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Biomedical subjects

M C Bell

Publications and source records attributed to M C Bell.

At least 37 records · Page 2Linked to original sources

Computed tomography-detected hydrometra before irradiation for cancer of the cervix.

OBJECTIVE: To describe the risk and outcome of women with pretreatment CT-detected hydrometra who were treated by radiation for cancer of the cervix. METHODS: Between 1979 and 1995, 27 women with cervical cancer and a pretreatment CT scan of the pelvic cavity underwent definitive radiotherapy (pelvic teleirradiation and intracavitary brachytherapy). We compared the survival and morbidity in women with [n = 12] and without [n = 15] CT-diagnosed hydrometra. RESULTS: Only one patient from the group with hydrometra was found to have pyometra. There were no statistical differences between the compared groups with respect to patient age, disease stage or applied total radiation doses. The estimated survival at 3 years was 35 +/- 27% for women with and 56 +/- 26% for patients without CT-detected hydrometra [p > 0.20] the corresponding morbidity rates were 25 +/- 26% and 0% [p < 0.05]. CONCLUSION: The presence of hydrometra may heighten the morbidity risk even though pyometra is seldom observed in patients with cervical cancer treated by radiation.

Adult↗

A cervical teratoma with invasive squamous cell carcinoma in an HIV-infected patient: a case report.

HIV infection among women is increasing in the United States. Since January 1993, cervical cancer has been considered an AIDS-defining illness. We report a rare case of squamous cell carcinoma arising in a teratoma of the uterine cervix in an HIV-infected patient. This patient was treated with a radical hysterectomy, para-aortic and pelvic lymphadenectomy. She is currently 1 year from treatment and is without evidence of recurrence.

Acquired Immunodeficiency Syndrome↗

Changeover behavior and preference in concurrent schedules.

Pigeons were trained on a multiple schedule of reinforcement in which separate concurrent schedules occurred in each of two components. Key pecking was reinforced with milo. During one component, a variable-interval 40-s schedule was concurrent with a variable-interval 20-s schedule; during the other component, a variable-interval 40-s schedule was concurrent with a variable-interval 80-s schedule. During probe tests, the stimuli correlated with the two variable-interval 40-s schedules were presented simultaneously to assess preference, measured by the relative response rates to the two stimuli. In Experiment 1, the concurrently available variable-interval 20-s schedule operated normally; that is, reinforcer availability was not signaled. Following this baseline training, relative response rate during the probes favored the variable-interval 40-s alternative that had been paired with the lower valued schedule (i.e., with the variable-interval 80-s schedule). In Experiment 2, a signal for reinforcer availability was added to the high-value alternative (i.e., to the variable-interval 20-s schedule), thus reducing the rate of key pecking maintained by that schedule but leaving the reinforcement rate unchanged. Following that baseline training, relative response rates during probes favored the variable-interval 40-s alternative that had been paired with the higher valued schedule. The reversal in the pattern of preference implies that the pattern of changeover behavior established during training, and not reinforcement rate, determined the preference patterns obtained on the probe tests.

Journal Article↗

Alterations in expression and function of signal-transducing proteins in tumor-associated T and natural killer cells in patients with ovarian carcinoma.

Tumor-associated lymphocytes (TALs) freshly isolated from patients with cancer usually manifest reduced proliferative and cytolytic functions. To determine whether alterations in signal transduction contribute to functional impairments seen in TALs, we purified populations of T and natural killer (NK) cells by negative selection from ascites of seven patients with ovarian carcinoma. The average purity was 84 +/- 5% for CD3(+) TALs and 77 +/- 10% for CD3(-)CD56(+)CD16(+) TALs. Expression of several signal transduction molecules, including the CD3-epsilon, CD3-zeta, and FcepsilonRI-gamma chains, p56(lck) protein tyrosine kinase, and phospholipase C-gamma1, was studied in these cells using Western blotting. A marked decrease in expression of zeta and FcepsilonRI-gamma associated with CD3 or FcgammaRIIIA was observed in T or NK cells obtained from TALs, as compared to T or NK cells purified from normal peripheral blood. Expression of CD3-epsilon, as assessed using flow cytometry, Western blotting, or ELISA was also reduced in purified TAL-T cells relative to that in normal peripheral blood T cells. Surface expression of CD3 on T cells and FcgammaRIIIA on NK cells obtained from TALs was significantly decreased in comparison to normal peripheral blood lymphocytes (PBLs): the mean fluorescence intensity of CD3 was 277 +/- 18 for TAL-T (n = 7) versus 349 +/- 13 for PBL-T (n = 9) and that of CD16 was 58 +/- 1 for TAL-NK (n = 7) versus 385 +/- 55 for PBL-NK (n = 23) cells. These observations suggest a defect in assembly of T cell receptor and FcgammaRIIIA multicomponent transmembrane receptors, which are zeta and gamma dependent. In addition to alterations in expression, the function of these receptors was also modified, since cross-linking of CD3 on TAL-T and CD16 on TAL-NK cells with the respective monoclonal antibodies resulted in a pattern of protein phosphorylation that was distinct from that observed in normal PBLs. Expression of tyrosine kinase p56(lck) and its kinase activity were also depressed, while expression of phospholipase C-gamma1 appeared to be normal in most preparations of the TALs tested. In vitro proliferation of TAL-T in response to anti-CD3 monoclonal antibody and TAL-NK cells to interleukin 2 were significantly depressed as was the ability to produce IFN-gamma. In contrast, TAL-T cells were able to produce interleukin 10 at levels similar to those secreted by normal PBLs. Thus, in TALs obtained from patients with advanced ovarian cancer, alterations in expression and activity of signaling molecules were associated with reduced cellular functions such as proliferation and production of certain cytokines.

Aged↗

Is there really a difference in survival of women with squamous cell carcinoma, adenocarcinoma, and adenosquamous cell carcinoma of the cervix?

BACKGROUND: The authors' aim was to assess whether there is a difference in biologic behavior and survival in comparing adenocarcinoma (AdCA), squamous cell carcinoma (SCC), and adenosquamous carcinoma (Ad/SC) of the cervix. METHODS: Cancer registrars at 703 hospitals submitted anonymous data on 11,157 patients with cervical cancer diagnosed and/or treated in 1984 and 1990 for a Patient Care Evaluation Study of the American College of Surgeons. Among these patients, 9351 (83.8%) had SCC; 1405 (12.6%), AdCA; and 401 (3.6%), Ad/SC cancers. There were no significant changes in percentages of the different histologic types between the study years 1984 and 1990, nor was the patient distribution different regarding age, race/ethnicity, and socioeconomic background for each histologic group. Furthermore, the distribution of patients who had had a hysterectomy did not change between 1984 and 1990. RESULTS: A larger percent of patients with SCC (63.8%) than those with Ad/SC (59.8%) or AdCA (50.2%) had tumors larger than 3 cm at greatest dimension. Early stage patients (IA, IB, IIA) often were treated by hysterectomy alone (45.5%) or combined with radiation (21.1%). The remaining patients (21.9%) received radiation alone. Of the patients with clinical stage I disease, 7.6% of Ad/CA patients, 15.5% of Ad/SC patients and 12.6% of SCC patients had positive nodes. Although patients with SCC had higher survival rates for all four clinical stages (I-IV), the differences were only significant for Stage II patients. Patients with clinical stage IB SCC and AdCA treated by surgery alone were found to have significantly better survival rates (93.1% and 94.6% at 5 years, respectively) than women treated by either radiation alone or a combination of surgery and radiation (P < 0.001, both histologic comparisons). For women with Ad/SC tumors, however, the 5-year survival rate was 87.3% for those receiving combined treatment compared with those receiving surgery alone (69.2%) or radiation alone (79.2%). However, these survival curves were not significantly different (P = 0.496). One hundred six patients with positive nodes were available for analysis. The 5-year survival rate of patients with SCC and positive nodes was 76.1%. Surprisingly, patients with Ad/SC and positive nodes had the highest 5-year survival rate (85.7%), whereas, women with AdCA and positive nodes had a sharply reduced 5-year survival rate (33.3%). The curves were significantly different (P < 0.01). For patients with clinical stage I, the risk factors for age, tumor size, nodal status, histologic features, and treatment were analyzed with Cox's multivariate regression. In this analysis, subset IB, greater tumor size, age 80 or older, and positive nodal status were each independently significant for poorer survival. Patients who were treated by surgery alone had a significantly better survival than patients who had other types of treatment or no treatment. Histologic characteristics had no significant effect on survival. In the analysis of patients with pathologic stage I disease, those with SCC had significantly poorer survival and those with Ad/SC had significantly better survival than patients with Ad/CA. Positive nodes had no significant independent effect on survival. In another analysis, tissue type was not found to be an important factor in recurrence time. CONCLUSIONS: 1. Ad/CA and Ad/SC tumors were found to represent 12.6% and 3.6%, respectively, of a large series (N = 11,157) of cervical cancers diagnosed in 1984 and 1990 and reported to the Commission on Cancer of the American College of Surgeons. 2. Two thirds of women with early clinical stage disease (IA, IB, IIA) had hysterectomy as all or part of their primary therapy. 3. No significant differences were found in 5-year survival among the three tissue types in any clinical stage except American Joint Committee on Cancer stage II.

Adenocarcinoma↗

Leukaemia inhibitory factor (LIF) suppresses proteoglycan synthesis in porcine and caprine cartilage explants.

Leukaemia Inhibitory Factor (LIF) has been implicated in connective tissue damage in arthritis. We have previously shown that LIF stimulates proteoglycan release in pig cartilage explants. The aim of this study was to determine whether LIF modulates proteoglycan synthesis in vitro. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagles medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative control) or LIF. During the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose-dependent suppression of proteoglycan synthesis was observed with murine and human recombinant LIF in pig and goat cartilage. The degree of inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inhibitor of proteoglycan synthesis in cultured pig and goat articular cartilage.

Animals↗

CD8+ T lymphocytes are recruited to neoplastic cervix.

ToliicIV distinguish normal cervical lymphocyte populations from phenotypes recruited to the cervix in response to cervical neoplasia, lymphocytes were isolated from normal and neoplastic cervix. A portion of the cervical transformation zone was obtained from 19 patients with pathologically confirmed cervical intraepithelial neoplasia and from 20 patients with normal cervices undergoing hysterectomy for benign indications. Mononuclear cells were harvested from cervical tissue using a serial, multienzymatic digestion procedure and enriched by density gradient centrifugation. Isolated cell populations were stained with surface marker-specific monoclonal antibodies and analyzed by fluorescent activated cell sorter to determine the percentage of B cells, total T cells, CD4+ T cells, CD8+ T cells, and natural killer (NK) cells. The distribution of circulating peripheral blood lymphocyte phenotypes was similar for both patients with neoplasia and normal controls. A marked disparity in the proportions of NK cells and T cells was demonstrated among lymphocyte phenotypes infiltrating the cervix. The percentage of CD4+ T cells and NK cells was significantly depressed (P = 0.04, P = 0.03, respectively) in dysplastic tissue as compared to normal cervical tissue. In contrast, the proportion of CD8+ T cells was significantly increased in the dysplastic tissue (P = 0.0001). Analysis of immunocompetent cells in the circulation appears to have little correlation with immunocytes present in the dysplastic epithelium. The depression in the proportion of CD4+ T lymphocytes and NK cells at the cervical squamocolumnar junction reflects a local recruitment of CD8+ T cells to the site of neoplasia in the cervix.

Adolescent↗

Leukemia inhibitory factor induces leukocyte infiltration and cartilage proteoglycan degradation in goat joints.

Recent studies have implicated leukemia inhibitory factor (LIF) in human joint disease. LIF is produced by cultured synovial cells and articular chondrocytes, stimulates cartilage and bone resorption, and has been detected in inflammatory exudates from arthritic joints. The aim of this study was to evaluate the effect of intraarticular injections of human recombinant LIF in the goat. Endotoxin-free, sterile normal saline containing 1 micrograms recombinant human LIF (rhLIF) was injected into the right radiocarpal joints (RCJs) of eight angora goats. The left RCJs were injected with an equivalent volume of vehicle alone (n = 6) or vehicle containing 1 micrograms human albumin (n = 2). Goat joints were examined for clinical features of inflammation, and synovial fluid (SF) was aspirated on days 0, 2, and 6 postinjection. Leukocyte counts and concentrations of keratan sulfate, IL-1 beta, and TNF-alpha were determined in the SF. Proteoglycan synthesis was determined ex vivo in cartilage explants obtained on day 6 postinjection. A statistically significant increase in joint swelling and effusion volume was observed in LIF-injected joints but not in control joints. In the LIF-injected RCJs, the leukocyte count increased from 82 +/- 9 cells/microliters before injection to 10,300 +/- 3357 cells/microliters at day 2 postinjection (p < 0.005) and declined to 678 +/- 113 cells/microliters at day 6 postinjection. Polymorphonuclear leukocytes and monocyte/macrophages predominated in the infiltrate. No appreciable change in leukocyte counts was observed in control joints.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

LLETZ is an acceptable alternative to diagnostic cold-knife conization.

Large loop excision of the transformation zone (LLETZ) provides a pathologic specimen similar to a cold-knife cone (CKC) biopsy of the cervix. One hundred twenty women with indications for a cone biopsy were evaluated with LLETZ to determine if this procedure is an acceptable alternative to traditional cold-knife conization of the cervix. All patients had LLETZ performed in the clinic under local anesthesia. An average of 2.1 slices was required to remove the transformation zone. Coagulation artifact interfered with histologic diagnosis in only 1.8% of specimens. The number of slices taken during the LLETZ procedure significantly correlated with the amount of heat artifact in the pathology specimen (P = 0.02) and interfered with the ability of the pathologist to determine complete excision of dysplasia (P = 0.03). LLETZ is an acceptable alternative to diagnostic CKC and can offer a substantial cost savings. To facilitate histopathologic interpretation, every effort should be made to minimize the number of slices and to maintain orientation of the LLETZ specimen. Endocervical curettage performed after LLETZ can identify a group of patients who are at high risk for CIN recurrence.

Adolescent↗

Leukaemia inhibitory factor stimulates proteoglycan resorption in porcine articular cartilage.

Leukaemia inhibitory factor (LIF) is a secretory glycoprotein produced by tumour, mesenchymal and haemopoietic cells. LIF has been found to have pleiotropic actions that include the capacity to regulate cell differentiation, promote acute-phase protein synthesis and stimulate calcium release in bone explants. In view of its similarity to other cytokines that affect cartilage metabolism, the effects of LIF on proteoglycan resorption were examined in pig cartilage explants. Endotoxin-free recombinant mouse LIF was found to produce a dose-dependent increase in sulphated glycosaminoglycan (S-GAG) release (ED50 = 123 U/ml, approx. 25-50 pM). Statistically significant stimulation was observed with doses of 100 U/ml or greater. When pig cartilage was stimulated with maximum concentrations of LIF and either interleukin 1 alpha (IL-1 alpha), interleukin 1 beta (IL-1 beta) or tumour necrosis factor alpha (TNF alpha), in each case a significantly greater release of S-GAGs was observed than with the respective cytokines alone (P < 0.05). Comparison of the areas under the curves showed that the action of LIF was additive, and not synergistic with other catabolic cytokines. Dose-response studies showed that transforming growth factor beta (TGF beta) produced a partial inhibition of LIF-stimulated release of S-GAGs (ED50 = 4.5 U/ml). Statistically significant inhibition was observed with doses of 2 U/ml or greater. These results showed that LIF stimulated proteoglycan resorption in vitro and that this effect was modulated by other cytokines. Whether LIF contributes to the progressive destruction of cartilage in septic or chronic inflammatory arthritis remains to be determined.

Absorption↗

Reduction of the concentration and total amount of keratan sulphate in synovial fluid from patients with osteoarthritis during treatment with piroxicam.

To study the effects of piroxicam on cartilage metabolism in vivo, a three phase (placebo/piroxicam 20 mg/day by mouth/placebo) double blind controlled trial was conducted in patients with osteoarthritis of the knee joint. Twenty one patients were recruited, 19 of whom (11 women, eight men, median age 70 years) completed the treatment schedule. The knee joint under study was aspirated to dryness at four week intervals. Treatment with piroxicam was accompanied by a decrease in the pain score, an improvement in the functional index, and an increased range of movement. Reductions in the concentration (mean (SEM) 120 (6) to 110 (8) micrograms/ml) and the total amount (1.22 (0.34) to 0.99 (0.37) mg) of keratan sulphate, but not the effusion volume (9.4 (2.5) to 8.3 (2.6) ml) were observed during treatment with piroxicam. These findings are consistent with decreased proteoglycan catabolism during treatment with piroxicam. Neither depressed synthesis nor enhanced clearance of degraded proteoglycan fragments can be excluded, however.

Adolescent↗

Intraosseous transfusion in an anesthetized swine model using 51Cr-labeled autologous red blood cells.

Peripheral venous access can often be difficult to obtain in infants and young children. Landmark articles in the 1940s showed that the intraosseous (IO) route was a viable one for resuscitation. While anecdotal reports and clinical experience suggest that blood products can be transfused via the IO route, it has not been specifically studied nor documented. We performed a prospective study to document the feasibility of red blood cell transfusion via the IO space. We studied the rapid infusion of 51Cr-labeled red blood cells via the IO space through an 18-gauge IO needle in three normovolemic immature swine. Serial central venous samples were removed at 30 seconds and at 1, 5, 15, 30, and 60 minutes and analyzed for evidence of radiolabeling. Our results revealed rapid delivery of radiolabeled red blood cells into the central circulation with no evidence of early heomolysis. Highest counts were seen in samples taken at 30 seconds to 1 minute. We conclude that the IO route is a viable means for blood transfusion in a nonhemorrhagic model.

Animals↗

Effects of hypomagnesemia on reactivity of bovine and ovine platelets: possible relevance to infantile apnea and sudden infant death syndrome.

Blood platelet function and possible involvement in death of hypomagnesemic ruminants was investigated with 26 Angus cows, 15 mature Hampshire wethers, eight Finnish-Hampshire ewes, and 36 growing Dorset lambs. Hypomagnesemia was induced by feeding vegetative spring tall fescue to 13 cows and semipurified diets low in Mg to nine wethers, four ewes, and 18 lambs. In comparison with controls, dietary treatments reduced plasma Mg concentrations 55% in cows, 36% in wethers, 66% in ewes, and 78% in lambs. Hypomagnesemia reduced in vitro reactivity of cow and lamb platelets to thrombin, ADP, and platelet active collagen, but in vitro tests may not accurately reflect in vivo platelet reactivity. Microscopic examination of platelet-rich plasma revealed a threefold increase in clumped platelets from four hypomagnesemic ewes compared to four normomagnesemic ewes. This suggests that in vivo activation and exhaustion of platelets may have contributed to reduced in vitro platelet reactivity. Six of 18 hypomagnesemic lambs died spontaneously in tetany after 2-12 months on low-Mg diets. Heart and lung lesions were markedly similar to pathological changes induced in other lambs by intravascular activation of platelets with 500 micrograms of vascular collagen fibrils per kg body weight injected intravenously. These results suggest the possibility of abnormal blood platelet activation as a significant mortality risk factor in severe hypomagnesemia.

Animals↗

Effect of magnesium administration route on plasma minerals in Holstein calves receiving either adequate or insufficient magnesium in their diets.

Rates of increase in plasma Mg following rectal or oral administration of solutions containing 30 g MgCl2.6H2O were compared in 10 Holstein bull calves receiving wheat straw (.07% Mg) and concentrates (.04 or .24% Mg) fed separately for ad libitum consumption. Treatments were administered in a sequence, which involved each calf with all combinations of MgCl2.6H2O dosing routes and dietary Mg within a 6-wk period. Plasma Mg concentration averaged 1.95 mg/dl initially but fell below 1 mg/dl within 2 wk after supplemental Mg was omitted. Maximum increases in plasma Mg concentration following oral or rectal dosing were 16 or 47% when dietary Mg was adequate and 48 or 124% when Mg was deficient. Calves fed either diet responded maximally to rectal infusion within 10 min, but plasma Mg of deficient calves increased throughout 160 min after oral dosing. Plasma Mg of deficient calves responded quicker and reached higher concentrations after rectal infusion, but the response was sustained longer after oral administration.

Administration, Oral↗

Intracerebral hemorrhage in young adults.

Nontraumatic intracerebral hemorrhage is an uncommon occurrence in young adults. Signs and symptoms may be subtle or atypical and predisposing factors absent in patients with computed tomography or magnetic resonance imaging-proven hemorrhage. Rapid evaluation and referral to a neurosurgeon are critical if consequent morbidity and mortality are to be minimized. Presented are the cases of two patients in their early thirties with computed tomography or magnetic resonance imaging-proven intracerebral hemorrhage. These cases vividly demonstrate that in young adults there is a need to maintain a high index of suspicion and consideration of intracerebral hemorrhage before signs and symptoms are attributed to less malignant disease processes.

Adult↗

Radiation effects on livestock: physiological effects, dose response.

Farm livestock show no measurable effects from being exposed to ionizing radiation unless the level is greatly in excess of the natural background radiation. Possible sources of ionizing radiation which might affect livestock or contribute to radioactivity in the food chain to humans are reactor accidents, fuel reprocessing plant accidents and thermonuclear explosions. Most data on ionizing radiation effects on livestock are from whole body gamma doses near the LD 50/60 level. However, grazing livestock would be subjected to added beta exposure from ingested and skin retained radioactive particles. Results of attempts to simulate exposure of the Hereford cattle at Alamogardo, NM show that cattle are more sensitive to ingested fallout radiation than other species. Poultry LD 50/60 for gamma exposure is about twice the level for mammals, and swine appear to have the most efficient repair system being able to withstand the most chronic gamma exposure. Productivity of most livestock surviving an LD 50/60 exposure is temporarily reduced and longterm effects are small. Livestock are good screeners against undesirables in our diet and with the exception of radiosotopes of iodine in milk, very little fission product radioactivity would be expected to be transferred through the food chain in livestock products for humans. Feeding of stored feed or moving livestock to uncontaminated pastures would be the best protective action to follow.

Animals↗