Biomedical subjects

L Jewell

Publications and source records attributed to L Jewell.

12 recordsLinked to original sources

PubMed2004

Interferon treatment of multiple pulmonary malignancies associated with papilloma virus.

Over a period of four years, beginning in spring 1988, a previously healthy man developed a primary squamous cell carcinoma of the tonsil, treated with radiotherapy, followed by 10 distinct, primary bronchial squamous cell carcinomas. Four of the cancers were surgically resected, all of which were positive by hybridization for human papilloma virus (type 16). Following the institution of alpha interferon, three smaller lesions disappeared and a larger one shrank in size, facilitating surgical resection. Over the following seven years no new ones have appeared. The finding of papilloma virus in malignancies should prompt consideration of antiviral therapy.

Adult↗

PubMed2001

Probiotic bacteria enhance murine and human intestinal epithelial barrier function.

BACKGROUND & AIMS: The probiotic compound, VSL#3, is efficacious as maintenance therapy in pouchitis and ulcerative colitis. The aim of this study was to determine the efficacy of VSL#3 as a primary therapy in the treatment of colitis in the interleukin (IL)-10 gene-deficient mouse. Mechanisms of action of VSL#3 were investigated in T(84) monolayers. METHODS: IL-10 gene-deficient and control mice received 2.8 x 10(8) colony-forming units per day of VSL#3 for 4 weeks. Colons were removed and analyzed for cytokine production, epithelial barrier function, and inflammation. VSL#3 or conditioned media was applied directly to T(84) monolayers. RESULTS: Treatment of IL-10 gene-deficient mice with VSL#3 resulted in normalization of colonic physiologic function and barrier integrity in conjunction with a reduction in mucosal secretion of tumor necrosis factor alpha and interferon gamma and an improvement in histologic disease. In vitro studies showed that epithelial barrier function and resistance to Salmonella invasion could be enhanced by exposure to a proteinaceous soluble factor secreted by the bacteria found in the VSL#3 compound. CONCLUSIONS: Oral administration of VSL#3 was effective as primary therapy in IL-10 gene-deficient mice, and had a direct effect on epithelial barrier function.

Animals↗

PubMed1998

A placebo-controlled trial of ICAM-1 antisense oligonucleotide in the treatment of Crohn's disease.

BACKGROUND & AIMS: Intercellular adhesion molecule 1 (ICAM-1) plays an important role in the trafficking and activation of leukocytes and is up-regulated in inflamed mucosa in Crohn's disease. ISIS 2302 is an antisense phosphorothioate oligodeoxynucleotide that inhibits ICAM-1 expression. The aim of this study was to obtain preliminary assessment of tolerability, pharmacology, and efficacy of ISIS 2302 in Crohn's disease. METHODS: Twenty patients with active, steroid-treated Crohn's disease were randomized (3:1, ISIS 2302 to placebo) to receive over 26 days 13 intravenous infusions of ISIS 2302 (0.5, 1, or 2 mg/kg) or saline placebo in a double-blinded study. The patients were followed up for 6 months. RESULTS: At the end of treatment. 47% (7 of 15) of ISIS 2302-treated and 20% (1 of 5) of the placebo-treated patients were in remission (Crohn's Disease Activity Index [CDAI] < 150). At the end of month 6, 5 of these 7 ISIS 2302-treated remitters were still in remission, and a 6th patient had a CDAI of 156. Corticosteroid usage was significantly lower (P = 0.0001) in the ISIS 2302-treated patients. These findings were corroborated by significant increases in beta7 and alpha d bearing CD3+ peripheral blood lymphocytes and by decreases in intestinal mucosal ICAM-1 expression during the treatment period. CONCLUSIONS: ISIS 2302 seems to be a well-tolerated and promising therapy for steroid-treated Crohn's disease.

Adolescent↗

PubMed1998

Cholestatic hepatocellular injury with azathioprine: a case report and review of the mechanisms of hepatotoxicity.

Azathioprine is a drug commonly used for the treatment of inflammatory bowel disease, organ transplantation and various autoimmune diseases. Hepatotoxicity is a rare, but important complication of this drug. The cases reported to date can be grouped into three syndromes: hypersensitivity; idiosyncratic cholestatic reaction; and presumed endothelial cell injury with resultant raised portal pressures, venoocclusive disease or peliosis hepatis. The components of azathioprine, 6-mercaptopurine and the imidazole group, may play different roles in the pathogenesis of hepatotoxicity. The strong association with male sex, and perhaps with human leukocyte antigen type, suggests a genetic predisposition of unknown type. Many of the symptoms of hepatotoxicity, such as nausea, abdominal pain and diarrhea, can be nonspecific and can be confused with a flare-up of inflammatory bowel disease. As well, the subtype resulting in portal hypertension can occur without biochemical abnormalities. A 63-year-old man with Crohn's disease who is presented developed the rare idiosyncratic form of azathioprine hepatotoxicity, but also had a severe disabling steroid myopathy, peripheral neuropathy, resultant deep venous thrombosis and pulmonary embolism related to immobility, and a nosocomial pneumonia. His jaundice and liver enzyme levels improved markedly on withdrawal of the drug, returning to almost normal in five weeks. Treating inflammatory bowel disease effectively while trying to limit iatrogenic disease is a continuous struggle. Understanding the risks of treatment is the first important step. There must be a low threshold for obtaining liver function tests, especially in men, and alertness to the need to discontinue the drug or perform a liver biopsy should patients on azathioprine develop liver biochemical abnormalities, unexplained hepatomegaly or signs of portal hypertension.

Azathioprine↗

PubMed1994

Colon carcinoid tumors. A population-based study.

PURPOSE: The aim of our investigation was to evaluate the clinical presentation of patients with carcinoid tumors of the colon and to estimate the survival and potential prognostic factors of this tumor type. METHODS: A population-based study was performed using data from the Alberta Cancer Registry between 1964 and 1988 (inclusive). The clinical records and the pathologic material of eligible patients were reviewed. Survival was estimated both as crude survival and with the Kaplan-Meier method. RESULTS: During the 25-year study period (1964-1988), 36 true carcinoid tumors of the colon were diagnosed in Alberta. Carcinoids of the ileocecal region and of the rectum were excluded from the study. The average age at time of diagnosis was 68.4 years; there were 20 males and 16 females. Symptoms (abdominal pain, diarrhea, weakness, anorexia) occurred late in the course of the disease: 64 percent of the lesions were in Dukes D stage and 22 percent were Dukes C at diagnosis. Only one patient presented with a malignant carcinoid syndrome. Lesions occurred most frequently in the cecum (39 percent), followed by transverse and sigmoid colon. Most of the patients were managed surgically. The perioperative mortality rate was with 22 percent, which is quite high. The average size of the lesions was 5.8 (range, 2-10) cm, and most tumors (31/36) had invaded the pericolic fat. The most common immunohistochemical pattern was argentaffin/argyrophil negative and neuron-specific enolase positive. Two-year and five-year actuarial (Kaplan-Meier) survival was 34 percent and 26 percent, respectively. Survival for carcinoids of the colon was significantly lower compared with carcinoids of the rectum or appendix, and with colon adenocarcinomas. Size of the tumor and tumor invasion into the muscularis propria--the two major histopathologic prognostic factors for carcinoids of the gastrointestinal tract--were not found to influence survival significantly. Rather, tumor stage, histologic pattern, tumor differentiation, nuclear grade, and mitotic rate were found to significantly influence the survival rate. CONCLUSION: Carcinoid tumors of the colon are extremely rare tumors, diagnosed late in the course of the disease, and they carry a bad prognosis. Prognostic factors are tumor stage, histologic pattern, differentiation, nuclear grade, and mitotic rate of the tumor.

Aged↗

PubMed1991

Male-sex-ratio trait in Drosophila pseudoobscura: frequency of autosomal aneuploid sperm.

Males with the SR X chromosome show the "sex-ratio" (sr) phenotype in which they produce almost entirely daughters. The few sons (about 1%) are invariably sterile X/O males and result entirely from nullo-XY sperm. The "male-sex-ratio" (msr) phenotype is a modified form of sr in which SR/Y males produce a higher frequency of sterile X/O sons. The msr trait is due to the presence of the SR X-chromosome in males which are also homozygous for one or more autosomes from the L116 strain. Here the frequency of nullo-3 and diplo-3 sperm from msr males was measured by crossing to a compound-3 strain and found to be 13.8% and 3.2%, respectively, of the total viable sperm. The sr males produced very low levels of nullo-3 sperm at a frequency not different from control X/Y males and a slightly elevated frequency of diplo-3 sperm over X/Y males. The msr males were found to have only 12% the fecundity of sr males and in matings to cause a high frequency of brown inviable eggs. These results indicate that high rates of autosomal aneuploidy are not restricted to chromosome 3 but also occur for chromosomes 2, 4 and 5. The overall frequency of autosomal aneuploid sperm is estimated to be approximately 50%. Microscopic studies of meiosis in testes from msr males indicates meiotic nondisjunction and meiotic chromosome loss are responsible for the msr phenotype. Last, microscopic studies of sperm cysts from msr males reveal high levels of spermiogenic failure.

Anaphase↗

PubMed1990

Ecology of depression in late childhood and early adolescence: a profile of daily states and activities.

This study investigated daily states and time use patterns associated with depression. Four hundred eighty-three 5th to 9th graders reported on their experience when signalled by pagers at random times. Depressed youth reported more negative affect and social emotions, lower psychological investment, lower energy, and greater variability in affect. These differences were weaker for 5th and 6th graders, suggesting that self-reported feeling states are a poor indicator of depression prior to adolescence. No differences were found in the daily activities of depressed youths nor in the amount of time spent alone, but depressed youths experienced other people as less friendly and more often reported wanting to be alone, especially when with their families. They also spent less time in public places and more time in their bedrooms. Finally, depressed boys, but not girls, spent much less time with friends, particularly of the same sex, suggesting that social isolation is more strongly associated with depression for boys.

Adolescent↗

PubMed1985

Massive gastrointestinal hemorrhage cecal ulcers and salmonella colitis.

A 65-year-old man presented with massive lower gastrointestinal tract hemorrhage. Minimal changes were noted on sigmoidoscopy, no bleeding lesions were identified on arteriography or red blood cell scan, and barium enema examination demonstrated only diverticular disease and minimal cecal deformity, interpreted as secondary to a recent appendectomy. Colonoscopy demonstrated multiple deep cecal ulcers. These were presumed to be due to an infectious etiology, since the stools were culture-positive for Salmonella typhimurium. The hemorrhage stopped within 24 hours of treatment with Ampicillin, Flagyl, and Gentamicin. The patient has remained well over a 12-month follow-up period. Repeat colonoscopy demonstrated healing of the cecal ulcers and there was also clearing of the Salmonella from the stools. This case report serves to remind us of the different methods used to diagnose lower gastrointestinal tract hemorrhage, and the importance of considering infectious causes of colitis.

Aged↗

PubMed1984

Polyclonal orbital and systemic infiltrates.

Two unusual cases of benign lymphoproliferative disease associated with orbital and systemic involvement are described. Both have occurred in adults with longstanding histories and clinical manifestations that have mimicked lymphomas. The orbital disease has been both antecedent and subsequent to the systemic lesions. These cases emphasize the spectrum of lymphoproliferative disorders and call attention to the possibility of multisystem disease in patients with benign lymphoproliferative lesions.

Aged↗

PubMed1984

Ranitidine in the treatment of symptomatic gastroesophageal reflux disease.

We undertook a multicenter double-blind study comparing ranitidine to placebo in 73 patients with symptomatic gastroesophageal reflux ranging in age from 22 to 80 years (mean 49). Initially, all patients had moderate to severe symptoms associated with abnormal endoscopic and/or microscopic appearance of the mucosa. After six weeks, 46% of ranitidine-treated patients had a one-grade improvement in their symptom of regurgitation, as compared with 19% treated with placebo (p less than 0.01); ranitidine was no better than placebo in the improvement of pain or dysphagia. Endoscopic improvement occurred in 61% of ranitidine- and 48% of placebo-treated patients (p less than 0.05). Histological improvement occurred in a similar and small portion of patients treated with ranitidine and placebo; there was no correlation between clinical, endoscopic, and histological improvement. Antacid consumption was only half as great in the ranitidine as in the placebo group. Therapy with ranitidine was maintained for up to 12 months. The patients remained free of regurgitation or pain and there was a trend towards further improvement in the endoscopic or histopathologic appearance of the esophagus. Ranitidine 150 mg b.i.d. is recommended for the relief of symptoms and improvement in the endoscopic appearance of the esophagus. Treatment should be for a minimum of 6 weeks, but may be continued for up to a year if the patient's symptoms persist or return.

Adult↗

PubMed1984

Gastroesophageal reflux and transit scintigraphy: a comparison with esophageal biopsy in patients with heartburn.

A method for combining scintigraphic studies of esophageal transit and gastroesophageal (GE) reflux is presented. Thirty-two patients with symptoms of GE reflux were studied. The severity of their symptoms was compared to nuclear medicine studies and esophageal mucosal biopsy. Fifteen healthy volunteers were studied as a control group for scintigraphy. The sensitivity of reflux scintigraphy to detect GE reflux as determined by esophageal histology was 70% and its specificity 87%. No relationship was observed between the magnitude of symptoms and the volume of GE reflux. A higher incidence of esophageal transit abnormalities was observed in those patients with histologic features of GE reflux than in those with normal histology. The combination of esophageal reflux and transit scintigraphy provides a way of studying some of the esophageal motor abnormalities associated with GE reflux. For clinical purposes GE reflux scintigraphy seems unsuitable as a single screening test.

Adolescent↗

PubMed1984

Cheilitis antedating Crohn's disease: case report and literature update of oral lesions.

Oral lesions occur in an impressive number of patients with Crohn's disease. The lesions often precede the intestinal symptoms, and follow a variable course from asymptomatic to severe. They are important because of their association with Crohn's disease and the possibility that they could lead to an earlier diagnosis of Crohn's disease. We present a patient with cheilitis which preceded the recognition of colonic and perianal Crohn's disease by 7 years. The cheilitis responded to injection of steroids into the lips, but was unaffected by oral prednisone, sulfasalazine, azathioprine, and metronidazole.

Adult↗