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Biomedical subjects

M Harris

Publications and source records attributed to M Harris.

At least 307 records · Page 17Linked to original sources

Early antibody response following vasectomy is related to fertility after vasovasostomy in glucocorticoid-treated and untreated Lewis rats.

The influence of treatment with a glucocorticoid on antisperm antibodies and fertility after vasectomy and vasovasostomy was studied in Lewis rats. Animals received a bilateral vasectomy followed 4 weeks later by bilateral vasovasostomy. Treatment with methylprednisolone for two months beginning at the time of the vasovasostomy resulted in a decrease in antisperm antibodies compared with nontreated vasovasostomized animals, but there was no difference in fertility between treated and nontreated vasovasostomized groups. However, when fertile vasovasostomized animals from treated and nontreated groups were compared with infertile vasovasostomized animals, antisperm antibodies were found to be significantly lower in fertile rats 2, 4 and 8 weeks after vasectomy, while antibodies did not differ between fertile and infertile animals at the end of the study (12 weeks). The observation that differences in antisperm antibodies appeared shortly after vasectomy, preceding either vasovasostomy or treatment, suggests that changes occurring very early after vasectomy have far-reaching effects and are among the factors that influence future fertility after vasovasostomy.

Analysis of Variance↗

Cancer experience in the relatives of an unselected series of breast cancer patients.

First- and second-degree relatives of an unselected series of 402 breast cancer patients have been studied for their cancer experience. In the first-degree relatives an excess of all cancers is seen [overall relative risk (RR) = 1.28, P = 0.002; males RR = 1.26, P = 0.047; females RR = 1.30, P = 0.022). There is a marked excess of sarcoma (RR = 4.26, P = 0.0064); females are at high risk of breast cancer (RR = 2.68, P < 0.0001) and males have an excess of carcinoma of the lip, oral cavity and pharynx (RR = 4.22, P = 0.0032). Second-degree relatives have a non-significant excess of all cancers (RR = 1.14, P = 0.14); females have a borderline excess of breast cancer (RR = 1.53, P = 0.08) and an excess of carcinoma of the kidney (RR = 7.46, P = 0.0012) and males have an excess of carcinoma of the trachea and lung (RR = 1.50, P = 0.032). No excess of prostate or ovarian carcinoma was seen. Relatives are at slightly higher risk if the index patient is diagnosed between the ages of 40 and 49 (first-degree RR = 1.64, P = 0.007; second-degree RR = 1.43, P = 0.02). The excess of cancers, including breast cancers, is not limited to a few high-risk families, but appears to be spread across many. These observations may be accounted for by shared environmental factors within families or a common predisposing gene with low penetrance.

Adolescent↗

Epidemiologic background and long-term course of disease in human immunodeficiency virus type 1-infected blood donors identified before routine laboratory screening. Transfusion Safety Study Group.

BACKGROUND: The long-term course of human immunodeficiency virus type 1 (HIV-1)-related disease among seropositive blood donors has not been described. The enrollment and epidemiologic background of HIV-1-infected donors in the Transfusion Safety Study and their immunologic and clinical progression are described. STUDY DESIGN AND METHODS: Through the testing of approximately 200,000 sera from donations made in late 1984 and early 1985, 146 anti-HIV-1-positive donors and 151 uninfected matched donors were enrolled. These two cohorts were followed with 6-month interval histories and laboratory testing. RESULTS: Seropositive donors detected before the institution of routine anti-HIV-1 screening disproportionately were first-time donors and men with exclusively male sexual contacts. The actuarial probability of a person's developing AIDS within 7 years after donation was 40 percent; the probability of a person's dying of AIDS was 28 percent. AIDS developed more often when the donor was p24 antigen-positive at donation. Over a 3-year period, significant decreases occurred in CD4+, CD2+CD26+, CD4+CD29+, and CD20+CD21+ counts, but not in CD8+ subsets, CD20+, or CD14+. CONCLUSION: The high proportions of first-time donations and exclusively homosexual men among seropositive donors suggest that test-seeking may have contributed to the high HIV-1 prevalence in the repository. Implementation of alternative test sites when routine donor screening began in 1985 may have averted many high-risk donations. The disease course in HIV-1-infected donors had the same wide spectrum of immunologic and clinical manifestations as were reported for other cohorts.

Acquired Immunodeficiency Syndrome↗

Weekly VAPEC-B chemotherapy for high grade non-Hodgkin's lymphoma: results of treatment in 184 patients.

UNLABELLED: BACKGROUND AND PATIENTS: A weekly schedule of chemotherapy (VAPEC-B) has been used to treat 184 consecutive patients with high grade non-Hodgkin's lymphoma (NHL). Median age for the group was 57 years (range 17-84) and 56% had stage IV disease. RESULTS: Following chemotherapy, 114 (62%) patients achieved CR or CR(u), 32 (17%) PR and 15 (8%) had not responded or progressed. Response to VAPEC-B was highly stage dependent with 70% or more of patients with stages I-III achieving CR or CR(u) but only 50% of those with stage IV. Twenty-four (15%) patients died during treatment with VAPEC-B and in 13 cases death was due to sepsis. This complication occurred mainly in patients with stage IV disease aged 60 years or older. After a median follow up period of 4.1 years, the actuarial 4 year survival for 184 patients is 45%, an overall result heavily influenced by the poor outcome for 103 patients with stage IV disease (4 year survival of 28%). Patients with earlier stage disease fared correspondingly better (44% for stage III, 68% for stage II and 80% for stage I). CONCLUSIONS: VAPEC-B gives similar results to other chemotherapy regimens currently used in the treatment of high grade NHL and has the advantage of brevity. Caution is advised in patients over the age of 60 especially in the presence of stage IV disease and dose reduction or haemopoietic growth factor support should be considered in these circumstances.

Adolescent↗

A phase I study of letrazuril in AIDS-related cryptosporidiosis.

OBJECTIVE: The intestinal parasite Cryptosporidium is a common cause of chronic diarrhoea in AIDS patients and is responsible for significant morbidity and mortality. No effective treatment is currently available for this condition. Here we aim to determine the safety, tolerance, and clinical effect of letrazuril in the treatment of AIDS-related Cryptosporidiosis. DESIGN: A prospective, open-label study of letrazuril was performed. SETTING: The study was conducted at the Immune Deficiency Treatment Centre (IDTC) of Montreal General Hospital, a tertiary-care centre with inpatient and outpatient facilities. PARTICIPANTS: All HIV-positive patients presenting to the IDTC between November 1991 and January 1993 who had symptomatic intestinal Cryptosporidiosis were enrolled in this protocol. Sixteen participants entered the study and 15 were available for evaluation, having completed at least 2 weeks on the study medication. INTERVENTIONS: Patients received letrazuril daily in escalating doses of 50 to 100 mg orally for 6 weeks. Clinical and laboratory evaluations were performed weekly during the treatment phase, with a follow-up evaluation 4 weeks after the end of this phase, for a total study period of 10 weeks. MAIN OUTCOME MEASURES: Response to letrazuril was assessed by eradication of Cryptosporidial oocysts from the stool and symptomatic improvement in diarrhoea and abdominal pain. Haematological, biochemical, and electrocardiographic parameters were also studied to evaluate potential toxicities of the treatment. RESULTS: Fourteen evaluable patients had baseline CD4 lymphocyte counts ranging from 3 to 99 x 10(6)/l cells (mean, 30 x 10(6)/l cells). (The fifteenth evaluable patient had a CD4 count 235 x 10(6)/l.) Of these 14 patients, five showed a major response (symptomatic improvement and eradication of Cryptosporidial oocysts from the stool), two had a minor response (symptomatic improvement with persistence of oocysts in stool), and seven had no response to therapy with letrazuril. Seven patients developed a transient drug-related rash. CONCLUSION: Fifty per cent of the AIDS patients in this study experienced an improvement in their Cryptosporidial disease while receiving letrazuril. No serious dose-related toxicities were observed. Larger Phase II trials are needed to evaluate the safety and efficacy of letrazuril in AIDS-associated intestinal Cryptosporidiosis.

AIDS-Related Opportunistic Infections↗

The Queen's Medical Center Honolulu, Hawaii.

The Queen's Medical Center created and almost fully realized a vision of professional nursing practice. This vision was mission-driven and philosophically oriented in that our Hawaiian heritage and commitment to a patient-centered focus dictated the direction taken. Utilizing the nursing process, we listened to our patients in identifying the nursing model to best meet their needs: primary nursing. In order to achieve that, the nurse at the bedside had to be empowered to make decisions directly impacting patient care. We further committed to treating the whole patient and considering complementary therapies. We have established an evaluation baseline and are committed to a process that will carry us into the year 2000.

Cultural Characteristics↗

Clinicopathologic correlation of the multiple recurrent serosanguineous retinal pigment epithelial detachments syndrome.

PURPOSE: Ocular clinicopathologic correlation in a patient with bilateral multiple recurrent hemorrhagic detachments of the sensory retina and retinal pigment epithelium (RPE), which eventually led to rubeosis and loss of useful vision in one eye, is described. The clinical appearance was most consistent with multiple recurrent serosanguineous RPE detachments syndrome (which may be similar to posterior uveal bleeding, or PUB, syndrome). METHODS: Light microscopic examination of 450 serial sections through a 3.7-mm area including the macula, optic nerve head, and superior and inferior peripapillary region of the eye that underwent diagnostic enucleation was performed. One fresh cap was used for immunohistochemical staining. Tissue from the posterior aspect of the other cap was prepared for electron microscopy. RESULTS: Microscopic examination disclosed extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane, and the presence of at least 23 choroidal blood vessels that traversed defects in Bruch's membrane. Immunohistochemical studies of inflammatory infiltrates within the choroid and fibrovascular tissue demonstrated both a B- and T-cell response. CONCLUSION: In this case, recurrent serosanguineous detachments of the sensory retina and RPE were secondary to choroidal neovascularization with extensive fibrovascular proliferation in the subretinal space and within Bruch's membrane. Marked lymphocytic infiltration was present throughout the choroid and the fibrovascular tissue. Clinical improvement in the fellow eye after immunosuppressive therapy suggested that an immunologic component might be a causative factor, although the waxing and waning course in this condition precludes any definitive evaluation for its use in multiple recurrent serosanguineous RPE detachments syndrome.

Bruch Membrane↗

Cerebral responses to pain in patients with atypical facial pain measured by positron emission tomography.

The localised PET cerebral correlates of the painful experience in the normal human brain have previously been demonstrated. This study examined whether these responses are different in patients with chronic atypical facial pain. The regional cerebral responses to non-painful and painful thermal stimuli in six female patients with atypical facial pain and six matched female controls were studied by taking serial measurements of regional blood flow by PET. Both groups displayed highly significant differences in responses to painful heat compared with non-painful heat in the thalamus, anterior cingulate cortex (area 24), lentiform nucleus, insula, and prefrontal cortex. These structures are closely related to the "medial pain system". The atypical facial pain group had increased blood flow in the anterior cingulate cortex and decreased blood flow in the prefrontal cortex. These findings show the importance of the anterior cingulate cortex and the reciprocal (possibly inhibitory) connections with the prefrontal cortex in the processing of pain in patients with this disorder. A hypothesis is proposed to explain the mechanisms of cognitive and pharmacological manipulation of these pain processes.

Adult↗

Patterns of respiration and heart rate during wakefulness and sleep in elephant seal pups.

Although breath holding during diving has been studied extensively in seals, the recent observation that these mammals also exhibit long-duration apnea while apparently sleeping has not been systematically examined. This project examined sleep apnea in northern elephant seal pups (Mirounga angustirostris). The animals exhibited a sequential sleep pattern of wakefulness-slow-wave sleep (SWS)-rapid eye movement (REM) sleep that resembled the normal pattern of mammalian sleep. The typical respiratory pattern during sleep in 4-mo-old pups consisted of short periods of continuous breathing separated by periods of apnea of up to 12 min. Several cycles of apnea and eupnea could occur during a single sleep episode. Breathing during a sleep cycle occurred only in SWS, never during REM sleep. The eupneic heart rate was characterized by significant sinus arrhythmia, and the apneic heart rate was similar to the minimum value during normal sinus arrhythmia. Patterns of change in breathing and heart rate associated with wakefulness and sleep were similar in seals sleeping underwater and on land. When sleeping underwater, the seals raised their heads to the surface to breathe without awakening. The changes in heart rate associated with normal sinus arrhythmia, sleep apnea, and diving apnea appear to be similar, suggesting regulation by a common homeostatic control mechanism.

Analysis of Variance↗

Preventive care for patients with chronic illness. Multivitamin use in patients with cystic fibrosis.

Routine supplementation with multivitamins is recommended for all patients with cystic fibrosis (CF). The purpose of this study was to investigate how well patients at a large CF clinic follow recommendations for taking multivitamins and what factors affect use. A questionnaire was developed and sent to the 150 patients actively followed at our center. Of the 80 patients who returned the survey, only 47% followed clinic recommendations. Of those patients not taking extra supplements, serum vitamin A and E levels varied widely, although most were within the normal range (vitamin A 11-87 micrograms/dL, tocopherol 0.4-2.3 mg/dL, tocopherol/cholesterol 3.0-9.6 mg/g). Only 25% of respondents had known insurance coverage for vitamins. Gender or educational level did not affect adherence; however, those with minimal pulmonary disease (forced vital capacity [FVC] greater than 70% of predicted) were more likely to take vitamins than those with moderate or severe disease (P < .05). In addition to malabsorption, poor adherence should be considered by both CF specialists and primary-care providers as a cause of low serum vitamin A and E levels, especially in patients with moderate to severe lung disease.

Child↗

Distribution of, and a putative role for, the cell-surface neutral metallo-endopeptidases during mammalian craniofacial development.

Endopeptidase-24.11 (neutral endopeptidase, neprilysin, 'enkephalinase', EC 3.4.24.11) and endopeptidase-24.18 (endopeptidase-2, meprin, EC 3.4.24.18) are cell-surface zinc-dependent metallo-endopeptidases able to cleave a variety of bioactive peptides including growth factors. We report the first study of the cellular and tissue distribution of both enzymes and of the mRNA for NEP during embryonic development in the rat. Endopeptidase-24.11 protein was first detected at E10 in the lining of the gut and, at E12, the enzyme was present on the notochord, medial and lateral nasal processes, otocyst, mesonephros, heart and neuroepithelium. In contrast, at this time endopeptidase-24.18 was present only on the apical surface of the neuroepithelial cells. By E14 and E16, NEP was also detected in a wide range of craniofacial structures, notably the palatal mesenchyme, the choroid plexus, tongue and perichondrium. The distribution of endopeptidase-24.18 at these stages was restricted to the inner ear, the nasal conchae, and ependymal layer of the brain ventricles and the choroid plexus. Although endopeptidase-24.11 had been detectable in the craniofacial vasculature at E12 and E14, this was no longer apparent at E16. Significantly, the distribution of endopeptidase-24.11 mRNA closely matched the immunolocalization of the protein at all stages investigated. In order to explore the functional role of these enzymes, inhibition studies were carried out using two selective inhibitors of endopeptidase-24.11, phosphoramidon and thiorphan. E9.5 and E10.5 embryos exposed to either inhibitor displayed a characteristic, asymmetric abnormality consisting of a spherical swelling, possibly associated with a haematoma, predominantly on the left side of the prosencephalon, and the severity of this defect appeared to be a dose-dependent phenomenon. This study suggests that these enzymes play previously unrecognized roles during mammalian embryonic development.

Animals↗

The power of boards in service providing agencies: three models.

Tensions in the relationship between boards and staff are a common feature of voluntary and nonprofit agencies which deliver services. Many of the difficulties reflect lack of clarity about the power of boards. The author describes three models of governance: traditional, membership, and entrepreneurial. Each model has different implications for the power of a board in relation to staff. Practitioners in nonprofit service delivering agencies in the UK have found the models to be a useful tool for explaining the practical difficulties they experience.

Community Health Services↗