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Biomedical subjects

A Goodman

Publications and source records attributed to A Goodman.

At least 73 records · Page 4Linked to original sources

A reference cross DNA panel for zebrafish (Danio rerio) anchored with simple sequence length polymorphisms.

The ultimate informativeness of the zebrafish mutations described in this issue will rest in part on the ability to clone these genes. However, the genetic infrastructure required for the positional cloning in zebrafish is still in its infancy. Here we report a reference cross panel of DNA, consisting of 520 F2 progeny (1040 meioses) that has been anchored to a zebrafish genetic linkage map by 102 simple sequence length polymorphisms. This reference cross DNA provides: (1) a panel of DNA from the cross that was used to construct the genetic linkage map, upon which polymorphic gene(s) and genetic markers can be mapped; (2) a fine order mapping tool, with a maximum resolution of 0.1 cM; and (3) a foundation for the development of a physical map (an ordered array of clones each containing a known portion of the genome). This reference cross DNA will serve as a resource enabling investigators to relate genes or genetic markers directly to a single genetic linkage map and avoid the problem of integrating different maps with different genetic markers, as must be currently done when using randomly amplified polymorphic DNA markers, or as has occurred with human genetic linkage maps.

Alleles↗

Cell surplus on sampling devices after routine cervical cytologic smears. A study of residual cell populations.

OBJECTIVE: To demonstrate whether considerable valuable cellular material remains on the sampling device after a conventional cervical cytologic smear and to investigate whether evidence of cervical disease may be present on the sampling device but missed because it is not represented on the first slide. STUDY DESIGN: Routine cervical cytologic smear material was taken from 60 women who were attending the colposcopy or gynecologic oncology clinic at New England Medical Center. At the time of the colposcopic examination, a cervical scrape was made using a Cytobrush followed by a Cervex brush. After the smear was made from each device, the sampling devices were also used to make four additional slides. Both the Cytobrush and Cervex brush were applied to each slide. RESULTS: Cytologically, all five slides were satisfactory for screening in the 60 cases. In all diagnostic cases but one, disease was well represented across all five slides. CONCLUSION: Cellular material collected in a cervical scrape is sufficient to prepare at least five satisfactory smears. The one case where an abnormality was detected only on the third slide suggests the possibility of nonrandom subsampling and of discarding the majority of the cellular material from the patient.

Cervix Uteri↗

Uterine papillary serous carcinoma (UPSC): a clinicopathologic study of 30 cases.

Between 1975 and 1989, 896 patients were treated for endometrial carcinoma at the Massachusetts General Hospital. Thirty patients were identified from the tumor registry as having uterine papillary serous carcinomas. The survival for all patients and for groups of patients stratified on clinical and pathological parameters was examined in the Kaplan-Meier survival curves. Curves for the different strata were compared using the logrank test. The 5-year survival for the 30 patients was 30% +/- 9%. Patients with surgical stage I and II tumors had a 5-year survival rate of 79% +/- 14% compared to 25% +/- 10% in patients with stage III and IV tumors (P = 0.02). Clinical stage, depth of myometrial invasion, lymph-vascular space invasion, tumor grade, and DNA aneuploidy were not found to significantly impact on survival. However, a survival advantage was seen in patients diagnosed with early surgical stage tumors, reinforcing the need for thorough staging at the time of laparotomy.

Aged↗

A genetic linkage map of the laboratory rat, Rattus norvegicus.

We report the construction of the first complete genetic linkage map of the laboratory rat. By testing 1171 simple sequence length polymorphisms (SSLPs), we have identified 432 markers that show polymorphisms between the SHR and BN rat strains and mapped them in a single (SHR x BN) F2 intercross. The loci define 21 large linkage groups corresponding to the 21 rat chromosomes, together with a pair of nearby markers on chromosome 9 that are not linked to the rest of the map. Because 99.5% of the markers fall into one of the 21 large linkage groups, the maps appear to cover the vast majority of the rat genome. The availability of the map should facilitate whole genome scans for genes underlying qualitative and quantitative traits relevant to mammalian physiology and pathobiology.

Animals↗

Localization of erythropoietin mRNA in the rat kidney by polymerase chain reaction.

Erythropoietin (Epo) is a glycoprotein secreted by kidney cells which plays an important role in the regulation of erythropoiesis. Localization of the Epo production by immunohistochemical studies and in situ hybridization has not been definitively established and is still a matter of controversy. Epo and glyceraldehyde 3-dehydrogenase (GAPDH) mRNA levels were determined in total RNA isolated from control and CoCl2-treated rats using a coupled reverse transcriptase/polymerase chain reaction method (RT/PCR). As indicated by the amount of amplification product, Epo mRNA levels were several-fold higher in CoCl2-treated rat kidney. In contrast, GAPDH mRNA levels were similar in control and CoCl2-treated rats. This RT/PCR method was also used to assess the level of Epo and GAPDH mRNA in microdissected nephron segments. All nephron segments tested lacked any detectable levels of Epo mRNA in either control or CoCl2-treated rats. On the other hand, peritubular cells (capillary fraction: afferent/efferent arteriole, vasa recta) were the only cells where the Epo mRNA was detected. Using a specific primer for GAPDH, the RT/PCR method could identify GAPDH mRNA in all microdissected nephron segments where the Epo mRNA was not expressed. Thus, a combination of microdissected nephron segments and RT/PCR enabled us to detect GAPDH mRNA populations in all nephron segments, whereas the failure to detect Epo mRNA in all segments but the capillary fraction, is due to the specific and localized expression of the Epo gene to this fraction.

Animals↗

Surgical stage IV endometrial carcinoma: a study of 47 cases.

Between 1976 and 1991, 47 patients with surgical Stage IV endometrial carcinoma were treated. Patients were identified from the tumor registry and charts were retrospectively reviewed. Surgical curves using the Kaplan-Meier product-limit method and Cox regression analysis were used to identify independent prognostic factors. Overall, median survival was only 12 months. Using univariate analysis there was no statistically significant difference in survival between age (P = 0.41), histology (P = 0.54), grade (P = 0.91), disease site (P = 0.32), or clinical stage (P = 0.87). In patients whose disease was surgically cytoreduced, the median survival was 18 months compared to 8 months in those who did not undergo surgery (P = 0.0001). Evaluation of other treatment modalities by univariate analysis revealed improved survival in those patients who received cyclophosphamide, doxorubicin, and cisplatin (P = 0.0007), decreased survival in those who received radiation therapy compared to surgery (P = 0.023), and no statistically significant difference in survival with progestins. By multivariate analysis successful cytoreduction was the only statistically significant prognostic variable (P = 0.04). This 15-year retrospective review confirms that prognosis for women with Stage IV endometrial cancer is extremely poor. However, if hysterectomy with cytoreduction is feasible, surgery should be performed because survival may be improved.

Aged↗

Molecular genetic changes associated with ovarian cancer.

Multiple specific chromosomal deletions can be found in human epithelial ovarian cancer by cytogenetic analysis or molecular techniques. Somatic allelic deletion or loss of heterozygosity (LOH) in a tumor is considered circumstantial evidence for the location of tumor suppressor genes. We have examined 27 primary epithelial ovarian tumors for the presence of LOH at 19 polymorphic markers on chromosomes 1, 5, 6, 9, 11, 13, and 17. Markers near the adenomatous polyposis coli (APC) gene at 5q21 showed LOH in 50% (10/20) of informative cases. LOH was seen in 53% (8/15) at the IFNA locus on 9p, another region implicated in other tumors, but not previously associated with ovarian cancer. We observed LOH for markers on 11p15 in 50% (12/24) of ovarian cancer DNAs from informative cases, while only 25% (4/16) at 11q13 and 29% (5/17) at 11q24 showed LOH. Only a portion of distal 11p was deleted in six cases. The incidence of LOH (50%) at HGH (17q22-q24) was greater than that at D17S579 (39%; 17q21), a locus tightly linked to BRCA1. Sixty-four percent (7/11) showed allelic loss at 17p11. LOH was infrequently observed at markers on chromosomes 1, 6, and 13q. Most cases showing LOH were stage III or IV, and most showed LOH at more than one locus. These studies support the concept that multiple genetic loci are involved in ovarian tumorigenesis. Two additional regions thought to harbor genes important in other cancers, 5q21 and 9p21, can now be added to the growing spectrum of molecular alterations seen in ovarian cancer.

Adult↗

Homogeneous sampling accounts for the increased diagnostic accuracy using the ThinPrep Processor.

Recent clinical trials indicated that the ThinPrep method of sample preparation has greater diagnostic sensitivity than the conventional direct Papanicolaou smear. The authors hypothesized that nonhomogeneous cell sampling during transfer from the sampling device to the microscope slide was a contributing factor to the reduced accuracy of the conventional direct Pap smears in these trials. To test this hypothesis, four direct smear methods were compared with the newly developed, fluid-based, filter-transfer method. Counts of epithelial cells on conventional smears showed that only a fraction of the available epithelial cells on the sampling devices (medians, 6.5% to 62.5%) was actually deposited on the slides. In all 27 cases studied with the ThinPrep method, equivalent diagnostic material was obtained on each of the replicate slides prepared per specimen. This identifies a new source of error, preparation error, in conventional smears.

Cell Biology↗

Chromic phosphate therapy in carcinoma of the ovary.

BACKGROUND: Adjuvant therapy with intraperitoneal (IP) chromic phosphate (P-32) instillation in both early and advanced carcinoma of the ovary requires adequate intra-abdominal distribution for maximum therapeutic benefit. Abdominal-pelvic computed tomographic (CT) scanning with water-soluble IP contrast to establish the absence of intra-abdominal adhesions prior to P-32 instillation has not been previously reported. STUDY DESIGN: Sixteen patients with carcinoma of the ovary who were offered IP P-32 therapy between January 1988 and December 1992 were retrospectively reviewed. Computed tomographic scans on 13 patients were reevaluated using a modification of Muggia and associates' distribution scoring system. RESULTS: Of the 16 patients, one had a negative second look operation for stage IIIc carcinoma of the ovary. The remaining 15 with stage I and II disease underwent at least a staging laparotomy, bilateral salpingo-oophorectomy, and omentectomy. The mean time from operation to IP P-32 attempt was 28 days with a range of 17 to 90 days. Adequate distribution was considered present in two of the three cases evaluated by technetium scanning and in four of the 13 cases studied by CT scanning. On review, 12 of 13 cases studied by CT scans revealed some areas of IP contrast exclusion and loculation. CONCLUSIONS: We suspect that uneven postoperative IP P-32 distribution is common and may be missed by two-dimensional imaging techniques such as technetium scanning or fluoroscopy.

Adult↗

Lead exposure among automobile radiator repair workers and their children in New York City.

Despite a comprehensive Occupational Safety and Health Administration lead standard, exposure to lead continues in many industries. This paper describes a blood lead screening and education program for automobile radiator repair workers and their families in New York City. Results showed that 67% of automobile radiator repair workers (n = 62) in 89% of the shops tested (n = 24) had blood lead levels in excess of 25 micrograms/dl. The vast majority of workers had never been tested previously, and none had received health and safety training regarding occupational lead exposure. Although none of the workers' children's blood lead levels were in excess of then-current guidelines, several had levels which may be associated with subclinical toxicity and in excess of the revised Centers for Disease Control guidelines of 10 micrograms/dl. This project demonstrates that lead exposure in the automotive radiator repair industry continues to be widespread and that local health departments can assist in hazard identification and remediation.

Adult↗

DNA ploidy status: its impact on early-stage endometrial adenocarcinoma.

DNA ploidy status, as determined by flow cytometry, has been useful in predicting survival in certain malignancies. Between January 1975 and January 1985, 85 cases that met the inclusion criteria-pathologic stage I endometrial adenocarcinomas, primary surgical therapy, endometrioid cell type, and adequate paraffin-block samples-were analyzed by DNA flow cytometry. Depth of myometrial invasion, tumor grade, and presence of lymphatic vascular space invasion were established in all cases. Ten of the 85 tumors (12%) were aneuploid. The median follow-up was 9 years with a range of 2 to 16 years. There were 9 recurrences with 5 deaths from cancer, and 8 patients died of intercurrent disease. The relative hazards for recurrence associated with aneuploidy, S-phase fraction, grade 3 histology, and any myometrial invasion were 3.1, 3.18, 3.2, and 4.9, respectively, but did not reach statistical significance. Because of the low recurrence and mortality rate in this homogeneous group, a larger sample will be necessary to fully establish a role for DNA ploidy status in identifying a poor prognostic subset.

Adenocarcinoma↗

Audit: the use of radiotherapy for NSCLC in the UK.

A questionnaire on the management of NSCLC was sent to all clinical oncologists in the UK. Responses were received from 121 individuals with at least one representative response from each of 54 British radiotherapy units. Results were then discussed at an open meeting attended by a cross section of clinical oncologists; a synopsis of responses to the questionnaire and discussion at this meeting is contained in this report. A majority of respondents estimated treatment of NSCLC to make up 10%-25% of their work-load. Radical and palliative treatments could be clearly distinguished, and aims of treatment, selection criteria and radiotherapy schedules were consistent with recommendations in the published literature. More than 90% of treatments were with palliative rather than radical intent. Radical treatment schedules could be divided according to dose (< 50 Gy, 50-55 Gy and >55 Gy), number of fractions (< 20, 20, > 20 fractions), overall time < 4/52, 4/52, > 4/52), dose per fraction (> 2.75 Gy, 2.1-2.75 Gy, < or = 2 Gy) and target volume (tumour alone, tumour and hilar nodes, or tumour, hilar and mediastinal nodes). Divided thus, radical techniques fell into three broad groups, each of the three techniques supported by a body of literature. Choice of schedule could be related to a heterogeneous referral pattern and unresolved controversies, identified as debate on the value of treating mediastinal lymphadenopathy with high dose radiation, the value of 'subradical doses' of radiation for microscopic disease, and the relative importance of volume treated, total dose, dose per fraction and overall treatment time in achieving an optimal therapeutic ratio.(ABSTRACT TRUNCATED AT 250 WORDS)

Carcinoma, Non-Small-Cell Lung↗

Diagnosis and treatment of sexual addiction.

Following a brief introduction to the concept of addiction, the definition of and diagnostic criteria for sexual addiction are presented. A theoretical framework for treatment of sexual addiction is then outlined, based on an understanding of the underlying addictive process: the compulsive dependence on external actions as a means of regulating one's internal states. Effective treatment addresses both addictive behavior and the addictive process. Addictive sexual behavior is addressed through behavioral symptom management, which includes relapse prevention and other cognitive-behavioral techniques. The addictive process is addressed by enhancing self-regulatory functions through individual psychotherapy, therapeutic group experience, and pharmacotherapy (medication treatment, when indicated). An integrated system for treatment of sexual addiction, which brings together these therapeutic methods in one theoretically coherent, clinically unified approach, is outlined.

Behavior, Addictive↗

Preoperative serum CA-125 levels in borderline tumors of the ovary.

Preoperative serum CA-125 levels were evaluated in 38 patients who underwent primary surgery for epithelial ovarian tumors of borderline malignancy at the Brigham and Women's Hospital and Massachusetts General Hospital between 1981 and 1990. Surgical staging was Stage I in 25 (66%) patients, Stage II in 2 (5%) patients, Stage III in 10 (26%) patients, and Stage IV in 1 (3%) patient. The mean sizes of mucinous and serous ovarian tumors were 21.9 and 10.3 cm, respectively (P = 0.0002). All 13 patients (100%) with mucinous tumors had Stage I disease, while 12 (50%) of 24 patients with serous tumors were Stage I. Combining all cell types, 10 (40%) of 25 patients with Stage I disease had an elevated preoperative CA-125 level, while 2 (100%) of 2, 9 (90%) of 10, and 1 (100%) of 1 patient with Stage II, III, and IV disease, respectively, had increased preoperative levels. Among patients with serous tumors, 3 (25%) of 12 Stage I patients had an elevated preoperative CA-125 level, while 11 (92%) of 12 Stage II-IV tumors had elevated levels (P less than 0.001). These data suggest that preoperative CA-125 level correlates with stage of disease in patients with serous borderline ovarian tumors.

Adult↗