Harris R. Clearfield

Hepatorenal toxicity from sniffing spot-remover (trichloroethylene): Report of 2 cases

SummaryTwo patients with hepatorenal toxicity resulting from sniffing a popular spotremover containing trichloroethylene are described. These complications are uncommon when trichloroethylene is used for clinical anesthetic purposes, suggesting that the closed-circuit type of inhalation employed by sniffers, and the alcoholic consumption which frequently accompanies the habit may potentiate the toxicity of the hydrocarbon. Although glue is more commonly sniffed by teenagers, spot-remover containing trichloroethylene appears to be associated with more serious complications and is another agent to be added to the causes forhippie hepatitis.

Mucoepidermoid (adenosquamous) carcinoma arising in Barrett's esophagus

SummaryA case of mucoepidermoid or adenosquamous carcinoma arising from the mucous epithelium of a Barretts esophagus is presented. Immunohistologic examination demonstrated carcinoembryonic antigen (CEA) in both the glandular and squamous components, but keratin only in the latter. Although mucoepidermoid carcinoma of the esophagus is believed to arise from submucosal glands, heterotopic gastric surface epithelium may also give rise to this uncommon neoplasm.

Gastrin's trophic effect in the colon : identification of a signaling pathway mediated by protein kinase C

In previous studies we have reported that gastrin exerts a trophic effect on rat colonic epithelial cells in vitro. The effect of gastrin appeared to be mediated through a protein kinase C mechanism. In this study, we have characterized the role of protein kinase C in the gastrin-induced stimulation. Gastrin, in a time- and dose-dependent manner, increased protein kinase C translocation from the cytosol to the membrane, an index of enzyme activation. Maximum translocation occurred in 1 to 2 min following exposure to gastrin (10(-8) M), before declining back to baseline level within 5 min. Gastrin did not change total protein kinase C activity in the colonic cells. Staurosporine, an inhibitor of protein kinase C, totally abolished the basal as well as the gastrin-stimulated activity of protein kinase C. The tumor promoter phorbol 12-myristate 13-acetate also stimulated colonic epithelial protein kinase C. However, prolonged treatment of cells with phorbol inhibited their subsequent response to gastrin stimulation. The response to gastrin was also prevented by the gastrin receptor antagonist proglumide. These observations suggest that protein kinase C mediates the stimulatory effect of gastrin on colonic epithelial cells, possibly through a receptor mechanism.

Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro.

Although the specific cause(s) of inflammatory bowel diseases (IBD) has not been identified, one theory suggests ischemia as the early event that occurs in IBD and reperfusion causes sustained release of oxyradicals, leading to inflammation and ulceration. In this study, we have confirmed that H2O2 in the concentration seen during ischemia/reperfusion is primarily responsible for cellular membrane damage in the rat colonic fragments in vitro. Hydrogen peroxide caused a time and dose-dependent increase in 6-keto-PGF1α and TXB2 release. Hydrogen peroxide-stimulated 6-keto-PGF1α release was blocked (50%) by phospholipase A2 (PLA2) inhibitors quinacrine and dimethyleicosodienoic acid at 5 min. Hydrogen peroxide-stimulated 6-keto-PGF1α release was completely blocked by idomethacin, significantly blocked (69%) by nordihydroguiaretic acid, and completely blocked by catalase. superoxide dismutase and uric acid failed to inhibit H2O2-stimulated 6-keto-PGF1α release. Endogenous catalase inhibitors 3-aminotriazole and sodium azide further enhanced the release of 6-keto-PGF1α stimulated by H2O2 by 29% and 73%, respectively. Xanthine-xanthine oxidase also increased 6-keto-PGF1α release from the fragments by 110%. This release was not inhibited by superoxide dismutase and uric acid, but was completely inhibited by catalase. These studies suggest a direct effect of H2O2 on colonic fragments leading to submicroscopic cellular membrane damage and excess prostanoid production utilizing a PLA2/cyclooxygenase and catalase-sensitive pathway without the formation of toxic hydroxyl ions. The quick release of 6-keto-PGF1α also suggests an early manifestation of H2O2-induced damage in rat colonic fragments.

Gastrin induction of mRNA expression in rat colonic epithelium in vitro

A newly developed system of isolated rat colonic epithelial cells was utilized for a comprehensive study of protein synthesis influenced by gastrin. We found that synthetic human gastrin (0.01-100 nM) increased the incorporation of [35S]methionine into proteins within 2 hours. Peak incorporation was observed with 10 nM gastrin to more than two-fold above maintenance levels. Actinomycin-D (10 micrograms/ml) inhibited the stimulated increases in total protein synthesis indicating that the peptides trophic effect was mediated by the synthesis of new mRNA species. The effect of gastrin was comparably stronger than the one induced by the mitogen bombesin (1 nM). However, bombesin, a neuromodulator of gastrin release, did not produce an additive effect beyond that of gastrin on total protein synthesis. Gastrin stimulated the synthesis of many polypeptides resolved on two-dimensional polyacrylamide gel, an indicator of gastrins influence on the expression of various mRNA species. Some of these polypeptides may be used as markers in investigating colonic epithelial response to gastrin.

How does IBD affect quality of life

The quality of life (QOL) for inflammatory bowel disease (IBD) patients understandably tends to vary with symptom severity.1 This would be expected for all chronic disorders but there are specific aspects of IBD worth highlighting. For instance, some illnesses are “socially acceptable.” One might casually mention to a friend or colleague that “my ulcer is acting up” or “I just had stents placed for coronary artery disease.” Other disorders such as AIDS, cancer, and IBD are less likely to be casually discussed with friends or family. In fact, IBD tends to be a “silent” disorder for many patients since any reference to crampy pain, bowel activity, or rectal bleeding is often embarrassing. Patients therefore may receive less understanding with regard to their social interactions and performance. IBD can affect work and social interactions in diverse ways. One of my patients with Crohn’s disease (CD) and bowel urgency declined a job at a life insurance company doing data entry since there were many workers in 1 large space and a bathroom that only accommodated 1 woman at a time. Patients with bowel urgency often cannot take a car trip into the countryside since they might not have immediate access to a bathroom facility. There are few things as embarrassing and devastating as a bowel accident in public. Some patients frequently fear bowel incontinence even though they have never experienced it. CD tends to have a greater negative impact on healthrelated quality of life (HRQOL) than ulcerative colitis (UC) and thus raises questions about studies that report on IBD patients as a group rather than distinguishing between the 2 disorders, recognizing that some overlap may occur in colitis patients. Some patients experience chronically poor QOL from IBD and consider this as a normal baseline. They may be quite surprised to find how much their sense of well-being improves after appropriate medical or surgical intervention.

Colorectal cancer in inflammatory bowel disease: molecular and clinical features.

The two forms of inflammatory bowel disease (IBD), Crohns disease and ulcerative colitis, are characterized by chronic and relapsing inflammation of the intestines. Initiating events presumably occur well before patients are symptomatic. Evidence gathered over the past decade from both IBD patients and animal models of intestinal inflammation have confirmed that IBD represents complex heterogenic forms of diseases, influenced by a combination of environmental, genetic, and immunologic factors working in concert to produce exaggerated immune responses, resulting in chronic and remitting inflammation.

Consultant strategies for the gastroenterologist.

Effective communication skills and the ability to respond to the needs of referring physicians are critical for the maintenance and enhancement of a referral base. One challenge is to determine the reason for the consultation and to respond to the referring physicians interests. The consultation letter should be formatted effectively and the “turn-around time” should be as brief as possible, perhaps by fax as well as mail. Prioritizing the differential diagnosis and diagnostic studies can be helpful to the referring physician. Strategies should be developed to address procedural referrals you may believe are inappropriate. A decision should be made as to whether the consultant or the primary care physician informs the patient of a serious disease diagnosis. Referral guidelines should be developed to assist primary care physicians to determine when a patient should be referred to the gastroenterologist or other specialist. Receptionists should avoid turning away new patients because of a “full schedule” and must determine if other arrangements can be made. A proper response to “hallway consultations” by referring physicians is important. Consultants should make efforts to increase their visibility in the medical community, either by newsletter or lectures to the medical staff. Every effort should be made to avoid speaking disparagingly about other physicians. Consultant strategies should be taught to house staff and fellows in a formal lecture format, in the outpatient clinics, and on hospital rounds.

Emphysematous gastritis secondary to lye ingestion: Report of a case

SummaryThis case of emphysematous gastritis emphasizes the effect that alkali ingestion may have on the stomach as well as on the esophagus. Roentgenogram examination provided a specific diagnosis. The esophageal and gastric lesions proceeded to stricture formation in spite of corticosteroid therapy.

Bile acid and pancreatic trypsin outputs are parallel during intraduodenal infusion of essential amino acids

There is disagreement as to whether contraction of the gallbladder occurs simultaneously with secretion of pancreatic enzymes during food ingestion. One study that employed exogenous cholecystokinin (CCK) alone showed dissociation of total bile acids (TBA) and trypsin outputs, while another study that employed exogenous CCK plus secretin showed parallel outputs of TBA and trypsin. Since previous studies have suggested that intraduodenal infusion of essential amino acids (EAA) evokes pancreaticobiliary secretion similar to that observed with food ingestion, we infused increasing doses of EAA intraduodenally in 10 subjects with intact gallbladder and in 10 subjects with previous cholecystectomy and measured total bile acids and trypsin outputs serially. In subjects with intact gallbladder, increasing molar doses of EAA induced parallel increases of TBA and trypsin outputs. In subjects with previous cholecystectomy trypsin outputs during infusion of EAA were similar to subjects with intact gallbladder, but their TBA outputs remained constant during the entire infusion period. Serial concentrations of plasma secretin did not change during intraduodenal infusion of EAA. These observations suggest that the gallbladder empties bile in concert with secretion of pancreatic enzymes following food ingestion.