Follow-up of American Cancer Society Special Postdoctoral Research Fellowship recipients.
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A follow-up study of the 44 recipients of American Cancer Society, Inc., Special Postdoctoral Research Fellowship from 1962 to 1973 revealed that 11 of 21 M.D. candidates obtained their second (Ph.D.) degree at the end of training. By contrast, all but one among the 23 Ph.D. candidates were awarded the second (M.D.) degree. A great majority of either group remain in active research, regardless of whether or not they obtained the second degree. A very high percentage of their research is cancer related. (+info)
Superimposed histologic and genetic mapping of chromosome 9 in progression of human urinary bladder neoplasia: implications for a genetic model of multistep urothelial carcinogenesis and early detection of urinary bladder cancer.
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The evolution of alterations on chromosome 9, including the putative tumor suppressor genes mapped to the 9p21-22 region (the MTS genes), was studied in relation to the progression of human urinary bladder neoplasia by using whole organ superimposed histologic and genetic mapping in cystectomy specimens and was verified in urinary bladder tumors of various pathogenetic subsets with longterm follow-up. The applicability of chromosome 9 allelic losses as non-invasive markers of urothelial neoplasia was tested on voided urine and/or bladder washings of patients with urinary bladder cancer. Although sequential multiple hits in the MTS locus were documented in the development of intraurothelial precursor lesions, the MTS genes do not seem to represent a major target for p21-23 deletions in bladder cancer. Two additional tumor suppressor genes involved in bladder neoplasia located distally and proximally to the MTS locus within p22-23 and p11-13 regions respectively were identified. Several distinct putative tumor suppressor gene loci within the q12-13, q21-22, and q34 regions were identified on the q arm. In particular, the pericentromeric q12-13 area may contain the critical tumor suppressor gene or genes for the development of early urothelial neoplasia. Allelic losses of chromosome 9 were associated with expansion of the abnormal urothelial clone which frequently involved large areas of urinary bladder mucosa. These losses could be found in a high proportion of urothelial tumors and in voided urine or bladder washing samples of nearly all patients with urinary bladder carcinoma. (+info)
Persistent damage to Enterocytozoon bieneusi, with persistent symptomatic relief, after combined furazolidone and albendazole in AIDS patients.
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AIM: To investigate morphological changes in Enterocytozoon bieneusi and the duration of symptomatic relief after combination treatment with furazolidone and albendazole in AIDS patients. METHODS: Four severely immunocompromised AIDS patients with symptomatic E bieneusi infection of the gut received an 18 day course of combined furazolidone and albendazole (500 + 800 mg daily). All patients were monitored for parasite shedding in stool by light microscopy at the end of treatment and monthly during follow up. At the end of treatment, duodenal biopsy specimens obtained from three patients were studied by transmission electron microscopy by two pathologists blind to the patients' treatment or clinical outcome. Duodenal biopsy specimens obtained from one of the patients two months after completion of treatment were also studied electronmicroscopically. RESULTS: All patients had long lasting symptomatic relief, with a major decrease--or transient absence--of spore shedding in stools from completion of treatment. After treatment, changes in faecal spores were persistently found by light microscopy in all cases, and there was evidence of both a substantial decrease in the parasite load and ultrastructural damage in the parasite in all biopsy specimens. The treatment was well tolerated, and no patient had clinical or parasitological relapse during follow up (up to 15 months). CONCLUSIONS: The long lasting symptomatic relief observed in all four treated patients correlated with the persistent decrease in parasite load both in tissue and in stool, and with the morphological changes observed in the life cycle of the protozoan. These data suggest that combined treatment with furazolidone and albendazole is active against E bieneusi and may result in lasting remission even in severely immunocompromised patients. (+info)
Expression of extracellular matrix proteins in cervical squamous cell carcinoma--a clinicopathological study.
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AIM: To evaluate the intracellular and peritumoral expression of matrix proteins in squamous cell carcinoma of the uterine cervix using immunohistochemistry. METHODS: 71 squamous cell carcinomas and 10 controls were stained for laminin, fibronectin, and collagen IV. Cytoplasmic staining in tumour cells and peritumoral deposition of matrix proteins were evaluated. The association between staining results and patient age, tumour stage, histological grade, and survival was studied. RESULTS: Positive cytoplasmic staining for laminin, fibronectin, and collagen IV was observed in 17 (23.9%), 27 (38%), and 10 (14.1%) cases, respectively. Staining for laminin was most pronounced in the invasive front of tumour islands, while for fibronectin and collagen IV it appeared to be diffuse. Peritumoral staining for laminin and collagen IV was detected in 12 cases (16.9%). Early stage (Ia1-Ia2) tumours were uniformly negative for all three proteins. Cytoplasmic staining for laminin correlated with positive staining for fibronectin and collagen IV, and with the presence of a peritumoral deposition of collagen IV and laminin. There was no correlation with any of the three markers between staining results and patient age, stage, grade, or survival. CONCLUSIONS: Expression of extracellular matrix proteins in some cervical squamous cell carcinomas might reflect the enhanced ability of these tumours to modify the peritumoral stroma. This ability seems to be absent in early stage tumours. The correlation between intracytoplasmic and peritumoral expression of matrix proteins supports the evidence of their synthesis by tumour cells. However, this property did not correlate with disease outcome in this study. (+info)
Reproductive factors and fatal hip fractures. A Norwegian prospective study of 63,000 women.
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STUDY OBJECTIVE: The aim of the study was to investigate the impact of reproductive variables (age at menarche, menopause, first and last birth as well as parity, lactation, and abortions) on hip fracture mortality. DESIGN AND SETTING: A prospective study in Norway with more than 60,000 women followed up for 29 years. A total of 465 deaths as a result of hip fracture were recorded. MAIN RESULTS: Statistically significant linear relations (p < or = 0.02) were found between both age at menarche and length of reproductive period (defined as age at menopause to age at menarche) and the mortality of hip fractures in women aged less than 80. The death rate for women with a late menarche (> or = 17 years) was twice that of the women with relatively early menarche (< or = 13 years). Compared with women with less than 30 years between menopause and menarche, the mortality rate ratio in women with more than 38 reproductive years was 0.5. We also found an inverse relation with age at first birth. CONCLUSIONS: This study supports by hypothesis that an early menarche and a long reproductive period protect against hip fracture mortality. High age at first birth may also be protective. (+info)
Reconstruction for chronic dysfunction of ileoanal pouches.
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OBJECTIVE: A retrospective review was performed to determine the results after surgical reconstruction for chronic dysfunction of ileal pouch-anal procedures for ulcerative colitis and familial colonic polyposis at a university medical center. METHODS: During the 20-year period from 1978 to 1998, 601 patients underwent colectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, familial colonic polyposis, or Hirschsprung's disease. A J pouch was used for 351 patients, a lateral pouch for 221, an S pouch for 6, and a straight pull-through for 23. Acute complications after pouch construction have been detailed in previous publications and are not included in this study. Chronic pouch stasis with diarrhea, frequency, urgency, and soiling gradually became more severe in 164 patients (27.3%), associated with pouch enlargement, an elongated efferent limb, and obstruction to pouch outflow, largely related to the pouch configuration used during the authors' early clinical experience. These patients were sufficiently symptomatic to be considered for reconstruction (mean 68 months after IPAA). Transanal resection of an elongated IPAA spout was performed on 58 patients; abdominoperineal mobilization of the pouch with resection and tapering of the lower end (AP reconstruction) and ileoanal anastomosis on 83; pouch removal and new pouch construction on 7; and conversion of a straight pull-through to a pouch on 16. RESULTS: Good long-term results (mean 7.7 years) with improvement in symptoms occurred in 98% of transanal resections, 91.5% of AP reconstructions, 86% of new pouch constructions, and 100% of conversions of a straight pull-through to a pouch. The average number of bowel movements per 24 hours at 6 months was 4.8. Complications occurred in 11.6% of reconstructed patients. Five of the 164 patients (3.1%) required eventual pouch removal and permanent ileostomy. The high rate of pouch revision in this series of patients undergoing IPAA is due to a policy of aggressive correction when patients do not experience an optimal functional result, or have a progressive worsening of their status. CONCLUSIONS: Although occasionally a major undertaking, reconstruction of ileoanal pouches with progressive dysfunction due to large size or a long efferent limb has resulted in marked improvement in intestinal function in >93% of patients and has reduced the need for late pouch removal. (+info)
Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors.
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OBJECTIVE: This study aimed to evaluate the long-term results of treatment and prognostic factors in patients with intrahepatic recurrence after curative resection of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Recent studies have demonstrated the usefulness of re-resection, transarterial oily chemoembolization (TOCE), or percutaneous ethanol injection therapy (PEIT) in selected patients with intrahepatic recurrent HCC. The overall results of a treatment strategy combining these modalities have not been fully evaluated, and the prognostic factors determining survival in these patients remain to be clarified. METHODS: Two hundred and forty-four patients who underwent curative resection for HCC were followed for intrahepatic recurrence, which was treated aggressively with a strategy including different modalities. Survival results after recurrence and from initial hepatectomy were analyzed, and prognostic factors were determined by univariate and multivariate analysis using 27 clinicopathologic variables. RESULTS: One hundred and five patients (43%) with intrahepatic recurrence were treated with re-resection (11), TOCE (71), PEIT (6), systemic chemotherapy (8) or conservatively (9). The overall 1-year, 3-year, and 5-year survival rates from the time of recurrence were 65.5%, 34.9%, and 19.7%, respectively, and from the time of initial hepatectomy were 78.4%, 47.2%, and 30.9%, respectively. The re-resection group had the best survival, followed by the TOCE group. Multivariate analysis revealed Child's B or C grading, serum albumin < or = 40 g/l, multiple recurrent tumors, recurrence < or = 1 year after hepatectomy, and concurrent extrahepatic recurrence to be independent adverse prognostic factors. CONCLUSIONS: Aggressive treatment with a multimodality strategy could result in prolonged survival in patients with intrahepatic recurrence after curative resection for HCC. Prognosis was determined by the liver function status, interval to recurrence, number of recurrent tumors, any concurrent extrahepatic recurrence, and type of treatment. (+info)
Serum triglyceride: a possible risk factor for ruptured abdominal aortic aneurysm.
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BACKGROUND: We aimed to determine the relationship between ruptured abdominal aortic aneurysm (AAA) and serum concentrations of lipids and apolipoproteins. METHODS: A cohort of 21 520 men, aged 35-64 years, was recruited from men attending the British United Provident Association (BUPA) clinic in London for a routine medical examination in 1975-1982. Smoking habits, weight, height and blood pressure were recorded at entry. Lipids and apolipoproteins were measured in stored serum samples from the 30 men who subsequently died of ruptured AAA and 150 matched controls. RESULTS: Triglyceride was strongly related to risk of ruptured AAA. In univariate analyses the risk in men on the 90th centile of the distribution relative to the risk in men on the 10th (RO10-90) was 12 (95% confidence interval [CI] : 3.8-37) for triglyceride, 5.5 (95% CI: 1.8-17) for apolipoprotein B (apoB) (the protein component of low density lipoprotein [LDL]), 0.15 (95% CI : 0.04-0.56) for apo A1 (the protein component of high density lipoprotein [HDL]), 3.7 (95% CI: 1.4-9.4) for body mass index and 3.0 (95% CI: 1.1-8.5) for systolic blood pressure. Lipoprotein (a) (Lp(a)) was not a significant risk factor (RO10-90 = 1.6, 95% CI: 0.6-3.0). In multivariate analysis triglyceride retained its strong association. CONCLUSION: Triglyceride appears to be a strong risk factor for ruptured AAA, although further studies are required to clarify this. If this and other associations are cause and effect, then changing the distribution of risk factors in the population (by many people stopping smoking and adopting a lower saturated fat diet and by lowering blood pressure) could achieve an important reduction in mortality from ruptured AAA. (+info)