The treatment of gastroesophageal reflux disease with proton-pump inhibitors and its implications on managed care--clinical overview of gastroesophageal reflux disease. Roundtable discussion.

The importance of gastroesophageal reflux disease (GERD) to managed health care systems cannot be overestimated. It contributes significantly to the use of health care resources, including doctor's services, medication consumption, and diagnostic testing. A roundtable meeting of 13 managed care experts was convened January 23, 2001 in Dallas, to discuss the implications of GERD on the managed care system. The following proceedings are published in five sections. In the first part, Jeffrey Danzig, MD, a gastroenterologist, provides the clinical foundation for the discussion, based on the existing literature and his personal practice.

Creation of genome-wide protein expression libraries using random activation of gene expression.

Here we report the use of random activation of gene expression (RAGE) to create genome-wide protein expression libraries. RAGE libraries containing only 5 x 10(6) individual clones were found to express every gene tested, including genes that are normally silent in the parent cell line. Furthermore, endogenous genes were activated at similar frequencies and expressed at similar levels within RAGE libraries created from multiple human cell lines, demonstrating that RAGE libraries are inherently normalized. Pools of RAGE clones were used to isolate 19,547 human gene clusters, approximately 53% of which were novel when tested against public databases of expressed sequence tag (EST) and complementary DNA (cDNA). Isolation of individual clones confirmed that the activated endogenous genes can be expressed at high levels to produce biologically active proteins. The properties of RAGE libraries and RAGE expression clones are well suited for a number of biotechnological applications including gene discovery, protein characterization, drug development, and protein manufacturing.

Gastrointestinal malignancy in patients with AIDS.

To clarify the prevalence and characteristics of gastrointestinal malignancy in patients with AIDS, we reviewed the demographics and clinical features of patients with AIDS and gastrointestinal neoplasms seen at North Central Bronx Hospital and Montefiore Medical Center during the past 8 yr. Malignant neoplasia complicated AIDS in 108/869 (12%) of the cases in our study. Most common was Kaposi's sarcoma (KS) (60%), followed by lymphoma (35%) and miscellaneous tumors (6.5%). The gastrointestinal tract was involved in 35/108 (32%) of patients with AIDS and neoplasia. Gastrointestinal tract involvement with KS usually was silent, although present, in every patient with KS who underwent autopsy. Lymphoma was most commonly non-Hodgkin's, and often produced symptoms. Uncommonly, the gastrointestinal tract was the primary site of neoplasms other than KS or lymphoma.

Clostridium septicum infection and associated malignancy. Report of 2 cases and review of the literature.

We report 2 patients with myonecrosis due to Clostridium septicum and associated colon carcinoma and have reviewed the English language literature for all reported cases of atraumatic C. septicum infection. A total of 162 cases of C. septicum infection have been reported. Eighty-one percent of these patients had an associated malignancy. Thirty-four percent of all patients had associated colon carcinoma, while 40% had a hematologic malignancy. Thirty-seven percent of reported patients had an occult malignancy at the time of their infection with C. septicum. In many patients, the portal of entry was found in the large intestine. In a particularly lethal form (79% mortality) of C. septicum infection, known as "distant myonecrosis," infection metastatic from the initial site of infection causes severe myonecrosis, gangrene, and often death within hours of clinical detection. Overall, survival of patients with C. septicum infection is only 35%. Review of all cases of C. septicum infection suggests several conclusions. 1) Patients with malignancy, particularly colonic or hematologic, and patients with cyclic neutropenia who develop signs and symptoms of sepsis, especially with associated findings of abdominal pain or pain in an extremity, should be treated for possible clostridial infection. 2) C. septicum infection does not appear to be a result of a single specific defect in either humoral or cell-mediated immunity. Rather, it may occur in patients who are granulocytopenic and therefore prone to an enterocolitis. 3) Patients in whom an infection with C. septicum is found must undergo a vigorous search for malignancy following acute therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma lactate and 3-hydroxybutyrate levels in patients with acute ethanol intoxication.

In order to assess the frequency and severity of lactic acidosis and 3-hydroxybutyric acidosis in ethanol abusers, 29 patients who presented to an emergency room with acute intoxication were tested. Most were also chronic ethanol abusers but were not otherwise seriously ill. Their serum ethanol concentrations averaged 226.5 +/- 94.8 mg/dl (range 98 to 426 mg/dl). In 20 patients, the plasma lactate level was elevated only mildly or not at all (1.1 to 3.0 mmol/liter). Seven patients had plasma lactate levels between 3.5 and 4.3 mmol/liter, and only two patients had moderately elevated levels, 5.1 and 8.7 mmol/liter. Thus, severe lactic acidosis was uncommon in these ethanol-intoxicated patients. Only two patients had even trivially elevated plasma levels of 3-hydroxybutyrate, 1.0 and 1.2 mmol/liter. Thus, these patients did not have unrecognized "alcoholic ketosis" manifested mainly as 3-hydroxybutyric acidosis. An unexpected and unexplained finding was the presence of hyperchloremia in 10 of the 29 patients, with serum chloride levels of more than 110 mmol/liter.