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Biomedical subjects

A J Coldman

Publications and source records attributed to A J Coldman.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1988

Cervical intraepithelial neoplasia in female prisoners in British Columbia.

The annual incidence rates of cervical intraepithelial neoplasia (CIN), grades I to III, from 1975 to 1983 among 2440 prisoners in British Columbia for whom a history of screening by means of the Papanicolaou test was available were two to three times higher than the expected rates in the general female population of British Columbia. The rates among the prisoners from 1970 to 1984, although small, increased with a trend similar to that in the general population. Despite increases in the general population we conclude that prisoners are still at high risk for CIN.

Adult↗
PubMed1988

Influence of estrogen receptor status on dietary risk factors for breast cancer.

It has been suggested that the relation between diet and breast cancer may depend on estrogen receptor (ER) status. We examined the responses to a self-administered questionnaire on frequency of consumption of various foods by 493 women with breast cancer (160 with ER-negative tumours and 333 with ER-positive tumours) and 527 controls whose menopausal status was known. Analysis of the reported consumption of foods selected for their fat or carotene content showed no clear distinction in dietary factors between the ER-negative and ER-positive groups. Frequent consumption of meat fats generally increased the risk of both ER-negative and ER-positive tumours; there were no clear trends in risk associated with vegetable consumption for either ER group. Fish was the only item affecting the risk for ER-negative and ER-positive tumours differently, frequent consumption reducing the risk for the former (p = 0.02). The results do not support the hypothesis that ER status influences the relation between dietary fat consumption and risk of breast cancer.

Adult↗