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Biomedical subjects

M McCabe

Publications and source records attributed to M McCabe.

At least 37 records · Page 2Linked to original sources
PubMed1996

Epidermal growth factor and platelet-derived growth factor-BB induce a stable increase in the activity of low density lipoprotein receptor-related protein in vascular smooth muscle cells by altering receptor distribution and recycling.

Low density lipoprotein receptor-related protein (LRP) is a multifunctional receptor, expressed by vascular smooth muscle cells (VSMCs) in normal arteries and in atherosclerotic lesions. In this investigation, we demonstrate a novel mechanism for the regulation of LRP activity in cultured rat aortic VSMCs. Cells that were treated with platelet-derived growth factor-BB (PDGF-BB) or epidermal growth factor (EGF) for 24 h bound increased amounts of the LRP ligand, activated alpha2-macroglobulin (alpha2M), at 4 degrees C. The Bmax for activated alpha2M was increased from 56 +/- 5 to 178 +/- 24 and 143 +/- 11 fmol/mg cell protein by PDGF-BB and EGF, respectively, while the KD was unchanged. Northern and Western blot analyses demonstrated that neither PDGF-BB nor EGF increase LRP mRNA or protein levels. Instead, LRP was redistributed to the cell surface and remained localized primarily in coated pits, as determined by surface protein biotinylation, affinity labeling, and immunoelectron microscopy studies. The increase in cell-surface LRP was partially explained by a 50% decrease in receptor endocytosis rate; however, at 37 degrees C, PDGF-BB- and EGF-treated VSMCs still bound/internalized increased amounts of activated alpha2M and subsequently released increased amounts of trichloroacetic acid-soluble radioactivity. The cytokine-induced shifts in LRP subcellular distribution were stable when VSMCs were challenged with a saturating concentration of ligand and then incubated, in the absence of cytokine, for 2.5 h at 37 degrees C. Regulation of LRP distribution and activity may be an important aspect of the VSMC response to the atherogenic cytokines, PDGF-BB and EGF.

Animals↗
PubMed1996

Phase I study of paclitaxel in combination with cyclophosphamide and granulocyte colony-stimulating factor in metastatic breast cancer patients.

PURPOSE: In vitro data suggest that prolonged exposure to paclitaxel enhances breast cancer cytotoxicity. Our objective in this phase I study was to determine the tolerability of paclitaxel administered by 72-hour continuous intravenous (i.v.) infusion (CIVI) in combination with high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) in the ambulatory setting to metastatic breast cancer patients. PATIENTS AND METHODS: Paclitaxel was administered over 72 hours by CIVI and cyclophosphamide was given daily by i.v. bolus on days 1, 2, and 3, followed by G-CSF every 21 days. The availability of ambulatory infusion pumps and paclitaxel-compatible tubing permitted outpatient administration. RESULTS: Fifty-five patients with metastatic breast cancer who had been previously treated with a median of two prior chemotherapy regimens were entered onto the study. Dose-limiting toxicity of grade 4 neutropenia for longer than 5 days and grade 4 thrombocytopenia occurred in three of five patients treated with paclitaxel 160 mg/m2 CIVI and cyclophosphamide 3,300 mg/m2 followed by G-CSF. The maximum-tolerated dose (MTD) was paclitaxel 160 mg/m2 CIVI and cyclophosphamide 2,700 mg/m2 in divided doses with G-CSF. Nonhematologic toxicities were moderate and included diarrhea, mucositis, and arthalgias. Although hemorrhagic cystitis developed in six patients, recurrence was prevented with i.v. and oral mesna, which permitted continued outpatient delivery. One hundred seventy-four cycles were safely administered in the ambulatory setting using infusional pumps and tubing. Objective responses occurred in 23 (one complete and 22 partial) of 42 patients with bidimensionally measurable disease (55%; 95% confidence interval, 38% to 70%), with a response rate of 73% (11 of 15) seen at the highest dose levels. CONCLUSION: Paclitaxel by 72-hour CIVI with daily cyclophosphamide followed by G-CSF can be administered safely in the ambulatory setting, has acceptable toxicity, and is an active regimen in the treatment of metastatic breast cancer.

Adult↗
PubMed1996

Phase I/II study of 72-hour infusional paclitaxel and doxorubicin with granulocyte colony-stimulating factor in patients with metastatic breast cancer.

PURPOSE: We conducted a phase I/II trial of concurrently administered 72-hour infusional paclitaxel and doxorubicin in combination with granulocyte colony-stimulating factor (G-CSF) in patients with previously untreated metastatic breast cancer and bidimensionally measurable disease. PATIENTS AND METHODS: We defined the maximum-tolerated dose (MTD) of concurrent paclitaxel and doxorubicin administration and then studied potential pharmacokinetic interactions between the two drugs. Forty-two patients who had not received prior chemotherapy for metastatic breast cancer received 296 total cycles of paclitaxel and doxorubicin with G-CSF. RESULTS: The MTD was determined to be paclitaxel 180 mg/m2 and doxorubicin 60 mg/m2 each by 72-hour infusion with G-CSF. Diarrhea was the dose-limiting toxicity (DLT) of this combination, with three of three patients developing abdominal computed tomographic (CT) scan evidence of typhlitis (cecal thickening) at the dose level above the MTD. All patients developed grade 4 neutropenia (absolute neutrophil count [ANC] < 500 microL), generally less than 5 days in duration. This combination was generally safely administered at dose levels at or below the MTD. The overall response rate was 72% (28 of 39 patients; 95% confidence interval [CI], 55% to 85%), with 8% complete responses (CRs) (three of 39; 95% CI, 2% to 21%) and a median response duration of 9 months. The median overall survival time for all patients is 23 months, with a median follow-up duration of 28 months. Pharmacokinetic studies showed that administration of paclitaxel and doxorubicin together by 72-hour infusion did not affect the steady-state concentrations of either drug. CONCLUSION: Concurrent 72-hour infusional paclitaxel and doxorubicin can be administered safely, but is associated with significant toxicity. The overall response rate of this combination in untreated metastatic breast cancer patients is similar to that achieved with other doxorubicin-based combination regimens. The modest complete response rate achieved suggests that this schedule of paclitaxel and doxorubicin administration does not produce significant additive or synergistic cytotoxicity against breast cancer.

Adult↗
PubMed1995

Dental caries and dental registration status in nursery school children in Newry, Northern Ireland.

294 children aged 2-4 yr attending nursery schools in Northern Ireland were examined for dental caries and dental registration status under the capitation system in general dental practice. Their mean age was 3 yr 10 months. Sixty eight per cent were caries free, mean dmft was 1.10 and dt, mt and ft scores were 0.74, 0.28 and 0.09, respectively. With increasing age the prevalence of caries increased, though the very low care index (d/dmft) did improve in the older children. Seventy per cent reported being registered for dental care and their levels of dental caries were significantly higher than those who were not yet enrolled (P < 0.001). For those not enrolled for dental care the main perceived barriers to seeking care related to lack of symptoms (33.6%) and apathy (31.6%) while few reported fear as a barrier (4.5%).

Age Factors↗
PubMed1995

Hepatitis B immunisation among invasive cardiologists: poor compliance with United Kingdom guidelines.

OBJECTIVES: To assess the compliance of invasive cardiologists in the United Kingdom with recently accepted national guidelines on the protection of health care workers and patients from hepatitis B. To determine levels of awareness of the infectivity and prevalence of the virus and current attitudes towards screening of patients before cardiac catheterisation and surgery. DESIGN: Anonymous postal survey by questionnaire from the University Hospital of Wales, Cardiff. The questionnaire established the respondent's position, knowledge of hepatitis B, current immunological state, and policy towards the routine screening of patients for hepatitis B carriage. PARTICIPANTS: All British cardiologists of consultant or senior registrar grade involved in invasive procedures. RESULTS: The response rate was 78% (211/271). 20% of respondents had never been vaccinated against hepatitis B and about a third of those vaccinated had not complied correctly with the recommended immunisation regimen. There was little uniformity in practices for screening patients for hepatitis B carriage before invasive procedures, and the level of knowledge concerning the prevalence of hepatitis B and the risks of inoculation was poor. CONCLUSIONS: Invasive cardiologists are at high risk of inoculation with hepatitis B. Nationally agreed guidelines are designed to protect both medical staff and patients against the risk of infection but currently they are ill heeded.

Attitude of Health Personnel↗
PubMed1995

Early diagnosis of cytomegalovirus pneumonitis in lung transplant patients.

Cytomegalovirus (CMV) pneumonitis is an important cause of morbidity and mortality in lung transplant patients and requires timely and accurate diagnosis. This study compares the diagnostic utility of the evaluation of transbronchial biopsy by histology, immunohistochemistry, and simultaneous culture of bronchoalveolar lavage in a population of 13 lung transplant patients who underwent 78 biopsies during a period of 27 months. Our study concludes that, in patients clinically symptomatic for CMV pneumonitis, histology alone is diagnostic for the presence of the virus, whereas culture of bronchoalveolar lavage fluid is not as helpful. In asymptomatic patients, however, immunohistochemistry utilizing monoclonal antibodies to immediate-early and early CMV nuclear antigens may indicate development of CMV pneumonitis before cytopathic changes are evident.

Adult↗
PubMed1995

Familial and maternal factors affecting the dental health and dental attendance of preschool children.

Factors affecting the dental health and dental registration of preschool children were examined. Questionnaires were completed for 340 randomly selected children and the dental caries status of 294 of these children was examined. There was a statistically significant relationship between the dental caries experience of the child and its position in the family, the lowest caries experience occurring in the second and third born. The peak age of new dental registration appeared to occur during children's third year. The person responsible for bringing the child for dental appointments was the mother in 290 instances out of 340. Maternal education level was significantly associated with child dental health. The caries prevalence in children whose mothers were educated to 3rd level was 10.6 per cent as compared to 38.1 per cent for 2nd level and 46.8 per cent for below '0' level mothers. Mothers who were relaxed about their own dental care were the most likely to have preschool children who were registered for dental care. Similarly those mothers whose last dental visit occurred in the previous six months were the most likely to have children who were registered.

Adult↗
PubMed1993

Depressive symptomatology, perceptions of attractiveness, and body image in children.

Fifty-seven children, aged 9-12 completed the Children's Depression Inventory, rated their bodies on dimensions of attractiveness, effectiveness and vulnerability, and rated themselves and three other children on global attractiveness. Dysphoria was significantly correlated with both measures of dissatisfaction of own attractiveness. No significant correlations occurred between CDI scores and effectiveness or vulnerability. Stepwise regression showed dysphoria to be predicted by dissatisfaction with the body's attractiveness and by age with the former being the most powerful. No subject differences were found on rating the attractiveness of other children. Results are compared to research with adult subjects.

Beauty↗
PubMed1993

A survey of basic resuscitation knowledge among resident paediatricians.

A telephone questionnaire was undertaken to evaluate the knowledge of resident paediatricians on the subject of the basic resuscitation of the acutely sick child. The questionnaire was targeted at 88 resident paediatricians in hospitals accepting paediatric emergencies in four health regions. Outcome was measured as a correct response to questions based on several emergency scenarios and on the confidence expressed of basic resuscitation knowledge. The subject of emergency management of the child with a compromised upper airway was poorly answered with 40/73 (55%) resident paediatricians suggesting an incorrect endotracheal tube size for an 8 year old child. Fluid management was also deemed unsatisfactory with only 36/73 (49%) providing adequate transfusion secondary to haemorrhagic shock. In addition only 19/73 (26%) mentioned the intraosseous route as a means of obtaining vascular access in a child in extremis. Confidence of the knowledge of basic resuscitation of children was low among resident paediatricians with only 30/73 (41%) expressing confidence and 69/73 (94%) expressing a desire for more formal training in paediatric resuscitation. Resident paediatricians are usually the key personnel in the management of very sick children. This survey demonstrates a low level of basic resuscitation knowledge among resident paediatricians of all grades that must be remedied at a local and national level.

Cardiopulmonary Resuscitation↗
PubMed1993

Telephone advice in the accident and emergency department: a survey of current practice.

The objective of this study was to assess the standard of advice given by telephone by accident and emergency (A&E) departments following patients' enquiries. In order to do this patient enquiries were simulated and a telephone questionnaire was carried out. The study was carried out in 18 major and 16 minor A&E departments in Wales. Results achieved were that overall, correct telephone advice was given to 72 of 97 simulated patients (74%). Sixty calls were dealt with by the nursing staff (62%) who gave correct advice on 41 (68%) occasions. No A&E department had a formal policy nor provided staff training for handling patients' enquiries by telephone. It is concluded that A&E departments should train designated members of staff, preferably the triage nurse, who would formally deal with telephone enquiries requiring medical advice. There should be formal documentation of the enquiry and advice proffered as part of a departmental policy.

Counseling↗