US Navy Seabees have been among the most symptomatic Gulf War veterans. Beginning in May 1997, the authors mailed Gulf War-era Seabees a health survey in serial mailings. As of July 1, 1999, 68.6% of ...17,559 Seabees contacted had returned the questionnaire. Compared with other Seabees, Gulf War Seabees reported poorer general health, a higher prevalence of all 33 medical problems assessed, more cognition difficulties, and a higher prevalence of four physician-diagnosed multisymptom conditions: chronic fatigue syndrome, posttraumatic stress disorder, multiple chemical sensitivity, and irritable bowel syndrome. Because the four multisymptom conditions were highly associated with one another, the authors aggregated them into a working case definition of Gulf War illness. Among the 3,831 (22% cases) Gulf War Seabee participants, multivariable modeling revealed that female, Reserve, and enlisted personnel and participants belonging to either of two particular Seabee units were most likely to meet the case definition. Twelve of 34 self-reported Gulf War exposures were mildly associated with meeting the definition of Gulf War illness, with exposure to fumes from munitions having the highest odds ratio (odds ratio = 1.9, 95% confidence interval: 1.5, 2.4). While these data do not implicate a specific etiologic exposure, they demonstrate a strong association and a high prevalence of self-reported multisymptom conditions in a large group of symptomatic Gulf War veterans.
2-Methoxyoestradiol (2-MeOE2) is an endogenous oestrogen metabolite that inhibits the proliferation of cancer cells in vitro, and it is also antiangiogenic. In vivo 2-MeOE2, when administered at ...relatively high doses, inhibits the growth of tumours derived from breast cancer cells, sarcomas and melanomas. Sulphamoylated derivatives of 2-MeOE2 are more potent inhibitors of in vitro breast cancer cell growth than 2-MeOE2. In the present study, we have compared the pharmacokinetic profiles and metabolism of 2-MeOE2 and its sulphamoylated derivative, 2-methoxyoestradiol-bis-sulphamate (2-MeOE2bisMATE), in adult female rats. Their ability to inhibit tumour growth was compared in nude mice bearing xenografts derived from MDA-MB-435 (oestrogen receptor negative) melanoma cancer cells. After a single oral 10 mg kg(-1) dose of 2-MeOE2bisMATE, significant concentrations of this compound were still detectable at 24 h. In contrast, no 2-MeOE2 or metabolites were detected in plasma at any time after a 10 mg kg(-1) oral dose. Thus, the bioavailability of 2-MeOE2 is very low, whereas for 2-MeOE2bisMATE it was 85%. No significant metabolites of 2-MeOE2bisMATE were detected in plasma after oral or intravenous dosing, showing that this drug is resistant to metabolism. In the tumour efficacy model, oral administration of 2-MeOE2bisMATE, at 20 mg kg(-1) day(-1) daily for 28 days, almost completely inhibited tumour growth. Inhibition of tumour growth was maintained for a further 28 days after the cessation of dosing. At this dose level, 2-MeOE2 did not inhibit tumour growth. The resistance to metabolism shown by 2-MeOE2bisMATE and its ability to inhibit tumour growth in vivo suggest that this compound should have considerable potential for development as a novel anticancer drug.
It is generally believed that many non-Korsakoff alcoholics have subtle defects in memory. To determine whether such defects vary as a function of length of abstinence (LOA), we performed extensive ...memory testing with: (1) recently detoxified (n = 31; LOA-29 days); (2) intermediate-term abstinent (n = 28; LOA = 1.9 years); (3) long-term abstinent (n = 32; LOA-7.0 years) alcoholics; and (4) nonalcoholic controls (n = 37). All subjects were matched on age and education. Alcoholics were matched on years of alcoholic drinking. Memory measures were divided into the following domains: verbal learning, verbal recall, visual learning, visual recall, and paired associate learning. A series of MANOVAs were conducted that revealed a significant relationship between visual learning and length of abstinence, and a significant interaction between age and length of abstinence on visual recall. Long-term abstinent subjects were not significantly different from controls on any test. We conclude that memory disturbance demonstrable among recently detoxified alcoholics in the early weeks of their abstinence is not evident in demographically matched long-term abstinent alcoholics with similar drinking histories.
Minimal deviation melanoma is a controversial entity encompassing a heterogeneous group of lesions cytologically in the spectrum between recognized subtypes of nevi and conventional “primary ...configuration” melanomas and reported to have a better prognosis than the latter. To evaluate the distinctiveness of minimal deviation melanoma, Ki-67 proliferation rates and p53 expression in minimal deviation melanomas were compared with those in compound nevi, Spitz nevi, and vertical growth phase superficial spreading malignant melanoma. Twelve examples of each lesion were immunostained with antibodies to the Ki-67 and p53 proteins and evaluated by a pathologist who was blind to the diagnoses. The mean Ki-67 (MIB-1) proliferation rates for the compound nevi, Spitz nevi, minimal deviation melanomas, and superficial spreading malignant melanomas were 0, 3%, 13%, and 25%, respectively. The mean Ki-67 proliferation rate was statistically greater in the minimal deviation melanomas than in the compound nevi or the Spitz nevi (P < .05), but the proliferation rates in the two melanoma subtypes were not statistically significant (P = .08). The mean p53 values for these lesions were 0, 9%, 9%, and 26%, respectively; the latter two were statistically different (P < .01). Based on these Ki-67 and p53 immunophenotypes, minimal deviation melanoma may represent a distinct entity.
The proportion of women in the U.S. military is increasing, and they are being selected into jobs that are more combat related. However, the mental health effects of working in combat support ...occupations among military women have not been previously evaluated.
Active-duty enlisted Navy and Marine Corps women in combat support (n = 10,299) and noncombat support (n = 63,478) occupations were followed for 2 years between January 1, 1994, and August 31, 2001. Hospitalization diagnoses were examined and organized into eight categories of mental disorders; Cox proportional hazards modeling was used to describe these outcomes.
Women in combat support occupations were found to be significantly less likely to be hospitalized for a mental disorder than women in all other military occupations.
These results are reassuring but may be confounded by a healthy worker selection effect. Further studies are needed to assess how service in combat support occupations affects the long-term health of U.S. military women.
We compared 1998 hospitalizations in active-duty US military personnel for possible temporal association with anthrax immunization. Immunization, demographic, and hospitalization data were analyzed ...using Cox proportional hazards modeling for hospitalization within 42 days of vaccination. Discharge diagnoses were aggregated into 14 International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) categories. Approximately 11% of subjects received one or more doses of vaccine during 1998; those immunized were more likely to be younger and male. Lower hospitalization rates were observed across doses and diagnostic categories among the immunized. Adjusted risk ratios for hospitalization by diagnostic category suggest that immunized service members were at equal or lesser risk for hospitalization than the non-immunized.
In the concept of MDM, the term melanoma has been reserved for lesions showing a vertical growth component. Vertical growth, divorced from any prognostic implications, is simply a morphologic ...designation. Such a maneuver also serves to validate the category of MDM, although it might then be inappropriate to characterize such lesions as melanoma. From my view, the modifier "minimal deviation" takes the onus of prognosis out of the equation. For common melanomas, size of a vertical growth component has relativity to prognosis. It is unlikely that, in comparable size-ranges, the MDM have a more aggressive nature than the common melanoma. It seems appropriate to propose that MDM measuring less than 1.5 mm in vertical dimensions could be characterized as melanocytic neoplasia of indeterminant malignant potential. Those less than 1 mm in vertical dimensions would be borderline variants and those in the range of 1 to 1.5 mm would be intermediate examples. Those greater than 1.5 mm could be characterized as melanocytic neoplasias of indeterminant (uncertain) malignant potential without additional qualifications.
We report four cases of an unusual uterine smooth muscle neoplasm. All patients were of reproductive age, ranging from 23 to 41 years old, and had a pelvic mass or an enlarged uterus. Two also had ...menstrual irregularities. At laparotomy, an exophytic congested bulky tumor resembling placental tissue extended from the uterine wall into the broad ligament and pelvic cavity. In one case the tumors were bilateral but unequal in size. On gross examination, these exophytic components were the most distinctive feature. On microscopic examination the basic lesion appeared to be a dissecting leiomyoma with growth at its periphery in sinuous dissecting patterns and extensive degenerative changes. Some microscopic features, including dissecting growth patterns, distinctive connective tissue alterations, and a rich component of vessels, overlap with those seen in several leiomyoma variants, including infiltrating leiomyoma, leiomyoma with perinodular hydropic degeneration, and intravenous leiomyomatosis. An intravascular component was not a feature. The distinctive gross appearance and microscopic features are embodied in the designation, "cotyledonoid dissecting leiomyoma." The follow-up information available for three cases supports the benign nature of the tumor.
The concept of minimal deviation melanoma is presented in diagrammatic form. In this approach, the precursors of melanoma are presented as having two dimensions and melanomas as having three ...dimensions. In turn, the relativity between dimensionalities and recommendations for treatment (as indirect correlates of prognostications) provides guidelines for the structuring of two major boundaries along the axis of the diagram. Finally, the domains defined by the two boundaries include borderline lesions, intermediate lesions, and “real melanomas.” The lesions in the borderline and intermediate categories qualify as melanocytic neoplasias of indeterminant malignant potential; in these two categories, the predictability of metastases hardly justifies the use of the designation, malignant melanoma.
We report eight cases of benign uterine smooth muscle neoplasms with unusual growth patterns and intramural dissection. All the patients in our series were of reproductive age or perimenopausal ...(range, 36-51 years) and had an enlarged uterus or a pelvic mass, with the exception of one lesion that was found incidentally in a patient treated for uterine prolapse. Three also had abnormal uterine bleeding. On gross examination, the lesions had an unusual appearance and were often lobulated and irregular with indistinct margins. On microscopic examination of all the lesions in this study, a dominant benign smooth muscle tumor was associated with intramural dissection of the myometrium by fascicles of neoplastic smooth muscle. Of the eight cases showing intramural dissection, four were intramural dissecting leiomyomas; three were examples of intravenous leiomyomatosis; and one was a multinodular leiomyoma with hydropic degeneration. We excluded cotyledonoid dissecting leiomyomas from the study. In two of the three cases of intravenous leiomyomatosis, extrauterine extensions in continuity with the intramural components were noted at surgery and on gross examination. Intramural dissection of the myometrium by a benign smooth muscle tumor is one additional possibility to be considered in the differential diagnosis of leiomyosarcoma and low-grade stromal sarcoma.
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