James M. Richter

Cryptosporidiosis in Immunocompetent Patients

The intestinal protozoan cryptosporidium is known to cause diarrhea in immunocompromised patients, but few cases have been reported in detail in immunocompetent persons. During a 12-month period, we identified cryptosporidium in the stools of 43 immunocompetent patients. The numbers of cases were increased in those under 4 years old and in those from 30 to 39 years old. Of 30 index cases, 23 (77 per cent) were diagnosed in the late summer or the fall. Fifteen of the 43 patients (35 per cent) had other gastrointestinal pathogens, of which only Giardia lamblia was statistically associated with cryptosporidium. In the 28 patients in whom other gastrointestinal pathogens were not identified, the clinical manifestations were predominantly watery, nonbloody diarrhea and, less commonly, abdominal discomfort, anorexia, fever, nausea, and weight loss. The infection was self-limited in all 43 patients. Clustering of cases occurred in a day-care center and in two families. These clinical observations confirm worldwide findings and suggest that cryptosporidium is a relatively common nonviral cause of self-limited diarrhea in immunocompetent persons in the northeastern United States.

Effectiveness of current technology in the diagnosis and management of lower gastrointestinal hemorrhage

Lower gastrointestinal hemorrhage is a common clinical problem for which multiple diagnostic tests and therapeutic interventions have been developed but no optimal approach has been established. We reviewed 107 consecutive patients admitted to the Massachusetts General Hospital for management of acute lower gastrointestinal hemorrhage to determine the effectiveness of diagnostic and management technologies, with particular attention to urgent colonoscopy. Colonoscopy yielded a diagnosis in 90% of patients, provided the opportunity for successful therapy in 9 of 13 patients (69%), and shortened hospital stay. Angiography performed after a scan positive for bleeding was often diagnostic, and angiography provided the means for successful therapy in 5 of 10 patients (50%). Barium enema and sigmoidoscopy had lower clinical yields. Although roles exist for other technologies, colonoscopy is the most convenient and effective first test in the evaluation of patients with significant lower gastrointestinal hemorrhage. Diagnostic yield, therapeutic opportunity, and cost effectiveness are maximized in early studies.

Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease

Introduction Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohns disease (CD) and ulcerative colitis (UC) are limited and conflicting. Methods We conducted a prospective study of women enrolled in the Nurses’ Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. Results Among 170 805 women, we confirmed 269 incident cases of CD (incidence 8/100 000 person-years) and 338 incident cases of UC (incidence 10/100 000 person-years) over 26 years and 3 317 338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). Conclusions A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.

Association of Pancreas Divisum and Pan reatitis and Its Treatment by Sphincteroplasty of the Accessory Ampulla

All 519 endoscopic pancreatograms performed in the Massachusetts General Hospital Endoscopy Unit from 1973 to 1980 were reviewed. Patients who underwent pancreatograms for documented pancreatitis were more likely (p less than 0.005) to have the duct anomaly pancreas divisum (12%) than those patients who had pancreatograms incidental to cholangiography (2.9%), or for unexplained chronic abdominal pain (3.3%). When compared with patients with pancreatitis and normal duct development, patients with pancreatitis associated with pancreas divisum tended to be younger and to have a clinical pattern of recurrent acute attacks of pancreatitis. Nine patients with recurrent pancreatitis or severe chronic abdominal pain and pancreas divisum were treated by surgical sphincteroplasty of the accessory ampulla. Five of the 6 patients with documented acute attacks of pancreatitis received good to excellent pain relief and had no further attacks of acute pancreatitis. None of the 3 patients with severe chronic abdominal pain without objective evidence of pancreatitis derived significant benefit. Accessory ampulla sphincteroplasty seems to relieve pain and prevent further attacks of acute pancreatitis in patients with pancreas divisum and recurrent pancreatitis. This response to sphincteroplasty adds further credence to the stated association between pancreas divisum and pancreatitis.

The cause and treatment of pancreatitis associated with pancreas divisum.

Recurrent pancreatitis is more prevalent in the 4% of people with pancreas divisum (nonfused dorsal and ventral ducts), and it has been proposed that the pancreatitis is caused by stenosis at the orifice of the dorsal duct. We have treated 40 patients with pancreas divisum and proven or probable pancreatitis. The diagnoses were made by endoscopic pancreatography showing a foreshortened (<6 cm) ventral duct (Wirsung) and confirmed by postoperative pancreatograms showing the separate main duct (Santorini) emptying via the accessory papilla. Of these, 32 patients (25 men, 7 women, median age 30) had recurrent acute pancreatitis (22) or persistent pain (10) without chronic inflammation or fibrosis. Twenty-nine have been treated by transduodenal sphincteroplasty of the accessory papilla; 22 were stenotic (0.75 mm or less) and 7 nonstenotic. Among 25 patients observed for longer than 6 months after surgery, the relief of pain and pancreatitis has been good in 17, fair in 1, and poor in 7. There was no difference between accessory papillotomy alone (10–0-3) v papillotomies of both accessory and major papillae (7–1-4). Patients with stenosis (16–1-1) fared better (p < 0.001) than those without stenosis (1–0-6). Those presenting with discrete attacks (12–1-2) also fared better (p < 0.05) than those presenting with chronic pain (5–0-5). The other eight patients (two women, six men, median age 28) had chronic pancreatitis proven by pancreatography and surgical biopsy. In this group, treatment by sphincteroplasty of the accessory papilla failed, and seven patients eventually required a pancreaticojejunostomy (3), distal pancreatectomy (2), or total pancreatectomy (2). In pancreas divisum, pancreatitis is caused by stenosis at the accessory papilla of Santorini. There may be progression from recurrent acute pancreatitis to irreversible fibrosis in some cases. Sphincteroplasty is effective for recurrent acute pancreatitis, but ductal drainage or resection becomes necessary once chronic pancreatitis is established. A preoperative test for stenosis of the accessory papilla is needed to identify patients whose symptoms are genuinely caused by their pancreas divisum.

Angiodysplasia clinical presentation and colonoscopic diagnosis

: Angiodysplasia is a recently recognized important cause of lower intestinal bleeding in older patients. Although angiography is an established procedure for the diagnosis of angiodysplasia, colonoscopy is being used increasingly for evaluation of lower intestinal bleeding. In order to define the nature of bleeding due to angiodysplasia and the appropriate role of colonoscopy, 80 patients diagnosed by angiography, pathology, or colonoscopy were reviewed. Bleeding attributable to angiodysplasia varied from acute life-threatening hemorrhage to occult blood in stools. Thirteen patients with angiodysplasia had no bleeding and were identified incidentally by colonoscopy performed for other indications. Eighty-nine percent of the lesions were located in the right colon and there was a mean of 1.5 angiodysplastic lesions per patient. The sensitivity of colonoscopy compared to angiography and pathology was 68% overall and 81% when the colon was completely examined and lesions were located in the colon. The predictive value of a positive colonoscopic diagnosis was 90% in this population. Colonoscopy should be employed as an initial study in patients with chronic or mild acute rectal bleeding.Angiodysplasia is a recently recognized important cause of lower intestinal bleeding in older patients. Although angiography is an established procedure for the diagnosis of angiodysplasia, colonoscopy is being used increasingly for evaluation of lower intestinal bleeding. In order to define the nature of bleeding due to angiodysplasia and the appropriate role of colonoscopy, 80 patients diagnosed by angiography, pathology, or colonoscopy were reviewed. Bleeding attributable to angiodysplasia varied from acute life-threatening hemorrhage to occult blood in stools. Thirteen patients with angiodysplasia had no bleeding and were identified incidentally by colonoscopy performed for other indications. Eighty-nine percent of the lesions were located in the right colon and there was a mean of 1.5 angiodysplastic lesions per patient. The sensitivity of colonoscopy compared to angiography and pathology was 68% overall and 81% when the colon was completely examined and lesions were located in the colon. The predictive value of a positive colonoscopic diagnosis was 90% in this population. Colonoscopy should be employed as an initial study in patients with chronic or mild acute rectal bleeding.

Rapid, efficient functional characterization and recovery of HIV-specific human CD8+ T cells using microengraving

The nature of certain clinical samples (tissue biopsies, fluids) or the subjects themselves (pediatric subjects, neonates) often constrain the number of cells available to evaluate the breadth of functional T-cell responses to infections or therapeutic interventions. The methods most commonly used to assess this functional diversity ex vivo and to recover specific cells to expand in vitro usually require more than 106 cells. Here we present a process to identify antigen-specific responses efficiently ex vivo from 104–105 single cells from blood or mucosal tissues using dense arrays of subnanoliter wells. The approach combines on-chip imaging cytometry with a technique for capturing secreted proteins—called “microengraving”—to enumerate antigen-specific responses by single T cells in a manner comparable to conventional assays such as ELISpot and intracellular cytokine staining. Unlike those assays, however, the individual cells identified can be recovered readily by micromanipulation for further characterization in vitro. Applying this method to assess HIV-specific T-cell responses demonstrates that it is possible to establish clonal CD8+ T-cell lines that represent the most abundant specificities present in circulation using 100- to 1,000-fold fewer cells than traditional approaches require and without extensive genotypic analysis a priori. This rapid (<24 h), efficient, and inexpensive process should improve the comparative study of human T-cell immunology across ages and anatomic compartments.

Physical activity and risk of inflammatory bowel disease: prospective study from the Nurses’ Health Study cohorts

Objective To examine the association between physical activity and risk of ulcerative colitis and Crohn’s disease. Design Prospective cohort study. Setting Nurses’ Health Study and Nurses’ Health Study II. Participants 194 711 women enrolled in the Nurses’ Health Study and Nurses’ Health Study II who provided data on physical activity and other risk factors every two to four years since 1984 in the Nurses’ Health Study and 1989 in the Nurses’ Health Study II and followed up through 2010. Main outcome measure Incident ulcerative colitis and Crohn’s disease. Results During 3 421 972 person years of follow-up, we documented 284 cases of Crohn’s disease and 363 cases of ulcerative colitis. The risk of Crohn’s disease was inversely associated with physical activity (P for trend 0.02). Compared with women in the lowest fifth of physical activity, the multivariate adjusted hazard ratio of Crohn’s disease among women in the highest fifth of physical activity was 0.64 (95% confidence interval 0.44 to 0.94). Active women with at least 27 metabolic equivalent task (MET) hours per week of physical activity had a 44% reduction (hazard ratio 0.56, 95% confidence interval 0.37 to 0.84) in risk of developing Crohn’s disease compared with sedentary women with <3 MET h/wk. Physical activity was not associated with risk of ulcerative colitis (P for trend 0.46). The absolute risk of ulcerative colitis and Crohn’s disease among women in the highest fifth of physical activity was 8 and 6 events per 100 000 person years compared with 11 and 16 events per 100 000 person years among women in the lowest fifth of physical activity, respectively. Age, smoking, body mass index, and cohort did not significantly modify the association between physical activity and risk of ulcerative colitis or Crohn’s disease (all P for interaction >0.35). Conclusion In two large prospective cohorts of US women, physical activity was inversely associated with risk of Crohn’s disease but not of ulcerative colitis.

Productivity, Quality, and Patient Satisfaction: Comparison of Part-time and Full-time Primary Care Physicians

AbstractCONTEXT: Although few data are available, many believe that part-time primary care physicians (PCPs) are less productive and provide lower quality care than full-time PCPs. Some insurers exclude part-time PCPs from their provider networks. OBJECTIVE: To compare productivity, quality of preventive care, patient satisfaction, and risk-adjusted resource utilization of part-time and full-time PCPs. DESIGN: Retrospective cohort study. SETTING: Boston. PARTICIPANTS: PCPs affiliated with 2 academic outpatient primary care networks. MEASUREMENTS: PCP productivity, patient satisfaction, resource utilization, and compliance with screening guidelines. RESULTS: Part-time PCP productivity was greater than that of full-time PCPs (2.1 work relative value units (RVUs)/bookable clinical hour versus 1.3 work RVUs/bookable clinical hour, P<.01). A similar proportion of part-time PCPs (80%) and full-time PCPs (75%) met targets for mammography, Pap smears, and cholesterol screening (P=.67). After adjusting for clinical case mix, practice location, gender, board certification status, and years in practice, resource utilization of part-time PCPs (

The Risks and Benefits of an Rx-to-otc Switch: The Case of Over-the-counter H2-blockers

138 [95% confidence interval (CI),