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Biomedical subjects

A J Coldman

Publications and source records attributed to A J Coldman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Sunlight exposure, pigmentary factors, and risk of nonmelanocytic skin cancer. I. Basal cell carcinoma.

BACKGROUND AND DESIGN: Basal cell carcinoma (BCC) of the skin is the most common neoplasm in white populations, and solar radiation is generally accepted to be the dominant environmental risk factor for this disease. However, little information is available on the nature of the relationship between BCC and sunlight. The purpose of this study was to evaluate the nature of the relationship between sunlight exposure, pigmentary factors, and BCC of the skin. A population-based case-control study of 226 male patients with BCC diagnosed from January 1, 1983, through December 31, 1984, and 406 randomly selected male control subjects was conducted in Alberta, Canada. The study was conducted using a standardized questionnaire, administered in person by trained interviewers. Data were analyzed using conditional logistic regression methods. RESULTS: After controlling for other host and pigmentary factors, the risk of BCC was increased in subjects with light skin color and those who freckled in childhood. A history of severe sunburn in childhood also increased risk. Subjects of southern European ethnic origin were at significantly lower risk of BCC. Surprisingly, no association was seen between mean annual cumulative summer sunlight exposure and risk of BCC. A significantly increased risk of BCC was seen in subjects with increased recreational sunlight exposure in adolescence and childhood (age, 0 to 19 years), although an inverse relationship was seen with lifetime recreation exposure. The relationship with childhood sun exposure was most pronounced among sun-sensitive subjects whose skin tended to burn rather than tan in the sun. CONCLUSIONS: The lack of association between cumulative sun exposure and BCC contradicts conventional wisdom about the cause of this tumor, and the increased risk with sun exposure at age 0 to 19 years suggests that childhood and adolescence may be critical periods for establishing adult risk for BCC.

Adult↗
PubMed1995

Sunlight exposure, pigmentation factors, and risk of nonmelanocytic skin cancer. II. Squamous cell carcinoma.

INTRODUCTION AND DESIGN: Squamous cell carcinoma of the skin (SCC), a common cancer in white populations, is related to sunshine exposure; however, relatively little information is available on how timing and character of exposure affect the relationship. The purpose of this study was to investigate the nature of the relationship of SCC to individual solar UV exposure after control for phenotype and pigmentary factors. All newly diagnosed cases of SCC were in men aged 25 through 79 years, ascertained in the province of Alberta from January 1, 1983, through December 31, 1984, who were approached for participation; 80% completed a standardized etiologic interview that was conducted in their homes by a trained interviewer. Control subjects were chosen at random from the Alberta Health Care Insurance Plan subscribers list, matched only by sex (male) and age (within a 5-year age group). The response rate among controls was 71%. RESULTS: Subjects with pale skin and red hair had an elevated risk of SCC. Subjects whose mother was of southern European ancestry had a reduced risk of SCC. After accounting for pigmentary factors, no association was seen between risk of SCC and cumulative lifetime sun exposure. However, a strong trend toward increasing risk was seen with increasing chronic occupational sun exposure in the 10 years prior to diagnosis. CONCLUSION: The results suggest that recent sun exposure (in the 10 years prior to diagnosis) may be important in accounting for individual risk of SCC.

Adult↗
PubMed1994

Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine.

The authors compared, in a double-blind, randomized, crossover study in 13 healthy adult volunteers, the single- and multiple-dose pharmacokinetics, relative bioavailability, and side effects of a new oral sustained-release formulation of codeine (SRC) containing 150 mg codeine base, with oral immediate-release codeine phosphate (IRC). Sustained-release codeine was given at a dose of 150 mg every 12 hours for 5 doses; IRC was given at a dose of 60 mg (2 x 30 mg) every 4 hours for the first 3 doses, and 30 mg every 4 hours thereafter for 12 doses. Plasma codeine levels were determined using a sensitive and specific high-performance liquid chromatography method and corrected for dose administered and codeine base equivalent. Mean values for single-dose pharmacokinetic parameters for SRC and IRC, respectively, were: Cmax of 217.8 and 138.8 ng/mL; Tmax of 2.3 and 1.1 hours; AUC0-inf of 1202.3 and 1262.4 ng.mL-1.hour-1; and t1/2el of 2.6 hours for both formulations. Their respective mean steady-state pharmacokinetic parameters were: Cmax of 263.8 and 222.9 ng/mL; Tmax of 3.2 and 1.1 hours; AUC0-12h of 1576.4 and 1379.1 ng.mL-1.hour-1; and t1/2el of 2.8 and 2.3 hours. These results indicate comparable bioavailability between both formulations with SRC providing delayed peak plasma levels. The sustained-release character of SRC can be explained by a delayed absorption, which is not limiting to drug elimination. Sustained-release codeine provides higher plasma codeine levels over a broader time interval and is expected to improve pain management.

Adult↗
PubMed1993

Relationship between variant forms of estrogen receptor RNA and an apoptosis-related RNA, TRPM-2, with survival in patients with breast cancer.

BACKGROUND: Although smaller variant forms of estrogen receptor (ER) messenger RNA (mRNA) have been detected in breast tumors, neither their prevalence nor their prognostic significance have been evaluated. Similarly, TRPM-2 mRNA, the product of a gene induced principally during the onset of apoptosis, is present in mouse and human breast cancer cell lines, but whether it also occurs in primary breast tumors and is related to disease outcome is unknown. METHODS: The relative expression and transcript size of ER mRNA and TRPM-2 mRNA in 126 primary breast tumors were measured by Northern analysis and compared with tumor grade, hormone receptor status, extent of tumor necrosis, and survival. RESULTS: In ER-positive tumors, 64% of the tumors had only the normal 6.5 kb ER mRNA, an additional 9% had the normal plus smaller ER mRNA, and 2% had variant forms. Only 8% of ER-negative tumors had ER mRNA transcripts. There were significant relationships between the occurrence of ER mRNA and low tumor grade, ER-positive receptor status, and better survival. In contrast, TRPM-2 mRNA was found in only 17% of breast tumors, none of which could be grouped with respect to grade, hormone receptor status, or survival. CONCLUSIONS: The presence of smaller variant forms of ER mRNA either alone or in association with the normal ER transcript is not indicative of an unfavorable prognosis, whereas TRPM-2 mRNA occurs in many primary breast tumors, but has no apparent relationship to survival.

Adult↗
PubMed1993

Chromatographic analysis and pharmacokinetics of liposome-encapsulated doxorubicin in non-small-cell lung cancer patients.

A sensitive and specific quantitative assay for total doxorubicin concentrations in plasma containing liposome-encapsulated doxorubicin hydrochloride (TLC D-99) was developed, with solvent extraction and reversed-phase high-performance liquid chromatography (HPLC). Separation of doxorubicin from its metabolites was accomplished with a 15 cm x 3.9 mm i.d., microBondapak phenyl analytical HPLC column. Optimum chromatographic conditions, obtained with a mobile phase gradient from 85 to 50% (v/v) 16 mM ammonium formate buffer in tetrahydrofuran at a flow rate of 2 mL/min, gave a detection limit of 0.3 pmol/injection. Eleven-point standard curves with from 0.00595 to 29.8 microM TLC D-99 and 0.1 microM internal standard in plasma were analyzed on three separate occasions to formally validate this assay. An overall correlation coefficient of 0.9985 was found for the logarithmic transformed data. The pharmacokinetic characteristics of doxorubicin were investigated after administration of TLC D-99 to 12 non-small-cell lung cancer patients as an intravenous infusion at doses of 60 and 75 mg/m2. The data are best described by a three-compartment model with alpha, beta, and gamma elimination half-lives of 0.0721, 2.84, and 25.2 h for the 60-mg/m2 group and 0.103, 2.56, and 14.9 h for the 75-mg/m2 patients. A mean plasma clearance of 9.89 L/h (range: 1.95 to 23.4 L/h) was found for the 60-mg/m2 patients, with that from the 75-mg/m2 group being within these values. Mean area under the plasma concentration versus time curve estimates of 37.1 and 47.9 microM/h were observed for the patients receiving 60 and 75 mg/m2, respectively. The plasma concentration-time course for total doxorubicin following administration of TLC D-99 suggests that the disposition of the liposomal formulation is determined more by the pharmacokinetics of the liposome than the encapsulated drug.

Adult↗
PubMed1992

Calculating the prevalence of cancer.

Incidence, prevalence and mortality are commonly used measures to assess the impact of disease on human populations. Prevalence, although regularly assessed for a number of different diseases, has only had recent use to measure the impact of cancer. The calculation of the prevalence of cancer presents several difficulties since there is no reporting mechanism established to measure the proportion of the community that has the disease. In the absence of such a mechanism, mortality data linked to incidence data from cancer registries have been used. The assumption is made that once diagnosed with cancer an individual remains a prevalent case until death. In this paper we present alternatives to this assumption and use them to produce estimates of cancer prevalence. We illustrate the effect of these assumptions on the calculated prevalence of cancer using data from the British Columbia Cancer Registry.

Algorithms↗
PubMed1992

Cigarette and alcohol use in patients with adenocarcinoma of the gastric cardia or lower esophagus.

The authors studied the cigarette and alcohol use of 243 patients with adenocarcinoma of the cardia or lower esophagus, including 66 with Barrett's metaplasia (esophagocardia group). They compared results of that investigation with the cigarette and alcohol use of 303 patients with squamous carcinoma of the esophagus, a cancer in which an etiologic association is proven, and of 338 patients with stomach cancer not involving the cardia, a cancer in which there is little or no association with cigarettes or alcohol. Controlled for other variables, patients with squamous cancer used more cigarettes and alcohol than the other two groups. There was no significant difference in cigarette or alcohol use between patients with esophagocardia and stomach cancer or between those in the esophagocardia group with or without Barrett's metaplasia. Because cigarette and alcohol use was not greater in patients with esophagocardia than in those with stomach cancer, the authors do not think that such factors explain the increasing incidence of adenocarcinoma of the cardia or lower esophagus.

Adenocarcinoma↗
PubMed1992

Reliability of dietary information from surrogate respondents.

A self-administered food frequency questionnaire was included as part of a case-control study of breast cancer in 1980-82. In 1986-87, a second food frequency questionnaire was sent to surviving cases and husbands of deceased cases; 30 spouses (86% response rate) and 263 surviving cases (88% response rate) returned questionnaires. The dietary questions concerned consumption of specific food items by the case before diagnosis of breast cancer. Missing values were less common in the second questionnaire; there was no significant difference in missing values between surviving cases and spouses of deceased cases. Kappa statistics comparing responses in the first and second questionnaires were significantly lower for spouses of deceased cases than for surviving cases. Reported level of confidence by the husbands regarding knowledge about their wives' eating habits did not influence the kappa statistics or the frequencies of missing values. The lack of good agreement has important implications for the use of proxy interviews from husbands in retrospective dietary studies.

Breast Neoplasms↗
PubMed1992

Human papillomavirus infection of the uterine cervix. Tissue sampling and laboratory methods affect correlations between infection rates and dysplasia.

Two common tissue sampling techniques--colposcopic biopsy and cervical scrape--and two common human papillomavirus (HPV) detection techniques--Southern blot and dot blot (SB and ViraPap [VP])--were compared to determine whether differences in these techniques alter correlations between "oncogenic" HPVs and cervical neoplasia. In 87 women with persistently abnormal Papanicolaou (Pap) smears, concurrent biopsy and scrape specimens contained HPV in 21 (24%) and contained no HPV in 26 (30%); 30 scrape specimens (34.5%) tested positive when the biopsy tested negative and 10 (11.5%) scrape specimens tested negative when the biopsy tested positive (overall concordance, 54%). Concordance for the most prevalent HPVs (16/18) was 59%. In carcinoma in situ, HPV was found in biopsy samples significantly more frequently than in scrape specimens: 17 of 23 (75%) biopsy samples versus 9 of 23 (39%) scrape specimens (P = 0.018). Conversely, in mild or no dysplasia, 0 of 42 biopsy samples tested positive for HPV 16/18 compared with 12 of 42 scrape specimens (29%; P = 0.0001). Of 229 specimens analyzed by SB and VP, 43 (19%) tested positive and 148 (65%) tested negative for HPV by both methods (concordance, 84%). Corroborative results indicated that 29 of 35 (83%) VP-positive SB-negative results were truly positive compared with none of three SB-positive VP-negative results. Both the cervical sampling technique and the method for HPV detection can significantly affect statistical correlations between cervical dysplasia and HPV type.

Biopsy↗
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

Identifying effective treatments for uremic pruritus.

The identification of effective treatments for uremic pruritus used a literature search of MEDLINE (1966 to March 1991), Index Medicus (1978 to March 1991), bibliographic reviews of textbooks, and pertinent articles. Only randomized controlled clinical trials were selected for analysis. Assessment of study quality was performed independently by two observers with specific methodologic criteria. A clinically significant therapeutic effect was defined as a statistically significant result in the proportion of patients improving and a reduction in pruritus score of at least 50%. Clinically significant outcomes were obtained for two of three whole-body ultraviolet B trials. Meta-analysis of the ultraviolet B trials retained the significant effect in analysis of proportions (pooled odds ratio 18; 95% confidence interval 4, 161). Trials of lidocaine, charcoal, and nicergoline demonstrated either statistically significant improvement in pruritus score or in proportions, but not both. Ultraviolet B phototherapy is the treatment of choice in moderate to severe uremic pruritus.

Clinical Trials as Topic↗
PubMed1991

Effectiveness of transcutaneous electrical nerve stimulation (TENS) for analgesia during biliary lithotripsy.

The effectiveness of transcutaneous electrical nerve stimulation (TENS) in controlling pain during biliary extracorporeal shockwave lithotripsy (BESWL) was assessed in 100 patients with symptomatic gallbladder calculi. Patients were divided into four groups: TENS electrodes were placed on the back at cutaneous anesthesia sites and on the right leg and the gallbladder acupuncture site in groups A and B. Electrodes were "turned on" only in group A. In groups C and D, electrodes were placed only on the back at cutaneous dermatomes. Electrodes were "turned on" in group C only. The TENS unit was stimulated at the pulse rate of 60 to 100 microseconds and frequency of 80 to 125 Hz. Lithotripsy was performed with the Lithostar Plus overhead module. The differences in the amount of analgesic used and the pain experiences by the patients in all groups were not statistically significant. The proportion of patients requiring intravenous analgesia in each group was also not significantly different (72%, 80%, 68%, 76% in groups A to D, respectively). Thus, TENS did not help in reducing the amount of intravenous analgesia required or the average pain perceived by the patient during lithotripsy treatment.

Analgesia↗
PubMed1991

Dose-intensity meta-analysis of chemotherapy regimens in small-cell carcinoma of the lung.

To determine if chemotherapy dose intensity (DI) influences treatment outcome, 60 published studies in limited- and extensive-stage small-cell carcinoma of the lung (SCCL) were retrospectively analyzed for relationship between intended DI and response (complete response [CR] or partial response [PR]) or median survival (MS). Agents used in the regimens included cyclophosphamide (C), doxorubicin (A), vincristine (V), etoposide (E), and cisplatin (P). Relative DI (RDI) of each study regimen was calculated against a reference regimen, and weighted regression analysis was used. Additionally, analysis of individual drug RDI within combinations was performed. For CAV, increasing RDI of the regimen showed no correlation with outcome. For the individual drugs, C RDI correlated positively, while A RDI correlated negatively with attainment of CR in limited disease, but both only after unduly influential observations were eliminated. In extensive-stage disease, A RDI correlated positively with CR+, PR but only in randomized trials, and this correlation lost statistical significance after unduly influential observations were eliminated. For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI. In limited disease, the C RDI correlated negatively with MS. For EP, no significant correlations were seen. We conclude that DI-outcome correlations are not consistent for these chemotherapy regimens in SCCL. Meta-analysis of retrospective data can generate hypotheses for testing in prospective clinical trials, but study sample and method of analysis can appreciably affect conclusions.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Loss of androgen dependence is associated with an increase in tumorigenic stem cells and resistance to cell-death genes.

Complete remissions of the androgen-dependent Shionogi mouse mammary carcinoma are observed after androgen withdrawal but invariably the disease recurs and is refractory to further hormonal manipulations. To determine the proportions of androgen-dependent (AD) and -independent (AI) tumorigenic stem cells in parent and recurrent tumors an in vivo limiting dilution assay was developed. There was a marked enrichment of stem cells in the recurrent tumors (1/200 tumor cells) relative to the parent tumors (1/4000 tumor cells) when assayed in male hosts. By assaying tumor takes in female mice, the proportion of AI stem cells was found to be 1/370,000 tumor cells in the parent vs 1/800 tumor cells in the recurrent carcinoma; a 500-fold increase in AI stem cells resulting from androgen-withdrawal. Unexpectedly, no enrichment of AI stem cells was evident in regressing parent tumors; rather, the proportion of such cells was very small (1/2,200,000 tumor cells). This finding implies that the AI cells which survive androgen withdrawal may result from the ability of small number of initially AD stem cells to adapt to an altered hormonal environment. This adaptive process was further defined in terms of the disappearance of androgen receptors from the nucleus and the expression of androgen-repressed genes including the proto-oncogenes, c-fos and c-myc, and the cell death gene, TRPM-2; all of which are constitutively active in recurrent AI tumor cells. Overall, our results indicate: (1) the tumor mass consists mainly of differentiated cells; (2) stem cells initially are AD but at most the killing effect of androgen-withdrawal will be limited to 2-3 logarithms before compensatory adaptive mechanisms supervene; and (3) progression of stem cells to an AI state, in which they are resistant to the killing effects of cell death genes, might be prevented by the inhibition of androgen-repressed adaptive mechanisms which come into play when androgens are withdrawn.

Androgens↗
PubMed1990

Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma.

The parent Shionogi mouse mammary carcinoma is androgen dependent but cells that survive hormone withdrawal progress and give rise to an androgen-independent tumor. To determine whether renewed growth might be attributed to the persistence or partial recovery of an androgenic stimulus, we compared the amount of dihydrotestosterone and nuclear androgen receptor in parent and recurrent tumors. The whole tissue concentration of dihydrotestosterone in the parent tumor before castration was 1.40 +/- 0.46 (SE) as compared with 0.22 +/- 0.10 pmol/mg of DNA in the recurrent tumor. The initial concentration of nuclear androgen receptor in the parent was 0.65 +/- 0.12 pmol/mg of DNA; this was reduced to zero within 24 h after castration. Also in keeping with the androgen independence, no receptor was detected in the nuclear fraction of the recurrent carcinoma. In an attempt to relate malignant potential to nonhormonal factors associated with progression, we compared the proportions of androgen-dependent and -independent tumorigenic (stem) cells in parent and recurrent tumors using an in vivo limiting dilution assay. The difference observed, i.e., one stem cell per 4000 tumor cells in the parent versus one stem cell per 200 tumor cells in the recurrent carcinoma, was consistent with a marked enrichment of stem cells in the latter. The proportion of androgen-independent stem cells was also determined by assaying tumor takes in female hosts. The difference, i.e., one stem cell per 370,000 tumor cells in the parent versus one stem cell per 800 tumor cells in the recurrent carcinoma, demonstrated a striking 500-fold increase in androgen-independent stem cells resulting from androgen withdrawal. Unexpectedly, no enrichment of androgen-independent stem cells was evident in regressing parent tumors; rather, the proportion of such cells was very small, i.e., one androgen-independent stem cell per 2,200,000 regressing parent cells. This finding implies that the androgen-independent state of cells which survive androgen withdrawal may result from the ability of a small number of initially androgen-dependent stem cells to adapt to an altered hormone environment.

Androgens↗
PubMed1990

Diet and histologic types of benign breast disease defined by subsequent risk of breast cancer.

The authors investigated the relation between diet and histologic types of benign breast disease defined by subsequent risk of breast cancer in a case-control study of volunteers who entered the Vancouver Center of the Canadian National Breast Screening Study between 1983 and 1985. Proliferative benign breast disease (n = 124) was inversely associated with vitamin A supplementation (vitamin A user vs. nonuser, odds ratio (OR) = 0.5) and frequent green vegetable consumption (frequent vs. rare consumption, OR = 0.3), whereas severe atypias and borderline carcinoma in situ (n = 32) were directly associated with frequent meat fats consumption (frequent vs. rare consumption, OR = 3.2) with no association with vitamin A or vegetable consumption. No dietary relations were found for histologic types of benign breast disease at no increased risk for subsequent breast cancer (n = 274). The implications of these findings in relation to the etiology of breast cancer are discussed.

Breast Neoplasms↗