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R Parsons

Publications and source records attributed to R Parsons.

At least 37 records · Page 2Linked to original sources
PubMed1999

Suicide within 12 months of contact with mental health services: national clinical survey.

OBJECTIVE: To describe the clinical circumstances in which psychiatric patients commit suicide. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: A two year sample of people who had committed suicide, in particular those who had been in contact with mental health services in the 12 months before death. MAIN OUTCOME MEASURES: Proportion of suicides in people who had had recent contact with mental health services; proportion of suicides in inpatients; proportion of people committing suicide and timing of suicide within three months of hospital discharge; proportion receiving high priority under the care programme approach; proportion who were recently non-compliant and not attending. RESULTS: 10 040 suicides were notified to the study between April 1996 and March 1998, of whom 2370 (24%; 95% confidence interval 23% to 24%) had had contact with mental health services in the year before death. Data were obtained on 2177, a response rate of 92%. In general these subjects had broad social and clinical needs. Alcohol and drug misuse were common. 358 (16%; 15% to 18%) were psychiatric inpatients at the time of death, 21% (17% to 25%) of whom were under special observation. Difficulties in observing patients because of ward design and nursing shortages were both reported in around a quarter of inpatient suicides. 519 (24%; 22% to 26%) suicides occurred within three months of hospital discharge, the highest number occurring in the first week after discharge. 914 (43%; 40% to 44%) were in the highest priority category for community care. 488 (26% excluding people whose compliance was unknown; 24% to 28%) were non-compliant with drug treatment while 486 (28%; 26% to 30%) community patients had lost contact with services. Most people who committed suicide were thought to have been at no or low immediate risk at the final service contact. Mental health teams believed suicide could have been prevented in 423 (22%; 20% to 24%) cases. CONCLUSIONS: Several suicide prevention measures in mental health services are implied by these findings, including measures to improve compliance and prevent loss of contact with services. Inpatient facilities should remove structural difficulties in observing patients and fixtures that can be used in hanging. Prevention of suicide after discharge may require earlier follow up in the community. Better suicide prevention in psychiatric patients is likely to need measures to improve the safety of mental health services as a whole, rather than specific measures for people known to be at high risk.

Adolescent↗
PubMed1999

Mental disorder and clinical care in people convicted of homicide: national clinical survey.

OBJECTIVES: To estimate the rate of mental disorder in those convicted of homicide and to examine the social and clinical characteristics of those with a history of contact with psychiatric services. DESIGN: National clinical survey. SETTING: England and Wales. SUBJECTS: Eighteen month sample of people convicted of homicide. MAIN OUTCOME MEASURES: Offence related and clinical information collected from psychiatric court reports on people convicted of homicide. Detailed clinical data collected on those with a history of contact with psychiatric services. RESULTS: 718 homicides were reported to the inquiry between April 1996 and November 1997. Of the 500 cases for whom psychiatric reports were retrieved, 220 (44%; 95% confidence interval 40% to 48%) had a lifetime history of mental disorder, while 71 (14%; 11% to 17%) had symptoms of mental illness at the time of the homicide. Of the total sample, 102 (14%; 12% to 17%) were confirmed to have been in contact with mental health services at some time, 58 (8%; 6% to 10%) in the year before the homicide. The commonest diagnosis was personality disorder (20 cases, 22%; 13% to 30%). Alcohol and drug misuse were also common. Only 15 subjects (18%; 10% to 26%) were receiving intensive community care, and 60 (63%; 53% to 73%) were out of contact at the time of the homicide. CONCLUSIONS: There are substantial rates of mental disorder in people convicted of homicide. Most do not have severe mental illness or a history of contact with mental health services. Inquiry findings suggest that preventing loss of contact with services and improving the clinical management of patients with both mental illness and substance misuse may reduce risk, but clinical trials are needed to examine the effectiveness of such interventions.

Adult↗
PubMed1999

Mutation of Pten/Mmac1 in mice causes neoplasia in multiple organ systems.

Pten/Mmac1+/- heterozygous mice exhibited neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus. Loss of the wild-type allele was detected in neoplasms of the thymus and liver. Surprisingly, tumors of the gastrointestinal epithelium developed in association with gut lymphoid tissue. Tumors of the endometrium, thyroid, prostate, and liver were not associated with lymphoid tissue and appeared to be highly mitotic. In addition, these mice have nonneoplastic hyperplasia of lymph nodes that was caused by an inherited defect in apoptosis detected in B cells and macrophages. Examination of peripheral lymphoid tissue including lymphoid aggregates associated with polyps revealed that the normal organization of B and T cells was disrupted in heterozygous animals. Taken together, these data suggest that PTEN is a regulator of apoptosis and proliferation that behaves as a "landscaper" tumor suppressor in the gut and a "gatekeeper" tumor suppressor in other organs.

Animals↗
PubMed1999

Nitroxide radicals protect DNA from damage when illuminated in vitro in the presence of dibenzoylmethane and a common sunscreen ingredient.

Indolinonic nitroxide radicals efficiently scavenge oxygen- and carbon-centered radicals. They protect lipid and protein systems against oxidative stress, but little is known about their capacity to protect DNA against radical-mediated damage. We compare indolinonic nitroxides and the piperidines TEMPO and TEMPOL for their ability to inhibit strand breaks inflicted on DNA when it is illuminated in vitro in the presence of dibenzoylmethane (DBM) and a relative, Parsol 1789, used as a UVA-absorbing sunscreen. We used spin-trapping EPR to examine the formation of radicals and plasmid nicking assays to evaluate DNA strand breakage. The results have a two-fold interest. First, they show that all the nitroxides tested efficiently prevent DNA damage in a dose-dependent fashion. Vitamin E had no effect under the conditions used. Second, they show that carbon-centered radicals are produced on illumination of DBM and its relative and that their formation is probably responsible for the direct strand breaks found when naked DNA is illuminated in vitro in their presence. Additional work on the ability of sunscreens to enter human cells and their response to the light that penetrates sunscreen-protected skin would be necessary before any conclusion could be drawn as to whether the results reported here are relevant to human use of sunscreens.

Antioxidants↗
PubMed1999

A 42-year-old woman with liver masses and long-term use of oral contraceptives.

A 42-year-old woman with a history of 25-year oral contraceptive use presented with abdominal pain and was found to have two exophytic liver masses. She had no known prior liver diseases, and her serum liver enzyme and AFP levels were normal. One of the masses was a hepatocellular adenoma and the other was a pigmented hepatocellular carcinoma. The exophytic appearance of both lesions was unusual. This case, once more, demonstrated the risk of hepatocellular adenomas to undergo malignant transformation. The reason for the brown pigment deposition in the hepatocellular carcinoma was not clear. The prognosis was expected to be excellent following complete surgical resection.

Adenoma, Liver Cell↗
PubMed1999

Analysis of PTEN mutations and deletions in B-cell non-Hodgkin's lymphomas.

The PTEN gene is involved in 10q23 deletions in several types of cancer, including glioma, melanoma, endometrial and prostate carcinomas. The PTEN gene product is a dual-specificity phosphatase with putative tumor suppressor function. Deletions and rearrangements of 10q22-25 have been reported in approximately 5%-10% of non-Hodgkin's lymphomas (NHLs), raising the possibility of PTEN involvement in these tumors. In order to address this question, we analyzed a panel of NHLs (n = 74) representative of the main histologic subtypes for mutations and homozygous deletions of PTEN. We report somatic coding/splice site mutations in 20% (2 of 10) of Burkitt's lymphoma cell lines and in 3% (2 of 64) of primary NHL cases analyzed. No homozygous deletions were found in these tumors. Interestingly, this study showed that cytogenetically characterized NHL cases (n = 6) with 10q22-q25 abnormalities displayed neither biallelic deletions nor mutations of PTEN. These results suggest that a tumor suppressor gene distinct from PTEN may be involved in 10q deletions in this subgroup of NHL cases.

Base Sequence↗
PubMed1998

The PTEN/MMAC1 tumor suppressor induces cell death that is rescued by the AKT/protein kinase B oncogene.

PTEN/MMAC1 is a tumor suppressor gene that is mutated in a variety of cancers. PTEN encodes a phosphatase that recognizes phosphoprotein substrates and the phospholipid, phosphatidylinositol-3,4,5-triphosphate. PTEN inhibited cell growth and/or colony formation in all of the epithelial lines tested with one exception. The decrease in cellular proliferation was associated with an induction of apoptosis and an inhibition of signaling through the phosphatidylinositol 3'-kinase pathway. Akt/protein kinase B, a gene whose antiapoptotic function is regulated by phosphatidylinositol-3,4,5-triphosphate, was able to rescue cells from PTEN-dependent death. PTEN, therefore, appears to suppress tumor growth by regulating phosphatidylinositol 3'-kinase signaling.

Apoptosis↗
PubMed1998

Mutational analysis of the PTEN gene in head and neck squamous cell carcinoma.

Loss of heterozygosity (LOH) at chromosome band 10q23 occurs frequently in a wide variety of human tumors. A recently identified candidate tumor suppressor gene, PTEN located on 10q23, is mutated in multiple advanced cancers. To explore whether PTEN is associated with human squamous cell carcinoma of the head and neck (SCCHN), DNAs from both normal muscle and tumor tissue in 19 SCCHN were used for detecting LOH at chromosome 10q23 and mutational analysis of PTEN by direct polymerase chain reaction (PCR)-DNA sequencing. LOH at 10q23 was identified in 6/15 SCCHN. Mutation of PTEN was identified in 3/19 SCCHN. Of these 3 patients, 2 had stage IV disease; the third patient, with recurrent, metastatic and stage III disease, showed a 36 bp germline heterozygous deletion within intron 7. Furthermore, a missense mutation at codon 501 (TCT --> TTT: Ser --> Phe) in exon 8 was also found in tumor from the same patient. Our results suggest that PTEN may play a role in the genesis of some SCCHNs.

Amino Acid Substitution↗
PubMed1998

Allelic loss of chromosome 10q23 is associated with tumor progression in breast carcinomas.

To determine the status of chromosome 10q23 in primary breast carcinomas, in situ and invasive carcinomas were analysed for allelic loss using microsatellite markers spanning the 10q23 region. No LOH was seen in pure intraductal carcinomas (0/20 cases). On the other hand, LOH was observed in 40% (17/42) of invasive carcinomas (P = 0.0005). Interestingly, in situ lesions found in invasive tumors displayed LOH. Allelic loss was also significantly associated with loss of the estrogen receptor (P = 0.011). Thus, loss of the 10q23 is strongly associated with tumor progression.

Breast Neoplasms↗
PubMed1998

Point mutation and homozygous deletion of PTEN/MMAC1 in primary bladder cancers.

A new tumor suppressor gene PTEN/MMAC1 was recently isolated at chromosome 10q23 and found to be inactivated by point mutation or homozygous deletion in glioma, prostate and breast cancer. PTEN/MMAC1 was also identified as the gene predisposing to Cowden disease, an autosomal dominant cancer predisposition syndrome associated with an increased risk of breast, skin and thyroid tumors and occasional cases of other cancers including bladder and renal cell carcinoma. We screened 345 urinary tract cancers by microsatellite analysis and found chromosome 10q to be deleted in 65 of 285 (23%) bladder and 15 of 60 (25%) renal cell cancers. We then screened the entire PTEN/MMAC1 coding region for mutation in 25 bladder and 15 renal cell primary tumors with deletion of chromosome 10q. Two somatic point mutations, a frameshift and a splicing variant, were found in the panel of bladder tumors while no mutation was observed in the renal cell carcinomas. To screen for homozygous deletion, we isolated two polymorphic microsatellite repeats from genomic BAC clones containing the PTEN/MMAC1 gene. Using these new informative markers, we identified apparent retention at the gene locus indicative of homozygous deletion of PTEN/MMAC1 in four of 65 bladder and 0 of 15 renal cell tumors with LOH through chromosome 10q. Identification of the second inactivation event in six bladder tumors with LOH of 10q implies that the PTEN/MMAC1 gene is occasionally involved in bladder tumorigenesis. However, the low frequency of biallelic inactivation suggests that either PTEN/MMAC1 is inactivated by other mechanisms or it is not the only target of chromosome 10q deletion in primary bladder and renal cell cancer.

Base Sequence↗
PubMed1998

Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN.

The tumor suppressor PTEN is a phosphatase with sequence similarity to the cytoskeletal protein tensin. Here the cellular roles of PTEN were investigated. Overexpression of PTEN inhibited cell migration, whereas antisense PTEN enhanced migration. Integrin-mediated cell spreading and the formation of focal adhesions were down-regulated by wild-type PTEN but not by PTEN with an inactive phosphatase domain. PTEN interacted with the focal adhesion kinase FAK and reduced its tyrosine phosphorylation. Overexpression of FAK partially antagonized the effects of PTEN. Thus, PTEN phosphatase may function as a tumor suppressor by negatively regulating cell interactions with the extracellular matrix.

3T3 Cells↗
PubMed1998

PTEN mutations in gliomas and glioneuronal tumors.

Cytogenetic and loss of heterozygosity studies have suggested the presence of at least one tumor suppressor gene on chromosome 10 involved in the formation of high grade gliomas. Recently, the PTEN gene, also termed MMAC1 or TEP1, on chromosomal band 10q23 has been identified. Initial studies revealed mutations of PTEN in limited series of glioma cell lines and glioblastomas. In order to systematically evaluate the involvement of PTEN in gliomas, we have analysed the entire PTEN coding sequence by SSCP and direct sequencing in a series of 331 gliomas and glioneuronal tumors. PTEN mutations were detected in 20/142 glioblastomas, 1/7 giant cell glioblastomas, 1/2 gliosarcomas, 1/30 pilocytic astrocytomas and 2/22 oligodendrogliomas. No PTEN mutations were detected in 52 astrocytomas, 37 oligoastrocytomas, three subependymal giant cell astrocytomas, four pleomorphic xanthoastrocytomas, 15 ependymomas, 16 gangliogliomas and one dysembryoplastic neuroepithelial tumor. In addition, all tumors were examined for the presence of homozygous deletions of the PTEN gene; these were detected in 7 glioblastomas that did not have PTEN mutations. Therefore, PTEN mutations occur in approximately 20% of glioblastomas but are rare in lower grade gliomas. These findings confirm that PTEN is one of the chromosome 10 tumor suppressor genes involved in the development of glioblastomas.

Female↗
PubMed1998

Varying strategies for endovascular repair of abdominal an iliac artery aneurysms.

Endovascular grafting for abdominal aortic aneurysm has evolved over the past 7 years from Parodi's simple tubular aortic endografts with uniform attachment systems to more complex "modular" designs that begin to provide some flexibility of graft construction at the time of implantation. The future of these systems likely resides in a series of devices that contain sufficient flexibility to permit the operator the option for in situ customization of graft dimensions in accordance with realtime operative/fluoroscopic findings.

Aortic Aneurysm, Abdominal↗
PubMed1998

Analysis of the PTEN gene in human meningiomas.

Previous observations demonstrated that the neurofibromatosis type 2 gene (NF2) plays an important role in the pathogenesis of the transitional, fibroblastic and malignant variants of human meningiomas. No specific genes have been associated with the pathogenesis of meningothelial meningiomas and with the progression to anaplastic meningiomas. However, allelic losses on chromosomal arms 1p, 10q and 14q have been implicated in the process of malignant progression. Recently, PTEN (phosphatase and tensin homolog deleted on chromosome ten) also termed MMAC1 (mutated in multiple advanced cancers 1) or TEP1 (TGF--regulated and epithelial cell-enriched phosphatase), emerged as a candidate gene on chromosome 10q23.3. Initial studies revealed mutations of PTEN in limited series of glioblastomas, breast, kidney and prostate carcinomas mainly as cell lines. In order to evaluate the involvement of PTEN in the development of meningiomas, we have analysed the entire coding sequence of the gene in a series of 55 meningiomas (WHO grade I). 10 atypical meningiomas (WHO grade II) and 10 anaplastic meningiomas (WHO grade III). No PTEN mutations were seen in the WHO grade I meningiomas. However, one of the anaplastic meningiomas carried a somatic mutation. In addition, all tumours were examined for the presence of homozygous deletions of PTEN but these were not detected in any of the meningiomas. Our data suggest that mutations in PTEN are not involved in the formation of low grade meningiomas, but may contribute to malignant progression in a fraction of anaplastic meningiomas.

Chromosomes, Human, Pair 10↗
PubMed1998

Phosphatases and tumorigenesis.

Phosphatases are regulatory enzymes that antagonize the action of kinases within the cell. An understanding of the contribution of kinases to cancer has emerged during the past two decades; however, our understanding of phosphatases in cancer has lagged behind. Currently, three phosphatases have been implicated in the etiology of tumors: protein phosphatase 2A, CDC25A/B, and PTEN (or MMAC1). Protein phosphatase 2A and PTEN behave as tumor suppressors, whereas CDC25A and -B act as oncogenes.

Animals↗
PubMed1998

Functional recovery and timing of hospital discharge after primary total hip arthroplasty.

BACKGROUND: Early discharge programmes in hospitals are encouraged to increase financial efficiency and bed availability, but standards of clinical care must not be compromised. Criteria for safe hospital discharge must be established and objective data are needed to assess how rapidly patients can achieve these discharge criteria. METHODS: A prospective study was performed on 65 patients (mean age = 71 years) scheduled for primary total hip arthroplasty (THA). The Modified Barthel Index (MBI) was measured pre-operatively and postoperatively at set intervals to asses recovery of function after THA. A score of 90 out of a possible 100 was used as a discharge criterion and indicated that the patient was functionally independent for safe hospital discharge. In addition, a combined score for thigh flexion and extension isokinetic peak strength was recorded for each patient before and after surgery. The number and nature of comorbidities and complications were also recorded. RESULTS: The length of hospital stay in this sample varied from 5 to 39 days. The MBI scores increased rapidly between days 3 and 5, then began to plateau from day 8 onwards. Based on the MBI, 58% of patients were fit for discharge at or before day 8. The remainder were fit for discharge from day 10 onwards (mean = 14.2 days). The latter group who required an extended hospital stay were older (P = 0.003), had more identified comorbidities (P = 0.01) and were weaker in their hip musculature prior to surgery (P = 0.001), compared to those who were discharged by day 8. A logistic regression analysis indicated that the pre-operative MBI score and hip strength score were strong predictors of timing for hospital discharge. CONCLUSIONS: A clinical pathway with functional milestones laid out over 8 days would be an appropriate criterion for the discharge of the majority of patients. However, approximately 40% of the patients presented in this study required a longer hospital stay before the criteria for safe discharge could be achieved. These patients can be identified pre-operatively by screening their MBI and composite hip strength scores.

Aged↗