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Biomedical subjects

P McKenzie

Publications and source records attributed to P McKenzie.

At least 19 recordsLinked to original sources

Assessing the utility of the stop dialysate flow method in patients receiving haemodiafiltration.

BACKGROUND: The stop dialysate flow (SDF) method of post-dialysis urea sampling is the most commonly used method in the UK. It can also be used with a published formula to predict 30 min equilibrated urea accurately. The method has not been validated in patients undergoing haemodiafiltration (HDF). Given the increased use of HDF across Europe, we felt it prudent to assess the utility of the SDF method and prediction equation in this modality. METHODS: Fourteen patients from two renal units were studied. Blood samples were taken at 1 min intervals from the arterial side of the dialysis circuit in the first 5 min after HDF had ceased whilst blood circulation continued. A peripheral sample was taken from the contralateral arm immediately after HDF had ceased and a 30 min sample was taken from the arterial needle. These samples were used to assess the utility of 5 min arterial blood urea and the 30 min prediction formula, respectively. RESULTS: Blood urea measured from the arterial circuit at 5 min correlated closely with the contralateral sample taken immediately post-HDF, with no significant difference (6.45+/-2.11 vs 6.52+/-2.19 mmol/l, P = 0.39). The use of 5 min arterial blood urea and prediction formula allowed an accurate prediction of 30 min urea (R2 = 0.96). CONCLUSIONS: The use of the SDF method with a 5 min post-HDF arterial sample is valid in patients receiving HDF. The previously published prediction formula for estimating 30 min urea is also valid using the 5 min post-HDF sample.

Biomarkers↗

Predicting the HER2 status of breast cancer from basic histopathology data: an analysis of 1500 breast cancers as part of the HER2000 International Study.

The tests that are currently available for the measurement of overexpression of the human epidermal growth factor-2 (HER2) in breast cancer have shown considerable problems in accuracy and interlaboratory reproducibility. Although these problems are partly alleviated by the use of validated, standardised 'kits', there may be considerable cost involved in their use. Prior to testing it may therefore be an advantage to be able to predict from basic pathology data whether a cancer is likely to overexpress HER2. In this study, we have correlated pathology features of cancers with the frequency of HER2 overexpression assessed by immunohistochemistry (IHC) using HercepTest (Dako). In addition, fluorescence in situ hybridisation (FISH) has been used to re-test the equivocal cancers and interobserver variation in assessing HER2 overexpression has been examined by a slide circulation scheme. Of the 1536 cancers, 1144 (74.5%) did not overexpress HER2. Unequivocal overexpression (3+ by IHC) was seen in 186 cancers (12%) and an equivocal result (2+ by IHC ) was seen in 206 cancers (13%). Of the 156 IHC 3+ cancers for which complete data was available, 149 (95.5%) were ductal NST and 152 (97%) were histological grade 2 or 3. Only 1 of 124 infiltrating lobular carcinomas (0.8%) showed HER2 overexpression. None of the 49 'special types' of carcinoma showed HER2 overexpression. Re-testing by FISH of a proportion of the IHC 2+ cancers showed that only 25 (23%) of those assessable exhibited HER2 gene amplification, but 46 of the 47 IHC 3+ cancers (98%) were confirmed as showing gene amplification. Circulating slides for the assessment of HER2 score showed a moderate level of agreement between pathologists (kappa 0.4). As a result of this study we would advocate consideration of a triage approach to HER2 testing. Infiltrating lobular and special types of carcinoma may not need to be routinely tested at presentation nor may grade 1 NST carcinomas in which only 1.4% have been shown to overexpress HER2. Testing of these carcinomas may be performed when HER2 status is required to assist in therapeutic or other clinical/prognostic decision-making. The highest yield of HER2 overexpressing carcinomas is seen in the grade 3 NST subgroup in which 24% are positive by IHC.

Adult↗

High grade abnormalities following an 'inconclusive' smear.

OBJECTIVE: The National Health and Medical Research Council (NHMRC) recommends a report of 'inconclusive possible high grade epithelial abnormality', but many laboratories only report 'inconclusive' with reference to any possible high grade disease elsewhere in the report. This study was performed to determine possible reasons for cytological difficulties resulting in this category of report and to determine the rate of significant disease within this category. DESIGN: Retrospective record review. Clinical details were extracted without patient-identifying data. SETTING: Gynaecological Oncology Department, King George V/Royal Prince Alfred Hospital. POPULATION: Two hundred patients referred with the cytological abnormality. MATERIALS AND METHODS: An adequate colposcopic diagram documenting size, distribution and grade of lesion was required. All patients had colposcopy with management according to colposcopic and histological results as appropriate to their disease. OUTCOME MEASURES: Colposcopic features, topography and size of any lesion, histological results, treatments performed and subsequent review of untreated patients. RESULTS: Colposcopy found high-grade lesions in 43% and carcinoma in 1%. Histopathology found 49% and 4% respectively. Treatment was performed in 124 patients. Inflammation was found in 27%, a small lesion in 43% and endocervical disease in 21%. CONCLUSIONS: The high rate of endocervical disease, inflammation and small lesions may explain the cytological difficulties leading to an 'inconclusive' result. The authors believe that the term 'inconclusive' alone does not adequately convey the high level of risk faced by these patients.

Adolescent↗

Effect of transfusional iron overload on immune response.

Increased susceptibility to infectious disease is observed in persons with transfusion-dependent thalassemia and iron overload who experience increased exposure to pathogens and chronic immune stimulation. An abnormal low CD8(+) T (LT8) immune phenotype defines a subgroup of patients. The CD8(+) T cell immunophenotype is stable despite continued blood transfusion and is independent of age. CD8(+) T cells, but not CD4(+) T cells, were modulated during intravenous chelation with deferoxamine. Return to characteristic pretreatment levels of CD8 was observed in both the low and the normal groups, suggesting the possibility of a set point. Proliferative response to mitogens and antigens was increased by chelation. Because CD8(+) T cells are important in immune response to infectious disease, these studies suggest that intrinsic CD8(+) T cell subset differences may be a critical factor in determining susceptibility to infection independent of transfusional iron overload or alloantigen exposure.

Adolescent↗

Controlled trial of an audit facilitator in diagnosis and treatment of childhood asthma in general practice.

OBJECTIVE: To test whether an audit facilitator could alter the pattern of diagnosis and treatment of childhood asthma. DESIGN: Randomised stratified controlled trial. SETTING: 12 general practices in Tayside. SUBJECTS: 3373 children aged 1-15 inclusive who had symptoms suggestive of asthma or possible asthma drawn from a systematic review of 10,725 general practice case records. INTERVENTION: Children were targeted for a clinical review by their general practitioner or practice nurses. MAIN OUTCOME MEASURES: Asthma related consultations, prescriptions, hospital attendances, and health service costs 12 months before and after study. RESULTS: Compared with controls (n = 1563) the intervention group (n = 1585) had more practice initiated consultations for asthma (relative risk 2.18 (95% confidence interval 1.74 to 2.73)), new diagnoses of asthma (2.83 (2.26 to 3.54)), and past diagnoses reaffirmed (1.30 (1.08 to 1.58)), and they were more frequently prescribed inhaled cromoglycate (1.52 (1.02 to 2.25)). Hospital inpatient day rates fell from 152 to 122 in the intervention group and rose from 69 to 117 in the control group between the year before and the year after study. Total primary care costs rose from 30,118 pounds to 37,243 pounds in the intervention group and fell from 29,131 pounds to 27,990 pounds in the control group. Hospital care cost fell in the intervention group from 25,406 pounds to 20,727 pounds and rose in the control group from 12,699 pounds to 19,650 pounds. CONCLUSION: An audit facilitator can favourably influence the pattern of diagnosis and treatment of childhood asthma in general practice. This may have an impact on health service costs.

Adolescent↗

Immunohistochemical detection of p53 protein expression in mammary carcinoma: a study of 80 cases.

Overexpression of p53 protein appears to be a common event in primary mammary carcinoma. This study was performed on 80 primary carcinomas of varying type and grade. Tumor p53 protein expression was detected by means of immunohistochemistry using the monoclonal antibody D07 on formalin fixed paraffin-embedded tissue sections. p53 overexpression was found in 50 (63%) of the 80 tumors. The correlation between p53 expression and high tumor grade, presence of in situ component and lymphocytic response was significant. However, no significant association was found between p53 expression and tumor size, age of the patients or tumor vascular invasion. Our study suggested that the immunohistochemical assay was a simple method of detection of mutant p53 proteins in routinely processed paraffin-embedded tissues of primary mammary carcinoma.

Adult↗

A longitudinal study of bacterial vaginosis during pregnancy.

OBJECTIVE: To determine the longitudinal changes in the incidence of vaginosis in pregnancy. DESIGN: A prospective study of women during pregnancy. SETTING: A District General Hospital in North-West London. SUBJECTS: Seven hundred and eighteen pregnant women attending antenatal clinics. At their first attendance and subsequently, Gram-stained vaginal smears were examined and Mycoplasma hominis and Gardnerella vaginalis were sought by culture. RESULTS: Initially, 87 (12%) women had bacterial vaginosis diagnosed on Gram-stained reading of the vaginal smears. Examination of further smears, obtained from 176 women at 36 weeks of gestation, showed that those whose vaginal flora was normal initially, and who went to term, rarely developed vaginosis (three of 127, 2.4%). Samples were obtained at 36 weeks gestation from 32 women who had bacterial vaginosis initially, and went to term. In almost 50% (15 of 32) of these a normal lactobacillus-dominated flora had regenerated. Thirty-five women (5%) had initial vaginal smears graded as intermediate. From this group, six of the 17 (35%) women from whom samples were obtained at 36 weeks gestation still had flora of an intermediate pattern; 10(59%) now had normal flora and only one (6%) had developed bacterial vaginosis. Women with bacterial vaginosis were more likely to be culture-positive for M. hominis than those with normal flora (34/78 versus 10/563, odds ratio 42.73 (18.9 to 102.3) P < 0.001), or to be culture-positive for G. vaginalis than those with normal flora (35/78 versus 21/563, odds ratio 21.0 (10.75 to 41.2) P < 0.001). CONCLUSION: Pregnant women do not commonly develop bacterial vaginosis after 16 weeks gestation, and if present, it remits spontaneously in approximately half of those who reach term. As bacterial vaginosis is associated with increased rates of second trimester miscarriage and preterm delivery, any treatment aimed at its eradication in pregnancy should be given no later than the beginning of the second trimester of pregnancy.

Adult↗

Tumor-associated glycoprotein expression in salivary gland mucoepidermoid carcinomas: an immunohistochemical study using the monoclonal antibody B72.3.

The monoclonal antibody B72.3 recognizes a mucin-like glycoprotein which is expressed in a variety of human malignancies including adenocarcinomas of the breast, colon, lung, endometrium, pancreas, and ovary. The antibody, an immunoglobulin G (IgG1) subclass monoclonal antibody, was generated from membrane-enriched fractions of metastatic mammary carcinoma. Because the antigen detected by B72.3 is expressed in a broad spectrum of human neoplasms, B72.3 is a potentially useful marker for glandular neoplasms. Despite its potential usefulness, there is only one previous comprehensive study which has examined the distribution of the tumor-associated glycoprotein (TAG-72), as detected by B72.3, in salivary neoplasms. We examined 21 mucoepidermoid carcinomas with the antibody. Twenty (95%) of the 21 carcinomas stained positively. The only carcinoma that did not stain was initially thought to be a high-grade mucoepidermoid carcinoma based on immunohistochemical staining. Further review, however, indicated that this lesion was most likely a pure squamous cell carcinoma, and the absence of TAG-72 antigen expression was helpful in this regard. Among those neoplasms which stained with B72.3, the strongest staining was seen in the low-grade carcinomas. These results suggest that B72.3 may be a useful marker for glandular differentiation in mucoepidermoid carcinomas.

Adolescent↗

A trainer's perspective of an innovative programme teaching health visitors about the detection, treatment and prevention of postnatal depression.

Health visitors in North Staffordshire, Edinburgh and Lewisham were given the opportunity to participate in a training programme in the detection, treatment and prevention of postnatal depression, based on previously reported successful intervention strategies. They were trained in the use of the Edinburgh Postnatal Depression Scale (EPDS), and given information about the value and practice of non-directive counselling and about preventative strategies. Knowledge acquisition was evaluation by self-report questionnaires given before and after training. The health visitors were encouraged to screen postnatal women at three specified times using the EPDS and to offer non-directive counselling to women who obtained high scores. A baseline measure of the incidence of postnatal depression was obtained by asking health visitors to give an EPDS form to all women in their caseload with a 6-month-old baby before training commenced. A comparison of the number of women with high EPDS scores at 6 months postnatally, before and after training, showed that participation in the programme enabled health visitors to positively influence the emotional well-being of postnatal women. These results have implications for the role of health visitors which is currently being challenged, as well as for components of their training and continuing professional development.

Community Health Nursing↗

Lincomycins in the treatment of bacteroides infections.

Lincomycin, or the closely related derivative clindamycin, was used to treat six patients with bacteroides infection. In five of the six there was a rapid clinical response to the treatment. Lincomycin and clindamycin seem to be the antibiotics of choice for such infections.

Adolescent↗