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Biomedical subjects

L Laine

Publications and source records attributed to L Laine.

At least 19 recordsLinked to original sources

A prospective outcome study of patients with clot in an ulcer and the effect of irrigation.

BACKGROUND: The proper management of patients with clots in an ulcer base has not been clearly defined by prospective studies. Variable prevalence and rebleeding rates may be explained by differing degrees of vigor used to clear the clot, as removal may reveal other stigmata. We prospectively assessed the natural histories of patients with clots after vigorous irrigation, employing a management strategy of endoscopic therapy for patients with high-risk stigmata and observation of those with clots resistant to washing or low-risk findings. METHODS: Forty-six patients with upper gastrointestinal bleeding found to have a clot in an ulcer had irrigation with a 3.2 mm bipolar probe for up to 5 minutes. Stigmata after washing were recorded; endoscopic therapy was given for active bleeding that persisted > or = 5 min or for nonbleeding visible vessels. Patients were observed in the hospital for > or = 3 days. RESULTS: Findings revealed after irrigation were adherent clot, 26 (57%); clean base, 1 (2%); flat spot, 5 (11%); nonbleeding visible vessel, 7 (13%); oozing, 6 (13%); and spurting, 1 (2%). Two of the 26 (8%) with adherent clots after washing rebled; endoscopic therapy resulted in no further bleeding. One of the 14 (7%) with active bleeding or visible vessels treated with hemostatic therapy rebled; repeat endoscopic therapy resulted in no further bleeding. No deaths occurred. CONCLUSIONS: Irrigation appears to be useful in patients with upper gastrointestinal bleeding who have ulcers with clots. The endoscopic findings present after washing can be used to dictate the appropriate management at initial endoscopy. Application of hemostatic therapy in patients with active bleeding or nonbleeding visible vessels and observation of patients with other stigmata, including clots resistant to washing, resulted in an excellent outcome.

Blood Coagulation

Randomized comparison of ligation versus ligation plus sclerotherapy in patients with bleeding esophageal varices.

BACKGROUND & AIMS: Combining endoscopic sclerotherapy with ligation has been proposed to hasten variceal eradication. A randomized trial was performed comparing combination ligation plus sclerotherapy with ligation alone in patients with major bleeding from esophageal varices. METHODS: Forty-one patients were randomly assigned to receive ligation or ligation plus 1 mL 1.5% tetradecyl injected just above each band. Treatment was repeated weekly until varices were eradicated. Repeat endoscopy was performed for rebleeding and every 3 months after eradication. RESULTS: No significant differences were found between combined therapy and ligation in rebleeding (29% vs. 30%), blood transfused (3.1 +/- 1.1 vs. 2.0 +/- 0.8 U), hospital days (9.3 +/- 2.1 vs. 7.5 +/- 1.2), complications (29% vs. 10%), or deaths (14% vs. 15%) during a mean follow-up period of 28 weeks. Combined therapy required significantly more sessions to achieve eradication (4.9 +/- 0.6 vs. 2.7 +/- 0.4) and greater time per treatment session (18.3 +/- 1.7 vs. 13.3 +/- 0.5 minutes). CONCLUSIONS: Combined ligation plus sclerotherapy does not reduce the number of treatment sessions required for variceal eradication as compared with ligation alone. Combined therapy lengthens the time required for treatment without improving efficacy or decreasing complications. Thus, combined ligation and sclerotherapy should not be used to treat patients with bleeding esophageal varices.

Adult

Thymidylate synthase mRNA level in adenocarcinoma of the stomach: a predictor for primary tumor response and overall survival.

PURPOSE: We tested the hypothesis that polymerase chain reaction (PCR) quantitation of the enzyme thymidylate synthase (TS) within a primary adenocarcinoma of the stomach, has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy. PATIENTS AND METHODS: Before systemic chemotherapy, the genetic expression of TS (TSmRNA level) was determined using a PCR method. Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene. Chemotherapy consisted of two cycles of protracted infusion (PI) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w. Cisplatin 100 mg/m2 was administered on day 1. RESULTS: Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3) (range, 0.9 to 20.1 x 10(-3)). Thirty-five percent of patients had measurable responses in their primary tumors. The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant (P < .001). The median survival time was 43+ months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median (P = .003). CONCLUSION: The genetic expression of TS (TSmRNA level) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer. Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor.

Adenocarcinoma

Endoscopic ligation compared with sclerotherapy for treatment of esophageal variceal bleeding. A meta-analysis.

PURPOSE: To compare the effect of endoscopic ligation with that of sclerotherapy in the treatment of patients with bleeding esophageal varices. DATA SOURCES: Strategies to identify published and unpublished research included searches of computerized bibliographic and scientific citations, review of citations in relevant primary articles, searches of services providing information on unpublished studies, contact with primary investigators and the ligation equipment manufacturer, and review of proceedings from pertinent scientific meetings. STUDY SELECTION: From 158 potentially relevant articles, duplicate independent review identified 7 relevant randomized trials that compared endoscopic ligation with sclerotherapy for the treatment of patients with bleeding esophageal varices. DATA ABSTRACTION: Independent, duplicate data abstraction of the population, intervention, outcome, and methodologic quality of the trials was done. DATA SYNTHESIS: Ligation therapy compared with sclerotherapy reduced the rebleeding rate (odds ratio, 0.52 [95% CI, 0.37 to 0.74]), the mortality rate (odds ratio, 0.67 [CI, 0.46 to 0.98]), and the rate of death due to bleeding (odds ratio, 0.49 [CI, 0.24 to 0.996]). Four patients would need to be treated with ligation instead of sclerotherapy to avert one rebleeding episode, and 10 would need to be treated with ligation instead of sclerotherapy to prevent one death. Esophageal strictures occurred less frequently with ligation (odds ratio, 0.10 [CI, 0.03 to 0.29]), but no significant differences were seen between treatments for pulmonary infections or bacterial peritonitis. Additionally, the number of endoscopic treatment sessions required to achieve variceal obliteration was lower with ligation than with sclerotherapy. CONCLUSIONS: On the basis of lower rates of rebleeding, mortality, and complications and the need for fewer endoscopic treatments, ligation should be considered the endoscopic treatment of choice for patients with esophageal variceal bleeding.

Cause of Death

Interobserver agreement and predictive value of endoscopic findings for H. pylori and gastritis in normal volunteers.

BACKGROUND: Endoscopic findings such as erythema are frequently labeled as gastritis. We sought to determine interobserver agreement for specific endoscopic features and assess the diagnostic value of features with good agreement for Helicobacter pylori and histologic gastritis. METHODS: Fifty-two healthy subjects without ulcers, erosions, or hemorrhages had a full endoscopy recorded on video tape. Biopsy specimens were examined for H. pylori and gastritis. Two endoscopists independently reviewed the tapes for predefined features (erythema, area gastricae, clefts, and nodularity) in the gastric body and antrum. Diagnostic value of endoscopic features with acceptable agreement (kappa > 0.40) was then determined for H. pylori and gastritis. RESULTS: Kappa was greater than 0.40 only for prominent body area gastricae (0.49), body nodularity (0.65), and antral nodularity (0.68). For antral nodularity, sensitivity was 32%, specificity was 96%, and positive predictive value was 90% for H. pylori. when both antral nodularity and body area gastricae were both present, sensitivity was only 18% but specificity and positive predictive value were 100%. CIRCULATION: Interobserver agreement is poor for some features such as erythema labeled as gastritis. Antral nodularity is a fairly reproducible finding and is very specific, though not sensitive, for H. pylori gastritis.

Adult

A randomized double-blind comparison of placebo, etodolac, and naproxen on gastrointestinal injury and prostaglandin production.

BACKGROUND: NSAIDs frequently cause gastrointestinal injury and increase the risk of ulcer complications. We compared an NSAID suggested to cause less gastric injury (etodolac) with a standard NSAID (naproxen) and a placebo in a 4-week double-blind trial assessing the effects on gastroduodenal injury, symptoms, and prostaglandin production in healthy volunteers. METHODS: Fifty-two healthy volunteers not taking NSAIDs, alcohol, antibiotics, bismuth, or anti-ulcer drugs: placebo, etodolac 400 mg, or naproxen 500 mg b.i.d. for 4 weeks. Endoscopies with biopsies were repeated at weeks 1 and 4. The number and dimensions of ulcers and erosions were recorded to quantitate injury. RESULTS: At week 1 the mean number and area of gastric ulcers per subject were greater with naproxen than placebo or etodolac (area: naproxen, 7.4 mm2; placebo, 0.6 mm2, p = 0.02 vs naproxen; etodolac, 2.1 mm2, p = 0.06 vs naproxen). Ulcer scores at week 4 were low and comparable in the three groups. The mean number and area of gastric erosions per subject were greatest with naproxen at both weeks 1 and 4 (week 4 area: naproxen, 58.3 mm2; placebo, 29.0 mm2; etodolac, 13.9 mm2, p < 0.02, naproxen vs placebo and vs etodolac). Placebo injury was presumably due to biopsies at prior endoscopy. Gastric mucosal prostaglandin E2 production did not change significantly from baseline after 1 or 4 weeks of treatment with placebo or etodolac, but did decrease significantly with naproxen (week 0, 1689; week 1, 479; week 4, 577 pg/mg protein). Gastrointestinal symptoms were present in only 1 (5%) of 20 visits in which endoscopy showed no erosions or ulcers vs 21 (26%) of 82 visits in which a mucosal defect was identified (p = 0.666). CONCLUSION: Gastric injury with 4 weeks of etodolac is comparable to that seen with placebo and significantly less than that occurring with naproxen, presumably due to the fact that etodolac does not suppress gastric mucosal prostaglandin production, whereas naproxen leads to a significant reduction.

Adult

Interaction of NSAIDs and Helicobacter pylori on gastrointestinal injury and prostaglandin production: a controlled double-blind trial.

BACKGROUND: H. pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) are major causes of gastroduodenal injury in man. We assessed the effect of daily NSAID ingestion on gastric histology and the interaction of H. pylori infection and NSAID ingestion on gross and histological injury and prostaglandin production. METHODS: Fifty-two healthy volunteers with normal baseline endoscopy were randomly assigned to receive identical-appearing naproxen 500 mg b.d., etodolac 400 mg b.d., or placebo b.d. for 4 weeks. The number and size of all erosions and ulcers were recorded by endoscopy at weeks 1 and 4. Biopsies taken at baseline, week 1 and week 4 were assessed for H. pylori, histology and gastric prostaglandin E2 production. RESULTS: No significant changes occurred with treatment in any histological feature in the three study groups or in H. pylori positive or negative subsets. Antral inflammation scores (scale, 0-6) for the NSAID group were: week 0--1.2 +/- 0.3; week 1--1.1 +/- 0.3; week 4--1.3 +/- 0.3; findings of 'chemical gastritis' were not seen. No significant difference in gross gastroduodenal injury (number or total surface area of ulcers or erosions) was seen between H. pylori positive and negative subjects in the three groups at week 1 or 4. Baseline prostaglandin E2 production was significantly higher in H. pylori positive subjects (2398 +/- 400 vs. 1064 +/- 255 pg/mg protein) and decreased significantly with 1 week of naproxen in H. pylori positive and negative subjects. CONCLUSIONS: NSAID ingestion does not cause diffuse histological injury. Any diffuse histological injury in the gastric mucosa is related to the presence of H. pylori, and this H. pylori-associated gastritis is not altered by NSAID ingestion. Furthermore, the development of gross gastroduodenal damage with 4 weeks of NSAID use is not influenced by underlying H. pylori infection.

Adolescent

Prospective study of fluconazole suspension for the treatment of oesophageal candidiasis in patients with AIDS.

BACKGROUND: Oesophageal candidiasis is the most common cause of oesophageal symptoms in patients with AIDS. Antifungal therapy, given as a suspension, may be better tolerated than capsules or tablets in children or patients with oesophageal symptoms. We performed a prospective study of the safety and efficacy of fluconazole suspension. METHODS: Patients with HIV infection; odynophagia, dysphagia, or retrosternal pain; endoscopic evidence of white plaques or exudate in the oesophagus; and microscopic confirmation of fungal infection on biopsy or brushing specimens were eligible. Patients received fluconazole oral suspension (200 mg loading dose followed by 100 mg q.d.s.). Therapy was continued for 2 weeks after symptom resolution. Repeat endoscopy was performed after completion of therapy. RESULTS: Forty-two patients enrolled in the study: 40 were male, mean (+/- s.e.) age was 37 +/- 2 years and mean CD4 cell count was 67 +/- 14/mm3. One patient was not evaluable because he received amphotericin during the first week of therapy. Symptoms resolved in all 41 evaluable patients; 17 (41%) had resolution by 1 week, 37 (90%) by 2 weeks, and 40 (98%) by 3 weeks. Endoscopic resolution occurred in 35 (95%) of 37 patients who underwent repeat endoscopy. Adverse events (skin rash in 1, nausea/vomiting in 2, elevated liver tests in 2) led to early termination of therapy in 5 patients, all of whom had clinical and endoscopic cure. CONCLUSIONS: Symptoms resolved in 100% of patients with AIDS and oesophageal candidiasis receiving an oral suspension of fluconazole, and 90% of patients had symptom resolution within 2 weeks. Determining whether the more rapid clinical cure in this study, compared with a previous trial which employed capsules, is related to an additional topical antifungal effect of the suspension, will require further study.

AIDS-Related Opportunistic Infections

Limited efficacy of omeprazole-based dual and triple therapy for Helicobacter pylori: a randomized trial employing "optimal" dosing.

OBJECTIVES: To evaluate the efficacy and side effects of dual omeprazole/amoxicillin therapy for Helicobacter pylori given in "optimal" fashion (omeprazole twice a 3 g of amoxicillin daily, drugs started concurrently, 2 wk of therapy) and to assess the utility of adding a second antibiotic, tetracyline. METHODS: Sixty healthy volunteers with H. pylori infection documented by 13C-urea breath test were randomly assigned to receive 2 wk of therapy with either 1) omeprazole 20 mg b.i.d. and amoxicillin 1 g t.i.d. (OA), or 2) OA plus tetracycline 500 mg t.i.d. (OAT). Patients returned after 2 wk for pill count and clinical assessment, and 13C-urea breath test was repeated 4 wk after the end of therapy. RESULTS: H. pylori was eradicated in 15 (50%) of 30 patients receiving OA therapy and in nine (30%) of 30 given OAT (p = 0.19). Side effects occurred in five (17%) patients in the OA group [two (7%) discontinued therapy due to side effects] and eight (27%) of the OAT group [three (10%) stopped therapy due to side effects]. Good compliance (> 80% of prescribed study drugs taken) was seen in 87% of each group, and eradication rates were 54% and 35% among patients with good compliance in the OA and OAT groups (p = 0.26). CONCLUSIONS: Dual therapy with omeprazole and amoxicillin, when given in "optimal" fashion, had limited efficacy, with an eradication rate of 50%. The addition of tetracycline to the dual therapy did not improve the rate of cure. Because virtually all of our subjects were from minority groups, with over three-fourths Hispanic, we speculate that differences in H. pylori strains or host factors may explain, at least in part, the discrepancy between our results and those in Northern European populations.

Adult

Esophageal disease in human immunodeficiency virus infection.

Up to 40% of patients with the acquired immunodeficiency syndrome may develop symptoms of esophageal disease. Candida esophagitis is responsible for the majority of the cases of esophageal disease; cytomegalovirus, herpes simplex, idiopathic esophageal ulcers, and Kaposi's sarcoma account for most of the remaining cases. Although endoscopy with esophageal biopsy and brushing is the gold standard for the diagnosis of esophageal disease in the acquired immunodeficiency syndrome, we generally recommend initial empiric therapy with an antifungal agent in patients with esophageal symptoms. Since effective treatment is available for most cases of esophageal disease in the acquired immunodeficiency syndrome, we recommend endoscopic evaluation in patients who do not respond to empiric therapy within 1 to 2 weeks.

Esophageal Diseases

The natural history of esophageal candidiasis after successful treatment in patients with AIDS.

BACKGROUND/AIMS: Antifungal therapy cures esophageal candidiasis in most patients with acquired immunodeficiency syndrome, but the subsequent course of these patients is not established. This study examines the natural history of esophageal candidiasis after successful treatment. METHODS: Patients with endoscopic and clinical resolution of esophageal candidiasis after therapy were followed up prospectively with monthly clinical assessment and repeat endoscopy every 3 months or earlier if esophageal symptoms recurred or if the patient was to begin antifungal therapy for another reason. RESULTS: Thirty-five patients met entry criteria; 21 agreed to enroll. The patients were followed up for a mean of 23 +/- 4 weeks after their initial posttreatment endoscopy. Nineteen patients (90%) had recurrent esophageal candidiasis at a mean of 11 +/- 2 weeks (range, 3-36 weeks). The 19 patients had 31 recurrences; 25 (81%) occurred < or = 10 weeks after documented cure of the prior episode of esophageal candidiasis. Twenty-two (71%) of the 31 recurrent episodes were symptomatic, and only 9 (29%) were associated with oral thrush. All symptomatic recurrences responded to treatment with fluconazole; 1 of 22 (5%) failed to show endoscopic resolution. CONCLUSIONS: Almost all patients with acquired immunodeficiency syndrome and successfully treated esophageal candidiasis develop a recurrence, usually within 2-3 months. Two thirds are symptomatic and one third are associated with oral thrush. Subsequent episodes of esophageal candidiasis respond well to oral therapy.

Acquired Immunodeficiency Syndrome

Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices.

OBJECTIVE: Comparison of the safety and efficacy of endoscopic sclerotherapy and ligation for the treatment of bleeding esophageal varices. DESIGN: Randomized, controlled trial. SETTING: An urban county hospital. PATIENTS: Patients with clinically severe bleeding from esophageal varices. INTERVENTION: A total of 77 patients were randomly assigned to receive sclerotherapy or ligation at the initial endoscopic examination. Treatment was repeated weekly until variceal obliteration was achieved. After eradication, patients had endoscopic examinations every 3 months or for any episode of rebleeding. Recurrent varices were treated with the originally assigned form of endoscopic therapy. MEASUREMENTS: Patients were assessed for further bleeding, for transfusion requirements, for time in hospital, for variceal eradication, for number of treatment sessions required, for complications, for treatment failure, and for risk of death. RESULTS: Rebleeding tended to be less frequent with ligation than with sclerotherapy: 10 of 38 (26%) compared with 17 of 39 (44%) (difference, 17% [95 CI, -4% to 38%]), but results in the two groups were comparable for blood transfusions, for length of hospital stay, and for risk of death. Comparison of Kaplan-Meier estimates of time to rebleeding and death showed no statistical differences between treatments. Complications were less common in the ligation group: fewer patients in the ligation group had esophageal strictures (0 of 38 compared with 13 of 39 [33%]; P < 0.001) and had complicated esophageal ulcers (1 of 38 [2.6%] compared with 6 of 39 [15%]; P = 0.11). In addition, fewer ligation treatments were required to achieve variceal eradication (4.1 +/- 0.3 compared with 6.2 +/- 0.4; P < 0.001). CONCLUSION: Endoscopic ligation causes statistically fewer local complications than sclerotherapy and achieves variceal eradication more rapidly. Ligation is a viable alternative to sclerotherapy and may have some advantages as a treatment for bleeding esophageal varices.

Adult