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Biomedical subjects

M McBride

Publications and source records attributed to M McBride.

17 recordsLinked to original sources

Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells.

We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL-60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype.

Cell Division

Lymphoproliferative disorders after renal transplantation in patients receiving triple or quadruple immunosuppression.

A retrospective review of 478 renal transplant recipients receiving cyclosporin A (CsA) was conducted to determine the incidence, relative risk, and outcome of lymphoproliferative disease after transplantation. Cases of neoplasm were identified by linking the computerized databases of the British Columbia (B.C.) Transplant Society and the B.C. Cancer Agency. B.C. Cancer Statistics for 1988 were used to determine relative risk. Patients were monitored for a total of 1,054 patient years with a mean follow-up time of 26 months (range, 0.1 to 63 months). A total of 334 patients were treated with triple immunosuppression (CsA), azathioprine, and prednisone), and 144 received adjunctive antilymphocyte globulin as induction immunosuppression. Sixty-nine patients received OKT3 for the treatment of transplant rejection. Twenty-two patients developed 23 malignancies (4.8%) at a mean interval of 16 months (range, 3 to 45 months) after transplantation. Non-Hodgkins lymphoma occurred in five patients, of whom two received triple (0.6%) and three received quadruple (2.1%) therapy. All five patients, in addition, received OKT3 for the treatment of graft rejection. The relative risk of developing a neoplasm among the defined sample adjusted for age and sex was 3.08 overall, increasing to 26.9 (P less than 0.005) for lymphoma. Six of the 22 patients (27%), including all 5 patients with lymphoma, died as a result of their tumor. Renal transplant recipients receiving CsA have a significantly elevated risk of developing a de novo lymphoreticular malignancy, which is comparable to that reported for those receiving azathioprine treatment, and which appears to be increased by the use of quadruple immunosuppression and the administration of OKT3 for the treatment of acute graft rejection.

Actuarial Analysis

1992 Canadian Cancer Statistics.

In Canada, it is estimated that in 1992 115,000 new cases of cancer will be diagnosed. This total excludes 47,200 estimated new cases of non-melanoma skin cancer. The number of new cases is increasing by about 3,000 per year due partly to the aging population, improved registration, earlier detection of cancer and real increases in the incidence of some types of cancer. It is estimated that there will be 58,300 cancer deaths in 1992. By 1992, prostate cancer will have overtaken lung cancer as the leading cancer among men in the four western provinces while lung cancer is expected to exceed breast cancer as the leading cause of cancer deaths among women in some provinces, notably British Columbia. In British Columbia, the relative survival rates for most cancers improved between the periods 1970 to 1974 and 1980 to 1984. However, stomach, lung and pancreatic cancers, which have low survival rates, showed little improvement. This article is based on 1992 estimates of cancer incidence and mortality, cancer trends in Canada and relative cancer survival rates in British Columbia, found in Canadian Cancer Statistics 1992. This publication was prepared at Statistics Canada through a collaborative effort involving the Canadian Cancer Society, Health and Welfare Canada and the provincial/territorial cancer registries.

British Columbia

Field of blood, field of the forgotten. The Potter's Field of Milwaukee County.

A recent discovery of a forgotten pauper cemetery at the Milwaukee County Medical Center has profound and far-reaching ramifications. More than 5,000 are buried in this graveyard, compelling an investigation into the circumstances surrounding its loss. That the cemetery lies beneath county buildings without official knowledge is a disgrace. The proper dignity of a marked and undisturbed grave was denied to these former county residents because of their poverty. How this discovery is managed will reflect our commitment to both high ideals and the law. This project endeavors to reconstruct the origins of the pauper cemetery, containing a brief history of the poor in Milwaukee County, and an examination of the Almshouse, Milwaukee County's first medical institution. Finally, a postscript offers a parallel between the writings of Charles Dickens and the pauper cemetery.

Burial

Role of low-affinity Fc receptors in antibody-dependent tumor cell phagocytosis by human monocyte-derived macrophages.

Human monocyte-derived macrophages (MDM) mediate efficient antibody-dependent cellular cytotoxicity (ADCC) against a variety of human tumor cell types in the presence of an anti-tumor monoclonal antibody. We have recently shown that the mechanism of this ADCC in our in vitro system involves phagocytosis of intact tumor cells. Some forms of macrophage ADCC have been reported to be inhibited by serum immunoglobulin, which competes with monoclonal antibodies for binding to the high-affinity Fc receptor (FcRI). In this study we investigated the role of the three macrophage FcR-gamma in antibody-dependent tumor cell phagocytosis. Hybridoma cells bearing surface antibody directed against either of the two low-affinity Fc receptors (FcRII or FcRIII) were efficiently phagocytosed by MDM, compared to hybridomas bearing irrelevant antibody. Soluble anti-receptor antibodies against FcRII and FcRIII were able to inhibit ADCC but only when both antibodies were simultaneously present. These data suggest that either low-affinity Fc receptor is capable of functioning independently to mediate phagocytosis of tumor cells. Consistent with a mechanism involving the low-affinity receptors rather than FcRI, antibody-dependent phagocytosis occurred in the presence of human serum, purified human IgG, and irrelevant murine antibody. Greater than 75% of the MDM in our culture system were able to ingest tumor cells when a suitable target was available. Optimal phagocytosis occurred at monoclonal antibody concentrations of 10-100 ng/ml. Like other forms of macrophage phagocytosis, ingestion of tumor cells required the presence of divalent cations (either Ca2+ or Mg2+) and an intact actin cytoskeleton (as indicated by sensitivity to cytochalasin D). Because FcRI is normally occupied in vivo by serum immunoglobulin, the participation of low-affinity FcR in tumor cell phagocytosis is potentially important in establishing the in vivo applicability of this efficient form of cytotoxicity.

Animals

Human papillomavirus and cervical intraepithelial neoplasia in women who subsequently had invasive cancer.

In a retrospective case-control study biopsy specimens of cervical intraepithelial neoplasia (CIN) lesions from 47 women in whom invasive cancer subsequently developed (cases) and from 94 control subjects in whom CIN was diagnosed within 6 months of the diagnosis for the matched case subject but invasive disease did not develop were tested for human papillomavirus (HPV) DNA with tissue in-situ hybridization. There were no significant differences in the frequency of detection of HPV DNA between the two groups. In a cross-sectional survey the prevalence of HPV DNA was found to be 11% in specimens without CIN, 27% in those with CIN I, 49% in those with CIN II and 56% in those with CIN III. The positivity rates for HPV 16/33 DNA increased with the severity of CIN, but this was not observed for HPV 6/11 and 18 DNA. A comparison of the results of the case-control and cross-sectional studies suggested that the younger cohort of women had higher prevalence rates of HPV DNA than the older cohort.

Adolescent

Drug-free therapeutic community: a ten-year follow-up.

Two previous follow-ups of 50 patients at the Veterans Administration Medical Center, Brentwood Division, West Los Angeles, Residential Treatment Center (RTC), were conducted in 1974 and 1981. This is a 10-year follow-up of the same cohorts conducted in 1984. We were able to locate 11 out of 50 candidates. Of the 11 candidates located, interviews were completed on six candidates. Of the remaining five patients, two are decreased and the other three were unable to be interviewed. Of the six patients that were interviewed, three were drug-free since treatment; one has been drug-free for the last five years. The other two patients had been drug-free approximately six months. It would appear that follow-up studies of this particular group of subjects are very difficult and that the outcome of treatment is difficult to evaluate due to difficulty in locating this group of subjects over a long term.

Adult

Replantation.

Replantation is firmly established as a viable treatment option in many accidental amputations involving the upper extremity. The clinical foundation was laid more than 100 years ago and it is a technique which is now available world wide. The success rate of replantation exceeds 80 per cent. More often than not, appropriately selected patients obtain a functional result which is better than currently available prosthetic devices. The experience gained from small vessel surgery in replantations has aided in the development of reconstructive procedures, including free composite tissue transfers such as toe-to-hand transfers and free flaps.

Amputation, Traumatic

Moyamoya disease in an infant with autonomic dysfunction: angiographic and MRI findings.

An infant with persistent Harlequinism went on to develop a hemiparesis secondary to Moyamoya disease at 2 1/2 months of age. The sympathetic nervous system is proposed to be an etiologic factor in the pathophysiology of Moyamoya disease as well as Harlequinism. This is one of the youngest patients reported in the English literature with Moyamoya disease and the only report of the coexistence of Moyamoya disease and atypical Harlequinism. Magnetic resonance imaging led to the diagnosis, which was confirmed by cerebral angiography.

Arterial Occlusive Diseases

The effect of glutaurine on thyroid hormones in the rat.

Glutaurine (gamma-L-glutamyl taurine), a proposed hormone isolated from parathyroid gland oxyphil cells, was examined for its effect on circulating thyroid hormones in the rat. In acute experiments performed over a 24 hr. period, glutaurine depressed plasma triiodothyronine (T3) levels in a dose-dependent manner; however, thyroxine (T4) levels were not affected significantly. In chronic experiments performed over a 2 wk. period, glutaurine significantly increased T3 levels, but, as with acute studies, the effect of T4 levels was not significantly altered. Following acute glutaurine administration, TSH levels were elevated above control. The increased T3 observed following chronic glutaurine administration may be due to a secondary increase in TSH levels. These data support the hypothesis that glutaurine aids in peripheral thyroid hormonal regulation. Observed differences between acute and chronic glutaurine action are though to result from the effect of glutaurine on the negative feedback inhibiting action of TSH.

Animals

Childhood antecedents of adult obesity. Do chubby infants become obese adults?

We investigated whether obese infants tend to become obese adults. Records of subjects born between 1945 and 1955 were reviewed to select three cohorts based on weight in the first six months of age, which exceeded the 90th percentile at least once, ranged between 25th and 75th percentiles or was below 10th percentile at least once. Three hundred and sixty-six subjects, now between 20 and 30 years of age, were located and their present height and weight determined. Thirty-six per cent of those exceeding the 90th percentile as infants were overweight adults, as compared to 14 per cent of the average age and light-weight infants. A significant increase (chi square = 17.2, p less than 0.001) in adult obesity was evident when the infant exceeded the 75th percentile that was independent of his height. Social class, educational level, and parental weight all correlated with adult weight (p less than 0.001). Sex and ordinal position of birth did not. The data suggest that infant weight correlates strongly with adult weight independently of other factors considered.

Adolescent

Post-operative respiratory function: a ventilation-perfusion study.

Many studies have shown that after uncomplicated abdominal surgery arterial hypoxaemia frequently occurs because of regional underventilation in relation to perfusion. This paper produced evidence that shows a small increase in physiological dead space to tidal volume ratio following general anaesthesia for abdominal surgery. This increase is thought to be due to tachypnoea rather than alteration in pulmonary blood flow.

Abdomen

Quality of life after heart transplantation in patients assigned to double- or triple-drug therapy.

The purpose of this study was to compare the quality of life after heart transplantation for patients treated with cyclosporine and azathioprine (double therapy) versus cyclosporine, azathioprine, and corticosteroids (triple therapy). This study was based on a randomized, prospective trial and was focused on patients from ages 17 to 57 years at 1-year after transplantation. Patients who received double therapy showed advantages on 10 of 11 measures of quality of life. Significant differences were found on measures of anxiety, sexual activity, physical well-being, and financial well-being. Patients who received double-drug therapy reported a lower frequency and less distress from the side effects of immunosuppression; a higher proportion of double-drug therapy patients had returned to full-time employment. In addition double-therapy patients were better able to control body mass. These features may explain why double-drug therapy patients reported a higher quality of life, and in the long term, could be important from a cost benefit analysis.

Adaptation, Psychological

Rehabilitation after heart transplantation: the Australian experience.

This study was designed to assess aspects of the quality of life and rehabilitation of heart transplant recipients who had transplantations at St. Vincent's Hospital, New South Wales, Australia, between February 1984 and March 1987. Factors determining return to full-time employment were delineated. A questionnaire was sent to 51 recipients. The response rate was 92%. The questionnaire measured employment status and satisfaction with family, social, marital, and sexual life. Financial status, exercise ability, and participation in daily activities were also assessed. Analysis showed that 53% of recipients had returned to either full-time or part-time employment, home duties, or full-time study. A further 28% were receiving a pension, 9% had chosen voluntary retirement, 6% were receiving unemployment benefits, and 4% were getting paid leave. Ability to exercise was improved for 77% of recipients and remained the same for another 14%. Financial status was unchanged for 45% and improved for 17%. Thirty-eight percent believed that they were worse off financially. Ratings of social, family, and marital life showed nearly complete or complete satisfaction in most cases. Satisfaction with sex life was less favorable. Comparison of the group who had returned to full-time employment with the group receiving a pension identified two variables of work status--length of time since transplantation and employment status before transplantation. There were also some differences between the two groups on quality of life ratings.

Adolescent