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N Engl J Med

Effect of computed tomography of the appendix on treatment of patients and use of hospital resources.

Rao PM. Rhea JT. Novelline RA. Mostafavi AA. McCabe CJ.
Department of Radiology, Massachusetts General Hospital, Boston 02114, USA.
BACKGROUND: In patients with clinically suspected appendicitis, computed tomography (CT) is diagnostically accurate. However, the effect of routine CT of the appendix on the treatment of such patients and the use of hospital resources is unknown. METHODS: We performed appendiceal CT on 100 consecutive patients in the emergency department who, on the basis of history, physical examination, and laboratory results, were to be hospitalized for observation for suspected appendicitis or for urgent appendectomy. Outcomes were determined at surgery and by pathological examination in 59 patients, and by clinical follow-up two months later in 41 patients. Treatment plans made before CT were compared with the patients' actual treatment. We also determined the costs of surgery that revealed no appendicitis (from data on 61 patients), one day of observation in the hospital (from data on 350 patient-days in patients with suspected appendicitis), and appendiceal CT (from data on all pelvic CT examinations in 1996). RESULTS: Fifty-three patients had appendicitis, and 47 did not. The interpretations of the appendiceal CT scans were 98 percent accurate. The results of CT led to changes in the treatment of 59 patients. These changes resulted in the prevention of unnecessary appendectomy in 13 patients, admission to the hospital for observation in 18 patients, admission to the hospital for observation before necessary appendectomy in 21 patients, and admission to the hospital for observation before the diagnosis of other conditions by CT in 11 patients. The effects of performing appendiceal CT on the use of hospital resources included the prevention of unnecessary appendectomy in 13 patients (for a savings of $47,281) and the prevention of unnecessary hospital admission for 50 patient-days (for a savings of $20,250). After the cost of 100 appendiceal CT studies ($22,800) was subtracted, the overall savings was $447 per patient. CONCLUSIONS: Routine appendiceal CT performed in patients who present with suspected appendicitis improves patient care and reduces the use of hospital resources.

A comparison of botulinum toxin and saline for the treatment of chronic anal fissure.

Maria G. Cassetta E. Gui D. Brisinda G. Bentivoglio AR. Albanese A.
Istituto di Clinica Chirurgica, Universita Cattolica del Sacro Cuore, Rome, Italy.
BACKGROUND: Chronic anal fissure is a tear in the lower half of the anal canal that is maintained by contraction of the internal anal sphincter. Sphincterotomy, the most widely used treatment, is a surgical procedure that permanently weakens the internal sphincter and may lead to anal deformity and incontinence. METHODS: We conducted a double-blind, placebo-controlled study of botulinum toxin for the treatment of chronic anal fissure in 30 consecutive symptomatic adults. All the patients received two injections (total volume, 0.4 ml) into the internal anal sphincter; the treated group (15 patients) received 20 U of botulinum toxin A, and the control group (15 patients) received saline. Success was defined as healing of the fissure (formation of a scar), and symptomatic improvement was defined as the presence of a persistent fissure without symptoms. RESULTS: After two months, 11 patients in the treated group and 2 in the control group had healed fissures (P=0.003); 13 in the treated group and 4 in the control group had symptomatic relief (P=0.003). The maximal voluntary pressures were similar to those at base line in both groups, and the resting anal pressure was reduced by 25 percent in the treated group but not in the control group. Three patients in the control group later underwent sphincterotomy, and 10 received botulinum-toxin injections (20 U). Of the latter, seven had healed fissures after two months; the other three left the study and underwent surgery. Four patients in the treated group were later re-treated (with 25 U of botulinum toxin); all had healed fissures after two months. One patient in the control group had temporary flatus incontinence after treatment with botulinum toxin. No relapses occurred during an average of 16 months of follow-up. CONCLUSIONS: Local infiltration of botulinum toxin into the internal anal sphincter is an effective treatment of chronic anal fissure.

Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.

Vento S. Garofano T. Renzini C. Cainelli F. Casali F. Ghironzi G. Ferraro T. Concia E.
Department of Infectious Diseases, University of Verona, Italy.
BACKGROUND: Hepatitis A virus (HAV) infection rarely causes fulminant hepatic failure in people with no underlying liver disease. There are limited data on the course of this infection in patients with chronic hepatitis B and chronic hepatitis C. METHODS: We prospectively followed, from June 1990 to July 1997, 595 adults with biochemical and histologic evidence of chronic hepatitis B (163 patients) or chronic hepatitis C (432 patients) who were seronegative for HAV antibodies. All were tested every four months for serum IgM and IgG antibodies to HAV. RESULTS: Twenty-seven patients acquired HAV superinfection, 10 of whom had chronic hepatitis B and 17 of whom had chronic hepatitis C. One of the patients with chronic hepatitis B, who also had cirrhosis, had marked cholestasis (peak serum bilirubin level, 28 mg per deciliter [479 micromol per liter]); the other nine had uncomplicated courses of hepatitis A. Fulminant hepatic failure developed in seven of the patients with chronic hepatitis C, all but one of whom died. The other 10 patients with chronic hepatitis C had uncomplicated courses of hepatitis A. CONCLUSIONS: Although most patients with chronic hepatitis B who acquired HAV infection had an uncomplicated course, patients with chronic hepatitis C had a substantial risk of fulminant hepatitis and death associated with HAV superinfection. Our data suggest that patients with chronic hepatitis C should be vaccinated against hepatitis A.

A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.

Year 1998
Yeomans ND. Tulassay Z. Juhasz L. Racz I. Howard JM. van Rensburg CJ. Swannell AJ. Hawkey CJ.
Department of Medicine, University of Melbourne, Western Hospital, Footscray, Victoria, Australia.
BACKGROUND: Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. METHODS: We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months. RESULTS: At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P

Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.

Year 1998
Hawkey CJ. Karrasch JA. Szczepanski L. Walker DG. Barkun A. Swannell AJ. Yeomans ND.
Division of Gastroenterology, University Hospital, Nottingham, United Kingdom.
BACKGROUND: Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs. METHODS: In a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months. RESULTS: At eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

Year 1998
Cook D. Guyatt G. Marshall J. Leasa D. Fuller H. Hall R. Peters S. Rutledge F. Griffith L. McLellan A. Wood G. Kirby A.
McMaster University, Hamilton, Ont., Canada.
BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

Liver failure and death after exposure to microcystins at a hemodialysis center in Brazil.

Year 1998
Jochimsen EM. Carmichael WW. An JS. Cardo DM. Cookson ST. Holmes CE. Antunes MB. de Melo Filho DA. Lyra TM. Barreto VS. Azevedo SM. Jarvis WR.
Hospital Infections Program, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
BACKGROUND: Hemodialysis is a common but potentially hazardous procedure. From February 17 to 20, 1996, 116 of 130 patients (89 percent) at a dialysis center (dialysis center A) in Caruaru, Brazil, had visual disturbances, nausea, and vomiting associated with hemodialysis. By March 24, 26 of the patients had died of acute liver failure. METHODS: A case patient was defined as any patient undergoing dialysis at dialysis center A or Caruaru's other dialysis center (dialysis center B) during February 1996 who had acute liver failure. To determine the risk factors for and the source of the outbreak, we conducted a cohort study of the 130 patients at dialysis center A and the 47 patients at dialysis center B, reviewed the centers' water supplies, and collected water, patients' serum, and postmortem liver tissue for microcystin assays. RESULTS: One hundred one patients (all at dialysis center A) met the case definition, and 50 died. Affected patients who died were older than those who survived (median age, 47 vs. 35 years, P

Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome).

Year 1998
Gahl WA. Brantly M. Kaiser-Kupfer MI. Iwata F. Hazelwood S. Shotelersuk V. Duffy LF. Kuehl EM. Troendle J. Bernardini I.
Heritable Disorders Branch, National Institute of Child Health and Human Development, Bethesda, MD 20892-1830, USA.
BACKGROUND: Hermansky-Pudlak syndrome is characterized by oculocutaneous albinism, a storage-pool deficiency, and lysosomal accumulation of ceroid lipofuscin, which causes pulmonary fibrosis and granulomatous colitis in some cases. All identified affected patients in northwest Puerto Rico are homozygous for a 16-bp duplication in exon 15 of a recently cloned gene, HPS. We compared the clinical and laboratory characteristics of these patients with those of patients without the 16-bp duplication. METHODS: Forty-nine patients -- 27 Puerto Ricans and 22 patients from the mainland United States who were not of Puerto Rican descent -- were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determine which patients carried the 16-bp duplication. RESULTS: Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication, whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-bp duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the predicted value. High-resolution computed tomography in 12 patients with the 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis in three and no fibrosis in the rest. Inflammatory bowel disease developed in eight patients (four in each group) between 3 and 25 years of age. CONCLUSIONS: The 16-bp duplication in exon 15 of HPS, which we found only in Puerto Rican patients, is associated with a broad range of pigmentation and an increased risk of restrictive lung disease in adults.

Incidence of hereditary nonpolyposis colorectal cancer and the feasibility of molecular screening for the disease.

Year 1998
Aaltonen LA. Salovaara R. Kristo P. Canzian F. Hemminki A. Peltomaki P. Chadwick RB. Kaariainen H. Eskelinen M. Jarvinen H. Mecklin JP. de la Chapelle A.
Department of Medical Genetics, Haartman Institute, University of Helsinki, Finland.
BACKGROUND: Genetic disorders that predispose people to colorectal cancer include the polyposis syndromes and hereditary nonpolyposis colorectal cancer. In contrast to the polyposis syndromes, hereditary nonpolyposis colorectal cancer lacks distinctive clinical features. However, a germ-line mutation of DNA mismatch-repair genes is a characteristic molecular feature of the disease. Since clinical screening of carriers of such mutations can help prevent cancer, it is important to devise strategies applicable to molecular screening for this disease. METHODS: We prospectively screened tumor specimens obtained from 509 consecutive patients with colorectal adenocarcinomas for DNA replication errors, which are characteristic of hereditary colorectal cancers. These replication errors were detected through microsatellite-marker analyses of tumor DNA. DNA from normal tissue from the patients with replication errors was screened for germ-line mutations of the mismatch-repair genes MLH1 and MSH2. RESULTS: Among the 509 patients, 63 (12 percent) had replication errors. Specimens of normal tissue from 10 of these 63 patients had a germ-line mutation of MLH1 or MSH2. Of these 10 patients (2 percent of the 509 patients), 9 had a first-degree relative with endometrial or colorectal cancer, 7 were under 50 years of age, and 4 had had colorectal or endometrial cancer previously. CONCLUSIONS: In this series of patients with colorectal cancer in Finland, at least 2 percent had hereditary nonpolyposis colorectal cancer. We recommend testing for replication errors in all patients with colorectal cancer who meet one or more of the following criteria: a family history of colorectal or endometrial cancer, an age of less than 50 years, and a history of multiple colorectal or endometrial cancers. Patients found to have replication errors should undergo further analysis for germ-line mutations in DNA mismatch-repair genes.

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