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Biomedical subjects

P Jones

Publications and source records attributed to P Jones.

At least 271 records · Page 15Linked to original sources

Theta class glutathione S-transferase GSTT1 genotypes and susceptibility to cervical neoplasia: interactions with GSTM1, CYP2D6 and smoking.

The factors that determine progression of cervical intra-epithelial neoplasia (CIN) to squamous cell carcinoma (SCC) are unknown. Cigarette smoking is a risk factor, suggesting polymorphism at loci that encode carcinogen-metabolizing enzymes such as glutathione S-transferase (GSTT1, GSTM1) and cytochrome P450 (CYP2D6) may determine susceptibility to these cancers. We have studied the frequency of the null genotype at the theta class GSTT1 locus in women with low-grade CIN, high-grade CIN and SCC. The control group comprised women with normal cervical pathology suffering menorrhagia. We found the frequency of GSTT1 null in the control and case groups was not significantly different, though frequency distributions of combinations of the genotype with smoking in mutually exclusive groups in the high-grade CIN group and the other case groups were significantly different. Interactive effects of GSTT1 null with the GSTM1 null and CYP2D6 EM genotypes, and cigarette smoking were also studied by comparing the multinomial frequency distributions of these factors over mutually exclusive categories. These showed no significant differences between the controls and SCC or low-grade CIN. Frequency distributions in high-grade CIN, however, were significantly different to the controls, and both SCC and low-grade CIN; frequency distributions of GSTT1 null with smoking and CYP2D6 EM, individually and in combination, were significantly different. However, inspection of our data does not indicate that GSTT1 null is a major factor mediating risk. Thus, comparison of chi 2 values for the differences between frequency distributions in high-grade CIN and other groups shows that values for combinations of GSTT1 null with other factors are lower than those for equivalent combinations with smoking and CYP2D6 EM. Interestingly, the combination GSTT1 null/GSTM1 null did not appear to influence susceptibility to CIN or SCC.

Adult↗

The self-concept of young people with spina bifida: a population-based study.

Seventy-nine young people with spina bifida were given a psychological, medical, carer and occupational therapy assessment. 79 matched able-bodied young people received the psychosocial interview. The disabled group felt themselves to be less competent in academic, athletic and social aspects of self-concept, less supported by classmates, equally supported by parents and friends and more supported by teachers than the able-bodied group. Disabled subjects did not discount the importance of any area of personal-social functioning, and experienced greater discrepancies between competence and importance in most academic, athletic, social and physical appearance aspects of self-concept. Disabled girls assigned very high importance to physical appearance. Physical appearance was more strongly associated with general self-esteem than any other area of self-concept.

Adolescent↗

Home infusion therapies for obstetric patients.

This article focuses on current indications for home intravenous therapy for the high-risk obstetric patient. Therapeutic indications and clinical care for obstetric patients in need of hydration/total parenteral nutrition, heparin infusion, terbutaline pump, and antibiotic therapies are presented.

Community Health Nursing↗

Total lymphoid irradiation in multiple sclerosis.

Following a report of the efficacy of total lymphoid irradiation (TLI) in the treatment of chronic progressive multiple sclerosis a further randomised double-blind placebo-controlled study was undertaken with the intention of entering 56 patients. In the event it was possible to recruit only 27 patients in a 2.5 year period. Three patients received active treatment openly and 24 were randomised to either active (14) or sham (10) treatment. Treatment was 1980 cGy to the lymphoid system and spleen or sham treatment after full simulation. The primary outcome measure was a comparison of the mean rates of change between treatment groups on the expanded Kurtzke disability scale (EDSS) over the two year follow up period. Patients were also assessed on other clinical outcome measures, psychometry, and serial MRI of the brain. Active treatment resulted in a profound and prolonged fall in T lymphocytes especially those with the CD4 marker and a reversal in CD4:CD8 ratio. No significant benefit was demonstrated on the rate of clinical disease progression (EDSS). A small but significant benefit was found on a score of bladder function. No significant benefit was demonstrated on other clinical or psychometric indices or on subjective visual analogue scales. There was a small but significant difference in the rate of accumulation of lesions on brain MRI favouring the treatment group. The treated group had a higher incidence of clinically relevant side effects, notably amenorrhoea and infections: three deaths (one in the TLI group, two in the sham treated group) occurred. A post hoc calculation indicates that the study had a possible 35% risk of a false negative result using the principal outcome measure. The study fails to confirm the previously reported clinical benefit of TLI although there may be a minor benefit on disease progression as indicated by MRI lesion counts. It is concluded that TLI cannot be recommended for the routine treatment of chronic progressive multiple sclerosis but the beneficial effect on MRI lesions, though modest, suggests that further research into immune modulation of this condition may be worthwhile.

Adult↗

Prevalence of delusional misidentification syndromes.

The prevalence of delusional misidentification syndromes (DMS) in a consecutive sample of 195 inpatient admissions with functional psychosis was found to be 4.1%. It is argued that DMS symptoms are more common than previously supposed.

Adult↗

Low birth weight and schizophrenia.

BACKGROUND: Low birth weight has been postulated to be a risk factor for schizophrenia. METHOD: Obstetric history, premorbid adjustment, and cognitive function during admission were assessed in 167 patients with DSM-III schizophrenia or affective psychosis. RESULTS: A birth weight of less than 2500 g was significantly more common in patients with schizophrenia than in those with affective psychosis. Schizophrenic patients as a group had significantly lower mean birth weight, a finding which was particularly marked after controlling for sociodemographic confounders. In schizophrenic men, lower birth weight was highly significantly correlated with poorer premorbid social and cognitive ability, and with impairment of adult cognitive function. CONCLUSIONS: Neurodevelopmental impairment may cause poor foetal growth, and schizophrenia in adult life.

Adolescent↗

Age at onset, sex, and familial psychiatric morbidity in schizophrenia. Camberwell Collaborative Psychosis Study.

BACKGROUND: Although a genetic component in schizophrenia is well established, it is likely that the contribution of genetic factors is not constant for all cases. Several recent studies have found that the relatives of female or early onset schizophrenic patients have an increased risk of schizophrenia, compared to relatives of male or late onset cases. These hypotheses are tested in the current study. METHOD: A family study design was employed; the probands were 195 patients with functional psychosis admitted to three south London hospitals, diagnosed using Research Diagnostic Criteria (RDC), and assessed using the Present State Examination (PSE). Information on their relatives was obtained by personal interview of the mother of the proband, and from medical records. Psychiatric diagnoses were made using Family History-Research Diagnostic Criteria (FH-RDC), blind to proband information. RESULTS: There was a tendency for homotypia in the form of psychosis within families. The lifetime risk of schizophrenia in the first degree relatives of schizophrenic probands, and the risk of bipolar disorder in the first degree relatives of bipolar probands, were 5-10 times higher than reported population risks. Relatives of female and early onset (< 22 years) schizophrenic probands had higher risk of schizophrenia than relatives of male and late onset schizophrenic probands. However, this effect was compensated in part by an excess of non-schizophrenic psychoses in the relatives of male probands. CONCLUSIONS: These results suggest a high familial, possibly genetic, loading in female and early onset schizophrenia, but do not resolve the question of heterogeneity within schizophrenia.

Adult↗

A case study in APR-DRGs: the Greater Southeast Community Hospital experience.

The need for accurate, valid, and reliable severity data has taken on increasing importance over the last several years. The impact of managed care has been particularly significant, with many conditions once treated on an inpatient basis now being managed in the outpatient setting or admitted to the hospital only after the condition has progressed to a more advanced stage. The results has been an increasingly sicker inpatient population. Both hospitals and managed care organizations need data that will measure the impact of case mix complexity and severity on outcomes. This case study reviews one health care system's experience in finding a severity system that would have the acceptance of its medical staff. The study also reviews the analytic methodology by which severity-adjusted data are used to improve utilization and quality.

Cost of Illness↗

A joint problem drinking clinic: the King's College and Maudsley hospitals initiative.

We describe the establishment of a joint alcohol misuse clinic, staffed by both a psychiatrist and a physician, in a London Teaching Hospital providing general as well as specialist medical services. The demographic and medicopsychiatric problems of the first 100 referrals (60% attendance rate) are described. The clinic provides an assessment and re-education role for most patients referred with alcohol misuse problems: the need for specialist alcohol treatment facilities, especially for in-patients, remains essential. In addition, the clinic provides a valuable training and research resource.

Adult↗

Ultrasound localization of screen detected impalpable breast tumours.

Accurate localization of a tumour is imperative before excision biopsy for impalpable breast lesions seen on screening mammography. Ultrasound localization has the advantages of being simple, quick and noninvasive. In a 3-year period from September 1989, 185 women have required localization of a breast tumour prior to biopsy, 159 were performed using a wire localization technique and 26 (14%) were performed using ultrasound alone. Twenty-two out of the 26 were malignant lesions. The mean maximum diameter of tumour diagnosed by ultrasound compared to histological sample was 10.6 mm (8.5-12.7*) to 11.1 mm (8.9-13.3*) with a correlation of r = 0.87. In the malignant cases the mean maximum diameter of tissue excised was 63.0 mm (57.2-65.9*). Complete excision was obtained in 21 out of the 22 patients with malignant disease by one operation. Ultrasound alone has been used successfully as a means of preoperative localization in selected cases prior to excision biopsy of a breast tumour.

Breast Neoplasms↗

Community-based parentcraft.

Some parents feel unable to ask advice from professionals, or that the advice offered is not appropriate to their own priorities. Lilian Chapman and Peter Jones describe a multi-agency, community-based approach to parentcraft teaching.

Community Health Services↗

EPR and ENDOR detection of compound I from Micrococcus lysodeikticus catalase.

We present the first EPR and ENDOR examination of a catalase compound I (Cat I), the one formed by peracetic acid treatment of Micrococcus lysodeikticus catalase. The Cat I rapid-passage EPR signal (g perpendicular eff = 3.32; g parallel eff approximately 2) appears quite different from those reported previously for the compounds I from horseradish peroxidase (HRP I) and chloroperoxidase. Nonetheless, all three signals can be explained by the same model for exchange coupling between an S = 1 oxoferryl [Fe = O]2+ moiety and a porphyrin pi-cation radical (S' = 1/2) (Schulz, C. E., et al. (1979) FEBS Lett. 103, 102-105). The signal for Cat I is unlike those for the two peroxidases in that it reflects a ferromagnetic rather than antiferromagnetic exchange. Preliminary 1H ENDOR spectra for Cat I appear to differ from the proton (1H) ENDOR spectra of HRP I; the latter, along with the 14N ENDOR spectra, indicate that the porphyrin radical in HRP I exhibits a predominantly A2u-like state having large spin densities on porphyrin N and C(beta). The proton ENDOR spectrum of Cat I is insensitive to H/D exchange, which indicates that the [Fe = O]2+ moiety is not protonated. Consideration of the EPR results for a series of compounds I suggests that the sign and magnitude of the exchange parameter (J) is correlated with the nature of the proximal axial ligand.

Catalase↗

Interaction of myeloperoxidase with peroxynitrite. A comparison with lactoperoxidase, horseradish peroxidase and catalase.

Polymorphonuclear neutrophils generate both nitric oxide and superoxide and these molecules can combine to form peroxynitrite. Neutrophils also contain myeloperoxidase which reacts with peroxynitrous acid (HOONO). On mixing myeloperoxidase with HOONO compound II was formed. Compound I could not be detected as an intermediate. The apparent second-order rate constant of formation of compound II was strongly pH-dependent (2.5 x 10(5) M-1 x s-1 at pH 8.9 and 6.2 x 10(6) M-1 x s-1 at pH 7.2). The pKa of this effect is 6.9 and it was concluded that the enzyme reacts with the protonated form of the peroxide, that is peroxynitrous acid, with a pH-independent second-order rate constant of 2.0 x 10(7) M-1 x s-1 at 12 degrees C. The interaction of HOONO with lactoperoxidase was studied for comparison. As was observed for myeloperoxidase, compound I could not be detected as an intermediate. The apparent second-order rate constant of compound II formation is pH-dependent and is 3.3 x 10(5) M-1 x s-1 at pH 7.4 and 8.4 x 10(4) M-1 x s-1 at pH 9.0. In contrast, horseradish peroxidase reacts with HOONO to form compound I, which is subsequently followed by the formation of compound II. The second-order rate constant for the formation of compound I is 3.2 x 10(6) M-1 x s-1 and is pH-dependent, the pKa for this effect is 6.8. Catalase (up to 3 microM) does not affect the rate of decomposition of peroxynitrite and no compound I formation is observed. Since nitrite may be present in the peroxynitrite preparation and to discriminate between the reaction of the enzyme with nitrite or peroxynitrite, the effect of nitrite on myeloperoxidase was studied. The dissociation constant for the myeloperoxidase-nitrite complex is pH-dependent and has values of 580 microM at pH 6.0 and 55 mM at pH 8.5.

Catalase↗

Does prediction of outcome alter patient management?

A patient's prognosis is a key factor for the clinicians involved in management. We set out to determine if provision of computer-based predictions of outcome after severe head injury resulted in measurable changes in patient management. In particular, we wondered whether introduction of the predictive system would alter the relation between severity of injury and "intensity" of management. 1025 patients admitted to four British neurosurgical units between 1986 and 1989 following a severe head injury, and who were either in coma for 6 h or had an operation for acute intracranial haematoma, were studied. Specified aspects of intensive management were recorded and all patients were followed up after six months. The study had three phases: a baseline period of at least one year before the introduction of computer-based outcome prediction, one year when predictions were provided at specified times, and a final six months when prediction was withdrawn. While predictions were being provided, there was an increase in the use of specified aspects of intensive care in patients predicted to have a good outcome, but a 39% reduction in the use of these same aspects of intensive care in patients predicted to have the worst outcome. There was no evidence that the provision of predictions affected overall outcome, length of stay, or the recording of explicit decisions to limit treatment. We have demonstrated that the introduction of a routine prediction service can alter patient management.

Adult↗