Search PubMed⌕ Search

Biomedical subjects

P Watson

Publications and source records attributed to P Watson.

At least 91 records · Page 5Linked to original sources
PubMed1999

Male breast cancer in the hereditary nonpolyposis colorectal cancer syndrome.

A male member of a large HNPCC kindred, affected by primary malignancies of the breast and colon, was identified. This individual was found to harbor a germline mutation of the MLH1 mismatch repair gene previously shown to segregate with disease in this kindred. The breast tumor exhibited somatic reduction to homozygosity for the MLH1 mutation, and microsatellite instability was evident in the breast tumor. We conclude that hereditary male breast cancer can occur as an integral tumor in the HNPCC syndrome.

Aged↗
PubMed1999

Five- to six-year results of a prospective clinical trial using the ENDOPORE dental implant and a mandibular overdenture.

This report is an update on a group of 46 clinical trial patients who each received 3 free-standing Endopore dental implants placed using a 2-stage surgical approach in the anterior mandible. After an initial healing interval of 10 weeks, the implants were used in each case to retain an over-denture, and at the time of the report, all patients had passed 5 years of continuous function. The 5-year cumulative "survival" rate based on a life table analysis was 93.4% and this remained unchanged after 6 years. The 5-year "success rate" was 83.3% when assessed qualitatively with the published criteria of others using a four-field table analysis categorizing every implant in the study as one of "Grade 1 Success", "survival", "unaccounted for" or "failure". Modified periodontal parameters verified continued peri-implant soft tissue health. No implant still in function had more than 1.8 mm cumulative bone loss during the first 5 years of function. These results provide clear evidence that Endopore implants despite their short lengths function at least as well as other dental implant designs used in much longer lengths.

Alveolar Bone Loss↗
PubMed1999

An RGS protein regulates the pheromone response in the fission yeast Schizosaccharomyces pombe.

The rate and extent of a cell's response to an extracellular stimulus is influenced by regulators that act on the intracellular signalling machinery. Although not directly involved in propagating the intracellular signal, regulators control the activity of the proteins that transmit the signals. To understand this aspect of cell signalling, we have studied the pheromone response pathway in the fission yeast Schizosaccharomyces pombe, a relatively simple signalling system in a genetically tractable organism. We demonstrate this approach by investigating the role of Rgs1, a member of the Regulator of G protein Signalling (RGS) family of proteins. The rgs1 gene was identified through the Sz. pombe genome sequencing project (accession number Q09777) and recognized as having similarity to RGS proteins [Tesmer et al. (1997) Cell 89: 251-261], but this is the first report concerning the activity of the protein. Strains lacking rgs1 (Deltargs1) are hypersensitive to pheromone stimulation and unable to conjugate with a mating partner. Inhibition of mating occurs at a relative late stage in the process as Deltargs1 strains exhibit pheromone-dependent transcription and form shmoos. Expression of SST2 (an RGS protein that regulates pheromone signalling in the budding yeast Saccharomyces cerevisiae) overcomes the hypersensitivity of the Deltargs1 strains but fails to rescue their mating defect.

Amino Acid Sequence↗
PubMed1999

Symptom priority ranking in the care of gastroesophageal reflux: a review of 1,850 cases.

BACKGROUND: Clinical history remains an important part of the medical evaluation of patients with gastroesophageal reflux disease (GERD). Heartburn, regurgitation, and dysphagia are considered typical symptoms of GERD. Priority rankings of these symptoms can be determined with a standardized questionnaire. OBJECTIVE: To determine whether symptom priority ranking and symptom severity grading can provide useful information in the evaluation of patients with GERD. METHODS: From 1,850 patients that were analyzed retrospectively, patients with dysphagia unrelated to GERD were excluded. A standardized questionnaire was applied before each patient underwent any esophageal diagnostic study. Priority of symptoms was determined to be primary, secondary, tertiary, or none based on the patient response to the questionnaire. Presence of a stricture was determined either by endoscopy, esophagraphy, or both studies. Stationary esophageal manometry and 24-hour pH monitoring were performed on all patients. Through bivariate and multivariate analysis, the relationships among typical GERD symptoms, esophageal reflux-related stenosis, lower esophageal sphincter pressure, and composite score were established. RESULTS: High priority ranking of the symptom dysphagia is predictive of the presence of an esophageal stricture, but has a negative association with abnormal manometric and pH studies. In contrast, high priority ranking of the symptom heartburn and regurgitation are positively associated with abnormal manometric and pH results. CONCLUSIONS: Priority ranking can be a valuable adjunct to objective testing in the evaluation of GERD. In certain clinical situations it can obviate the need for 24-hour pH monitoring.

Adult↗
PubMed1999

Neuropsychological assessment of older adults with Down's syndrome: an epidemiological study using the Cambridge Cognitive Examination (CAMCOG).

OBJECTIVES: The Cambridge Cognitive Examination (CAMCOG) was designed for the general elderly population to assess cognitive impairments characteristic of dementia. CAMCOG yields a total score as well as separate scores on seven subscales. In this study the suitability of the CAMCOG for older adults with Down's Syndrome (DS) at the age of risk for dementia was assessed. DESIGN: A near total population sample of people with DS aged 30 years and over (range 30-65 years) living in a single Health Authority catchment area was identified and assessed using the CAMCOG. The use of an unselected sample ensured that the value of this assessment instrument could be established across all levels of disability in those with DS. A lower age limit of 30 years was used, as from this age significant Alzheimer-like neuropathology is present and prevalence rates of Alzheimer's disease begin to increase. METHODS: The CAMCOG was administered in a familiar setting together with other neuropsychological tests. Gender and age differences and the characteristics of those at the floor of the test were investigated. RESULTS: Of the 77 people with DS aged 30 years or older, 74 agreed to take part. Scores on the CAMCOG were well distributed, with only eight participants (11%) scoring 0 on the test. This contrasted favourably with performance on the Mini-Mental State Examination where there was a narrower range of scores and a higher percentage scoring 0. There was a significant difference in cognitive performance between younger (30-44 years) and older (45+ years) participants on the total CAMCOG score and on six out of the seven CAMCOG subscales. CONCLUSIONS: The CAMCOG, with minor modifications, is a useful test to assess those areas of cognitive function known to decline with dementia. Apart from those with pre-existing severe learning disability, severe sensory impairments and/or already advanced dementia, people with DS were able to score above the floor of the test.

Adult↗
PubMed1999

Effects of transforming growth factor-beta1 on renal extracellular matrix components and their regulating proteins.

Transforming growth factor-beta1 (TGF-beta1) is widely regarded as a potent fibrogenic renal growth factor. In cell culture, TGF-beta1 has been shown to increase various extracellular matrix (ECM) proteins and tissue inhibitors of metalloproteinases (TIMP), while decreasing matrix metalloproteinases (MMP), providing the optimum environment for progressive ECM accumulation. This study, which uses the isolated perfused rat kidney (IPRK), describes for the first time in a whole kidney preparation the action of TGF-beta1 on factors associated with ECM processing. This model allows the study of the intact rat kidney with physiologic cell-cell interactions in the absence of confounding systemic influences. Left kidneys were removed from male Wistar rats by a nonischemic technique and perfused with a sterile, apyrogenic, endotoxin-free perfusate, based on the plasma volume expander Hemaccel (polygeline), at constant pressure in a recirculating IPRK system. Kidneys were perfused for 1 h either with (n = 3) or without (n = 3) recombinant human TGF-beta1 (20 ng/ml). The effects of perfusion were controlled by comparison with the nonperfused contralateral kidney (n = 6). TGF-beta1 was measured in the perfusate and urine, at the start and end of the experiment using an enzyme-linked immunosorbent assay to its biologically active form. After perfusion, sections of the kidneys were analyzed for changes in mRNA by Northern blotting. Significant increases in mRNA for fibronectin (7.5-fold, P < 0.01), heparan sulfate proteoglycan core protein (53-fold, P < 0.001), laminin beta1 (12-fold, P < 0.001), collagen alpha1(IV) (17-fold, P < 0.001), collagen alpha1(III) (fourfold, P < 0.001), and MMP9 (twofold, P < 0.05) were observed after perfusion with TGF-beta1. Measurement of TIMP1, TIMP2, TIMP3, MMP1, and MMP2 mRNA demonstrated no detectable change, whereas determination of mRNA for tissue transglutaminase, an enzyme capable of cross-linking many ECM components, showed an eightfold increase (P < 0.01). This study suggests that in the IPRK and in the absence of other exogenous growth factors, TGF-beta1 selectively increases the synthesis of ECM and tissue transglutaminase without changes that would result in the reduction of ECM degradation.

Animals↗
PubMed1999

The human orphan receptor PXR messenger RNA is expressed in both normal and neoplastic breast tissue.

The expression of PXR mRNA and a variant PXR mRNA, deleted in 111 nucleotides in the ligand-binding domain, was detected by reverse transcription-PCR amplification in both normal and neoplastic human breast tissues. The level of PXR mRNA did not differ between breast tumors and their adjacent matched normal breast tissues. However, the expression of PXR mRNA did vary among breast tumors. A statistically significant inverse relationship was found between the level of PXR mRNA expression and estrogen receptor (ER) status, as defined by ligand binding analysis. The level of PXR mRNA expression in ER+ tumors (median = 22.4, n = 15) was significantly lower (P = 0.04) than the level of PXR mRNA expression in ER-tumors (median = 46.7, n = 15). No relationship with progesterone receptor status was found. These data raise the possibility that PXR has a role in human breast tissues.

Alternative Splicing↗
PubMed1999

Coronary-subclavian steal associated with severe aortic stenosis treated with combined percutaneous stenting and minimally invasive aortic valve replacement.

We describe coronary-subclavian steal restricting flow to the left internal mammary artery (LIMA) associated with critical aortic stenosis treated with combined percutaneous transluminal stenting and minimally invasive aortic valve replacement (AVR). An 86-year-old patient had coronary artery bypass graft placement (CABG) seven years prior with the LIMA anastomosed to the left anterior descending coronary artery (LAD). At the time of CABG, the patient had mild aortic stenosis and normal left ventricular function. By the time of re-presentation with refractory angina and heart failure, the patient had developed critical aortic stenosis. Because repeat CABG with median sternotomy risked damaging the LIMA, pre-operative revascularization was planned to minimize the likelihood of peri-operative ischemia. Stenting of the subclavian artery was performed prior to minimally invasive AVR.

Aged↗
PubMed1999

CQI: hemodialysis vascular access flow monitoring.

One of the main ongoing challenges in nephrology is maintaining a good, well-functioning vascular access. Vascular access problems lead to complications such as access recirculation causing decreased adequacy of dialysis as shown by kinetic modelling and access clotting. Access flow measurement using ultrasound dilution technique is an accurate and better indicator of impending access stenosis than recirculation (urea method). The measurement is non-invasive, the procedure simple, and the monitor accessible at the bedside. The Adam Linton Dialysis Unit of the London Health Sciences Centre, Victoria Campus is currently monitoring access flows (Qa) as a continuous quality initiative using ultrasound dilution technique. Access recirculation (AR) is determined and Qa measurements are done bimonthly on all chronic in-centre and self-care dialysis patients with either arteriovenous fistula or Gore-tex grafts. Qa's of <550 ml/min or 20% decrease in flows are investigated by angiography and early intervention is instituted either by angioplasty or fistula repair. Our unit's goal is to be proactive in our investigation and in our nursing and medical interventions. From our experience, the problem with responding to poor clearances by checking for recirculation after the fact is that valuable time is lost for proactive intervention to preserve the access site and may in fact be too late. In four different patient situations we are able to show how our different interventions have improved Qa's and eliminated AR resulting in increased Kt/V. The intent of this article is to show that Qa measurement can be an ideal way to monitor hemodialysis vascular accesses over time. It provides a means to detect impending access dysfunction before the Qa has decreased enough to have induced AR and/or under-dialysis. By early intervention, optimum dialysis efficiency is achieved and the prescribed Kt/V [urea] is delivered.

Angiography↗
PubMed1998

Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC.

BACKGROUND: Small bowel carcinoma is uncommon. However, hereditary nonpolyposis colorectal carcinoma (HNPCC) patients are at increased risk of small bowel carcinoma. The purpose of this study was to characterize small bowel tumors in HNPCC patients. METHODS: A questionnaire was mailed to the members of International Collaborative Group on HNPCC (ICG-HNPCC) requesting clinicopathologic data in their registries on HNPCC patients with small bowel carcinoma. Survival was estimated utilizing the Kaplan-Meier method. RESULTS: Forty-two individuals from 40 HNPCC families developed 42 primary and 7 metachronous small bowel tumors. There were 46 adenocarcinomas and 3 carcinoid tumors. The median age at diagnosis of the index small bowel tumor was 49 years. Mismatch repair gene mutations were present in 15 of 42 patients (36%). There were nine hMLH1 and six hMSH2 mutations. The small bowel was the first site of carcinoma in 24 patients (57%). The median survival for the 42 patients was 47 months (range, 0-447 months). The overall 5- and 10-year survival rates were 44% and 33%, respectively. CONCLUSIONS: Small bowel tumors can be the presenting neoplasms in HNPCC patients. Similar to colorectal carcinoma in HNPCC, small bowel adenocarcinomas in HNPCC patients occur at an earlier age and appear to have a better prognosis than those occurring in the general population.

Adenocarcinoma↗
PubMed1998

Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members.

BACKGROUND: Patients with hereditary nonpolyposis colorectal carcinoma (HNPCC) reportedly have better prognoses than sporadic colorectal carcinoma (CRC) patients, but it has been unclear whether this could be due to differences in stage at diagnosis. The current study compared stage and survival in a retrospective cohort of HNPCC family members who developed CRC with the same factors in an unselected hospital series of patients with sporadic CRC. METHODS: This retrospective cohort study compared HNPCC cases (274 cases from 98 HNPCC families) with an unselected hospital series comprising 820 consecutive CRC cases. All patients were staged according to the TNM system of the American Joint Committee on Cancer and the International Union Against Cancer. Median follow-up among living patients was > 10 years and 8.5 years, respectively, for the two cohorts. Cox regression was used to compare survival in stage-stratified analyses of time from diagnosis to death. RESULTS: Compared with the unselected series, the HNPCC cases had lower stage disease (P < 0.001), and fewer had distant metastases at diagnosis (P < 0.001 in an analysis stratified by T classification). In stage-stratified survival analysis, the HNPCC cases had a significant overall survival advantage regardless of adjustment for their younger age. A conservative estimate of the hazard ratio (of HNPCC cases to the unselected series) was 0.67 (P < 0.0012). CONCLUSIONS: HNPCC patients had lower stage disease at diagnosis than the unselected CRC cases, mainly due to rarer distant metastases at diagnosis. They survived longer than unselected CRC patients with tumors of the same stage. The estimated death rate for the HNPCC cases, adjusted for stage and age differences, was at most two-thirds of the rate for the hospital series.

Adult↗
PubMed1998

Infection in surgical patients: effects on mortality, hospitalization, and postdischarge care.

In-hospital mortality, length of stay (LOS), and level of postdischarge care in infected and noninfected surgical patients were studied. An analysis was conducted of a database that included diagnostic, procedure, and drug data collected when surgical patients were discharged from the hospital. Hospitals consisted of 90 nongovernment, nonspecialty, teaching, and nonteaching acute care hospitals of more than 100 beds. Patients in the database included 288,906 patients of all ages hospitalized between July and September 1994. Patients selected of those who had undergone procedures likely to pose a moderate to high risk of infection. Of the 288,906 patients, 12,384 had undergone a moderate- to high-risk procedure; of these, 1,479 (11.9%) had had an infection during their hospitalization. Infection rates ranged from 1.9% to 25.4%, depending on the procedure. The in-hospital mortality rate in infected patients was 14.5%, versus 1.8% for noninfected patients. Similarly, LOS in infected patients (median, 14 days) was substantially greater than in noninfected patients (4 days). About 24% of infected patients required additional professional care after discharge, compared with 7% of noninfected patients. Infection occurs in a substantial portion of surgical patients and is associated with a higher death rate, longer hospitalization, and more intense postdischarge care.

Hospitalization↗
PubMed1998

Characterization of the Prk1 protein kinase from Schizosaccharomyces pombe.

We report the isolation and characterization of a protein kinase from the fission yeast Schizosaccharomyces pombe. The proposed Prk1 protein contains 352 amino acids and has significant homology to the Ume5p kinase (also known as Srb10p, Ssn3p and Are1p) of the budding yeast Saccharomyces cerevisiae, a cyclin-dependent kinase involved in regulating the transcription of a diverse set of genes. Disruption of the prk1 gene increases flocculation but does not appear to have any other significant effect on cell behaviour. This defect can be overcome by expressing the UME5 gene, indicating that Prk1 is the fission yeast homologue of Ume5p.

Amino Acid Sequence↗
PubMed1998

Colorectal and extracolonic cancer variations in MLH1/MSH2 hereditary nonpolyposis colorectal cancer kindreds and the general population.

PURPOSE: This clinical case review aimed to identify phenotypic variations in colorectal and extracolonic cancer expression between hereditary nonpolyposis colorectal cancer (HNPCC) families with MLH1 and MSH2 germline mutations and the general population. METHODS: Colorectal cancer onset and site distribution were compared among 67 members of MLH1 kindreds, 45 members of MSH2 kindreds, and 1,189 patients from the general population. Synchronous and metachronous cancer rates, tumor stage, extracolonic cancer incidence, and survival were also compared. RESULTS: Mean ages of colorectal cancer onset were 44, 46, and 69 years for MLH1, MSH2, and the general population, respectively (P < 0.001). More proximal and fewer distal colon cancers were noted in HNPCC than the general population (P < 0.001, P = 0.04). Site distribution showed disparity of rectal cancers (8 percent MLH1 vs. 28 percent MSH2; P = 0.01) based on genotypes. Overall, synchronous colorectal cancer rates were 7.4, 6.7, and 2.4 percent for MLH1, MSH2, and the general population, respectively (P = 0.016). Annual metachronous colorectal cancer rates were 2.1, 1.7, and 0.33 percent for MLH1, MSH2, and the general population, respectively (P = 0.041). Colorectal cancer stage presentation was lower in HNPCC than the general population (P = 0.0028). Extracolonic cancers were noted in 33 percent of MSH2 patients, compared with 12 percent of MLH1 patients and 7.3 percent of the general population with colorectal cancers (P < 0.001). Combined MLH1 and MSH2 ten-year survival was 68.7 percent compared with 47.8 percent for the general population (P = 0.009 stage stratified, hazard ratio 0.57). CONCLUSION: The presence of rectal cancer should not preclude the diagnosis of HNPCC, because the incidence of rectal cancer in MSH2 was comparable with that in the general population. Phenotypic variations, including the preponderance of extracolonic cancers in MSH2 patients, did not result in survival differences between genotypic subgroups. These phenotypic features of HNPCC genotypes may have clinical significance in the design of specific screening, surveillance, and follow-up for affected individuals.

Adaptor Proteins, Signal Transducing↗
PubMed1998

The pathophysiological role of estrogen receptor variants in human breast cancer.

The accumulated evidence supports the expression of estrogen receptor variants at both the mRNA and protein levels. The relative level of expression of some estrogen receptor variant mRNAs and possibly progesterone receptor variant mRNAs is altered during breast tumorigenesis and breast cancer progression. The altered expression of estrogen receptor variants may effect estrogen signal transduction as well as the interpretation of assays where the estimation of estrogen receptor levels is used as a guide to treatment strategies and prognosis.

Breast Neoplasms↗