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Biomedical subjects

M Evans

Publications and source records attributed to M Evans.

At least 19 recordsLinked to original sources
PubMed1992

Circulating stem cells in mice treated with cyclophosphamide.

Chemotherapy has been used clinically to mobilize hematopoietic progenitor cells into the peripheral blood so that they can be harvested for autologous transplantation. In humans, this is demonstrated by the presence of circulating granulocyte-macrophage colony-forming cells (CFU-GM) and CD34-positive cells, but it has not been possible to confirm the presence of marrow-repopulating stem cells. In this study, we treated mice with 200 mg/kg cyclophosphamide (CY) and measured the numbers of white blood cells, day 12 CFU-S (CFU-S12), and CFU-GM in the peripheral blood. There was a peak in the numbers of CFU-S12 and CFU-GM 8 days after treatment with cyclophosphamide. Peripheral blood cells taken at this time rescued lethally irradiated mice and engraftment of donor cells was confirmed after 140 days in sex mismatched recipients using a Y chromosome-specific probe. In vitro culture of the blood cells harvested after cyclophosphamide showed that they proliferated in suspension cultures for at least a year in the presence of interleukin-3. The cultured cells rapidly lost their abilities to rescue irradiated mice and to form colonies in vitro, but they did not become leukemic. Also, CY-treated mice were irradiated with a leukemogenic dose of x-rays to coincide with peak circulating cell numbers but these animals did not develop an excess of leukemias over mice given irradiation alone.

Animals↗
PubMed1992

Optimization of non-isotopic in situ hybridization on formalin-fixed, paraffin-embedded material using digoxigenin-labelled probes and transgenic tissues.

The sensitivity of non-isotopic in situ hybridization (NISH), particularly on formalin-fixed, paraffin-embedded (FFPE) clinical tissues, has been the subject of controversy. Generally, NISH has been regarded as being less sensitive than radiolabelled procedures, although some reports have contradicted this. Accordingly, tissues from mice which were transgenic for variable amounts of the human alpha-1-antitrypsin gene were used to optimize the NISH procedure and to estimate the sensitivity. This approach showed that prolonged incubation of slides in final substrate resulted in high sensitivity--about 13 kb of target DNA. However, this prolonged incubation crucially depended on achieving minimal non-specific background staining. Many factors affected the degree of background staining, but five were particularly important. First, the method of mounting cut sections onto slides. Second, the length of the probe (ideally less than 400 bp). Third, the procedure for proteolytic digestion. Fourth, the denaturation technique, and fifth, the quality of the dextran sulphate used in the hybridization mix. The optimized protocol showed variable patterns of mRNA distribution in the transgenic mouse livers, while DNA distribution appeared uniform.

Animals↗
PubMed1992

Subxiphoid approach for implantable cardioverter defibrillator in patients with previous coronary bypass surgery.

From February 1988 until August 1991, 28 patients with prior coronary artery bypass grafting (CABG) received implantable cardioverter defibrillator (ICD) therapy via a subxiphoid approach. Only one patient required conversion to a median sternotomy incision. The mean defibrillation threshold was 11.9 +/- 4.4 J. The mean R wave was 8.2 +/- 3.7 mV. One perioperative death occurred due to heart failure (mortality rate 1/28 [3.50%]). No patient required reexploration for bleeding. The subxiphoid method for ICD electrode implantation is safe and reliable in patients with prior CABG surgery.

Coronary Artery Bypass↗
PubMed1992

Sister chromatid exchange (SCE) frequency in lymphocytes of patients with colorectal carcinoma treated with razoxane.

The increased risk of neoplasia following cytotoxic therapy for both malignant and nonmalignant disease is well known. Sister chromatid exchange (SCE) frequencies in patients receiving such chemotherapy are often elevated, and the persistence of high levels after treatment may provide an indicator for susceptibility to secondary neoplasia. The cytostatic drug razoxane has been used for the treatment of psoriasis, acute myeloid leukemia (AML), and colorectal carcinoma. Prolonged use of this drug, however, has been associated with the subsequent development of AML and, up to November 1987, 16 cases of acute leukemia following razoxane treatment have been reported. We report the SCE frequencies for 34 patients with colorectal carcinoma who were receiving or had previously been treated with razoxane. Our results show no significant increase in SCE levels in the razoxane group compared with either normal controls or untreated patients.

Acute Disease↗
PubMed1992

Poor prognosis acute myeloid leukaemia treated by matched unrelated donor marrow transplant without preceding total body irradiation.

Two patients with acute myeloid leukaemia, one in relapse after autologous bone marrow transplantation (BMT) (aged 52 years) and the other with primary resistant disease secondary to previously treated malignancy, have received marrow transplants from matched unrelated donors. Cytoreductive conditioning in both cases was with high-dose combination chemotherapy alone. Engraftment was aided by the administration of total lymphoid irradiation together with in vivo antilymphocyte antibody prior to marrow infusion. Both patients survive in complete remission, currently at 12 and 15 months post-BMT respectively. The avoidance of total body irradiation in BMT patients at high risk of early treatment-related mortality may be advantageous.

Adult↗
PubMed1991

Bone density in women receiving depot medroxyprogesterone acetate for contraception.

OBJECTIVE: To determine if the use of the injectable contraceptive depot medroxyprogesterone (DMPA), which reduces ovarian oestrogen production, is associated with changes in bone density. DESIGN: Population study. DMPA users were compared with two control groups selected from larger population studies and individually matched for several putative determinants of bone density (age, race, body mass index, and years of oestrogen deficiency). Controls and DMPA users were matched without prior knowledge of their bone density measurements. SETTING: Teaching hospital and community family planning clinics. SUBJECTS: 30 current users of DMPA with a minimum five years' previous use, 30 premenopausal controls, and 30 postmenopausal controls. MAIN OUTCOME MEASURE: Lumbar spine and femoral neck bone mineral density assessed by dual energy x ray absorptiometry. RESULTS: Compared with premenopausal controls matched for age, race, and body mass index, DMPA users had significantly reduced bone density in the lumbar spine (mean difference 7.5% (95% confidence interval 1.9% to 13.1%), p = 0.002) and in the femoral neck (6.6%, (0.8% to 12.3%), p = 0.007). Compared with postmenopausal controls matched for body mass index and duration of oestrogen deficiency, DMPA users had greater bone density in the lumbar spine (8.9% (4.3% to 13.5%), p = 0.001), but in the femoral neck the difference in bone density was less (4.0% (-0.4% to 8.5%), p = 0.04). CONCLUSIONS: Women using DMPA have bone density values intermediate between those of normal premenopausal and postmenopausal controls; thus, the degree of oestrogen deficiency induced by DMPA may have an adverse effect on bone density.

Absorptiometry, Photon↗
PubMed1991

Treatment of Paget's disease of bone with a combination of intranasal salmon calcitonin and oral calcium and thiazide.

The purpose of this study was to establish the smallest dose of nasally administered salmon calcitonin (SCT) which, if given in conjunction with a previously published calcium/thiazide treatment, would be as effective as parenteral SCT in the treatment of Paget's disease of bone. Forty patients suffering from symptomatic Paget's disease were treated with 0.5 g calcium three times daily, 10 mg/day clopamide, and 400 IU nasally administered salmon calcitonin given once or twice weekly. This regimen was given for 5 months, after which all treatment was ceased for 4 months. Parenteral SCT (100 IU) was then given three times weekly for 5 months to 25 of the patients. With the oral/nasal treatment, the plasma alkaline phosphatase level (AP) decreased by 30 +/- 15 (SD)% when the SCT was given once weekly and by 39 +/- 11% (P less than 0.05) when the SCT was given twice weekly. There were similar decreases in the fasting urinary hydroxyproline:creatinine ratios. The parenteral SCT reduced the AP by 33 +/- 23%. Though reduction in bone pain was similar with both treatments, most patients preferred the oral/nasal treatment. It is concluded that the oral/nasal treatment, when the SCT is given twice weekly, has similar efficacy to parenteral SCT, and is a well tolerated, effective initial treatment for Paget's disease of bone.

Administration, Intranasal↗
PubMed1991

The muscle-sparing thoracotomy in infants and children.

Deformities of the chest wall, breast, shoulder girdle, and spine are well-documented sequelae of major thoracotomies that transect muscles, divide major motor nerves, resect ribs, or cause them to fuse. These deformities are probably aggravated by the growth process. This is why we make a plea for the routine use, in infants and children, of a muscle-sparing thoracotomy that will minimize these sequelae without sacrificing exposure. Major (lateral) thoracotomy by this technique involves these steps: (1) creating a transverse incision below the tip of the scapula, or a vertical axillary incision; (2) elevating the skin flaps to expose the muscles; (3) retracting the latissimus dorsi posteriorly; (4) retracting the serratus anterior and scapula superiorly; (5) disinserting the lower origins of the serratus if required only; (6) opening the desired intercostal space; (7) reapproximating the ribs without crowding, using a pericostal suture that is passed along the inferior rib subperiosteally, to avoid any compression on the neurovascular bundle; and (8) allowing the muscles to fall back into place, reattaching the serratus insertions as indicated. Lessened postoperative pain and improved respiratory function are additional benefits.

Child↗
PubMed1991

Kinetochore analysis of micronuclei allows insights into the actions of colcemid and mitomycin C.

We have induced micronuclei in two strains of diploid human fibroblasts with a known aneugen, colcemid, and a known clastogen, mitomycin C. Using immunofluorescence to detect the presence of kinetochores in micronuclei, we were able to demonstrate a 26.8-fold increase in fluorescence-positive micronuclei (aneuploidy) in colcemid-treated cells. However, colcemid also induced an increase in kinetochore-negative micronuclei. Our findings support previous reports that suggest colcemid may induce chromosome breakage in addition to its major aneugenic effect. The frequency of kinetochore-negative micronuclei (chromosome breakage) in mitomycin C-treated cells rose an average of 7.9-fold in the two test strains, a clear reflection of its clastogenic action. However, a 4-fold increase in the kinetochore-positive fraction was seen. We conclude that the fibroblast micronucleus assay, coupled with kinetochore immunofluorescence, provides a useful screening approach for genotoxic agents. The delineation of the precise mechanism by which an agent perturbs the rates of chromosomal breakage or lag may require more detailed analysis.

Aneuploidy↗
PubMed1991

Trends in the spatial dimensions of the long term care delivery system. The case of New York State.

Over the past twenty years, the long term care sector of the health delivery system has sought to shift the delivery of services away from costly (nodalized) facilities to community-based (dispersed) delivery structures. An anti-institutional societal view has influenced the formation of current long term care policy. While home is the preferred site for elderly in need of care, the health services literature suggests that the cost and personal functional benefits expected to result from community-based long term care occur only for a small segment of the dependent elderly. This paper also looks at health planning policy as it has been carried out in New York State during the 1980s to find that, despite mid-1980s thrusts to disperse care in the community, an expansion of residential health care facilities is underway as of the end of the decade. Moreover, congregate care provided in group homes (supportive housing) is being added to the care spectrum.

Community Health Services↗
PubMed1991

Idiotypic and immunochemical differences of anti-DNA antibodies of a lupus patient during active and inactive disease.

IgG anti-DNA antibodies of a lupus patient during active and inactive stages of her disease were studied. There were no significant differences in the amounts, in double-stranded DNA-binding activity, or in complement-fixing ability between purified IgG anti-DNA antibodies of both stages. However, their idiotype (Id) expressions were different as revealed by binding to rabbit anti-Ids raised against each of the anti-DNA antibodies. Moreover, the active stage anti-DNA antibodies had higher activity and less cross-reactivity with polynucleotides. Dominant anti-DNA populations during the active and inactive stages of systemic lupus erythematosus are clonally and qualitatively different.

Antibodies, Antinuclear↗