Biomedical subjects
Publications and source records attributed to D Murray.
Injuries to the sagittal band with subsequent instability of the extensor digitorum communis tendon are uncommon. In an unusual presentation, a laceration to the radial sagittal band of the little finger was manifest as an abduction deformity of the digit. This injury was treated by repair of the sagittal band and extensor digiti minimi tendon transfer.
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The relationships between DNA damage and the survival of murine bone marrow cells irradiated in situ were examined. Cell survival was assayed by the ability of bone marrow cells from irradiated mice to form colonies in vitro (CFU-C). DNA double-strand breaks (DSBs) were measured by neutral (nondenaturing) filter elution and pulsed-field gel electrophoresis (PFGE). Double-strand breaks were measured in the proliferating bone marrow cells, identified by injecting the mice with [3H]dThd at various times before gamma irradiation, as a model of the behavior of the radiosensitive target cells. To assess how the DNA lesions measured using these techniques correlated with cell killing, the effect of the radioprotective agent WR-2721 on the induction of DSBs in proliferating bone marrow cells was compared with its effect on CFU-C survival. WR-2721 protected against the killing of both granulocyte-macrophage and erythroid burst-forming CFU-C by a factor of about 2. In contrast, little (1.2-fold) protection was observed in the PFGE assay at radiation doses between 5 and 20 Gy. Similarly, at the lowest dose studied (5 Gy) there was little protection against DSBs as measured by neutral elution; only after doses of between 10 and 30 Gy was significant protection observed. Thus the previously reported predictive relationship between DSBs and cell survival in vitro does not appear to extend directly to murine bone marrow cells irradiated in vivo.
BACKGROUND: Tamoxifen, a widely used drug in adjuvant therapy of breast carcinoma, is now being tested for its effectiveness in chemoprevention. Although its side effects are few, tamoxifen increases the incidence of proliferative lesions of the endometrium, which theoretically should be preventable with progestational agents. CASES: Two postmenopausal women treated with tamoxifen and progestational agents for breast carcinoma developed uterine enlargement and intermittent spotting. Hysterectomy revealed benign endometrial megapolyps with marked stromal decidualization and edema. CONCLUSIONS: The value of multihormonal therapy in breast carcinoma is not established, and the addition of progestogens to tamoxifen may not reduce of developing endometrial lesions, including carcinoma. In both our cases, such a regimen did not prevent the occurrence of endometrial polyps which, although histologically benign, were usually large and thought clinically to be malignant. Periodic gynecologic assessment should be part of the follow-up of all women on long-term tamoxifen therapy.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Sixty Sprague-Dawley rats were pair-fed one of three nutritionally identical diets. One diet contained "low-fiber" (3.8% crude fiber); the others contained "high fiber" (28.7% crude fiber) composed of either cellulose or lignin. Although both "high fiber" diets had similar stool bulking effects, only the cellulose diet was associated with a reduction in 1,2-dimethylhydrazine (DMH)-induced colon neoplasms. The cellulose diet was also associated with distinct changes in the gut bacterial profile and with a lowered serum cholesterol.
PURPOSE: To describe the epidemiology and characteristics of gross hematuria in elderly residents of nursing homes and to identify the associations of gross hematuria with urinary infection and the potential contribution of urinary infection to morbidity. PATIENTS AND METHODS: This was a prospective, descriptive study of episodes of gross hematuria identified by the nursing staffs at two long-term-care facilities over 2 years. Episodes were characterized with respect to patient variables, presence of bacteriuria, duration of hematuria, therapeutic interventions, and genitourinary investigations. Clinical and serologic criteria were used to identify invasive infection. RESULTS: The incidence of gross hematuria was 31/100,000 resident days. Bacteriuria was present in 58 (74%) of 78 episodes with evaluable cultures. Fifty-two (61%) episodes lasted more than 24 hours, 25 (29%) were temporally associated with fever, and antimicrobials were given for 53 (61%) episodes. Gross hematuria occurred more frequently in men than in women and was more frequently associated with fever in men. Twenty-four (28%) episodes occurred in subjects with indwelling catheters, 30 (34%) in subjects with known genitourinary abnormalities, 26 (30%) in subjects with no genitourinary investigations, and 4 (4.6%) in subjects with genitourinary investigations but no abnormalities identified. No adverse clinical outcomes were identified in patients in whom antimicrobial therapy was not initiated. The maximal estimated incidence of invasive urinary infection associated with hematuria was 5.8/100,000 resident days, and of bacterial hemorrhagic cystitis, 6.3/100,000 resident days. CONCLUSIONS: These data suggest that underlying genitourinary abnormalities are present in most elderly institutionalized subjects with gross hematuria when genitourinary investigations are performed. Although bacteriuria is usually present, urinary infection, by itself, is an infrequent cause of gross hematuria. Afebrile hematuria without irritative symptoms probably does not require antimicrobial therapy. A standard approach to this clinical problem in the institutionalized elderly should be developed to optimize patient management and appropriate use of antimicrobial therapy.
To characterize further the nature of the defects underlying the differential radiosensitivities of the Chinese hamster ovary cell lines NM2, EM9, and UV41, we compared the abilities of anoxia and of the thiol WR-1065 to protect these mutants and their parent cell line, AA8, from the lethal effects of gamma-radiation. Wide differences in oxygen enhancement ratios (OERs) for cell killing were observed in the different cell lines, those for UV41 and NM2 cells (1.8 and 2.1, respectively) being reduced and that for EM9 cells (3.3) being slightly (although significantly) increased compared with wild-type AA8 cells (2.9). These OER data support the hypothesis that repair-deficient mutants are hypersensitive to radiation under redox conditions that favour the formation of the particular lesions that correspond to their repair defect, and also support the earlier suggestion that the underlying molecular bases of the radiosensitivity of EM9 and NM2 cells are very different. In contrast to protection by anoxia, a 30-min preirradiation treatment with WR-1065 (4 mmol dm-3) protected aerated AA8, EM9, NM2, and UV41 cells to a similar extent with respect to both cell killing and the efficiency of DNA double-strand break (dsb) induction as measured by neutral elution. This observation is in marked contrast with reports of a greatly reduced protection by thiols for some repair-deficient cell lines and with the above-mentioned anoxia data. Thus, the particular types of mutations characteristic of NM2, EM9, and UV41 cells that give rise to their unusual OERs have little impact on the ability of WR-1065 to modify either cell killing or dsb induction, supporting radiochemical evidence that the types of deoxyribose radicals modifiable by oxygen and thiols are qualitatively different. Furthermore, because the extent of protection of these CHO mutants by thiols and anoxia show no correlation, oxygen depletion cannot be a major component of protection of aerated cells by thiols under these conditions.
We examined the effect of manipulating the levels of two endogenous radioprotectors, glutathione (GSH) and polyamines, on the ability of exogenous aminothiols to protect Chinese hamster ovary cells from the lethal effects of gamma-radiation. Treatment with 0.5 mmol dm-3 buthionine sulfoximine (BSO) for 24 h depleted GSH levels to < 1% of control and significantly sensitized the cells to irradiation in air. Undepleted control cells were protected by WR-1065 (4 mmol dm-3; 30-min preirradiation treatment at 37 degrees C) by 2.09-fold (range 1.98-2.21) at the 10% survival level, whereas BSO-treated cells were protected by a factor of 1.98 (range 1.95-2.14) at this survival level. Thus, GSH depletion had no significant effect on the radioprotective capacity of WR-1065. Treating cells with 1 mmol dm-3 alpha-difluoromethyl ornithine (DFMO) for 48 h depleted the polyamines putrescine and spermidine to very low levels, while spermine was not significantly depleted. DFMO also sensitized cells to aerobic irradiation. WR-1065 protected DFMO-treated cells by 2.29-fold (range 2.08-2.53), whereas undepleted control cells were protected by 2.09-fold (range 1.98-2.21) at the 10% survival level. Thus, WR-1065 appeared to offset the radiosensitizing effect of the DFMO treatment. Cysteamine, on the other hand, protected control and DFMO-treated cells to the same extent. We also examined the effect of combinations of exogenous thiols on radiosensitivity. Cells were treated with WR-1065 (4 mmol dm-3) for 30 min and then with increasing concentrations of dithiothreitol for 5 min prior to irradiation. The protective effects of these two thiols were simply additive.
The DNA ploidy status of 53 fresh primary breast carcinomas was analyzed in a comparative study of flow cytometric (FCM) and image cytometric (ICM) analyses. Samples for FCM analysis were obtained with an in vitro fine-needle aspiration technique. Touch imprints from the same tumors were analyzed by three independent observers by ICM analysis. An ICM comparative study of "sequential" and "visually selected" nuclei also was performed. There was an overall concordance of 0.85 in the classification of diploid and nondiploid tumors by FCM and ICM analyses. In most discordant cases, a nondiploid population was identified by FCM analysis alone. This is attributed to the superior resolution of and sampling/preparatory method used for FCM analysis. There was an overall concordance of 0.91 in the classification of diploid and nondiploid tumors by ICM analysis. Selective analysis of atypical nuclei resulted in increased sensitivity in the detection of DNA aneuploid populations by ICM analysis.