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C M Wilcox

Publications and source records attributed to C M Wilcox.

At least 73 records · Page 4Linked to original sources
PubMed1997

A randomized, double-blind comparison of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis.

This multicenter, randomized, double-blind study compared the efficacy and safety of itraconazole oral solution and fluconazole tablets in the treatment of esophageal candidiasis. One hundred twenty-six immunocompromised patients with esophageal candidiasis were treated with itraconazole oral solution or fluconazole tablets (both at 100-200 mg) once daily for 3-8 weeks, for 2 weeks beyond the resolution of symptoms, and were then followed for 4 more weeks. Severity of symptoms was assessed weekly during treatment and every 2 weeks during follow-up. Patients treated with itraconazole oral solution had a rate of clinical response (cured or improved) comparable to that of patients treated with fluconazole (94% vs. 91%). The mycologic eradication rate was 92% for itraconazole and 78% for fluconazole. Both treatments were well tolerated. Results from treatment with once-daily itraconazole oral solution was clinically comparable to those with fluconazole and is an alternative for the treatment of esophageal candidiasis in immunocompromised patients.

Administration, Oral↗
PubMed1997

A prospective characterization of upper gastrointestinal hemorrhage presenting with hematochezia.

BACKGROUND: Although hematochezia is well recognized to occur in patients with upper GI hemorrhage (UGIH), its prevalence, clinical presentation, causes, and outcome in these patients are not well defined. METHODS: Consecutive patients evaluated for UGIH by the gastroenterology service at a large inner city hospital from August 1, 1990, through September 31, 1994, were prospectively identified. Vital signs and stool color were recorded on admission to the emergency department. Endoscopy was performed in all patients, usually within 48 h of admission. The cause of bleeding was determined by endoscopy, surgery, or autopsy. RESULTS: Over the 50-month study period, 727 patients with UGIH meeting the inclusion criteria were evaluated, with 104 (14%) presenting with hematochezia (18 with bright red blood and 86 with maroon blood). The most common causes of bleeding were duodenal ulcer (44%) and gastric ulcer (20%). In comparison with patients with melena (N = 441), patients with hematochezia were older (55 vs 50 yr, p < 0.01) and more likely to present with duodenal ulcer bleeding (43 vs 25%, p < 0.01); no differences in vital signs, including prevalence of shock, or admission Hb concentration were found. However, transfusion requirements (5.4 vs 4.0 units, p = 0.01), need for surgery (11.7 vs 5.7%, p = 0.03), and mortality (13.6 vs 7.5%, p = 0.05) were significantly higher in patients with hematochezia than in those with melena, suggesting more severe bleeding and a worse outcome. CONCLUSIONS: Hematochezia is common in patients with UGIH, and the presenting features are similar to those of patients with melena. Duodenal ulcer is the most common cause of bleeding associated with hematochezia. Patients with UGIH and hematochezia seem to have a worse prognosis.

Adolescent↗
PubMed1997

Features associated with painless peptic ulcer bleeding.

BACKGROUND: Painless peptic ulcer bleeding is well recognized, although clinical features associated with the absence of abdominal pain have received little attention. METHODS: Patients admitted for upper GI bleeding at a large inner-city hospital were questioned prospectively at the time of initial evaluation regarding the presence of any dyspepsia and/or abdominal pain, including nocturnal symptoms, within 1 wk of admission. A number of other clinical and endoscopic features were also recorded. The cause of upper GI bleeding was determined in most patients by endoscopy. Patients were excluded if a reliable history could not be obtained or if the ulcer was malignant. RESULTS: Over the 50-month study period, 449 patients with upper GI bleeding caused by peptic ulcer were evaluated, including 236 with gastric ulcer (53 prepyloric) and 213 with duodenal ulcer (28 with channel ulcer). Of these patients, abdominal pain was absent in 191 (43%; 95% confidence interval, 38-47%). There appeared to be no relationship of pain to race, gender, alcohol use, ulcer location, use and duration of nonsteroidal anti-inflammatory drugs, history of ulcer, or comorbidity. The only statistically significant correlates with abdominal pain were ulcer size (77% of patients with ulcers >2 cm reported pain as compared with 49% of patients with ulcers <1 cm; p < 0.001), tobacco use (p = 0.041), and age <80 yr (p = 0.02). CONCLUSIONS: Approximately half the patients with a bleeding peptic ulcer have no abdominal pain. Large ulcer size, use of tobacco, and age <80 yr seem to be the main determinants of ulcer-related pain in this setting.

Adult↗
PubMed1997

Blood urea nitrogen to creatinine concentration in gastrointestinal bleeding: a reappraisal.

BACKGROUND: The blood urea nitrogen to creatinine ratio (BUN/CREAT) is believed to reliably discriminate upper gastrointestinal bleeding (UGIB) from lower gastrointestinal bleeding (LGIB). However, studies evaluating subsets of bleeders in whom this ratio may have real diagnostic utility are lacking. METHODS: Over a 50-month period, all patients evaluated for UGIB and LGIB by our gastroenterology consultative service had demographic, clinical, and laboratory findings recorded on admission. Endoscopic evaluation was performed in most patients for diagnosis. RESULTS: A total of 790 patients with UGIB and 162 with LGIB were studied. Peptic ulcer disease (57%) and esophageal varices (10%) were the most common causes of UGIB, whereas diverticulosis was etiologic in 54% of LGIB episodes. The mean (+/- SD) BUN/CREAT ratio was significantly higher in UGIB than LGIB (22.5 +/- 11.5 vs 15.9 +/- 8.2; p = 0.0001). When comparing UGIB patients without hematemesis or diagnostic nasogastric aspirate to patients with LGIB, significant differences were found for patients with melena (20.1 +/- 8.4 vs 15.9; p = 0.001) but not hematochezia (18.6 +/- 9.1 vs 15.9; p = 0.12), and overlap was great. Using a ratio of < or = 33, the sensitivity and specificity for LGIB was 96 and 17%, respectively. There was a significant correlation of transfusion requirements and admission hematocrit to this ratio, whereas admission vital signs were not found to correlate significantly. CONCLUSIONS: Although the BUN/CREAT ratio is higher in UGIB compared with LGIB, the degree of overlap, especially in patients without hematemesis, suggests this value to have poor discriminatory ability. The degree of elevation correlates best with transfusion requirements rather than admission vital signs.

Aged↗
PubMed1996

Etiology, evaluation, and outcome of jaundice in patients with acquired immunodeficiency syndrome.

Although liver test abnormalities are frequently identified in patients with acquired immunodeficiency syndrome (AIDS), the causes, evaluation, and outcome of jaundice in these patients have not been systematically evaluated. From August 1, 1990 through September 1, 1994, all human immunodeficiency virus (HIV)-infected patients with liver test abnormalities seen by the gastroenterology service at a large, inner-city hospital were prospectively identified. Jaundice was defined as a serum bilirubin concentration > or = 3 mg/dL. The etiology of jaundice was determined by the pattern of liver biochemistry test abnormalities, radiographic studies, liver biopsy, clinical follow-up, and autopsy. During the study period, 541 HIV-infected patients (511 with AIDS) were evaluated for liver disease by our service; 36 of these patients had jaundice (7 percent). The most common causes of jaundice were drug-induced hepatitis, occurring in 11 patients (31 percent), and alcoholic liver disease, occurring in 5 (13 percent). Opportunistic infections or neoplasms were identified as the cause of jaundice in 11 patients (30 percent), with 4 having intrahepatic disease and 7 having extrahepatic disease. Multiple potential causes were seen in 3 patients. Abdominal ultrasonography (US) and computed tomography (CT) were helpful in suggesting the underlying cause of disease. The short-term mortality was high, with 9 patients dying during the hospitalization (25 percent) and 7 patients dying within 6 months of evaluation. Liver disease was the cause of death in 7 of these patients. In conclusion, jaundice is uncommon in AIDS and may result from a variety of both opportunistic and non-opportunistic etiologies. Drug-induced hepatitis is the most common cause and may be fatal. Long-term survival was poor.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Long-term use of nonsteroidal antiinflammatory drugs and other chemopreventors and risk of subsequent colorectal neoplasia.

Our objective was to study the relationship between dispensed aspirin, nonaspirin nonsteroidal antiinflammatory drugs (NSAIDs), steroidal antiinflammatory drugs (SAIDs), acetaminophen, calcium, psyllium, and multivitamin preparations and the risk for subsequent colorectal adenoma and adenocarcinoma. The design was a case-control study. The patient population was from a large municipal teaching hospital in Atlanta, Georgia. In logistic regression models, the risk of colorectal adenoma or adenocarcinoma decreased in the first two years of continuous NSAID use in a linear, time-dependent manner. The risk of colorectal neoplasia after two years of continuous NSAID use was reduced significantly (P < 0.01) as compared to nonusers. Risk reduction appeared greater for adenocarcinoma than adenoma. The use of SAIDs, calcium, multivitamins, and psyllium, as prescribed to our patient population during the mean six-year study period, conferred no measurable risk reduction. These results suggest that in prospective chemoprevention trials, a significant risk reduction can be expected after only two years of aspirin use, in doses similar to those recommended for the prevention of cardiovascular disease, or nonaspirin NSAIDs [correction of nonaspirin. NSAIDs], in doses commonly prescribed for the management of musculoskeletal pain. The results also imply that any short-term reduction in the incidence of colorectal adenoma detected in a phase II trial would underestimate the chemopreventive effect of NSAIDs on the risk of adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Endoscopic-pathologic correlates of Candida esophagitis in acquired immunodeficiency syndrome.

Although Candida esophagitis is one of the most common opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS), there has been no systematic study of the endoscopic and pathologic manifestations of this disease. During a 53-month period, 141 patients with AIDS and Candida esophagitis were studied. All patients had the severity of esophagitis graded prospectively and esophageal mucosal biopsies performed. Tissue biopsies were evaluated for histologic evidence of ulceration, extent of candidiasis, and presence of viral cytopathic effect. Follow-up was obtained. There appeared to be a uniform endoscopic appearance; with increasing severity, the scattered mucosal plaques coalesced, resulting in circumferential disease and luminal impingement. The pathologic pattern of Candida esophagitis was homogenous. Plaque material was composed primarily of desquamated superficial hyperplastic hyperkeratotic squamous epithelium and inflammatory cells, with infiltration by fungal elements and bacteria consistent with superinfection. Although endoscopic and histopathologic ulcer was commonly seen in these patients (32%), only four patients had ulcer believed secondary to Candida esophagitis alone. In conclusion, in patients with AIDS, Candida esophagitis is a superficial mucosal infection resulting in characteristic endoscopic and histopathologic patterns.

AIDS-Related Opportunistic Infections↗
PubMed1996

Etiology of esophageal disease in human immunodeficiency virus-infected patients who fail antifungal therapy.

PURPOSE: To determine the etiologies of esophageal symptoms in human immunodeficiency virus (HIV)-infected patients failing antifungal treatment. METHODS: Between August 1, 1990 and December 31, 1994, all HIV-infected patients seen at a large inner-city hospital who had esophageal complaints despite being on antifungal therapy were prospectively evaluated for the cause of symptoms. Thus, the population studied included patients given empiric antifungal therapy for esophageal symptoms and patients who developed symptoms while on long-term antifungal therapy. Endoscopy was performed in all patients. The cause of symptoms was determined by the clinical, endoscopic, and pathologic findings, and follow-up after treatment. RESULTS: Over the 53-month study period, 74 patients failing empiric antifungal therapy were identified. The majority (77%) of these patients had esophageal ulcers; 25 patients had idiopathic ulcers and 24 had cytomegalovirus. In 2 patients, Candida was present with other causes of ulcerative esophagitis. Candida esophagitis alone was diagnosed in only 3 patients. No endoscopic abnormalities were observed in 14 patients (19%). An additional 24 patients developed esophageal symptoms while receiving antifungal therapy; endoscopic findings in these patients included ulceration in 16 (67%), Candida esophagitis alone in 2, and normal in 6. Empirically treated patients in whom odynophagia was not the only symptom, those with dysphagia alone, and those with a CD4 count > 100/mm3 were less likely to have an endoscopic diagnosis. CONCLUSIONS: Esophageal ulceration is the most common cause of esophageal symptoms in HIV-infected patients failing empiric antifungal therapy and those developing symptoms while receiving antifungal agents. Given these findings, endoscopy should be the test of choice for these nonresponders, rather than escalating the dose of antifungal agent, adding other empiric treatments, or performing barium esophagography.

Adult↗
PubMed1996

Prospective evaluation of biopsy number for the diagnosis of viral esophagitis in patients with HIV infection and esophageal ulcer.

BACKGROUND: Establishing a diagnosis of viral esophagitis in patients with human immunodeficiency virus (HIV) infection has important clinical relevance. However, the number of biopsies required to diagnose viral esophagitis is currently unknown. METHODS: Over a 34-month period, all HIV-infected patients with esophageal ulcer underwent 10 biopsies of the largest and/or most accessible lesion, primarily from the ulcer base. The first 3 specimens were placed in one formalin container, the second 3 in another, and 4 additional specimens in the third. Standard histopathologic methods were employed, as well as in situ hybridization or immunohistochemical studies in most patients, and viral cytopathic effect was defined using previously proposed criteria. Patients were then treated on the basis of the results of the initial biopsy specimens with both clinical and endoscopic follow-up. RESULTS: One hundred HIV-infected patients with esophageal ulcer were studied. Cytomegalovirus (CMV) was considered etiologic in 50 patients. Of these 50 patients, the first three biopsy specimens were sufficient to diagnosis CMV in 40 (80%). In 5 patients (10%), the first two sets were negative with only the third set of biopsies positive. Similarly, of the 4 patients with simultaneous CMV and herpes simplex virus (HSV) esophagitis, three sets of biopsy specimens were required for diagnosis of both agents in 3 patients. HSV esophagitis alone was found in 2 patients; diagnostic viral inclusions were present in the first 3 biopsies in each patient. Thirty-five patients had HIV-associated idiopathic esophageal ulcer; only one of these patients was misdiagnosed. CONCLUSIONS: At least 10 biopsies may be required to exclude viral esophagitis in HIV-infected patients. If biopsy specimens are adequate and no evidence of viral cytopathic effect has been found, the patient may be treated on the basis of the results of the initial clinical, endoscopic, and pathologic findings with close clinical follow-up rather than repeat endoscopy.

AIDS-Related Opportunistic Infections↗
PubMed1996

Use of sterile compared with tap water in gastrointestinal endoscopic procedures.

BACKGROUND: Because of the concern for infection risk, use of sterile water has been recommended in the water bottle for endoscopic equipment, although studies evaluating prevalence of contamination of the water bottle with clinical outcomes have not been performed. METHODS: Over a 12-week period in three endoscopy rooms at a university teaching hospital, the water bottles were filled on a weekly schedule with either sterile (one room) or tap water. The water bottles were sterilized on a weekly basis with an automated endoscope washer. At the end of each week, an aliquot of the remaining water was transferred to a sterile container, and quantitative cultures for aerobic and facultative anaerobic bacteria were performed by use of a 0.01 ml calibrated loop according to standard protocols. Cultures were performed in a blinded fashion without knowledge of the water source. Follow-up was performed on all patients within 2 weeks of the procedure to determine any potential infectious complications. RESULTS: During the study period, 437 procedures were performed (203 endoscopy, 68 colonoscopy, 38 sigmoidoscopy, 128 endoscopic retrograde cholangiopancreatography). Of a total of 36 cultures (12 sterile), the results of nine (25%) were positive, including three bottles where sterile water was used. Bacterial isolates included five Flavobacterium sp., four Acinetobacter sp., two Pseudomonas sp., and one Stenotrophomonas maltophilia. Colony counts ranged from 900 to more than 10,000 per ml. On follow-up no patient had development of a clinical infection from any of these organisms. CONCLUSIONS: Bacterial growth in the water bottle was infrequent, consisted predominantly of nonpathogenic organisms, and was not associated with clinical complications. Our pilot study suggests that the use of tap water as compared with sterile water may be practical as well as provide cost savings.

Bacteria↗
PubMed1996

Chronic unexplained diarrhea in human immunodeficiency virus infection: determination of the best diagnostic approach.

BACKGROUND & AIMS: Chronic unexplained diarrhea is a common complication of human immunodeficiency virus infection, although the best diagnostic approach is unknown. The purpose of our study was to evaluate the clinical use of endoscopy for the evaluation of this problem. METHODS: Patients infected with human immunodeficiency virus with chronic unexplained diarrhea underwent upper endoscopy to the jejunum followed by colonoscopy. RESULTS: Forty-eight patients were evaluated. A potential cause of diarrhea was found in 21 patients (44%; 95% confidence interval, 30%-58%). Colonoscopy with biopsy identified an etiology in 13 patients, including cytomegalovirus colitis alone in 9. In all but 1 patient with colonic disease, the diagnosis was made by biopsy of the rectosigmoid colon. Upper endoscopy with biopsy identified microsporidiosis in 7 patients and cryptosporidiosis in 2 patients. Logistic regression analysis identified weight loss and duration of diarrhea (P < 0.001) as the only independent predictors for diagnosis. No patient without weight loss and a CD4 lymphocyte count of > 100/mm3 had a diagnosis established. Of the 25 patients without a diagnosis in whom long-term follow-up was available, improvement or spontaneous resolution of diarrhea occurred in 9 (38%). CONCLUSIONS: Clinical parameters are helpful in predicting which patients may benefit from endoscopic examination.

Adult↗
PubMed1996

Fluconazole compared with endoscopy for human immunodeficiency virus-infected patients with esophageal symptoms.

BACKGROUND & AIMS: The best initial treatment of human immunodeficiency virus (HIV)-infected patients with esophageal symptoms is unknown. The outcome, including safety and cost-effectiveness, of fluconazole compared with endoscopy as a treatment strategy for HIV-infected patients with new-onset esophageal symptoms was evaluated. METHODS: During a 53-month period, 134 HIV-infected patients with esophageal symptoms were randomized prospectively to groups receiving either standard doses of fluconazole or endoscopy. RESULTS: Among the 68 patients in the fluconazole group, a complete symptomatic response was observed in 56 patients (82%), usually within 1 week. The most common endoscopic findings in the 66 patients in the endoscopy group included Candida esophagitis alone in 42 patients (64%) and ulcerative esophagitis in 10 patients (15%). Patients responding to empirical antifungal therapy or who had Candida esophagitis alone at endoscopy were less like to have severe symptoms (P = 0.027) or odynophagia as the only symptom (P < 0.001) but more frequently had odynophagia and dysphagia (P = 0.007) and thrush (P = 0.002). Empirical fluconazole was cost-effective, saving $738.16 per patient. CONCLUSIONS: Empirical oral antifungal therapy with fluconazole is highly efficacious, safe, and cost-effective for HIV-infected patients with new-onset esophageal symptoms.

Adult↗
PubMed1996

Atovaquone is effective treatment for the symptoms of gastrointestinal microsporidiosis in HIV-1-infected patients.

OBJECTIVE: To report the clinical response to atovaquone in HIV-1-infected patients with symptomatic intestinal microsporidiosis. DESIGN: A retrospective review of a cohort of AIDS patients with symptomatic intestinal microsporidiosis who received atovaquone. SETTING: Infectious Disease Program of the Grady Memorial Hospital, Veterans Affairs Medical Center and private physicians' offices in Atlanta, Georgia. PATIENTS AND METHODS: HIV-1-infected patients (n = 371) were offered a complete stool evaluation and monthly follow-up. Among them, 22 were diagnosed with intestinal microsporidial infection using stool smears stained with modified trichrome stain. Species confirmation was made by light microscopy or electron microscopy on small intestinal biopsy specimens in some patients. MAIN OUTCOME MEASURE: Differences in symptoms, number of stools, and body weight were compared before and after a minimum of 1 month of atovaquone therapy. RESULTS: Eight patients received atovaquone treatment. The mean onset of clinical improvement after beginning treatment was 13 days (SEM, +/- 2). The mean number of stools per day decreased from 10 +/- 2.5 to 2 +/- 1 (P = 0.02, paired t test). The mean weight gain was 3 +/- 2 kg. The parasite was continuously present in the repeated stool specimens. However, semiquantitative analysis performed on two patients' stool specimens showed a decreased parasite burden. Four patients underwent small intestinal endoscopy was consistent with Enterocytozoon bieneusi in all four patients. Only one out of these four patients demonstrated a decrease in parasite burden in the biopsy specimen. Ultrastructural analysis performed in another of these four patients following treatment demonstrated the presence of electron-dense granules in spores, suggestive of toxic effects. CONCLUSION: Atovaquone demonstrates promise as a symptomatic treatment for intestinal microsporidiosis. A double-blind and placebo-controlled clinical trial is currently in progress.

AIDS-Related Opportunistic Infections↗
PubMed1996

Symptom-specific use of upper gastrointestinal endoscopy in human immunodeficiency virus-infected patients yields high dividends.

The yield of upper gastrointestinal endoscopy (esophago-gastroduodenoscopy; EGD) in human immunodeficiency virus (HIV)-infected patients based on presenting symptoms has not been well studied. We studied consecutive patients with documented HIV infection undergoing EGD at a large innercity hospital between August 1, 1990 and December 31, 1993; all had presenting symptoms and indications for EGD prospectively recorded at the time of EGD. All endoscopic abnormalities were routinely subjected to biopsy, and extensive histopathological evaluation was performed. EGD was considered helpful when the findings stimulated specific therapeutic intervention other than antifungal or antacid medications. The specific indications for EGD in 156 patients were as follows: esophageal symptoms, 102 patients (65%); abdominal pain, 18 (12%); upper gastrointestinal bleeding, 25 (16%); refractory nausea and vomiting, 11 (7%). Overall, pathologic findings were identified in 116 patients (74%): in refractory esophageal symptoms, 82%; upper gastrointestinal bleeding, 92%; abdominal pain, 39%; nausea and vomiting, 27%. EGD with biopsy identified a specifically treatable opportunistic disorder other than Candida in 80 patients (51%), including idiopathic esophageal ulcer (22%) or viral esophagitis and/or duodenitis (29%). EGD was not helpful in 22.3% of cases, those involving Candida (12.3%) and peptic ulcer disease (PUD)-related causes (10%). The mean CD4 count of patients with opportunistic pathologic findings (24/mm3, n = 79) was significantly lower than that of patients with PUD/gastroesophageal reflux disease (GERD) (167/mm3, n = 9) or negative EGDs (165/mm3, n = 35). Overall, the results of EGD influenced patient management in 78% of cases. We conclude that selective symptom-specific use of EGD, particularly in patients with esophageal symptoms refractory to antifungal therapy or gastrointestinal bleeding, usually identifies specifically treatable abnormalities, whereas EGD is less useful for the evaluation of abdominal pain or nausea and vomiting.

Abdominal Pain↗
PubMed1996

A prospective endoscopic evaluation of the causes of upper GI hemorrhage in alcoholics: a focus on alcoholic gastropathy.

OBJECTIVE: To determine prospectively the causes of upper GI hemorrhage (UGIH) in alcoholics, focusing on the prevalence of alcoholic gastropathy, and to compare the etiology of bleeding in patients who drink alcohol to that of nondrinkers. METHODS: From August 1, 1990 through September 9, 1994, all patients evaluated by the gastroenterology consultative service at a large inner-city hospital presenting with UGIH were prospectively identified. Patients had to have a subnormal hematocrit on or within 12 h of admission or a fall of at least 5 points from a previous baseline determination to be included. Upper GI endoscopy was performed in all patients within 48 h of admission. Alcohol use was quantitated as chronic (80 g or more per day for at least 1 month), binge, occasional, or none. RESULTS: Over the 4-yr study period, 727 patients met the inclusion criteria, and of these, 212 (29%) were classified as chronic alcohol users. Overall, peptic ulcer disease was the most common cause of bleeding (60%). Gastropathy (diffuse subepithelial hemorrhage) was considered etiological in only 32 patients (4%). The most common causes of gastropathy were portal hypertension in 22 patients and nonsteroidal anti-inflammatory drug use in five. Only three patients were identified in whom alcoholic gastropathy was considered etiological; in these patients, bleeding was mild and self-limited. When the causes of bleeding were compared between drinkers and nondrinkers, drinkers were more likely to bleed from varices (p = 0.024) or other portal hypertension-related causes (p < 0.01), whereas peptic ulcer was more common in nondrinkers compared with chronic users (67 vs 53%; p < 0.01). Esophagitis (p = 0.95) and Mallory-Weiss tear (p = 0.15) prevalences were not significantly different between the two groups. CONCLUSION: In the actively drinking patient, the most common causes of UGIH are peptic ulcer and disorders related to portal hypertension. Alcoholic gastropathy appears to be a rare and previously overemphasized cause of bleeding.

Adult↗