Endoscopic cryotherapy: experimental results and first clinical use.

BACKGROUND: Cryotherapy or the application of extreme cold has many potential applications in gastroenterology including tissue destruction and hemostasis but until now its development has been prevented by the lack of a delivery device suitable for use through the endoscope. We report here our experience with prototype devices using both liquid nitrogen driven by a cryosurgical system and cryogenic refrigerants (nitrous oxide and carbon dioxide) at or near ambient temperature. METHODS: Cryotherapy was applied to the distal esophageal mucosa of dogs via a flexible catheter passed through an upper endoscope. In other dogs, cryotherapy was used for hemostasis in a bleeding ulcer model. The procedure was also used for palliation in a 58-year-old man with unresectable adenocarcinoma of the stomach with pyloric channel obstruction. RESULTS: Freezing of the superficial mucosa was nearly instantaneous. All dogs survived the procedure and appeared to thrive. Histologic evaluation revealed significant necrosis of the superficial epithelial layer accompanied by a fibrinocellular infiltrate on the surface. These markers of acute injury subside by the fourth to sixth day and are replaced by regenerating epithelium, a process that is virtually complete by day 10. In the hemostasis experiments, bleeding ceased immediately after cryospraying of the lesions but resumed on thawing in most cases. Application of cryotherapy in the patient resulted in reduction of the pyloric mass with no immediately apparent adverse effects. CONCLUSIONS: These data, although preliminary, demonstrate the feasibility of endoscopic cryotherapy using a simple hand-held device. This device has broad potential for use in gastroenterology including ablation of superficial epithelium, debulking of large tumors and hemostasis.

Clinical usefulness of 3% hydrogen peroxide in acute upper GI bleeding: a pilot study.

BACKGROUND: A major problem in the endoscopic management of acute upper gastrointestinal (GI) bleeding is the presence of blood and clots overlying the bleeding source, preventing visualization of the lesion. A simple alternative is to alter the characteristics of blood such that it not only becomes easier to remove but also becomes translucent. We report the results of a pilot study on the use of hydrogen peroxide in patients with acute upper GI bleeding. METHODS: Patients with acute upper GI bleeding were studied if the presence of blood or clots obscured the site of bleeding. The potential site of bleeding was initially sprayed with 200 mL water and then with 200 mL 3% hydrogen peroxide mixed with simethicone. RESULTS: In 6 patients with acute upper GI bleeding, hydrogen peroxide spray resulted in good to excellent visualization of the bleeding source. Hemostasis occurred in 2 patients who were actively bleeding. There were no adverse effects or complications. CONCLUSIONS: Hydrogen peroxide significantly enhanced clot dissolution and endoscopic visualization in patients with acute upper GI bleeding.

Cephalosporin antibiotics accelerate gastric emptying in mice.

Gastroparesis is a common debilitating complication in many diabetic patients. While several drugs are available for gastroparesis, many patients are not adequately treated. Many patients do not respond to available drugs or appear to develop tachyphylaxis after an initial response. New agents are needed. Erythromycin is a macrolide antibiotic that accelerates gastric emptying through interaction with motilin receptors. Many antibiotics, like erythromycin itself, have significant gastrointestinal side effects. We investigated the ability of cephalosporin antibiotics to alter gastric emptying in mice by employing phenol red spectrophotometry to monitor gastric emptying. Our results indicate that several cephalosporin antibiotics, particularly cefazolin, accelerate gastric emptying. In some cases these drugs appear more efficacious than either erythromycin or metoclopramide. At very high doses, many drugs, including erythromycin, appear to delay gastric emptying. We hypothesize that the gastrointestinal side effects of nausea and vomiting may result from delayed gastric emptying occurring at high doses while lower doses are prokinetic in the stomach.

Antineoplastic activity, synergism, and antagonism of triarylalkylphosphonium salts and their combinations.

Previously, some of us demonstrated that monocationic phosphonium salt [4-(formylphenyl)methyl]triphenylphosphonium chloride (A) and [4-(hydrazinocarboxy)-1-butyl]tris(4-dimethylaminophenyl)phosph oni um chloride (B) in combination, exhibit inhibitory synergism against ELA mammary carcinoma. Here we show that A + B also exhibits synergism against cultured MB49 murine bladder carcinoma, but antagonism against HT-29 human colon carcinoma. This is probably due to assembly of the hydrazone (C) in situ: synthetic C is a more potent growth inhibitor than either A or B for MB49 and ELA, yet inferior to B for HT-29 cells. A, B, C, [4-(hydrazinocarboxy)-1-butyl]tris(3-tolyl)phosphonium chloride (D) and [4-(methylcarboxy)butyl]triphenylphosphonium chloride (F) selectively inhibit carcinoma growth relative to untransformed cells, most likely due to high carcinoma transmembrane potentials. D and F are tolerated in mice at 100 mg/kg. Intraperitoneal administration of D slows subcutaneous HT-29 xenograft growth by 41 to 59% versus controls in nu/nu mice, and intraperitoneal administration of B slows MB49 xenograft growth by 46 to 57% versus controls and extends the median lifespan of mice bearing ELA breast carcinoma allografts by 86%. Triarylalkylphosphonium salts represent a promising class of antineoplastic cations exhibiting unusual selectivity and synergism.

The role of lipids in Plasmodium falciparum invasion of erythrocytes: a coordinated biochemical and microscopic analysis.

The role of lipids in Plasmodium falciparum invasion of erythrocytes was investigated by biochemical and fluorescent microscopic analysis. Metabolic incorporation of radioactive oleate or palmitate and fractionation of radiolabeled phospholipids by thin-layer chromatography revealed no difference in the major phospholipid classes of schizonts and early ring forms after merozoite invasion. Fluorescent anthroyloxy derivatives of oleate and palmitate were also metabolically incorporated into parasite phospholipids. By microscopic analysis, the fluorescent phospholipids were seen localized in the plasma membrane and, within the merozoite, concentrated near the apical end. During invasion fluorescent phospholipid appeared to be injected from the apical end of the merozoite into the host membrane, both within and outside the parasite-host membrane junctions. After invasion fluorescent lipid was only found in the parasite plasma membrane and/or parasitophorous vacuole membrane. Parallel experiments with a fluorescent cholesterol derivative, incorporated into parasite membranes by exchange, revealed neither heterogeneous distribution of label within the parasite nor evidence for cholesterol transfer from merozoite to host cell membrane. Results suggest that during invasion no major covalent alteration of parasite lipids, such as lysophospholipid formation, occurs. However, invasion and formation of the parasitophorous vacuolar membrane apparently involves insertion of parasite phospholipids into the host membrane.