Faculty Bibliography

OBJECTIVES: To evaluate the safety and efficacy of two reduced dosing regimens of sodium phosphate tablets (Visicol, InKine Pharmaceutical Co. Inc., Blue Bell, PA, USA) for colon cleansing prior to colonoscopy. METHODS: In a randomized, multicentre, endoscopist-blinded clinical study, adults undergoing colonoscopy received either 28 tablets (42 g) or 32 tablets (48 g) of sodium phosphate for colon cleansing. The endoscopist used a validated four-point scale to rate the overall quality of colon cleansing, as well as cleansing in the ascending colon. Adverse events were collected and evaluated. RESULTS: The quality of overall colon cleansing was 'excellent' or 'good' in 84% or more of both groups, with no significant difference between the two doses. No patient had a preparation rated as 'inadequate' or required a repeat procedure. All patients were able to complete the assigned dose of tablets, and there were no deaths, serious adverse events or dropouts from the study. CONCLUSIONS: A reduced tablet regimen for sodium phosphate tablets, using either 28 or 32 tablets, is well tolerated and effective for colon cleansing prior to colonoscopy.

Since the first description by Frantz in 1959 of a papillary cystic tumor of the pancreas, solid pseudopapillary tumors have been increasing in incidence. However, management of these lesions remains controversial. Patients under the age of 20 years more often undergo local excision than do their older counterparts, resulting in increased recurrence rates. The cause of this discrepancy is not clear but may be related to an inability to make a definitive preoperative diagnosis. The authors report a case of a solid pseudopapillary tumor of the pancreas in a 13-year-old girl in which the diagnosis was established preoperatively by endoscopic ultrasound scan with fine-needle aspiration (EUS-FNA). EUS-FNA represents a diagnostic technique commonly used in adults that may be useful in identifying the rare pediatric patient with pancreatic malignancy

We developed a method for passing the enteroclysis catheter at endoscopy in patients requiring upper endoscopy and enteroclysis. This method reduced patient discomfort, the time needed for fluoroscopic tube placement, and overall radiation doses. We conclude that endoscopy and enteroclysis performed together is practical in these patients.

The diagnosis of protein-losing enteropathy (PLE) should be considered in all patients with hypoalbuminemia and edema without other known causes, and established by plasma alpha(1)-antitrypsin (alpha(1)-AT) clearance or nuclear studies. The therapy for PLE should focus principally on the treatment of the underlying disease after it has been identified. Therapeutic goals should include improvement of hypoalbuminemia, edema, and lymphopenia. The existing primary literature for therapy of PLE syndromes consists mainly of case reports and expert opinions, subject to substantial reporting bias and unknown rates of spontaneous remission; the rarity of and the diversity among this set of diseases make future large randomized trials unlikely. Therapeutic choices, therefore, must involve clinical acumen, empiricism, and understanding of the pathophysiology of the underlying disease process, and must be tailored to each individual patient's syndrome. Dietary interventions including hypolipidic, high-protein regimens, supplemented by medium-chain triglycerides (MCTs), are extremely useful, particularly in protein loss due to increased lymphatic pressure. Corticosteroids can be very useful in certain cases of PLE (though not without substantial long-term toxicity) when clinical serologic or histologic markers of inflammatory disease are present. Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration. Octreotide is a well tolerated drug that has been demonstrated to improve PLE in some patients, and is worth consideration. Surgery finds its best role in treating gastrointestinal protein loss from neoplasia, inflammatory bowel disease, and hypertrophic gastritis. Most other PLEs are distributed too widely for surgical intervention. Protein-losing gastropathy (PLG) behaves somewhat differently from the general group of PLE, marked by excellent responses to elimination of Helicobacter pylori, antisecretory therapy, and surgical resection. Protein-losing enteropathy stemming from cardiovascular disease is best treated by medical or surgical cardiovascular interventions; however, some patients may respond to mucosa-directed therapy.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) may have an important role in the clinical exacerbation of sarcoidosis. OBJECTIVE: To treat sarcoidosis with infliximab, a chimeric human-murine anti-human TNF-alpha monoclonal antibody. DESIGN: Case report. SETTING: U.S. academic medical center. PATIENT: A 72-year-old woman with sarcoidosis presenting with severe protein-losing enteropathy, hypoalbuminemia, and proximal myopathy who had not responded adequately to corticosteroid therapy and whose clinical course was further complicated by acute tubular necrosis and renal failure requiring long-term hemodialysis. INTERVENTION: Intravenous infusion of infliximab, 5 mg/kg of ideal body weight; infusion was repeated at 2 and 6 weeks. MEASUREMENTS: Clinical response of enteropathic and myopathic symptoms and serum albumin level. RESULTS: Enteropathic and myopathic symptoms resolved after infliximab therapy, and the serum albumin level also improved. However, the clinical course was complicated by the development of a hypercoagulable state associated with circulating anticardiolipin antibodies, which prompted discontinuation of infliximab therapy. CONCLUSIONS: Infliximab therapy was successful in a patient with sarcoidosis. Tumor necrosis factor-alpha may be an important mediator of clinical disease in sarcoidosis and could be an attractive target for therapeutic intervention. However, infliximab may cause adverse effects associated with cytokine cascade manipulation.

PURPOSE: We sought to determine whether illness severity and anticipated level of function, as evaluated at the time of admission, were associated with outcomes and costs of care for patients admitted to the medical service. METHODS: All 1,759 patients admitted to the medical service at a large urban academic medical center between July 1, 1997, and September 30, 1997 (excluding those admitted directly to the intensive care units or for protocol chemotherapy), were evaluated and categorized by the admitting intern by illness severity (not ill, mildly ill, moderately ill, severely ill, or moribund) and anticipated level of function at discharge (excellent, good, fair, or poor) as part of their routine sign-out process. Interns' ratings were always available within 24 to 28 hours of admission. In-hospital mortality, length of stay, cost of hospitalization, and anticipated billing revenue were evaluated. RESULTS: Patients who were more severely ill had significantly greater in-hospital mortality. For example, mortality was 1.1% (11 of 972) among those who were not ill or mildly ill, 3.6% (26 of 724) among those who were moderately ill, and 15% (9 of 60) among those who were severely ill. Illness severity (P = 0.003) and anticipated functional status (P < 0.01) were significant predictors of in-hospital mortality. Illness severity and function were also significant predictors of greater length of stay and greater costs of hospitalization (all P < 0.0001). The 389 patients who were moderately ill with fair or poor anticipated function were associated with the largest cumulative losses (about $330,000 during the 3-month period), whereas the 798 mildly ill patients with good or excellent function were associated with the largest cumulative profits ($550,000). CONCLUSION: Physicians' estimates of patients' illness severity and anticipated function at the time of discharge, as made by interns using a system designed to help them sign out to their colleagues, predict outcomes and costs of hospitalization. Such a system may be useful in developing new approaches to management strategies based on prognosis.

Clostridium difficile is the leading cause of nosocomially acquired intestinal infection in the United States, affecting virtually all cases of pseudomembranous colitis and up to 20% of cases of antibiotic-associated diarrhea. Even after receiving antibiotic treatment with either metronidazole or vancomycin, 20% of patients will have recurrent Clostridium difficile diarrhea. An innovative approach to the problem involves the introduction of competing, nonpathogenic (probiotic) organisms into the intestinal tract to restore microbial balance. The theoretical premise behind this approach is that the protective intestinal microflora is damaged by antibiotic treatment; the initial antibiotic exposure thus leaves the host susceptible to colonization and subsequent infection by Clostridium difficile. A so-called "second-hit" to the intestinal microflora occurs when the infected host is treated with flagyl or vancomycin, further destroying susceptible bacterial flora. Probiotic agents, such as Lactobacillus GG and Saccharomyces boulardii, have been studied for the treatment of Clostridium difficile. We are currently running a prospective, randomized, placebo-controlled trial of Lactobacillus GG in combination with standard antibiotics for the treatment of Clostridium difficile infection. Although it is too early to draw statistically significant conclusions, two patterns seem to be emerging: Lactobacillus GG is effective in reducing the 3-wk recurrence rate of Clostridium difficile, and patients feel better when taking Lactobacillus GG, as compared with the placebo, with early disappearance of abdominal cramps and diarrhea. In conclusion, the use of probiotics for the treatment of primary and recurrent Clostridium difficile diarrhea looks promising. Patients seem to have less recurrent Clostridium difficile diarrhea and early symptomatic improvement when using the probiotic Lactobacillus GG.

We have evaluated the diagnostic value of the fecal occult blood test (FOBT) in hospitalized patients. We reviewed the medical records of patients who had a positive FOBT not associated with a large gastrointestinal bleed, and who had a subsequent complete evaluation of their gastrointestinal (GI) tract. Of the 50 subjects who met the study criteria, 21 had various GI symptoms and 13 reported weight loss. Patients taking medications that may influence the FOBT result were distributed as follows: 15 were taking nonsteroidal antiinflammatory drugs, eight were taking iron supplementation, three were using steroid drugs, and three were taking anticoagulant drugs. Nonneoplastic lesions were found in 47 patients. Neoplastic lesions were discovered in 11 patients: seven had adenomatous polyps, two had colorectal cancer, one had gastric cancer, and one had duodenal cancer. Only two of seven patients with adenomatous polyps had lesions > 1 cm. In the study population, the positive predictive value of FOBT for finding colonic neoplasms was 18% and for any GI neoplasm it was 22%. Our data indicate that in hospitalized patients (a) the yield of colonic neoplasms from FOBT is approximately 50% less than that in healthy outpatients, and (b) a positive FOBT test is unlikely to lead to the detection of GI malignancy in the absence of suggestive clinical findings.

The two major proteins in the I-bands of skeletal muscle, actin and tropomyosin, were each labeled with fluorescent dyes and microinjected into cultured cardiac myocytes and skeletal muscle myotubes. Actin was incorporated along the entire length of the I-band in both types of muscle cells. In the myotubes, the incorporation was uniform, whereas in cardiac myocytes twice as much actin was incorporated in the Z-bands as in any other area of the I-band. Labeled tropomyosin that had been prepared from skeletal or smooth muscle was incorporated in a doublet in the I-band with an absence of incorporation in the Z-band. Tropomyosin prepared from brain was incorporated in a similar pattern in the I-bands of cardiac myocytes but was not incorporated in myotubes. These results in living muscle cells contrast with the patterns obtained when labeled actin and tropomyosin are added to isolated myofibrils. Labeled tropomyosins do not bind to any region of the isolated myofibrils, and labeled actin binds to A-bands. Thus, only living skeletal and cardiac muscle cells incorporate exogenous actin and tropomyosin in patterns expected from their known myofibrillar localization. These experiments demonstrate that in contrast to the isolated myofibrils, myofibrils in living cells are dynamic structures that are able to exchange actin and tropomyosin molecules for corresponding labeled molecules. The known overlap of actin filaments in cardiac Z-bands but not in skeletal muscle Z-bands accounts for the different patterns of actin incorporation in these cells. The ability of cardiac myocytes and non-muscle cells but not skeletal myotubes to incorporate brain tropomyosin may reflect differences in the relative actin-binding affinities of non-muscle tropomyosin and the respective native tropomyosins. The implications of these results for myofibrillogenesis are presented.

alpha-Actinins, isolated from muscle and nonmuscle sources and labeled with various fluorescent dyes, were microinjected into living PtK2 cells during interphase to observe the reformation of stress fibers following cell division. Fluorescently labeled ovalbumin and bovine serum albumin were also injected as control proteins. alpha-Actinin was incorporated into stress fibers within 5 minutes after injection and remained present in the fibers for up to 11 days. The pattern of incorporation was the same regardless of whether the alpha-actinin was isolated from muscle or nonmuscle tissues or whether it was labeled with fluorescein, Lucifer Yellow, or rhodamine dyes. In contrast, neither labeled ovalbumin nor bovine serum albumin were incorporated into stress fibers. When the injected cells entered prophase, all stress fibers disassembled, resulting in a distribution of the fluorescent alpha-actinin throughout the cytoplasm. During cytokinesis, the fluorescent alpha-actinin was concentrated in the broad area between the separated chromosomes and along the edge of the cell in the cleavage area. Within 10 minutes after the completion of cleavage, the first fluorescent stress fibers reformed parallel to the spreading edges of the daughter cells and in close association with the midbody with a concomitant loss of alpha-actinin in the former cleavage furrow. Additional fibers formed adjacent to these first stress fibers. In some cases, new stress fibers formed between two existing stress fibers and some stress fibers moved up to 4 micron apart from one another in the course of 2 hours. Thus, fluorescent alpha-actinin, injected into living cells, undergoes the same cyclical changes in distribution as endogenous alpha-actinin during the cell cycle: from stress fibers to cleavage furrow and back to stress fibers.