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Biomedical subjects

M L Welton

Publications and source records attributed to M L Welton.

17 recordsLinked to original sources
PubMed1999

The clinical effectiveness and cost-effectiveness of screening for anal squamous intraepithelial lesions in homosexual and bisexual HIV-positive men.

CONTEXT: Homosexual and bisexual men infected with human immunodeficiency virus (HIV) are at increased risk for human papillomavirus-related anal neoplasia and anal squamous cell carcinoma (SCC). OBJECTIVE: To estimate the clinical benefits and cost-effectiveness of screening HIV-positive homosexual and bisexual men foranal squamous intraepithelial lesions (ASIL) and anal SCC. DESIGN: Cost-effectiveness analysis performed from a societal perspective that used reference case recommendations from the Panel on Cost-Effectiveness in Health and Medicine. A state-transition Markov model was developed to calculate lifetime costs, life expectancy, and quality-adjusted life expectancy for no screening vs several screening strategies for ASIL and anal SCC using anal Papanicolaou (Pap) testing at different intervals. Values for incidence, progression, and regression of anal neoplasia; efficacy of screening and treatment; natural history of HIV; health-related quality of life; and costs were obtained from the literature. SETTING AND PARTICIPANTS: Hypothetical cohort of homosexual and bisexual HIV-positive men living in the United States. MAIN OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy, quality-adjusted years of life saved, lifetime costs, and incremental cost-effectiveness ratio. RESULTS: Screening for ASIL increased quality-adjusted life expectancy at all stages of HIV disease. Screening with anal Pap tests every 2 years, beginning in early HIV disease (CD4 cell count >0.50 x 10(9)/L), resulted in a 2.7-month gain in quality-adjusted life expectancy for an incremental cost-effectiveness ratio of $13,000 per quality-adjusted life year saved. Screening with anal Pap tests yearly provided additional benefit at an incremental cost of $16,600 per quality-adjusted life year saved. If screening was not initiated until later in the course of HIV disease (CD4 cell count <0.50 x 10(9)/L), then yearly Pap test screening was preferred due to the greater amount of prevalent anal disease (cost-effectiveness ratio of less than $25,000 per quality-adjusted life year saved compared with no screening). Screening every 6 months provided little additional benefit over that of yearly screening. Results were most sensitive to the rate of progression of ASIL to anal SCC and the effectiveness of treatment of precancerous lesions. CONCLUSIONS: Screening HIV-positive homosexual and bisexual men for ASIL and anal SCC with anal Pap tests offers quality-adjusted life expectancy benefits at a cost comparable with other accepted clinical preventive interventions.

Adult↗
PubMed1999

The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer.

PURPOSE: To assess the outcome and tolerance of HIV-positive patients with anal cancer to standard therapy based on their pretreatment CD4 count. METHODS AND MATERIALS: Between 1991 and 1997, 17 HIV-positive patients with anal cancer and documented pretreatment CD4 counts were treated at the University of California, San Francisco or its affiliated hospitals with either concurrent chemotherapy and radiation or radiation alone. The outcome and complications of treatment were correlated with the patients' pretreatment CD4 count. RESULTS: Disease for all 9 patients with pretreatment CD4 counts > or = 200 was controlled with chemoradiation. Although four required a treatment break of 2 weeks because of toxicity, none required hospitalization. Of the 8 patients with pretreatment CD4 counts < 200, 4 experienced decreased counts, intractable diarrhea, or moist desquamation requiring hospitalization. Additionally, 4 of these 8 ultimately required a colostomy either for a therapy-related complication or for salvage. Nevertheless, 6/7 in this group who received concurrent chemotherapy and radiation had their disease controlled, whereas the patient treated with radiation alone failed and required a colostomy for salvage. CONCLUSION: Patients with CD4 > or = 200 had excellent disease control with acceptable morbidity. Patients with CD4 < 200 had markedly increased morbidity; however, disease was ultimately controlled in 7/8 patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Local excision of rectal carcinoma.

HYPOTHESIS: Selected clinicopathologic characteristics of locally treated rectal cancers are predictive of recurrence. DESIGN: Case series review with median follow-up of 6 years. SETTING: University medical center. PATIENTS: Fifty-eight patients with rectal cancer who underwent local excisions from February 1, 1982, to December 31, 1998. MAIN OUTCOME MEASURES: Local and distant recurrence rates and overall survival. RESULTS: Overall local recurrence rate was 14% (8 patients). There were no local recurrences among patients treated with chemotherapy or radiation. Of patients not treated, local recurrence rates were 33%, 5%, 45%, and 25% for T0, T1, T2, and T3 tumors, respectively. No clinicopathologic factor predicted local recurrence. Two patients developed distant recurrence. Overall survival was 98%, 93%, and 84% at 1, 3, and 5 years, respectively. CONCLUSION: In selected patients, outcomes for local excision combined with additional therapy may be equivalent to those for radical resection.

Adenocarcinoma↗
PubMed1998

Surgical options in the management of perianal Crohn's disease.

Perianal complications of Crohn's disease are common, and surgical management has been controversial. Over the last 10 years, improved outcomes have defined a more prominent role for operative interventions, especially with respect to management of focal perineal sepsis and fistulas. Liberal placement of drainage catheters and noncutting setons, advancement flap closure of perineal fistulas, and selective construction of diverting stomas have good results when combined with optimal medical therapy to induce remission of inflammation. Proctectomy, which is infrequently required, can often be postponed for several years when complementary surgical and medical treatments are provided.

Adult↗
PubMed1997

Biofeedback is effective therapy for fecal incontinence and constipation.

OBJECTIVE: To define the role of biofeedback in fecal incontinence and constipation. DESIGN: A case series of patients with fecal incontinence or constipation with pelvic floor dysfunction. SETTING: Tertiary care center with an anorectal physiology laboratory. PATIENTS: Patients with 1 of the following: (1) chronic or acute fecal incontinence, (2) fecal incontinence and neurologic injury, or (3) constipation with pelvic floor dysfunction. INTERVENTION: Electromyogram-guided biofeedback retraining of the pelvic floor. MAIN OUTCOME MEASURES: Resolution of electromyographic abnormalities and subjective resolution of fecal incontinence or constipation. RESULTS: Of the patients with fecal incontinence, 92% experienced significant improvement with biofeedback without significant improvement in electromyographic values. Of the patients with constipation and pelvic floor dysfunction 80% experienced improvement with biofeedback without significant change in electromyographic values. CONCLUSION: Biofeedback is effective in selected patients with fecal incontinence and constipation with pelvic floor dysfunction.

Acute Disease↗
PubMed1997

Selective arterial embolization for the control of lower gastrointestinal bleeding.

BACKGROUND: Transcatheter embolization is accepted as a safe method for treating acute bleeding from the upper gastrointestinal (GI) tract. Hesitancy persists using this technique below the ligament of Treitz, based on the belief that the risk of intestinal infarction is unacceptably high, despite mounting clinical evidence to the contrary. METHODS: A series of 17 consecutive patients with angiographically demonstrated small intestinal or colonic bleeding was retrospectively reviewed. The success and complication rate of subselective embolization was assessed. RESULTS: Bleeding was stopped in 13 of 14 patients (93%) in whom embolization was possible, and in 13 of 17 patients (76%) where there was an intention to treat. Sufficiently selective catheterization to permit embolization could not be achieved in 3 patients. No clinically apparent bowel infarctions were caused. CONCLUSION: Subselective embolization is a safe treatment option for lower GI bleeding, suitable for many patients and effective in most. Careful technique and a readiness to abandon embolization when a suitable catheter position cannot be achieved are important.

Adolescent↗
PubMed1997

Human colonic microvascular endothelial cells is a model of inflammatory bowel disease.

BACKGROUND: The pathophysiology of inflammatory bowel disease remains elusive primarily because of the limitations of the models available for study in the basic science laboratories. We propose a new model for the study of inflammatory bowel disease. DATA SOURCES: Research and review articles published in the English literature. CONCLUSIONS: The human colonic microvascular endothelial cell in culture is a legitimate model for the study of the human colon in the normal and diseased states.

Bradykinin↗
PubMed1997

The pelvic floor in health and disease.

Normal pelvic floor function involves a set of learned and reflex responses that are essential for the normal control and evacuation of stool. A variety of functional disturbances of the pelvic floor, including incontinence and constipation, are not life threatening, but can cause significant distress to affected patients. Understanding the normal anatomy and physiology of the pelvic floor is essential to understanding and treating these disorders of defecation. This article describes the normal function of the pelvic floor, the diagnostic tools available to investigate pelvic floor dysfunction, and the etiology, diagnosis, and management of the functional pelvic floor disorders that lead to incontinence and constipation.

Constipation↗
PubMed1996

Retrospective review of colorectal cancer in ulcerative colitis at a tertiary center.

OBJECTIVE: To review patient characteristics, surgical indications, operative procedures, and survival of patients with ulcerative colitis who develop colorectal cancer. DESIGN: Retrospective medical record review. SETTING: Tertiary referral center. PATIENTS: Of 493 patients who underwent surgery for ulcerative colitis between 1978 and 1994, 25 patients had colorectal cancer. INTERVENTION: All patients underwent surgical exploration and either a biopsy, segmental resection, total abdominal colectomy, or restorative proctocolectomy was performed. MAIN OUTCOME MEASURE: Duration of postoperative disease-free survival. RESULTS: The average duration of illness prior to surgery was 18.5 years (range, 0.25-40 years). Surgical indications were intractability for 3 patients (12%); dysplasia as revealed by colonoscopic biopsy for 8 patients (32%); and preoperatively diagnosed cancer for 14 patients (56%). Three patients (12%) underwent exploratory laparotomy, 3 (12%) underwent right hemicolectomy, 5 (20%) underwent total proctocolectomy with ileostomy, 3 (12%) underwent total proctocolectomy with continent ileostomy, and 12 (48%) underwent restorative proctocolectomy. Pathological stage was carcinoma in situ for 3 patients (12%), stage I for 7 patients (28%), stage II for 4 patients (16%), stage III for 6 patients (25%), and stage IV for 5 patients (20%). Five-year survival was 100% (3/3) for patients with carcinoma in situ, 100% (4/4) for those with stage I disease, 50% (2/4) for those with stage II, 25% (1/4) for those with stage III, and 0% (0/5) for those with stage IV. Of the 12 patients treated with a restorative proctocolectomy, 6 are 5-year survivors, and 4 are alive at 24, 36, 38, and 48 months. CONCLUSIONS: Twelve percent of the patients in this series had no preoperative evidence of colorectal malignant neoplasms but had invasive cancer in the resected specimen. Therefore, duration of disease alone may be an indication for surgery. A restorative proctocolectomy is a satisfactory procedure in selected patients with malignant neoplasms.

Adult↗
PubMed1996

Benign colorectal polyps. Endoscopic surveillance guidelines and effects on colorectal cancer risk.

In the past several years, there have been major advances in the understanding of colorectal cancer from both the clinical and basic science level. Although there are various techniques for colorectal cancer screening and surveillance, the most cost-effective approach has yet to be determined. As molecular biology techniques are improved and incorporated into clinical practice, identification of high-risk populations seems possible. With future advances in endoscopy and imaging, patient compliance can be improved. With the proper combination of both clinical and basic science techniques, it seems reasonable that a further reduction in the mortality from colorectal cancer can be accomplished.

Colonoscopy↗
PubMed1991

Surgical treatment of pancreatic cancer. The United States experience.

About 28,000 new cases of pancreatic cancer are diagnosed yearly in the United States. The diagnosis is now made up to two months more quickly than just a few years ago, but this has had no impact on survival. In most institutions, 20-25% of patients have resectable lesions. The standard operation is still the Whipple pancreaticoduodenectomy, but many surgeons now use the pylorus preserving modification of that procedure. The operative mortality rate has fallen to less than 5%. The five-year survival rate after a resection for attempted cure is about 9%. Palliation requires cholecysto(docho)jejunostomy and gastrojejunostomy, which is often done prophylactically. The operative mortality rate in patients undergoing palliation is less than 10% (recent UCLA experience), and the average survival is seven months.

Adenocarcinoma↗
PubMed1989

Vasoactive intestinal polypeptide receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Vasoactive intestinal polypeptide (VIP) is a putative neurotransmitter in both the brain and peripheral tissues. To define possible target tissues of VIP we have used quantitative receptor autoradiography to localize and quantify the distribution of [125I]VIP receptor binding sites in histologically normal human surgical specimens. While the distribution of VIP binding sites was different for each gastrointestinal segment examined, specific vasoactive intestinal polypeptide binding sites were localized to the mucosa, the muscularis mucosa, the smooth muscle of submucosal arterioles, the circular and longitudinal smooth muscle of the muscularis externa, the myenteric plexus, and lymph nodules. In most segments, the mucosal layer expressed the highest concentration of VIP binding sites, with the duodenal and jejunal mucosa showing the highest density of receptors. These results identify putative VIP target tissues in the human gastrointestinal tract. In correlation with physiological data, VIP binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including mucosal ion transport, gastric secretion, hemodynamic regulation, gastric and intestinal motility, neuronal excitability, and modulation of the immune system.

Digestive System↗
PubMed1988

Receptors.

Explore the source record for details and available documents.

Humans↗
PubMed1988

Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn disease.

Several lines of evidence indicate that tachykinin neuropeptides [substance P (SP), substance K (SK), and neuromedin K (NK)] play a role in regulating the inflammatory and immune responses. To test this hypothesis in a human inflammatory disease, quantitative receptor autoradiography was used to examine possible abnormalities in tachykinin binding sites in surgical specimens from patients with inflammatory bowel disease. Surgical specimens of colon were obtained from patients with ulcerative colitis (n = 4) and Crohn disease (n = 4). Normal tissue was obtained from uninvolved areas of extensive resections for carcinoma (n = 6). In all cases, specimens were obtained less than 5 min after removal to minimize influences associated with degradation artifacts and were processed for quantitative receptor autoradiography by using 125I-labeled Bolton-Hunter conjugates of NK, SK, and SP. In the normal colon a low concentration of SP receptor binding sites is expressed by submucosal arterioles and venules and a moderate concentration is expressed by the external circular muscle, whereas SK receptor binding sites are expressed in low concentrations by the external circular and longitudinal muscle. In contrast, specific NK binding sites were not observed in any area of the human colon. In colon tissue obtained from ulcerative colitis and Crohn disease patients, however, very high concentrations of SP receptor binding sites are expressed by arterioles and venules located in the submucosa, muscularis mucosa, external circular muscle, external longitudinal muscle, and serosa. In addition, very high concentrations of SP receptor binding sites are expressed within the germinal center of lymph nodules, whereas the concentrations of SP and SK binding sites expressed by the external muscle layers are not altered significantly. These results demonstrate that receptor binding sites for SP, but not SK or NK, are ectopically expressed in high concentrations (1000-2000 times normal) by cells involved in mediating inflammatory and immune responses. These data suggest that SP may be involved in the pathophysiology of inflammatory bowel disease and might provide some insight into the interaction between the nervous system and the regulation of inflammation and the immune response in human inflammatory disease.

Autoradiography↗
PubMedDate not supplied

Substance P and substance K receptor binding sites in the human gastrointestinal tract: localization by autoradiography.

Quantitative receptor autoradiography was used to localize and quantify the distribution of binding sites for 125I-radiolabeled substance P (SP), substance K (SK) and neuromedin K (NK) in the human GI tract using histologically normal tissue obtained from uninvolved margins of resections for carcinoma. The distribution of SP and SK binding sites is different for each gastrointestinal (GI) segment examined. Specific SP binding sites are expressed by arterioles and venules, myenteric plexus, external circular muscle, external longitudinal muscle, muscularis mucosa, epithelial cells of the mucosa, and the germinal centers of lymph nodules. SK binding sites are distributed in a pattern distinct from SP binding sites and are localized to the external circular muscle, external longitudinal muscle, and the muscularis mucosa. Binding sites for NK were not detected in any part of the human GI tract. These results demonstrate that: 1) surgical specimens from the human GI tract can be effectively processed for quantitative receptor autoradiography; 2) of the three mammalian tachykinins tested, SP and SK, but not NK binding sites are expressed in detectable levels in the human GI tract; 3) whereas SK receptor binding sites are expressed almost exclusively by smooth muscle, SP binding sites are expressed by smooth muscle cells, arterioles, venules, epithelial cells of the mucosa and cells associated with lymph nodules; and 4) both SP and SK binding sites expressed by smooth muscle are more stable than SP binding sites expressed by blood vessels, lymph nodules, and mucosal cells.

Amino Acid Sequence↗
PubMedDate not supplied

Receptors for sensory neuropeptides in human inflammatory diseases: implications for the effector role of sensory neurons.

Glutamate and several neuropeptides are synthesized and released by subpopulations of primary afferent neurons. These sensory neurons play a role in regulating the inflammatory and immune responses in peripheral tissues. Using quantitative receptor autoradiography we have explored what changes occur in the location and concentration of receptor binding sites for sensory neurotransmitters in the colon in two human inflammatory diseases, ulcerative colitis and Crohn's disease. The sensory neurotransmitter receptors examined included bombesin, calcitonin gene related peptide-alpha, cholecystokinin, galanin, glutamate, somatostatin, neurokinin A (substance K), substance P, and vasoactive intestinal polypeptide. Of the nine receptor binding sites examined only substance P binding sites associated with arterioles, venules and lymph nodules were dramatically up-regulated in the inflamed tissue. These data suggest that substance P is involved in regulating the inflammatory and immune responses in human inflammatory diseases and indicate a specificity of efferent action for each sensory neurotransmitter in peripheral tissues.

Animals↗