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Biomedical subjects

H K Silver

Publications and source records attributed to H K Silver.

At least 19 recordsLinked to original sources
PubMed1996

Randomized, double-blind, placebo-controlled trial comparing the response rates of carmustine, dacarbazine, and cisplatin with and without tamoxifen in patients with metastatic melanoma. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: We designed and conducted a randomized, double-blind, placebo-controlled trial to compare the response rates and survival of patients with metastatic melanoma who received carmustine (BCNU), dacarbazine (DTIC), and cisplatin with tamoxifen, or the same chemotherapy with placebo. PATIENTS AND METHODS: Eligible patients with metastatic melanoma received either BCNU 150 mg/m2 intravenously (i.v.) on day 1, DTIC 220 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24, and cisplatin 25 mg/m2 i.v. daily on days 1 to 3 and on days 22 to 24 with placebo every 6 weeks, or the same chemotherapy with tamoxifen 160 mg orally daily for 7 days before chemotherapy and 40 mg orally daily throughout the remainder of the treatment cycle. Patients were treated on protocol for up to three cycles depending on the type of response. Assuming that a minimum increase in response rate of 20% would be necessary to conclude that tamoxifen conferred a clinically important benefit, we designed the study with an 80% chance of detecting that difference at the 5% level (two-sided). RESULTS: Between February 1992 and January 1995, 211 patients were accrued, 199 of whom were considered assessable for response and toxicity. The overall response rate was 21% in the placebo group and 30% in the tamoxifen group (P = .187). Complete and partial responses were 3% and 27%, respectively, for the tamoxifen group and 6% and 14%, respectively, for the placebo group. Poor performance status and liver involvement were associated with a reduced likelihood to respond to treatment. Major toxicities were similar in both groups with no statistically significant difference in the rates of deep vein thrombosis, pulmonary thromboembolus, grade 4 neutropenia, or grade 4 thrombocytopenia. CONCLUSION: These results demonstrate that the addition of high doses of tamoxifen to this chemotherapy regimen does not increase the response rate compared with chemotherapy alone in unselected patients with metastatic melanoma.

Adult↗
PubMed1995

Markedly elevated serum CA 19-9 levels in a case of chronic pancreatitis.

Serum levels of carbohydrate antigen (CA) 19-9 exceeding 1000 U/mL are considered highly specific for pancreatic cancer and have not been reported in nonmalignant pancreatic disease. A young man with obstructive jaundice, a serum CA 19-9 level of 2350 U/mL and a mass in the head of the pancreas, seen on computed tomography, was found to have chronic pancreatitis without malignant disease. This case demonstrates that a markedly elevated serum level of CA 19-9 can occur in nonmalignant pancreatic disease and emphasizes the need for a histologic diagnosis of malignancy even if the clinical diagnosis of pancreatic cancer seems certain.

Adult↗
PubMed1991

Relative operating characteristic analysis and group modeling for tumor markers: comparison of CA 15.3, carcinoembryonic antigen, and mucin-like carcinoma-associated antigen in breast carcinoma.

Relative operating characteristic (ROC) analysis was used to examine the clinical applicability of 3 breast carcinoma tumor markers, CA 15.3, carcinoembryonic antigen, and mucin-like carcinoma-associated antigen. Each tumor marker was quantitated in single serum samples collected from 100 normal blood donors, 60 patients with nonmalignant diseases, 33 women at high risk for breast carcinoma, 30 patients with malignancies other than breast carcinoma, and 158 breast carcinoma patients including 67 with no evidence of disease following surgery, 46 with a tumor burden less than 5 g, and 45 with a tumor burden greater than 5 g. These were used to construct models for early diagnosis among those at high risk for breast carcinoma, the influence of nonmalignant disease on early diagnosis, discrimination of breast carcinoma from other adenocarcinomas, detection of early recurrence, and assessment of change in tumor burden. For each model ROC data permitted the unbiased selection of the most appropriate critical values based on the interaction of sensitivity and specificity. ROC analysis indicated that in practice the assays were remarkably similar. While CA 15.3 generally performed best, there was significant variation among models. Optimal marker selection can thus depend on specific clinical application. In some cases ROC identified a combination of markers as superior to any single assay, but this was not statistically significant.

Adolescent↗
PubMed1991

Melanocytic nevus density in Asian, Indo-Pakistani, and white children: the Vancouver Mole Study.

Melanocytic nevus density in 378 Asian and 68 Indo-Pakistani school children 6 to 18 years of age was compared with that in 1146 white children of the same age range. At all ages, the number of melanocytic nevi 2 mm or larger per square meter of body surface area was substantially lower in Asians and Indo-Pakistanis than in white persons. Among white persons characteristics associated with a higher risk of cutaneous melanoma in adults, that is, light skin color, a propensity to burn rather than tan in the sun, and a history of numerous or severe sunburns, are also associated with the highest melanocytic nevus density in children. Examination of these same host pigmentation and sunburn factors among Asian children revealed no association with nevus density.

Adolescent↗
PubMed1991

Improved survival in patients with poor-prognosis malignant melanoma treated with adjuvant levamisole: a phase III study by the National Cancer Institute of Canada Clinical Trials Group.

Five hundred forty-three patients with completely resected malignant melanoma who were considered to have a significant risk of developing recurrent disease were randomized to one of four study groups. One group received levamisole 2.5 mg/kg on 2 consecutive days weekly for 3 years, a second group received bacillus Calmette-Guérin (BCG) for 3 years. A third group alternated 8-week courses of BCG and levamisole for 3 years and a fourth group underwent clinical assessment at the same frequency as the three treatment groups. The median duration of follow-up is 8.5 years. The percentage of reduction in the death rate and the recurrence rate in the treatment groups compared with the control group was calculated using the Cox proportional hazards model and adjusted for age, sex, and stage as covariants. The patients treated with levamisole were estimated to have a 29% reduction in both the death rate (P = .08) and the recurrence rate (P = .09) compared with patients receiving no further treatment. Fifty-five patients discontinued levamisole early because of gastrointestinal intolerance or arthralgia, myalgia, fever, and immune leukopenia. The patients treated with BCG alternating with levamisole experienced a 10% reduction in the death rate and a 6% reduction in the recurrence rate, and the patients treated with BCG alone experienced a 4% reduction in the death rate and a 3% increase in the recurrence rate compared with the control group. The degree of improvement experienced by the patients that were treated by levamisole is of sufficient magnitude to warrant further investigation of this dose of levamisole as adjuvant treatment in patients with melanoma.

Adolescent↗
PubMed1991

Ocular pharmacokinetics of dacarbazine following subconjunctival versus intravenous administration in the rabbit.

The authors assessed the ocular toxicity and pharmacokinetics of subconjunctivally and intravenously administered dacarbazine in New Zealand white rabbits. Nine rabbits received a subconjunctival injection of 5 mg (three animals), 10 mg (three animals) or 25 mg (three animals) of dacarbazine in 0.5 mL of sterile water; 10 mg was found to be a well-tolerated dose. This dose was given as a bolus to 42 other rabbits either subconjunctivally (21 animals) or intravenously (21 animals). In both groups the dacarbazine concentrations in the ocular humours, serum and urine were measured by means of high-pressure liquid chromatography at 0.5, 1, 2, 4, 8, 12 and 24 hours, three animals being assessed at each interval. The peak serum levels of the drug were similar with the two routes of administration. The mean peak dacarbazine levels in the aqueous humour and vitreous humour after subconjunctival administration were 250 to 380 times those achieved after intravenous administration. The bioavailability of the drug over 24 hours was 107 micrograms/h.mL in the aqueous and 34 micrograms/h.mL in the vitreous after subconjunctival administration, compared with 0.65 and 0.14 micrograms/h.mL respectively after intravenous administration. Our results provide a solid pharmacokinetic basis for considering subconjunctivally administered dacarbazine in the treatment of human ocular melanoma.

Animals↗
PubMed1990

In vivo induction of lymphokine-activated killer cells by interleukin-2 splenic artery perfusion in advanced malignancy.

In an effort to stimulate in vivo LAK cell activity at relatively nontoxic doses, 20 patients with advanced metastatic malignancy (13 renal cell carcinoma, 6 melanoma, 1 lymphoma) were treated with recombinant human interleukin-2 (IL-2) by continuous 5-day splenic artery perfusion using the femoral approach. Two treatment cycles were administered 3 weeks apart; IL-2 doses ranged from 1.5-4 x 10(4) Cetus units/kg/day. Peripheral blood lymphocyte cytotoxicity in a 4-h 51Cr release assay was measured using as tumor cell targets K562 for natural killer (NK) activity, Daudi for LAK, and Daudi plus in vitro IL-2 for inducible LAK (I-LAK). For the 20 patients, an increase in mean peak percent cytotoxicity from pretreatment levels was seen for NK (36% to 53%), LAK (8% to 37%) and I-LAK (20% to 53%) activity, all significant at P = 0.001. On day 43, 16 days after completing the second cycle of treatment, NK activity remained elevated at 47% and I-LAK at 40% (P = 0.008 and 0.01, respectively). Lymphocyte phenotype analysis by flow cytometry demonstrated increases from pretreatment levels in Leu 11+ (13 to 23%), Leu 19+ (10 to 21%), Leu 11+ 19+ (7 to 17%), IL-2r+ (4 to 17%), and HLA-DR+ (12 to 25%) subsets, all significant at P less than or equal to 0.01. Dose effect was studied at 3 dose levels: 1.5, 3, and 4 x 10(4) Cetus units/kg/day. At the higher doses mean peak NK (57%) and I-LAK (57%) activity were greater than at the low dose (42 and 31%, respectively), both significant at P less than 0.05. A trend to positive dose effect was seen in LAK activity (P = 0.08). Splenic artery perfusion with IL-2 can result in significant in vivo peripheral LAK cell generation as well as enhancement of I-LAK and NK activity that persists at least 16 days after the cessation of treatment. Such sustained activity would not be expected with conventional high dose i.v. therapy.

Antigens, CD↗
PubMed1990

Medical student abuse. Incidence, severity, and significance.

In a survey of the incidence, severity, and significance of medical student abuse as perceived by the student population of one major medical school, 46.4% of all respondents stated that they had been abused at some time while enrolled in medical school, with 80.6% of seniors reporting being abused by the senior year. More than two thirds (69.1%) of those abused reported that at least one of the episodes they experienced was of "major importance and very upsetting." Half (49.6%) of the students indicated that the most serious episode of abuse affected them adversely for a month or more; 16.2% said that it would "always affect them." Students identified various types of abuse and proposed a number of measures for the prevention and management of abuse in medical school. We conclude that medical student abuse was perceived by these students to be a significant cause of stress and should be a major concern of those involved with medical student education.

Adult↗
PubMed1990

Anatomic distribution of acquired melanocytic nevi in white children. A comparison with melanoma: the Vancouver Mole Study.

The presence of acquired benign nevi is a risk factor for cutaneous melanoma, yet relatively little is known about the etiology of nevi. We have conducted a study of the prevalence of melanocytic nevi among 1146 white Vancouver (Canada) schoolchildren aged 6 to 18 years. Numbers of nevi per square meter of body surface area increase with age in children of both sexes. Male adolescents have more nevi than female adolescents on the head and neck as well as on the trunk, while prevalence in females is higher on the upper and lower limbs. This distribution parallels that of cutaneous melanoma in British Columbia adults. Nevi are more common in children on intermittently exposed body sites than on constantly or minimally sun-exposed sites. This suggests that exposure to strong intermittent sunlight in childhood (a risk factor for cutaneous melanoma) may also be important in the etiology of acquired benign nevi.

Adolescent↗
PubMed1990

Suntan, sunburn, and pigmentation factors and the frequency of acquired melanocytic nevi in children. Similarities to melanoma: the Vancouver Mole Study.

The association between prevalence of benign melanocytic nevi and a number of skin cancer risk factors was examined among 913 white Vancouver (Canada) school children aged 6 to 18 years. Subjects with light skin, with a propensity to burn rather than tan in the sun, and with numerous or severe sunburns in the previous 5 years had significantly higher nevus counts than individuals without these characteristics. Subjects who acquired deeper tans tended to have fewer nevi than those who did not tan. Finally, children who freckled had higher nevus counts than those who did not freckle. These findings in children are similar to those seen in studies of malignant melanoma among adults and suggest that strategies to reduce melanoma incidence should begin with young children.

Adolescent↗
PubMed1989

Nuclear DNA, serum sialic acid and measured depth in malignant melanoma for predicting disease recurrence and survival.

In a previous multivariate analysis of 151 malignant melanoma patients we identified measured depth of primary lesion (Breslow) and serum N-acetyl-neuraminic acid (NANA) concentration as significant independent predictors of recurrence. Our present study examines the contribution of flow cytometric DNA analysis to prediction of recurrence and survival. Fixed, paraffin-embedded specimens of primary lesions were evaluated from 63 of the previously studied patients. These were prepared for DNA analysis. Of the 28 primaries identified as aneuploid 17 later recurred, while this was true for only 9 of the 35 diploid tumors. On multivariate analysis measured depth was again the most significant predictor of recurrence (p less than 0.001). Additional independent predictors were DNA ploidy (p = 0.02) and NANA (p = 0.05). For survival the independent predictors were measured depth (p = 0.003) and NANA (p = 0.05). Measured depth, DNA ploidy and NANA can be used to construct a model predicting the recurrence risk for stage-I melanoma.

Cell Nucleus↗
PubMed1988

Survival, response and immune effects in a prospectively randomized study of dose strategy for alpha-N1 interferon.

Several tumour sites have now demonstrated objective responses to alpha interferons in a diversity of doses and schedules. Since effectiveness should be enhanced with the identification of an optimal dose strategy, we undertook a prospectively randomized study to compare an intermittent high dose escalating strategy (HDS) vs. a fixed low dose treatment in relation to clinical outcome and laboratory correlates of immune function. HDS patients received interferon alpha-N1 (lymphoblastoid interferon) 5M units m-2 by continuous i.v. infusion over 24 h, escalating by 5 M units m-2 day-1 as tolerated over 10 days, and repeated every 28 days. The low dose strategy (LDS) consisted of a fixed dose of 2 M units m-2 by intramuscular injection daily for 28 days, then daily for 7 days every other week. There were 53 evaluable patients. In keeping with earlier preliminary results there was evidence of improved immune function for HDS patients. They demonstrated a significant increase in the number of CD2+ (sheep red blood cell binding) cells and CD4+ (helper-inducer/suppressor-inducer) cells along with enhanced activity of natural killer cell, and mixed leukocyte culture activity. In addition to improved immune function, HDS patients survived longer than LDS (P = 0.04). Analysis of survival in relation to response suggested that monitoring of minor responses may be of interest for biological agents such as interferon.

Adult↗