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Biomedical subjects

K Wilkinson

Publications and source records attributed to K Wilkinson.

At least 37 records · Page 2Linked to original sources

The carry-through of residues of maleic hydrazide from treated potatoes, following manufacture into potato crisps and 'jacket' potato crisps.

Potatoes, which had been treated 'in the field' with a commercial formulation of maleic hydrazide, were processed into potato crisps and jacket potato crisps on a factory production line using standard manufacturing conditions. Samples were taken at strategic points throughout the process and analysed to determine the degree of carry-through of residues. Results demonstrated that ca 56% of the maleic hydrazide residue in a potato could be carried through into the potato crisps, irrespective of which type of crisp was being manufactured. Results from a similarly constructed study investigating the fate of pesticides applied post-harvest showed that carry-through was less than 10%. This difference is explained in terms of the different modes of action of the two classes of pesticides being investigated. It is known that, as maleic hydrazide is a systemic pesticide, it will be located within the flesh of the potato tuber and is therefore likely to be protected from the various stages of the crisping process. However, the post-harvest non-systemic pesticides are applied to the exterior surface of the tuber and are therefore not likely to be protected in the same way. The results also showed that, due to the concentration effect caused by the loss of moisture during crisp manufacture, the levels of maleic hydrazide residues in crisps (on a mg/kg product basis) were approximately twice those measured in the original potatoes.

Agrochemicals↗

Loss of Bcl-2 expression correlates with tumour recurrence in colorectal cancer.

AIMS: To investigate the association between immunohistochemical expression of Bcl-2 and p53 in colorectal cancer and tumour recurrence following surgery. METHODS: Sixty six cases of Dukes' B colorectal carcinoma were studied. All tumours were moderately differentiated and were shown to be histologically clear of the resection margins. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for p53 and Bcl-2. The Bcl-2 staining was assessed separately for relative intensity of staining and percentage of positive tumour cells and given a final score which combined the two factors. The p53 staining was assessed on number of positive tumour cells only. The patterns of immunostaining of those cases in which there had been tumour recurrence were compared with those cases in which there was no tumour recurrence (controls). RESULTS: A statistically significant inverse association was found between Bcl-2 score and tumour recurrence (median Bcl-2 score of 6 (interquartile range (IQR) 2-9) in patients with recurrent disease; median Bcl-2 score of 8 (IQR 6-10) in those without recurrence; p = 0.03). When examined separately, both the intensity of expression and percentage of positive tumour cells were significantly associated with tumour recurrence (p = 0.04 in each case). There was no association between p53 staining and tumour recurrence. CONCLUSION: Results suggest that, when controlled for differentiation, Bcl-2 expression is a prognostic marker and may be useful as an adjunctive test in clinical decision making.

Biomarkers, Tumor↗

Nurse triage for house call requests in a Tyneside general practice: patients' views and effect on doctor workload.

BACKGROUND: Demand for consultations in primary care has risen recently, necessitating a change in working practices. As part of this process, the possible contribution of practice nurses in the telephone assessment of home visit requests merits attention. AIMS: To survey the views of our patients encountering our nurse triage system for home visit requests, set up in June 1995, and to plot its effect on the routine visiting workload of our doctors and thus their availability at the surgery. METHOD: The outcome of each request was categorized as: doctor to visit (DV), surgery consultation with doctor (SC), nurse advice given and accepted (NA), or call passed to doctor for advice (DA). Frequency data from September 1995 to December 1996 were recovered. Questionnaires for self-completion were sent to all those requesting a routine weekday house call during two four-week periods in 1995 and 1996. RESULTS: Analysable activity data revealed 1764 house call requests, with 41% DV, 18% SC, 24% NA, and 8% DA. In the first survey, 121 questionnaires were sent out and 84 returned (69% response rate) and, in the second, the corresponding figures were 113, 85, and 75%. About 80% of responders reported that they were satisfied with the help received from the nurse. CONCLUSIONS: Nurse triage of house call requests has led to more efficient care for our patients, as we have increased the availability of surgery consultations by reducing the number of house calls made by our general practitioners.

Family Practice↗

Paediatric index of mortality (PIM): a mortality prediction model for children in intensive care.

OBJECTIVE: To develop a logistic regression model that predicts the risk of death for children less than 16 years of age in intensive care, using information collected at the time of admission to the unit. DESIGN: Three prospective cohort studies, from 1988 to 1995, were used to determine the variables for the final model. A fourth cohort study, from 1994 to 1996, collected information from consecutive admissions to all seven dedicated paediatric intensive care units in Australia and one in Britain. RESULTS: 2904 patients were included in the first three parts of the study, which identified ten variables for further evaluation. 5695 children were in the fourth part of the study (including 1412 from the third part); a model that used eight variables was developed on data from four of the units and tested on data from the other four units. The model fitted the test data well (deciles of risk goodness-of-fit test p = 0.40) and discriminated well between death and survival (area under the receiver operating characteristic plot 0.90). The final PIM model used the data from all 5695 children and also fitted well (p = 0.37) and discriminated well (area 0.90). CONCLUSIONS: Scores that use the worst value of their predictor variables in the first 12-24 h should not be used to compare different units: patients mismanaged in a bad unit will have higher scores than similar patients managed in a good unit, and the bad unit's high mortality rate will be incorrectly attributed to its having sicker patients. PIM is a simple model that is based on only eight explanatory variables collected at the time of admission to intensive care. It is accurate enough to be used to describe the risk of mortality in groups of children.

Adolescent↗

Tumour recurrence is associated with Jass grouping but not with differences in E-cadherin expression in moderately differentiated Dukes' B colorectal cancers.

AIMS: To assess whether immunohistochemical expression of the putative invasion suppressor, E-cadherin, is associated with tumour recurrence in colorectal cancer, independent of Dukes' stage and degree of differentiation, and thus to determine whether measurement of E-cadherin is clinically useful. METHODS: 90 moderately differentiated Dukes' B colorectal carcinomas from patients who had been followed up for at least six years were examined. All were from curative resections performed at St Mark's Hospital and the tumours were shown, on histology, to be clear of all resection margins. Tumours were reviewed and additionally classified in accordance with the Jass grouping system. Immunohistochemical analysis of E-cadherin expression was performed for each tumour using the monoclonal antibody HECD 1. RESULTS: The Jass group ranged between I and III and there was a significant association between Jass group and tumour recurrence (p < 0.05). Positive E-cadherin expression was seen in 40/69 (58%) of non-recurrent and 13/21 (62%) recurrent cases respectively. There was no significant difference in E-cadherin expression between the two groups of tumours. CONCLUSIONS: Even when controlled for Dukes' stage and differentiation, the Jass grouping system yields useful prognostic information; E-cadherin, however, does not predict outcome in the important group of moderately differentiated Dukes' B colon cancers, and may be of little independent prognostic value in other colon cancers.

Cadherins↗

Extraction of maleic hydrazide residues from potato crisps and their determination using high-performance liquid chromatography with UV and atmospheric pressure chemical ionisation mass spectrometric detection.

A method was required for the determination of maleic hydrazide residues in potato crisps. A published method for the extraction of the analyte from onions and potatoes was evaluated and found to be inappropriate due to the inability of the extracting solvent to penetrate the oily matrix. A method was developed to overcome this problem; the resulting recovery data (mean = 92.9%, R.S.D. = 8.3%, n = 16) confirmed its efficiency, and was used to analyse 48 retail potato crisp samples. To confirm possible residues identified by screening with HPLC-UV, an HPLC-atmospheric pressure chemical ionization MS method was developed. There was good agreement between the data obtained from the two detection techniques (R2 = 0.978, slope = 1.11).

Chromatography, High Pressure Liquid↗

Phase I clinical trial with a human major histocompatibility complex nonrestricted cytotoxic T-cell line (TALL-104) in dogs with advanced tumors.

The human TALL-104 cell line is endowed with a uniquely potent MHC nonrestricted tumoricidal activity across several species. In view of the potential applicability of TALL-104 cells as an anticancer agent, this study was conducted to evaluate the possible toxicity and efficacy of this new cell therapy in a superior animal model with spontaneous tumors. Nineteen canine cases with advanced, refractory malignancies of various histological types were entered in the study. All dogs had failed all other available treatments and had very limited life expectancy. Cyclosporin A was administered p.o. (10 mg/kg/day) starting from the day before TALL-104 cell administration throughout the treatment to prevent rejection of the xenogeneic effectors. Lethally irradiated (40 Gy) TALL-104 cells (10(8)/kg) were administered systemically following two treatment schedules. In the first schedule, the cells were given every other day for 2 weeks in a row and then once a week for 3 additional weeks; in the second schedule, TALL-104 cells were administered daily for a total of 5 days. None of the 19 cases showed significant clinical or laboratory toxicity; in addition, none of the dogs had to be withdrawn from the study because of immediate adverse reactions to the infusions. The severe side effects usually associated with classical lymphokine-activated killer therapy in association with high doses of interleukin 2, such as "capillary leak syndrome," were absent in this study. Remarkably, TALL-104 therapy induced various degrees of antitumor effects in 7 of the 19 dogs, including 1 complete response (continuing at +13 months), three partial responses (duration of 2 months, 3 months, and continuing at +2 months), and three transient responses. Clinical responses and immunological parameters correlated well in each case. Taken together, these data indicate that systemic administration of lethally irradiated TALL-104 cells in the absence of exogenous interleukin 2 may be regarded as a safe and promising adjuvant type of treatment for advanced cancer patients.

Animals↗

Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer.

Using quantitative zymography, we measured activity of the type IV collagenases metalloprotease 2 (MMP-2) and MMP-9 in 192 biopsies from colorectal carcinomas, adenomas, and normal bowel. The median level of MMP-9 in samples from Dukes' stage A (n = 18) or C (n = 48) tumors was significantly higher than in stage B carcinomas (n = 65), adenomas (n = 25), and normals (n = 36; P = 0.0001). The median level of active MMP-2 was significantly higher in stage A or C compared with adenomas (P = 0.0001) and normals (P = 0.0001). The median level of inactive MMP-2 was higher in all Dukes' stages compared with normals and adenomas (P = 0.0001). There was a significant increase in inactive MMP-2 from Jass prognostic groups I-IV (P = 0.006) but no correlation with the active enzyme. MMP activity was not related to tumor differentiation, colon versus rectal location, or disease-free, 5-year survival. All groups expressed mRNA for both enzymes, but there were quantitative and locational differences in MMP-2 mRNA expression between normal, benign, and malignant tissues. Thus MMP-2 is controlled at the level of mRNA and protein production and activation in colorectal cancer, and active MMP-2 and MMP-9 enzymes are associated strongly with Dukes' A and C stages of the disease. Variations in MMP levels with the stage or prognostic group of colorectal cancer reflect their differing stromal content.

Adenoma↗

The concept of hope in life-threatening illness.

Achievable goals are important in fostering hope. The presence of hope is an important component of spiritual well-being. Being unrealistic may help the patient to cope. Nurses need to help patients achieve a balance between hopelessness and unrealistic hope.

Adaptation, Psychological↗

Unsuspected Pneumocystis carinii pneumonia and vertically acquired HIV infection in infants requiring intensive care.

When an infant develops acute respiratory failure of sufficient severity to necessitate supportive mechanical ventilation a cause should always be sought. A chest radiograph showing predominantly interstitial lung disease and an infant's failure to respond to standard antibiotic treatment are indications for non-bronchoscopic bronchoalveolar lavage. If P carinii pneumonia is diagnosed a congenital immunodeficiency should be sought and the parents counselled about HIV infection. Earlier investigation may be indicated by features of immunodeficiency when taking a history, performing a general examination, or analysing the results of basic haematological testing.

Female↗

Cloning and analysis of expression of a ubiquitin carboxyl terminal hydrolase expressed during oogenesis in Drosophila melanogaster.

Using the enhancer trap approach we have searched for genes with important functions in oogenesis. We selected a line of flies with a P insertion, carrying the Escherichia coli lac Z gene, which showed beta-galactosidase expression in the nurse cell nuclei during oogenesis. Surrounding the P insertion we discovered a cluster of transcription units with enriched expression in the ovary. One of these encodes a protein with extensive sequence similarity to the human and yeast ubiquitin carboxyl terminal hydrolase. Analysis of a fusion protein including the putative ubiquitin carboxyl terminal hydrolase indicated that this protein does have the appropriate enzyme activity, and the gene was assigned the name ubiquitin carboxyl terminal hydrolase uch-D. The expression of this gene is enriched in the nurse cells and transcripts are transported to the embryo. Transcripts are abundant for the first few hours of development. The transcripts are found to be enriched on the ventral side of the oocyte and nurse cells. Rather little is known about the ubiquitin pathway in Drosophila and the discovery of this gene enables us to make predictions as to the roles it may play during early embryogenesis.

Amino Acid Sequence↗

The incomplete cone biopsy: a comparison of conservative and surgical management.

OBJECTIVE: to determine the reliability of conservative management of cone biopsies showing apparently incomplete excision of cervical intraepithelial neoplasia (CIN) by comparing surgical and conservative management. DESIGN: a retrospective study. SUBJECTS: 74 consecutive cone biopsies with a histology report of apparently incomplete excision of CIN 2 or CIN 3 from a series of 738 cone biopsies. MAIN OUTCOME MEASURES: the presence of CIN at hysterectomy against the pick up rate in conservatively managed patients. RESULTS: where excision appeared incomplete at the ectocervix this was confirmed in 1 of 6 (16.7%) of patients managed surgically and 2 of 17 (11.8%) of patients managed conservatively (P = 0.40). Where excision appeared incomplete at both endo- and ectocervix, 5 of 6 (83.3%) were confirmed to have incomplete excision in the surgical group, and 3 of 5 (60%) had further proven CIN in the conservative group (P = 0.34). Where excision appeared incomplete at the endocervix only, this was confirmed in 7 of 22 (32%) of cases managed surgically, but only 2 of 18 (11.1%) of cases managed conservatively had further proven CIN (P = 0.14). Combining all patients with incomplete excision at the endocervix irrespective of the ectocervix status revealed confirmation of residual CIN in 12 of 28 (42.9%) patients managed surgically and in 5 of 23 (21.7%) patients managed conservatively (P = 0.097). CONCLUSIONS: management should depend on the site of the apparent incomplete excision. Where excision appears incomplete at the ectocervix only, cytological follow up should be employed. If the endocervix is involved, further excisional surgery may be more appropriate.

Biopsy↗

Methadone maintenance program for AIDS-affected opiate addicts.

To slow the spread of AIDS, it may be important for substance abuse treatment programs to give priority admission to patients who are HIV-infected and infectious. A new program is described that provides methadone maintenance treatment to opiate addicts who are "AIDS affected"--heroin addicts diagnosed with AIDS, AIDS-related complex (ARC), or other significant symptoms of HIV infection. The program aims to protect the health of patients and to protect the general public by slowing the spread of the human immunodeficiency virus (HIV). This article describes the program's history and goals, its referral and patient admission process, methods of assessment and treatment planning, medical care, counseling procedures, tolerance for misbehavior, philosophy toward eventual detoxification, and procedures that maintain confidentiality.

AIDS-Related Complex↗

Dural punctures.

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Dura Mater↗