Chronic corrosive injuries of the stomach-a single unit experience of 109 patients over thirty years.

BACKGROUND: Corrosive gastric injuries are not uncommon in developing countries because acids, which are more frequently associated with gastric injury, constitute the major type of offending chemical. The spectrum of gastric injury may vary from acute to varying types of chronic gastric involvement. METHODS: The 109 consecutive patients with chronic corrosive gastric injuries treated in a single tertiary care superspecialty institute over a period of 30 years were reviewed with special reference to presentation and problems in management. RESULTS: Acids contributed to 82.6% of chronic injuries. Chronic gastric injuries were usually one of five types in these patients. The majority had prepyloric strictures (83.5%). The remaining strictures were antral (4.6%), body (3.7%), pyloroduodenal (2.7%), or diffuse (5.5%).Twenty-one (22.8%) patients had a delayed gastric outlet obstruction, and18 patients had a concomitant esophageal stricture requiring a bypass. Most of the patients with chronic injury underwent surgical correction with Billroth I gastrectomy (77.1%), loop gastrojejunostomy (11.0%), and distal gastrectomy with Polya reconstruction (3.7%). Other procedures performed were pyloroplasty in 1 patient and colonic conduit jejunal anastomosis in 6 patients. One patient (1%) died in the postoperative period. CONCLUSIONS: The management of chronic corrosive gastric injury depends on the type of gastric involvement, the presence of co-existent esophageal stricture, and the general condition of the patient. A limited resection of the affected stomach is the ideal procedure for the common type of gastric injury. In patients whose general condition prohibits major resection or where the stricture extends to the antrum the best treatment is a loop gastroenterostomy. Type III, IV, V strictures require individualized treatment. Delayed gastric outlet obstruction affects the treatment plan of combined gastric and esophageal injuries.

Primary leiomyosarcoma of the breast: A case report and review of literature.

Leiomyosarcomas of the breast are rare tumours. Only 18 such cases have been reported in the literature so far. We describe herein a case of primary leiomyosarcoma of the breast in a 54-year-old woman whose preoperative clinical and cytological findings indicated a benign breast tumour. However, a core needle biopsy of the lesion showed malignant spindle cells without any ductal elements. Histopathological examination of the mastectomy specimen suggested a diagnosis of leiomyosarcoma, which was subsequently confirmed by immunohistochemical analysis. Primary leiomyosarcoma of the breast is very rare and is difficult to diagnose preoperatively as it needs immuno-histochemical staining. It is necessary to excise the tumour with sufficient margins to prevent local recurrence. The role of postoperative adjuvant chemotherapy is not well documented.

Assessment of vagotomy status with postprandial urinary alkaline tide.

AIM: This study was carried out to assess whether the postprandial urinary alkaline tide, as a marker for the completeness of vagotomy, is dependent on the nature of the test meal, whether it is affected by proton pump inhibitor therapy, and whether it is reliable. METHODS: The postprandial urinary alkaline tide (PUAT) pattern was prospectively assessed in three different study groups and one control group of healthy volunteers. The three study groups were as follows; A (n = 20) i.e. the Proton Pump Inhibitor (PPI) Group; B (n = 25) i.e. the Truncal Vagotomy (TV) Group; and C (n = 5) i.e. the Recurrent Ulcer (RU) Group. Urinary pH was measured by a pocket digital pH meter. RESULTS: Postprandial urinary alkaline tide in the control group was significantly higher compared to the fasting levels. Liquid diet did not elicit a significant urinary alkaline tide response. There was a statistically significant fall in both fasting urinary pH (5.34 +/- 0.70 vs. 4.80 +/- 0.61, p = 0.031) and the postprandial alkaline tide (6.99 +/- 0.79 vs. 4.94 +/- 0.63, p = 0.0001) after taking proton pump inhibitors. In the truncal vagotomy and gastrojejunostomy group it was found that there was a significant fall in both the mean fasting (5.28 +/- 0.58, vs. 4.92 +/- 0.66, p = 0.032) and the postprandial urinary pH (6.29 +/- 0.92 vs. 5.09 +/- 0.73, p = 0.0001) following surgery. CONCLUSION: This study establishes that simple measurement of the urinary pH before and after a standard test meal can be used as an accurate routine test for the completion of vagotomy. It also showed that proton pump inhibitors abolish the alkaline tide and therefore must be discontinued before measuring the alkaline tide. Liquid test meal was not effective in eliciting an alkaline tide as compared to a solid meal.

Recombinant interleukin-4 enhances Campylobacter jejuni invasion of intestinal pig epithelial cells (IPEC-1).

Campylobacter jejuni, a leading cause of bacterial gastroenteritis, has a diverse spectrum of disease expression. Polymicrobial infections may contribute to this, such as Trichuris, which elicits type 2 cytokines (including IL-4) and downregulates type 1 immunity. In previous studies, gnotobiotic piglets infected with C. jejuni and Trichuris suis had bloody diarrhea and marked gastrointestinal pathology, including bacterial invasion into epithelial cells and macrophages. Neonatal swine given these dual infections had elevated IL-4 and IL-10 responses in feces. In the studies reported here, we hypothesized that IL-4 or IL-10 enhances invasion of intestinal pig epithelial cells (IPEC-1) by C. jejuni. 10-14-day-old IPEC-1 cells were pretreated with recombinant IL-4 (rIL-4) or rIL-10 for 5h and then challenged with C. jejuni. Cells pretreated with rIL-4 were viable and showed approximately 6-fold increases in C. jejuni (but not Escherichia coli DH5alpha) internalization compared to cells with no pretreatment. Enhanced C. jejuni invasion was rIL-4 dose-dependent and reversed by addition of anti-IL-4 antibody. Preincubation with rIL-10 did not significantly alter C. jejuni internalization. Transepithelial electrical resistance (TEER) was significantly reduced following rIL-4 treatment, but not rIL-10 treatment. After rIL-4 pretreatment and C. jejuni challenge, light microscopy showed vacuolated cells with damaged paracellular junctions. Transmission electron microscopy (TEM) showed multiple internalized bacteria. Most were in the cytoplasm, but some were within or adjacent to vacuoles. We conclude that rIL-4 damages paracellular junctions and alters the physiology of these epithelial cells allowing increased invasion of C. jejuni.

Sternocleidomastoid muscle myocutaneous flap for corrosive pharyngoesophageal strictures.

BACKGROUND: Strictures at the pharyngoesophageal junction represent a subgroup of corrosive esophageal strictures requiring a specialized management approach. Non-dilatable cricopharyngeal strictures need surgical intervention. We report the use of the sternocleidomastoid muscle myocutaneous inlay flap (SCMMIF) for reconstruction of the cervical esophagus in patients with corrosive strictures. METHODS: A SCMMIF was used in four patients with cricopharyngeal strictures. The surgical technique is described. All patients had complete dilatation of the stenosed cricopharyngeal segment as seen on postoperative endoscopy and contrast studies. One patient was managed successfully for a short midesophageal stricture by serial endoscopic dilatations. Another patient underwent an esophagocoloplasty subsequently for bypass of the long distal esophageal stricture The last two patients await esophagocoloplasty. CONCLUSIONS: This is the first report on the use of sternocleidomastoid muscle myocutaneous inlay flap for corrosive cricopharyngeal strictures. The flap is simple to construct, is effective and can be performed in a short time, and yields good cosmetic results.

Serum pepsinogen I and II levels in various gastric disorders with special reference to their use as a screening test for carcinoma stomach.

INTRODUCTION: The role of serum pepsinogen in the diagnosis of gastric carcinoma is well established. Its role in other common upper alimentary disorders has not been widely studied. The aim of this study was to describe the effect of various gastric disorders on the levels of pepsinogen I, pepsinogen II and pepsinogen I/II ratio, with an emphasis on the diagnosis of carcinoma stomach in the South Indian population. METHODS: A total of 210 patients in seven groups, including one control group, were studied. The groups included patients with carcinoma stomach, Helicobacter pylori gastritis, peptic ulcer, portal hypertensive gastropathy, non-ulcer dyspepsia and erosive gastritis. Serum pepsinogen I, pepsinogen II and pepsinogen I/II ratio were estimated using an enzyme-linked immunosorbent assay technique. RESULTS: Patients with carcinoma of the stomach, when compared with controls, had a significantly lower pepsinogen I level (87.2 microg/L vs. 158.1 microg/L, p=0.0002) and pepsinogen I/II ratio (4.3 vs. 7.2, p = 0.0001). No significant change in pepsinogen levels occurred in the other groups. The cut-off levels of pepsinogen I (115.3 microg/L) and pepsinogen I/II ratio (6.2), determined by THE ROC curve, when applied in parallel provided a sensitivity of 97% and a negative predictive value of 91.4% for the diagnosis of carcinoma stomach. When the tests were applied in parallel, the likelihood ratio of a negative test was 0.06, indicating that individuals without carcinoma stomach were 16 times more likely to have a negative test than those with carcinoma. This fulfilled the essential prerequisites of an ideal screening test. CONCLUSION: Serum pepsinogen estimation is a useful diagnostic tool in the diagnosis of carcinoma stomach. The significance of serum pepsinogen level in portal hypertensive gastropathy, non-ulcer dyspepsia, peptic ulcer, Helicobacter pylori gastritis and erosive gastritis was not established.

Trichuris suis excretory secretory products (ESP) elicit interleukin-6 (IL-6) and IL-10 secretion from intestinal epithelial cells (IPEC-1).

Immune responses to gastrointestinal helminth infections have received increasing attention due to similarities to allergen-induced responses. In fact, the whipworm parasite of swine, Trichuris suis, has been used in beginning clinical trials as an antidote to inflammatory bowel disease. This strategy was based on this similarity and the recognition that other worms have been documented to induce anti-inflammatory responses in the host. In an effort to understand the basis for this response, we hypothesized that the proteins and peptides secreted by T. suis stimulate local intestinal epithelial cells to produce anti-inflammatory cytokines. To test this hypothesis in a correlate system of the natural swine host, T. suis excretory secretory products (ESP) were used to treat both differentiated and undifferentiated intestinal pig epithelial cells (IPEC-1) in vitro as a model for the effect on villus tip and crypt epithelial cells in the vicinity of the worms. IPEC-1 were exposed to low-level doses (0.3mg/ml) of T. suis ESP, and IL-4, IL-6 and IL-10 cytokine responses were measured by an enzyme-linked immunosorbant assay (ELISA). IL-6 was the predominant cytokine produced, accompanied by moderate IL-10 secretion from both differentiated and undifferentiated cells. As expected, IL-4 was not produced by IPEC-1. Additionally, IL-6 and IL-10 cytokines were produced within 24h, suggesting that these two cytokines form part of the primary host response to T. suis infections. These data suggest that T. suis ESP could enhance host immune responses and modulation through the induction of enteric IL-6 and IL-10.

Disordered to ordered folding in the regulation of diphtheria toxin repressor activity.

Understanding how metal binding regulates the activity of the diphtheria toxin repressor protein (DtxR) requires information about the structure in solution. We have prepared a DtxR mutant construct with three additional N-terminal residues, Gly-Ser-His-DtxR(Cys-102 --> Asp), that retains metal-binding capabilities, but remains monomeric in solution and does not bind DNA under conditions that effect dimerization and DNA binding in the functional DtxR(Cys-102 --> Asp) construct. Although the interaction properties of this inactive mutant in solution are very different from that of active repressors, crystallization imposes the same dimeric structure as observed in all crystal forms of the active repressor with and without bound metal. Our solution NMR analyses of active and inactive metal-free diphtheria toxin repressors demonstrate that whereas the C-terminal one-third of the protein is well ordered, the N-terminal two-thirds exhibits conformational flexibility and exists as an ensemble of structural substates with undefined tertiary structure. Fluorescence binding assays with 1-anilino naphthalene-8-sulfonic acid (ANS) confirm that the highly alpha-helical N-terminal two-thirds of the apoprotein is molten globule-like in solution. Binding of divalent metal cations induces a substantial conformational reorganization to a more ordered state, as evidenced by changes in the NMR spectra and ANS binding. The evident disorder to order transition upon binding of metal in solution is in contrast to the minor conformational changes seen comparing apo- and holo-DtxR crystal structures. Disordered to ordered folding appears to be a general mechanism for regulating specific recognition in protein action and this mechanism provides a plausible explanation for how metal binding controls the DtxR repressor activity.

Transition state structure of arginine kinase: implications for catalysis of bimolecular reactions.

Arginine kinase belongs to the family of enzymes, including creatine kinase, that catalyze the buffering of ATP in cells with fluctuating energy requirements and that has been a paradigm for classical enzymological studies. The 1.86-A resolution structure of its transition-state analog complex, reported here, reveals its active site and offers direct evidence for the importance of precise substrate alignment in the catalysis of bimolecular reactions, in contrast to the unimolecular reactions studied previously. In the transition-state analog complex studied here, a nitrate mimics the planar gamma-phosphoryl during associative in-line transfer between ATP and arginine. The active site is unperturbed, and the reactants are not constrained covalently as in a bisubstrate complex, so it is possible to measure how precisely they are pre-aligned by the enzyme. Alignment is exquisite. Entropic effects may contribute to catalysis, but the lone-pair orbitals are also aligned close enough to their optimal trajectories for orbital steering to be a factor during nucleophilic attack. The structure suggests that polarization, strain toward the transition state, and acid-base catalysis also contribute, but, in contrast to unimolecular enzyme reactions, their role appears to be secondary to substrate alignment in this bimolecular reaction.

Expression, purification from inclusion bodies, and crystal characterization of a transition state analog complex of arginine kinase: a model for studying phosphagen kinases.

Phosphagen kinases catalyze the reversible transfer of a phosphoryl group between guanidino phosphate compounds and ADP, thereby regenerating ATP during bursts of cellular activity. Large quantities of highly pure arginine kinase (EC 2.7.3.3), the phosphagen kinase present in arthropods, have been isolated from E. coli, into which the cDNA for the horseshoe crab enzyme had been cloned. Purification involves size exclusion and anion exchange chromatographies applied in the denatured and refolded states. The recombinant enzyme has been crystallized as a transition state analog complex. Near complete native diffraction data have been collected to 1.86 A resolution. Substitution of a recombinant source for a natural one, improvement in the purification, and data collection at cryo temperatures have all yielded significant improvements in diffraction.

Effect of RMI 12,936 on early pregnancy in mice.

Treatment with RMI 12,936 blocked the mitotic shift from epithelial to stromal cells normally observed in the uterus on Day 4 of pregnancy, and inhibited implantation. While progesterone alone could reverse the change in pattern of cell division in the preparation of the uterus for implantation, both oestradiol and progesterone were necessary to induce implantation and maintain pregnancy. A reduction in the activity of delta 5-3 beta-hydroxysteroid dehydrogenase in the ovaries of RMI 12,936-treated mice suggests that the compound affects luteal synthesis of oestrogen and progesterone in mice.