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Biomedical subjects

P Watson

Publications and source records attributed to P Watson.

At least 163 records · Page 9Linked to original sources
PubMed1995

Prophylactic oophorectomy in inherited breast/ovarian cancer families.

Prophylactic oophorectomy is chosen by some women at high risk of ovarian cancer due to inherited predisposition. Unfortunately, this surgery is not 100% effective in preventing intra-abdominal carcinomatosis that histologically resembles ovarian cancer. To determine the incidence of post-oophorectomy carcinomatosis and to quantify the effectiveness of preventive surgery, a multicenter study is ongoing between the National Cancer Institute (NCI), Creighton University, and the United Kingdom. The prospective incidence of malignancy, especially of tissues derived from coelomic epithelium (primarily ovary, fallopian tube, and peritoneum), was compared between women of similar genetic risk who have or have not undergone oophorectomy. Analysis of 12 NCI families has been completed. Prospective observation ran from the date of family ascertainment until the date of cancer incidence, death, or December 31, 1992. Approximately 1600 person-years of observation occurred among 346 first-degree relatives of a breast or ovarian cancer case patient for women who had not undergone oophorectomy. Eight ovarian cancers occurred, compared with two carcinomatosis cases during 460 person-years of observation among 44 oophorectomized women. Compared with Connecticut Tumor Registry data adjusted for age, race, and birth cohort, there was an approximately 24-fold excess of ovarian cancer among non-oophorectomized women and a 13-fold excess of "ovarian" cancer among oophorectomized women, though this difference was not statistically significant. The confidence intervals around these numbers were large, and a collaborative analysis will be required to determine whether this apparent protective effect is real.

Breast Neoplasms↗
PubMed1995

The right ventricle in mitral regurgitation: evaluation by electron beam tomography.

Mitral valve regurgitation affects heart ventricle volumes, which can be accurately measured by electron beam tomography (EBT). Most studies have focused on the left ventricle, but findings have failed to resolve some crucial clinical issues. We reviewed EBT studies of 35 patients with moderate mitral valve regurgitation but no ischemia, aortic valve regurgitation, or left ventricular failure to investigate the relationship between right ventricle volumes and ejection fraction and extent of mitral regurgitation. EBT in cine mode was performed during exercise and at rest in 839 patients from 1990-1994. Sixty-one of these showed evidence of significant mitral regurgitation, 35 of whom met the criteria for inclusion in this study. Left and right end-diastolic and end-systolic volumes were computed from the scans, and ventricular stroke volumes, ejection fractions, regurgitant stroke volume, and regurgitant fraction were computed from these values. Correlation coefficients between ventricular values and regurgitant fraction were computed. Regurgitant fraction was significantly and negatively associated with the ejection fraction in the right ventricle (r = -0.55, p < 0.001) but not in the left. Ten of the 35 patients studied had right ventricular ejection fractions of less than 45%. In addition, there was evidence for a subgroup of cases with moderate amounts of regurgitation and dilation of the right ventricle. It is concluded that reduced right ventricular ejection fraction is a common finding in patients with mitral regurgitation without left ventricular failure. It is most commonly observed in cases with large regurgitant fraction and/or with a large right ventricular end-diastolic volume/left ventricular end-diastolic volume ratio. Identification of mitral regurgitation patients with reduced right ventricular ejection fraction may have clinical significance, indicating a sub-group of patients with more severe disease prior to the development of left ventricular dysfunction.

Aged↗
PubMed1994

Internal carotid artery thrombosis after cervical corpectomy.

SUMMARY OF BACKGROUND DATA: A 74-year-old man suffered an extensive right hemispheric infarct 72 hours after undergoing anterior corpectomies of the C4 and C5 vertebrae for cervical myelopathy resulting from ossification of the posterior longitudinal ligament. RESULTS: Angiography revealed proximal right internal carotid artery thrombosis with atherosclerosis and a normal left internal carotid artery. The thrombosis may have been due to stasis during lengthy retraction of an atherosclerotic carotid artery. CONCLUSIONS: Preoperative screening of internal carotid artery blood flow with Doppler ultrasonography is recommended before contemplating extensive anterior cervical surgery in middle-aged and elderly patients at significant risk for atherosclerotic disease.

Aged↗
PubMed1994

hMSH2 mutations in hereditary nonpolyposis colorectal cancer kindreds.

It has recently been shown that hereditary nonpolyposis colorectal cancer (HNPCC) is caused by hereditable defects in DNA mismatch repair genes. However, the fraction of HNPCC due to defects in any one repair gene and the nature of these mutations are not known. We analyzed 29 HNPCC kindreds for mutations in the prototype DNA mismatch repair gene hMSH2 by a combination of linkage analysis, polymerase chain reaction-based screening, and sequencing of the coding region. The complete intron/exon structure of the gene was ascertained to facilitate this analysis. The results suggest that at least 40% of classic HNPCC kindreds are associated with germline mutations in hMSH2 and that most of these mutations produce drastic alterations in the predicted protein product.

Amino Acid Sequence↗
PubMed1994

Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients.

A replication error (RER) phenotype has been documented both in sporadic colorectal tumors and in tumors from patients with hereditary nonpolyposis colorectal cancer (HNPCC). In the current study 8 of 49 (16%) sporadic colorectal cancers (CRCs) and 25 of 29 (86%) CRCs from HNPCC patients were found to be RER+. All 9 (100%) CRCs from HNPCC patients with germline mutations of the mismatch repair gene MSH2 were found to be RER+, while 16 of 20 CRCs from HNPCC kindreds unlinked or not studied for linkage to MSH2 were RER+. Corresponding analysis in colorectal adenomas revealed that only 1 of 33 (3%) sporadic tumors but 8 of 14 (57%) HNPCC tumors were RER+. Moreover, RER was found in all 6 extracolonic cancers (endometrium, 2; kidney, 1; stomach, 1; duodenum, 1; and ovary, 1) derived from members of HNPCC families. These data suggest the involvement of mismatch repair deficiency in the premalignant stage of tumorigenesis in HNPCC cases, and suggest that mismatch repair genes (MSH2 or others) are defective in the germline of nearly all these patients.

Adenoma↗
PubMed1994

In vivo sensitivity of Plasmodium falciparum to chloroquine in rural areas of Côte d'Ivoire.

In vivo testing of Plasmodium falciparum sensitivity to chloroquine was carried out in four rural sites of differing socio-geographical environment in Côte d'Ivoire. Of a total of 1282 patients of all ages with fever or previous history of fever, 649 were slide positive, with 435 patients with a pure P. falciparum infection; 191 fulfilled all the criteria for inclusion in this study, and 113 completed it. Treatment failure rates ranged from 9.7% (Djébonoua) to 38.1% (Tiéviéssou), and were most often associated with higher degrees of resistance (RII = 54.2%; RIII = 37.5%). Blood chloroquine levels measured by ELISA test suggest that many people take chloroquine routinely; furthermore 37.5% of resistance cases occurred in subjects who had high blood chloroquine concentrations on day 0. Twenty-three out of 24 cases of resistance were found in children under 7 years of age. Nearly all children with persisting parasitaemia were afebrile on day 7, even those (7/8) with RIII resistance. Children aged < 7 years represent the the best sentinel group for monitoring P. falciparum sensitivity to chloroquine in Côte d'Ivoire.

Adolescent↗
PubMed1994

The risk of endometrial cancer in hereditary nonpolyposis colorectal cancer.

PURPOSE: Hereditary nonpolyposis colorectal cancer (HNPCC) is characterized by increased risk for cancer, especially colorectal cancer. It has been recommended that colon cancer control programs for family members be expanded to include endometrial cancer, the commonest extracolonic cancer observed in HNPCC families. We estimated the age-specific and cumulative endometrial cancer risk for women at high risk for HNPCC. PATIENTS AND METHODS: Family history data from three large HNPCC registries were combined for this study. High risk family members were identified without regard to extracolonic cancer. Life table methods were used to calculate estimates of risk. RESULTS: One thousand eighteen women from 86 families were included in the study. Cumulative incidence was 20% by age 70, compared to 3% in the general population. Risk was highest in women most likely to carry the HNPCC gene (P < 0.001). In this group, during the highest risk years (age 40 to 60), average annual risk exceeded 1%. There was no significant difference among the registries, despite different ascertainment practices regarding endometrial cancer. CONCLUSION: Interventions to reduce endometrial cancer morbidity and mortality are justified by the risk levels observed. Prophylactic total hysterectomy and bilateral salpingo-oophorectomy should be recommended to women in HNPCC families who have a syndrome cancer or offspring with a syndrome cancer. Endometrial cancer screening should be available to women at high risk. Studies of screening protocols are needed.

Colorectal Neoplasms, Hereditary Nonpolyposis↗
PubMed1994

Familial aggregation of carcinoma of the endometrium.

OBJECTIVE: Our purpose was to describe histologically verified endometrial carcinoma and other cancer types manifested through three generations in a pedigree, where these findings do not fit any classic hereditary cancer syndrome. STUDY DESIGN: Our family study protocol used detailed patient interviews whenever possible and questionnaires with permission forms that, when signed, enabled retrieval of pertinent medical-genetic and pathologic study documents. RESULTS: Endometrial carcinoma was histologically verified in five women through three consecutive generations. The triad of obesity, hypertension, and diabetes mellitus was not observed. Primary carcinomas of both the endometrium and ovary and endometrium and lymphoma were documented in two relatives in the direct genetic lineage of the pedigree. CONCLUSION: An aggregation of endometrial carcinoma in families, even when classic hereditary cancer syndrome identification is lacking, nevertheless merits surveillance and management strategies targeted to putative high-risk family members.

Endometrial Neoplasms↗
PubMed1994

Stereotactic biopsy of 100 intracerebral lesions at Sir Charles Gairdner Hospital.

The pathological findings in a retrospective review of 100 consecutive intracranial stereotactic biopsies are presented. Definite diagnosis could be established in the majority (89) of cases and included 85 neoplasms (69 primary cerebral tumors, 10 non-Hodgkin's lymphomas and 6 metastases) and 4 non-neoplastic processes. In the remaining 11 samples the findings were non-diagnostic; 2 consisted of normal glial tissue, while the remainder variously showed changes of necrosis, hematoma, histiocytic reaction or astrocytic proliferations of uncertain nature. Verification of the stereotactic diagnosis by examination of lesional tissue obtained at subsequent craniotomy or postmortem was possible in 7 of 10 cases. Two broad categories of diagnostic difficulty were identified in interpreting stereotactic biopsies: (1) accurate tumor typing and grading, and (2) the distinction between reactive and neoplastic astrocytic proliferations. Two essential components in the diagnostic process are: (1) careful correlation with the clinical and radiological findings; and (2) use of intraoperative smear and/or frozen section preparations to confirm specimen adequacy. By adhering to these principles accurate intraoperative diagnosis can usually be established, particularly for high grade astrocytoma, lymphoma and metastasis. Tumor typing is aided by the use of immunohistochemistry and ultrastructural examination and the examination of serial sections is of value in grading.

Adolescent↗
PubMed1994

A critical analysis of laparoscopic assisted vaginal hysterectomies compared with vaginal hysterectomies unassisted by laparoscopy and transabdominal hysterectomies.

The first 115 laparoscopically assisted vaginal hysterectomies (LAVH) done by our faculty surgeons were compared with 220 vaginal hysterectomies (VH) and 194 abdominal hysterectomies (AH) done in our affiliated hospitals over the same period of time. Logistic regression analysis indicates that LAVHs were done for cases that would significantly be more likely selected for AH than for VH (p less than 0.0001). Matched case control studies with 28 LAVH/VH and 34 LAVH/AH pairs and bivariate analyses demonstrated that LAVH can be accomplished with low morbidity, short lengths of stay, and little, if any, increase in operating times compared with VH and AH. The LAVH procedure can be expected to replace many AHs in the future.

Adolescent↗
PubMed1994

A laparoscopic intraperitoneal onlay mesh technique for the repair of an indirect inguinal hernia.

OBJECTIVE: This study was done (1) to determine whether congenital indirect inguinal hernias in male pigs could be repaired by placing a polypropylene mesh prosthesis over the defect intra-abdominally, (2) to measure the incidence of adhesions between intra-abdominal viscera and the prosthesis with and without the adhesion barrier oxidized regenerated cellulose, (3) to determine the incidence of other complications, and (4) to assess the effect on fertility. SUMMARY BACKGROUND DATA: Several techniques for laparoscopic inguinal herniorrhaphy are currently being evaluated to determine whether there are advantages over conventional inguinal herniorrhaphy. Perhaps the most controversial is the intraperitoneal onlay mesh procedure (IPOM). Its advantage is its simplicity (in that the repair is accomplished by placing a prosthesis over the hernia defect intra-abdominally, avoiding a groin dissection). Its disadvantage is the potential for complications because the prosthesis is in contact with the intra-abdominal viscera. METHODS: In male pigs, polypropylene mesh alone or polypropylene mesh plus the adhesion barrier oxidized regenerated cellulose (composite prosthesis) was fixed to the peritoneum surrounding the hernia defect. In phase 1 (6-week follow-up), two groups of 13 pigs each underwent herniorrhaphy at laparotomy or laparoscopy. In phase 2 (7.1-month follow-up), 21 pigs underwent laparoscopic herniorrhaphy. RESULTS: All IPOM herniorrhaphies were successful. The prostheses adhered most frequently to the bladder, followed by small bowel, peritoneum, and cord structures. Prosthetic erosion into these organs was not observed. Laparoscopically placed prostheses in phases 1 and 2 had significantly less surface covered by adhesions (13% +/- 13% and 19% +/- 27%, respectively) and a lower adhesion tenacity grade (1.5 +/- 0.9 and 1.3 +/- 1.1, respectively) than those placed at laparotomy (44% +/- 27% and 2.5 +/- 0.7, respectively; p < 0.01). In phase 1, a histologic evaluation of laparoscopically placed specimens demonstrated significantly thinner above-mesh fibrotic tissue compared with the prostheses implanted at laparotomy (p < 0.04). In either phase, the use of the adhesion barrier did not produce any histologic difference between the polypropylene alone and the composite prosthesis. Fertility studies were performed in phase 2 and showed no adverse effects caused by either prosthesis. CONCLUSIONS: This study demonstrated that the intraperitoneal placement of a polypropylene prosthesis was an effective technique for indirect inguinal herniorrhaphy in a pig. Furthermore, with laparotomy, the addition of oxidized regenerated cellulose significantly decreased the rate of adhesion formation to the prosthesis. However, oxidized regenerated cellulose would appear to have no value when used with a prosthesis placed laparoscopically.

Animals↗
PubMed1994

Public health medicine and the district health authority.

The 1991 National Health service reforms have greatly changed the role of district health authorities. These bodies employ most public health physicians in England and thus the focus of public health departments has changed with the reforms. Presents the results of a series of semi-structured interviews with the board members of two health authorities about the role of public health. Board members outlined several roles for the specialty including defining key issues, interpreting technical issues, intelligence gathering, developing links with clinicians and legitimizing health authority decisions. There were some concerns about the corporacy of public health departments. There was a great deal of support for health promotion, but some reluctance to be drawn into political issues. Also explored were alternative sources of advice on health policy, such as the views of general practitioners.

Health Care Reform↗
PubMed1994

Treatment of Graves' disease with the block-replace regimen of antithyroid drugs: the effect of treatment duration and immunogenetic susceptibility on relapse.

Antithyroid drugs are commonly used as first-line treatment for Graves' disease, but the optimum regimen for inducing remission remains unclear. We gave the block-replace regimen of carbimazole plus thyroxine to 100 patients for 6 or 12 months, to determine whether prolonged treatment is associated with fewer relapses. The remission rate one year after cessation of treatment was 59% with the 6 month course and 65% with 12 months; this was not significantly different. We also analysed HLA markers identified by restriction fragment length polymorphisms and could not confirm the recently reported associations of outcome with HLA-DR4 or with an HLA-DQA2 allele. These results show that six months treatment with a block-replace regimen of antithyroid drugs is probably sufficient, in the UK, to achieve maximum remission of Graves' disease and that there are no HLA markers which clearly predict outcome.

Adult↗
PubMed1994

Surveillance in Lynch syndrome: how aggressive?

OBJECTIVE: To identify colorectal cancers occurring after colonoscopic screening in patients at risk for Lynch syndrome. METHODS: All cancers in Lynch syndrome families on file at the Creighton University Hereditary Cancer Institute were reviewed for history of prior colonoscopy. RESULTS: Of 225 individuals with 313 colon cancers, six patients from different families had colon cancers arising within 4 1/2 yr of colonoscopic surveillance. Another 17 patients had metachronous colon cancers within 5 yr of resection of their first colon cancer. CONCLUSION: Of 225 colorectal cancer patients from Lynch syndrome families, 10.2% of patients had colorectal cancer within 5 yr of colonoscopy or colon resection. In Lynch syndrome, the potential for interval neoplasms and the malignant potential of missed diminutive adenomas may differ from cases in the general population.

Adult↗