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Biomedical subjects

A M Goldstein

Publications and source records attributed to A M Goldstein.

At least 91 records · Page 5Linked to original sources
PubMed1995

Genetic epidemiology of familial melanoma.

Genetic epidemiology focuses on the role of genetic factors and their interaction with environmental factors in the occurrence of disease. Approximately 8% to 12% of malignant melanoma cases occur in individuals with a familial predisposition. To date, loci on chromosomes 1p and 9p have been implicated in the development of familial melanoma. Genetic epidemiologic techniques provide tools to study the heterogeneity of familial melanoma and to examine the interaction between genetic and nongenetic components of melanoma. Management of high-risk individuals from melanoma-prone families should aim to prevent disease by reducing exposure to known and suspected risk factors and to detect early melanoma by recognizing and performing biopsies on suspicious-looking nevi.

Humans↗
PubMed1995

Hemoperitoneum due to spontaneous rupture of the umbilical vein.

Portal hypertension often leads to collateralization of blood flow via variceal vessels that shunt blood from the portal to the systemic circulation. Rupture of an intra-abdominal varix is an unusual complication of portal hypertension that can lead to life-threatening hemoperitoneum. We describe a patient with portal hypertension secondary to liver cirrhosis who presented with acute intra-abdominal hemorrhage. At laparotomy, she was found to have a rupture of the umbilical vein. The vessel was ligated, and the patient recovered uneventfully. The causes of hemoperitoneum in cirrhosis are discussed, and the previously reported cases of intra-abdominal variceal bleeding are reviewed.

Female↗
PubMed1994

Increased risk of neuroectodermal tumors and stomach cancer in relatives of patients with Ewing's sarcoma family of tumors.

BACKGROUND: Previous studies of the genetic epidemiology of Ewing's sarcoma have shown neither an increased incidence nor a distinct pattern of cancers in family members of Ewing's sarcoma patients. PURPOSE: Because of a new biologic and cytogenetic classification of Ewing's sarcoma family of tumors, we wanted to reinvestigate the incidence and distribution of cancers in relatives of probands with Ewing's sarcoma family of tumors. METHODS: Patients treated at the Pediatric Branch and the Radiation Oncology Branch of the National Cancer Institute between 1965 and December 1992, or their next of kin, were asked to complete a questionnaire on the history of cancer in all first- and second-degree relatives. The incidence of cancer in family members was compared with Connecticut Tumor Registry rates specific for sex, age, and 5-year calendar-year intervals. Observed/expected (O/E) ratios, 95% confidence intervals (CIs), and tests of homogeneity were calculated. RESULTS: Four thousand six hundred seventy-eight family members with 196,640 person-years at risk entered the analysis. Overall, there was no increased risk of cancer (observed 472; O/E = 0.9; 95% CI = 0.8-1.0). However, several tumor types were found in significant excess. These tumors included stomach cancer (observed 34; O/E = 2.0; 95% CI = 1.4-2.8), melanoma (observed 23; O/E = 1.9; 95% CI = 1.2-2.8), brain tumor (observed 18; O/E = 1.9; 95% CI = 1.1-3.0), and bone cancer (observed 7; O/E = 4.2; 95% CI = 1.7-8.6). Risks of these cancers were higher among maternal than paternal relatives, but these differences were not statistically significant. There was a significant deficit of bladder cancer (observed 5; O/E = 0.2; 95% CI = 0.1-0.5) and rectal cancer (observed 0; O/E = 0.0; 95% CI = 0.0-0.1). Second-degree relatives had a significant cancer deficit (observed 389; O/E = 0.9; 95% CI = 0.8-0.95). This deficit was accounted for by the observed deficit of bladder and rectal cancer and is probably related to under-reporting or misclassification of cancer in second-degree relatives. Family members of 10 probands with second malignancies did not have an increased risk of all cancers (observed 20; O/E = 1.2; 95% CI = 0.7-1.8) but had an increased risk of both melanoma (observed 3; O/E = 7.3; 95% CI = 1.5-21.0) and breast cancer (observed 8; O/E = 3.2; 95% CI = 1.4-6.3). CONCLUSION: Finding an increased risk of neuroectodermal tumors and stomach cancer in families of patients with Ewing's sarcoma family of tumors suggests that these tumors might share a common etiology. Further studies should try to confirm this hypothesis and to examine if genetic factors may have a role in these families by assessing the mode of inheritance and examining families with multiple affected members.

Adolescent↗
PubMed1994

Age at diagnosis and transmission of invasive melanoma in 23 families with cutaneous malignant melanoma/dysplastic nevi.

BACKGROUND: Familial melanoma patients tend to have an earlier age at first melanoma diagnosis, thinner lesions, a different histologic distribution, and a higher frequency of multiple primary melanomas than patients with nonfamilial melanoma. Previous examination of a large melanoma kindred from Texas suggested that although cutaneous malignant melanoma (CMM) was transmitted in an autosomal dominant fashion, there were sex differences in penetrance and disease expression. PURPOSE: This study further evaluated the age at diagnosis, sex difference in penetrance and disease expression, and segregation of familial CMM. METHODS: We evaluated the age at diagnosis and transmission of CMM in 23 U.S. white families with CMM/dysplastic nevi who had been followed 5-17 years. We estimated the median and mean ages at diagnosis of invasive melanoma for all individuals, for men and women separately, and by generation. Using the computer program BMDP1L, we also estimated the cumulative probability of an offspring developing CMM as a function of age according to whether the mother or father had melanoma. In addition, we used a life-table approach to estimate the probability that offspring of CMM parents were affected with CMM (penetrance). RESULTS: The median age at diagnosis in the 23 kindreds (n = 106) was 33 years, substantially less than that of patients with sporadic melanomas in the U.S. white population. For females, the median age at diagnosis was 29 years; for males, it was 36 years. Nine percent of the case patients developed CMM before age 20 compared with 2% in the general population. There was little difference in the transmission pattern of melanoma between males and females in the 23 families, although sons of CMM parents had a higher risk of CMM than daughters of CMM parents. This difference was, however, based on small numbers and was not statistically significant. The penetrance estimates for CMM were high. They rose rapidly from 6% at age 18 to 85% by age 48. The median age at diagnosis of invasive melanoma decreased dramatically in successive generations; the reduction was 11-16 years per generation and was statistically significant (P < .0001). CONCLUSIONS AND IMPLICATIONS: Although this reduction in median age at diagnosis may result partly from increased surveillance in hereditary melanoma families and the fact that individuals in the younger generations have not yet reached the highest at-risk ages for developing melanoma, the possibility of changes in melanoma risk and risk factors, genetic and/or environmental, across generations should be considered.

Adolescent↗
PubMed1994

Clinical findings in two African-American families with the nevoid basal cell carcinoma syndrome (NBCC).

The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder with variable expressivity. We present the clinical findings on 11 African-American NBCC cases from 2 families and a review of the literature of NBCC in African-Americans. The 2 new families, as well as those previously reported, suggest minimal expression of the basal cell carcinomas and full expression of the other components of the syndrome. The 3 most common findings in the 11 cases were jaw cysts, palmar and/or plantar pits, and calcification of the falx cerebri. Only 44% (4/11) of these cases had one or more confirmed basal cell carcinomas. This frequency is substantially less than that observed in whites (90% with basal cell carcinomas). The relative lack of these skin tumors in African-Americans partly reflects ultraviolet radiation protection resulting from increased skin pigmentation. Future research should help identify the specific mutation(s) in blacks as well as other modifying genes and environmental exposures that may contribute to the varied manifestations of the syndrome.

Abnormalities, Multiple↗
PubMed1994

Familial risk in oral and pharyngeal cancer.

We examined the relationship between a family history of cancer and risk of oral and pharyngeal cancer using epidemiological data from a large case-control investigation of these tumours. 487 (45.7%) of the cases and 485 (41.0%) of the controls reported cancer in a parent or a sibling. After controlling for age, race, sex, study location, respondent status and smoking and alcohol use, the OR associated with any cancer in the family was 1.1 [95% confidence interval (CI) 0.9-1.3]. Risks were non-significantly elevated among those with a history of cancers arising from the oral cavity/pharynx (OR = 1.2, 95% CI 0.7-2.3), oesophagus/larynx (OR = 1.6, 95% CI 0.7-3.8) and lung (OR = 1.2, 95% CI 0.8-1.8), with the excess risk primarily among those for whom a male relative, particularly a brother, was affected with these smoking-related cancers. In addition, an elevated risk of oral/pharynx cancer was found among those whose sisters developed other cancers (OR = 1.6, 95% CI 1.1-2.2). Subsite analyses revealed stronger elevated risks of smoking-related cancers in relatives of pharyngeal cancer cases (OR = 1.7, 95% CI 1.1-2.8) than of oral cancer patients. The data indicate that there is at most a weak familial aggregation of oral/pharynx cancers. Furthermore, since the excess familial risk of oral/pharynx cancer was associated with smoking-related cancers among male but not female relatives, it seems likely that environmental factors (notably smoking and drinking) contribute to the familial tendency observed in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Case-Control Studies↗
PubMed1994

Germline p16 mutations in familial melanoma.

The p16 gene is located in chromosome 9p21, a region that is linked to familial melanoma and homozygously deleted in many tumour cell lines. We describe eight p16 germline substitutions (one nonsense, one splice donor site and six missense) in 13/18 familial melanoma kindreds. Six of these mutations were identified in 33/36 melanoma cases in nine families, whereas two were detected in normal controls and are not disease-related. The melanoma-specific mutations were detected in 9p21-linked, but not in 1p36-linked, families, thereby confirming previous reports of genetic heterogeneity. Functional analyses of these mutations will confirm those causally related to the development of familial melanoma.

Base Sequence↗
PubMed1994

Fine mapping of the locus for nevoid basal cell carcinoma syndrome on chromosome 9q.

The nevoid basal cell carcinoma syndrome is an autosomal dominant disorder characterized primarily by multiple basal cell carcinomas, odontogenic keratocysts, and pits of the palms and soles. Tumor deletion studies and linkage analysis in Caucasians have revealed that the gene is on chromosome 9q. To further refine the location of the nevoid basal cell carcinoma syndrome locus, we tested linkage to this region in three families. Evaluation of recombinants suggested that the nevoid basal cell carcinoma syndrome locus lies in the interval defined distally by D9S127. Our data, together with existing published data defining D9S12 as a proximal flanking marker, refine the location of nevoid basal cell carcinoma syndrome to an 8.3-cM interval. Two of the families studied were African-American and show a notable variation in phenotypic expression in which affected individuals developed few skin cancers. However, despite clinical heterogeneity, our data are consistent with the hypothesis that the same locus is involved in these African-American families.

Adolescent↗
PubMed1994

Localization of the gene for the nevoid basal cell carcinoma syndrome.

The nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder characterized by multiple basal cell carcinomas, jaw cysts, pits of the palms and/or soles, ectopic calcification, and skeletal malformations. The NBCC gene has recently been mapped to chromosome 9q22.3-9q31. In order to further define the region containing the NBCC gene, we have analyzed 137 individuals from eight families for linkage, using 11 markers from the region. Eight markers showed statistically significant evidence for linkage to NBCC. Three markers (D9S180, ALDOB, and D9S173) showed no definite recombination with the disease locus. All families showed some evidence for linkage to markers in this region. On the basis of the inspection of individual recombinants and previously published information about map location, we suggest the following order for the markers: D9S119-D9S12-D9S197-D9S196-(NBCC,D9S180 -D9S173,ALDOB)-D9S109- D9S127-(D9S53,D9S29). We are currently developing YAC contigs for the most closely linked markers, to further refine the location of the NBCC gene.

Alleles↗
PubMed1994

Linkage of cutaneous malignant melanoma/dysplastic nevi to chromosome 9p, and evidence for genetic heterogeneity.

We examined the relationship between cutaneous malignant melanoma/dysplastic nevi (CMM/DN) and chromosome 9p in 13 pedigrees with two or more living cases of invasive melanoma. We used two highly informative (CA)n repeats, D9S126 and IFNA, previously implicated in familial malignant melanoma (MLM), to conduct linkage analysis. Three analyses were performed: (1) CMM alone--all individuals without either confirmed melanoma or borderline lesions were considered unaffected (model A); (2) CMM/DN with both variable age at onset and sporadics (model B); and (3) CMM affecteds only--all individuals either without confirmed melanoma or with borderline lesions were designated "unknown" (model C). There was significant evidence for linkage to IFNA in all three models. For CMM alone, the maximum lod score (Zmax) was 4.36 at theta = .10 for model A and 3.39 at theta = .10 for model C. For CMM/DN (model B), Zmax = 3.05 at theta = .20. There was no significant evidence for linkage between CMM alone or CMM/DN and chromosome 9p marker D9S126. In addition, there was significant evidence for heterogeneity when a homogeneity test allowing for linkage to chromosome 9p or chromosome 1p or neither region was used. These results suggest that there is an MLM susceptibility locus on chromosome 9p but that familial melanoma is heterogeneous and not all families with CMM/DN are linked to a locus in this region.

Adolescent↗
PubMed1993

Clustering of high density lipoprotein cholesterol levels in premenopausal and postmenopausal female twins.

Previous family and twin studies indicate that genetic variation makes an important contribution to individual variation in high density lipoprotein cholesterol (HDL) levels, even after adjustment for covariates (such as obesity and alcohol consumption) that also cluster in families. However, most studies assume that genetic mechanisms affecting variation in HDL level are the same in all subgroups of the population (e.g., men versus women, by age). Using data from the Kaiser-Permanente Women Twins Study, we found different patterns of clustering for monozygotic (MZ) and dizygotic (DZ) twins depending on menopausal status. Premenopausal MZ twins were more similar than postmenopausal MZ twins (r(i) = 0.79 and r(i) = 0.61, respectively, after adjustment for age, alcohol consumption, smoking status, degree of obesity, and leisure-time exercise); premenopausal and postmenopausal DZ twins were alike to the same extent (r(i) = 0.31 and r(i) = 0.32, respectively, adjusted as above). These data suggest that either postmenopausal MZ twins have a greater degree of shared environment than postmenopausal DZ twins (e.g., postmenopausal female hormone use) or that genetic mechanisms that affect individual variation in HDL level differ in pre- and postmenopausal women. Data were not available on postmenopausal female hormone use. If genetic mechanisms that influence variation in HDL levels differ between pre- and postmenopausal women, genetic epidemiologic methods that assume that genetic and environmental sources of variation are the same for all groups of individuals may lead to false conclusions.

Adult↗
PubMed1993

Sun exposure and basal cell carcinomas in the nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCC) is an autosomal dominant multisystem disorder. Persons with the NBCC gene have varied susceptibility to basal cell carcinoma (BCC) development. OBJECTIVE: We examined the anatomic site-specific distribution of BCCs and the relation between sun exposure and numbers of BCCs in NBCC cases. METHODS: A questionnaire asking about lifetime sun exposure, sun behavior habits, and number of BCCs was sent to 16 families with NBCC evaluated between 1985 and 1991. The results were compared with previously published data for the general population. RESULTS: In the general population, 88% of all BCCs in women and 86% in men occurred on the face, head, neck, and arms versus 59% in women with NBCC and 65% in men with NBCC. Of BCCs in the general population 9% and 12% occurred on the trunk versus 38% and 32% of BCCs in NBCC cases, in women and men, respectively. We did not observe a strong relation between numbers of BCCs and history of lifetime sun exposure. CONCLUSION: The anatomic-site distribution of BCCs suggests that frequent sun exposure may not be essential for the development of BCCs in patients with NBCC. However, the observation that there are more tumors on sun-exposed areas suggests that exposure to the sun promotes the development of BCCs in patients with NBCC.

Adolescent↗
PubMed1993

Nonoperative management of blunt abdominal trauma: the role of sequential diagnostic peritoneal lavage, computed tomography, and angiography.

STUDY OBJECTIVE: To determine the usefulness of sequential nonoperative diagnostic studies in the evaluation and treatment of stable patients after blunt abdominal trauma. DESIGN AND SETTING: Retrospective review of a prospective treatment plan in a large urban Level I trauma center. PARTICIPANTS: Fifty-two patients deemed stable after initial evaluation following blunt abdominal trauma. INTERVENTIONS: Patients with a positive diagnostic peritoneal lavage for red blood cells underwent abdominal computed tomography (CT) scanning. If CT demonstrated a visceral injury, it was followed by diagnostic angiography. Attempts were made to treat on-going bleeding by transcatheter embolization. RESULTS: Fifteen patients had negative CT scans and were successfully observed. In the other 37 patients, CT identified 17 liver, 16 splenic, and eight kidney injuries; eight extra-peritoneal bleeds; and one mesenteric hematoma. Six of these patients were observed. Thirty underwent diagnostic angiograms. Twelve had no active bleeding, and all were observed successfully. Seventeen underwent successful embolization of the bleeding site(s). One had injuries not controllable by embolization and required exploration. Six patients required laparotomy later in their course, but none had intra-abdominal bleeding or a missed intestinal injury. Despite being performed after diagnostic peritoneal lavage, CT missed only two injuries. There was one main complication, delayed recognition of a diaphragmatic injury. Three patients died, two from multiple organ failure and one from a pulmonary embolus; none was believed to be related to this technique. With our algorithm, 45 patients (86%) were spared laparotomy. CONCLUSION: Diagnostic peritoneal lavage and CT are complementary when evaluating blunt abdominal trauma. Diagnostic peritoneal lavage is an effective screening tool. CT may be reserved for stable patients with a positive diagnostic peritoneal lavage to specify the organs injured. Bleeding often may be treated by embolization, limiting the rate of surgery.

Abdominal Injuries↗
PubMed1993

Etiology, epidemiology, risk factors, and public health issues of melanoma.

Evidence for an increase in the incidence of melanoma and nonmelanoma skin cancers continues to accumulate. Survival after early melanoma is greater than 90%. Survival decreases as tumor thickness increases in a relationship that appears to be more smooth than stepwise. Further evidence that early intermittent sun exposure is a major determinant of risk for melanoma was derived from a case control study in a low-risk population and in a study on migrants to Australia. There is also additional evidence that clinically atypical nevi (dysplastic nevi) are strong predictors of melanoma risk. For public health efforts to be effective in reducing the mortality and morbidity from melanoma and nonmelanoma skin cancers, it is essential to understand the responses of the public and the professional to skin cancer detection efforts and educational programs. Results from several such programs are reviewed. An understanding of the genetics of melanoma continues to grow yet remains complex.

Health Education↗
PubMed1993

The inheritance pattern of dysplastic naevi in families of dysplastic naevus patients.

Dysplastic naevi (DN) are the major precursor lesions of malignant melanoma, yet the presumed mode of inheritance or genetic aetiology of DN remains controversial. The inheritance pattern of DN in families from a randomly selected population of 26 dysplastic naevus patients was investigated by estimating the segregation ratio in families ascertained through an offspring with DN (incomplete ascertainment). For families ascertained through a parent with DN (complete ascertainment) the transmission pattern was examined by comparing the observed number of affected offspring to the expected number using a chi 2 goodness-of-fit test. Results from the chi 2 tests and the estimated segregation ratio of 0.52 (95% confidence interval: 0.31, 0.73) suggest that the inheritance pattern for dysplastic naevi in these families is consistent with autosomal dominant transmission, although the present study was limited because of a small sample size. The findings, therefore, need to be confirmed by a much larger study that is able to test more rigorously specific genetic hypotheses.

Dysplastic Nevus Syndrome↗
PubMed1993

Risk of melanoma and other cancers in melanoma-prone families.

We evaluated the risk of developing melanoma over time in members of 23 melanoma-prone families. All 23 families had dysplastic nevi as well as melanoma. Forty-seven melanomas occurred prospectively, all in family members with dysplastic nevi. The prospective melanomas were markedly thinner than the melanomas diagnosed prior to or at the time of the subject's entry into the study. The cumulative risk of melanoma by age 50 years among people with dysplastic nevi was 48.9% +/- 4.2%. Overall, the relative risk of a prospective melanoma among family members with previous melanoma was 229 (95% confidence interval 110-422). The risk varied by time interval and was 362 in the first 5 years, decreasing to 120 after 5 years. The risk of developing melanoma was 85 times increased (95% confidence interval 41-156) in family members with dysplastic nevi and also declined over time in this group. There was no significant excess of cancers other than melanoma. Close surveillance of these high-risk families has led to diagnosis of melanoma at an earlier developmental stage, which should result in a decrease in mortality over time.

Adolescent↗
PubMed1993

Thrombocytopenia following administration of phenytoin, dexamethasone and cimetidine: a case report and a potential mechanism.

Cimetidine and phenytoin are useful medications often used together in patients with seizure disorders secondary to brain masses or metabolic abnormalities. We describe a case of thrombocytopenia in the setting of concurrent phenytoin, dexamethasone and cimetidine administration, and compare it with previously described cases of thrombocytopenia induced by concurrent use of phenytoin, cimetidine, and glucocorticoids. The similarities between these cases suggest mechanisms by which these agents may induce thrombocytopenia, specifically through potential downregulation of epoxide hydrolase by glucocorticoids.

Aged↗