although NE has a stimulatory effect on LPL activity, the primary influence of the neural input to IBAT on this enzyme is inhibitory. These data exemplify dramatic differences between rats and hamsters in the mechanisms controlling BAT thermogenesis and white and brown adipose tissue LPL activity.

Adipose Tissue, Brown↗
PubMed1989

Regional differences in fat pad responses to short days in Siberian hamsters.

Siberian hamsters exhibit decreased body weight and fat after initial exposure to short photoperiods and increased body weight and fat after extended short photoperiod exposure. The purpose of the present experiments was to determine if uniform changes in white adipose tissue (WAT) pad weights and lipid metabolism correspond to these short photoperiod-induced changes in body fat. Carcass lipid content and testes and fat pad weights [retroperitoneal WAT (RWAT), epididymal WAT (EWAT), and inguinal and dorsal subcutaneous WAT, respectively] were decreased in male hamsters relative to their long day counterparts after 6 and 12 wk of short-day exposure. Moreover, EWAT and RWAT weight, EWAT specific lipoprotein lipase activity, and specific and total lipogenesis were disproportionately decreased relative to the subcutaneous fat pads. The changes in fat pad weight and metabolism were generally reversed coincident with the return to a long-day-like reproductive status after prolonged short-day exposure (24 and 30 wk). In a less detailed experiment, female Siberian hamsters had decreased body, fat pad, and uterine weights after 6 wk of short-day exposure; however, no fat pad-specific changes in weight were observed. The results of these experiments demonstrate that short-day-exposed male Siberian hamsters may be a useful model for examining mechanisms underlying fat pad-specific responses. In addition, gender appears to influence the pattern of short-day-induced lipid depletion in this species.

Acclimatization↗
PubMed1988

Lipectomy does not impair fattening induced by short photoperiods or high-fat diets in female Syrian hamsters.

Syrian hamsters (Mesocricetus auratus) exhibit seasonal fluctuations in body fat that are triggered by changes in photoperiod and/or diet. Body fat accumulates when hamsters are switched to a short photoperiod or high-fat diet. The effects of surgical reduction of adipose tissue (lipectomy) on these responses were tested in adult female hamsters. Dorsal-inguinal subcutaneous, parametrial, and retroperitoneal white adipose tissues were removed bilaterally from some hamsters, while others received sham surgery. Hamsters from each surgical group were then fed a high-fat diet for the next 12 or 30 weeks, or were exposed to a short photoperiod for 13 weeks. Restoration of previously excised pads was for the most part incomplete, yet all lipectomized hamsters fully regained total body lipid, which suggests compensatory hypertrophy in other depots. Consistent with this, we found a significant increase in the weight of the previously undisturbed axillary subcutaneous pad, but this increase was small and not sufficient to offset the deficits remaining in the regenerated pads. Thus, restoration of total body lipid mass was achieved by a general increase in deposition over all depots rather than a specific renewal of removed tissue. This ability to recover completely from lipectomy is similar to that previously reported in ground squirrels. In contrast, rats and mice are frequently unable to replace lost adipose tissue. Both hamsters and squirrels adjust their levels of body fat according to season, which may afford them an enhanced ability to recover from surgical reductions of adipose tissue.

Adipose Tissue↗
PubMed1987

Genetic association between nest building and brown adipose tissue thermogenesis in female house mice.

Mice selectively bred for either high or low levels of thermoregulatory nest building were cold-acclimated (5 degrees C) for 3 weeks without nesting material; then body weight and food intake were measured. The mice selected for low nest building (Lows) of both sexes showed lower feed efficiencies than the high nest-building mice (Highs), although their body weights were not significantly different (Table 1). This adds to a large body of evidence which suggests that nest building and feed efficiency were influenced by a common mechanism (Lacy et al. 1978; Sulzbach and Lynch 1984; Lynch et al. 1981; Lynch and Roberts 1984). Brown adipose tissue mitochondrial GDP binding and cytochrome c oxidase activity were measured in the above mice. In females, the Lows had 100% higher levels of total GDP binding than the Highs, while no difference between the lines was seen in males. Thus in the High females, lower energy expenditure through brown fat thermogenesis may account for their greater feed efficiency. In males, the genetic differences in feed efficiency must be due to differences in either thermogenesis in tissues other than brown fat, or mechanisms which reduce heat loss.

Adipose Tissue, Brown↗