Reproducibility of assessing fecal microbiota in chronic constipation.

BACKGROUND: While limited data suggest that the fecal microbiota in healthy people is stable over time, the intraindividual variability of the fecal microbiota in constipated patients is unknown. METHODS: This study evaluated the intraindividual reproducibility of fecal microbiota analyzed with 16S rRNA gene sequencing in two stool samples collected without and after a laxative, respectively, in 25 healthy people and 25 constipated women. Participants completed a food record for 3 d before the stool collection. Colonic transit was measured with scintigraphy. KEY RESULTS: The constipated patients were older (48±15 vs 39±10 y, P=.02) than healthy participants but had a similar BMI. The total daily caloric intake was less (P=.005) in constipated (1265±350 kcal) than healthy participants (1597±402 kcal). Fourteen patients but only two controls (P<.005), had delayed colonic transit. For most measures of alpha (eg, Observed OTU number, Shannon index) and beta diversity (eg, Bray-Curtis dissimilarity, UniFrac, phyla level abundance), the ICCs between two stool samples were high, indicating moderate or strong agreement, and similar in healthy people and constipated patients. The ICC for the weighted UniFrac distance, which is weighted by abundance, was lower than its unweighted counterpart, indicating that the unweighted measure is more robust and reproducible. CONCLUSIONS AND INFERENCES: The intraindividual reproducibility of fecal microbiota in constipated patients is high and comparable to healthy participants. For most purposes, evaluating the fecal microbiota in a single stool sample should generally suffice in adequately powered studies of healthy and constipated patients.

Assessing the colonic microbiome, hydrogenogenic and hydrogenotrophic genes, transit and breath methane in constipation.

BACKGROUND: Differences in the gut microbiota and breath methane production have been observed in chronic constipation, but the relationship between colonic microbiota, transit, and breath tests remains unclear. METHODS: In 25 healthy and 25 constipated females we evaluated the sigmoid colonic mucosal and fecal microbiota using 16S rRNA gene sequencing, abundance of hydrogenogenic FeFe (FeFe-hydA) and hydrogenotrophic (methyl coenzyme M reductase A [mrcA] and dissimilatory sulfite reductase A [dsrA]) genes with real-time qPCR assays, breath hydrogen and methane levels after oral lactulose, and colonic transit with scintigraphy. KEY RESULTS: Breath hydrogen and methane were not correlated with constipation, slow colon transit, or with abundance of corresponding genes. After adjusting for colonic transit, the abundance of FeFehydA, dsrA, and mcrA were greater (P<.005) in colonic mucosa, but not stool, of constipated patients. The abundance of the selected functional gene targets also correlated with that of selected taxa. The colonic mucosal abundance of FeFe-hydA, but not mcrA, correlated positively (P<.05) with breath methane production, slow colonic transit, and overall microbiome composition. In the colonic mucosa and feces, the abundance of hydrogenogenic and hydrogenotrophic genes were positively correlated (P<.05). Breath methane production was not associated with constipation or colonic transit. CONCLUSIONS & INFERENCES: Corroborating our earlier findings with 16S rRNA genes, colonic mucosal but not fecal hydrogenogenic and hydrogenotrophic genes were more abundant in constipated vs. healthy subjects independent of colonic transit. Breath gases do not directly reflect the abundance of target genes contributing to their production.

Determinants and clinical impact of pressure drift in manoscan anorectal high resolution manometry system.

BACKGROUND: Pressure drift (PD), resulting from differences between room and body temperature, reduces the accuracy of pressure measurements with the Manoscan high resolution manometry (HRM) system. Our aims were to assess PD during anorectal HRM. METHODS: Defined as the residual pressure measured immediately after the catheter was removed, PD was calculated for each sensor and averaged across all 12 sensors in 454 anorectal consecutive studies recorded with 3 HRM catheters. The relationship between PD and study duration, number of prior uses of a catheter, and peak and average pressure exposure during a study were evaluated. The correction of PD with a software algorithm (thermal compensation) was evaluated in 76 studies where the most distal sensor was outside the body. KEY RESULTS: The PD varied among sensors and across catheters. The average PD (7.3 ± 0.2 mmHg) was significantly greater for newer catheters, during longer studies, or when sensors were exposed to higher pressures. Together, these factors explained 81% of the variance in overall PD. After thermal compensation, the uncorrected median PD for the most distal sensor was 2.5-5 mmHg over the study duration. Correcting this changed the interpretation (e.g., as abnormal instead of normal) of at least 1 anorectal parameter in eight of 76 studies. CONCLUSIONS & INFERENCES: During anorectal HRM, PD declines with catheter use and is greater for newer catheters, when sensors are exposed to higher pressures, and for studies of longer duration. While PD is partially corrected with thermal compensation algorithms, the impact on interpretation is modest.

Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation.

BACKGROUND: Neostigmine, an acetyl cholinesterase inhibitor, stimulates colonic motor activity and may induce vagally mediated cardiovascular effects. Our aim was to evaluate effects of i.v. neostigmine on colonic compliance and its safety in patients with chronic constipation. METHODS: We retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. These patients had undergone intracolonic motility and compliance measurements with an infinitely compliant balloon linked to a barostat. Data abstracted included barostat balloon mean volumes with increases in pressure (4 mmHg steps from 0 to 44 mmHg) before and after i.v. neostigmine. Vital signs and oxygen saturation before and after neostigmine were recorded. KEY RESULTS: Of the 144 patients, 133 were female, mean age was 41.0 ± 15.4 years (SD), and duration of constipation was 12.9 ± 13.8 years. Among patients who had undergone colonic transit measurement by scintigraphy, the overall colonic transit at 24 h (geometric center, GC24 [n = 115]) was 1.5 ± 0.7 (normal >1.3), and at 48 h (GC48 [n = 75]) it was 2.3 ± 0.9 (normal >1.9). Neostigmine decreased colonic compliance at lower distension pressures (e.g., 12 and 20 mmHg [both p < 0.001]), but not at 40 mmHg. There were expected minor changes in vital signs in response to neostigmine in 144 patients; however, one patient developed unresponsiveness, significant bradycardia, hypotension, and muscular rigidity that responded to 400 mcg i.v. atropine. CONCLUSIONS & INFERENCES: Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine.

Diaphragmatic breathing for rumination syndrome: efficacy and mechanisms of action.

BACKGROUND: While high resolution esophageal manometry combined with impedancometry has demonstrated that gastric pressurizations lead to rumination, the contribution of upper esophageal sphincter (UES) and esophagogastric junction (EGJ) function to rumination is unclear. Behavioral therapy with diaphragmatic breathing (DB) can reduce rumination. We aimed to evaluate the pressures in the stomach, EGJ and UES during rumination and the effects of DB augmented with biofeedback therapy. METHODS: Sixteen patients with rumination were studied with manometry and impedancometry before and after a meal. The postprandial assessment comprised three periods: before, during, and after DB augmented with biofeedback therapy. KEY RESULTS: All patients had postprandial rumination, which was associated (p < 0.001) with increased gastric pressure and reversal of the postprandial gastroesophageal pressure gradient from -4 (-43 to 18) before to 20 (7-79) mmHg during rumination. The EGJ pressure was lower (p < 0.001) during gastric pressurizations that were associated with rumination vs those that were not. The UES also relaxed, almost completely, during rumination. Patients had a median (range) of 5 (2-10) rumination episodes before, 1 (0-2) (p < 0.001) during, and 3 (1-5) after (p < 0.001 vs during) diaphragmatic breathing. During manometry and impedancometry, DB was well-tolerated and learned within 5 min. Diaphragmatic breathing increased EGJ pressure (p < 0.001) and restored a negative gastroesophageal pressure gradient (-20 mmHg [-80 to 7]). CONCLUSIONS & INFERENCES: Diaphragmatic breathing aided with high resolution esophageal manometry is well-tolerated, effective and averts the gastroesophageal pressure disturbance that leads to rumination.

Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders.

BACKGROUND: Acetylcholinesterase inhibitors (ACIs), e.g., neostigmine, are known to increase upper and lower gastrointestinal (GI) motility and are used to treat acute colonic pseudoobstruction. However, their effects on gastroduodenal motility in humans are poorly understood. Our hypotheses were that, in patients with suspected GI motility disorders, neostigmine increases gastric and small intestinal motor activity, and these effects are greater in patients with cardiovagal neuropathy, reflecting denervation sensitivity. METHODS: In this open label study, the effects of neostigmine (1 mg intravenously) on gastroduodenal motor activity recorded with manometry were assessed in 28 patients with a suspected GI motility disorder. Cardiovagal function was assessed with the heart rate response to deep breathing and GI transit by scintigraphy. KEY RESULTS: The final diagnoses were gastroparesis (6 patients), gastroparesis with intestinal neuropathy (3 patients), intestinal neuropathy or pseudoobstruction (5 patients), functional dyspepsia (6 patients), chronic abdominal pain (3 patients), mechanical small intestinal obstruction (3 patients), and pelvic floor dysfunction (2 patients). Neostigmine increased both antral and intestinal phasic pressure activity (p < 0.001). Neostigmine increased antral and intestinal pressure activity in 81% and 50% of patients with reduced postprandial antral and intestinal contractile responses to meal, respectively. The antroduodenal pressure response to neostigmine was not higher in patients with cardiovagal dysfunction. CONCLUSIONS & INFERENCES: Neostigmine increased antral and intestinal motor activity in patients with hypomotility, including intestinal dysmotility. These responses to neostigmine were not greater in patients with cardiovagal dysfunction. The use of longer-acting ACIs for treating antroduodenal dysmotility warrant further study.

Isolation of Mycobacterium tuberculosis from sputum of tribal, non-tribal pulmonary tuberculosis patients of Andaman & Nicobar islands by conventional culture method and assessment of first line anti-tuberculosis drug susceptibility patterns.

BACKGROUND: Drug resistance surveys have not yet conducted in these Islands and as such no data exists on drug resistance currently. AIMS: the present study was initiated with the objective of isolation and assessment of Drug resistance patterns of Mycobacterium tuberculosis isolates from sputum specimens collected from different categories of Tribal, Non-Tribal pulmonary tuberculosis patients treated under DOTS and Non-DOTS program by conventional culture and Proportion sensitivity (PST) method to detect patients with Multidrug resistant strains. METHODS: The investigation was hospital based laboratory surveillance study carried out for a period of 3 years at the selected hospitals of Andaman district (TB ward GB Pant Hospital at Port Blair, CHC Bamboflat at Port Blair and CHC Rangat at Rangat) and Nicobar district (CHC Nancowry at Nancowry groups of Islands), among the new cases and re-treatment cases of tuberculosis patient under DOTS program and Non-DOTS patients attended selected hospitals of Andaman & Nicobar districts chosen for the study. RESULTS: 83 culture positive isolates obtained (74 identified as M. tuberculosis) from the sputum specimen of 162 cases of tuberculosis patient by conventional culture method. 60 M. tuberculosis isolates subjected to drug susceptibility test using PST method, 7 patients (11.67%) found to be Multidrug resistant tuberculosis (MDR-TB), resistant patterns were S + H + R + E = 1(Cat II-DOTS),H + r = 3(Cat-I DOTS = 1, Cat II-DOTS-1,Non-DOTS = 1), Rifampicin resistant alone = 2 (Non-DOTS = 1, Cat II-DOTS = 1) and R + E = 1(Cat I-DOTS). CONCLUSIONS: Laboratory finding suggested that nine MDR-TB strains detected in DOTS and Non-DOTS among 60 M. tuberculosis isolates were selected for drug susceptibility testing but two isolates detected as MDR-TB from patients was already on Second line drugs treatment were not included in the MDR-TB detection criteria. Hence 7 patients (11.67%) declared to be Multidrug resistant tuberculosis (MDR-TB). 2 MDR-TB strains with resistant patterns H + r = 1(Cat II-DOTS), Rifampicin resistant alone = 1(Non-DOTS) detected from 12 isolates of Tribal patients from Nicobar district and 5 MDR-TB strains with resistant patterns S + H + R + E = 1 (Cat II-DOTS), H + r = 2(Cat I-DOTS = 1,Non-DOTS = 1), Rifampicin resistant alone = 1 (Cat II-DOTS) and R + E = 1(Cat I-DOTS) detected from 48 isolates of Non-Tribal patients from Andaman district. To assess the MDR-TB burden in the islands, systematic drug resistant surveillance study needs to be conducted.

Acute corrosive injuries of the stomach: a single unit experience of thirty years.

Introduction. The spectrum of gastric injury due to corrosives can vary. This paper presents a single center experience of over 30 years of corrosive gastric injuries of 39 patients with acute gastric injuries from 1977 till 2006. Patients and Methods. Two thirds of the patients in the acute injury group had a concomitant esophageal injury. The age of the patients ranged from 4 years to 65 years with a slight preponderance of males. (M : F ratio 22 : 17). Results. 36 out of 39 acute gastric injuries were due to ingestion of acids. Three patients had history of caustic soda ingestion. Oral hyperemia or ulcers of varying extent were seen in all patients. The stomach showed hyperemia in 10, extensive ulcers in 13, and mucosal necrosis in 10 patients. Fifteen patients (15/39, 38.5%) were managed conservatively. Twenty four patients (24/39, 61.5%) underwent laparotomy: one for frank peritonitis, 10 for gastric mucosal necrosis, and 13 others for extensive gastric ulcerations. Overall the mortality rate was 29.6 %. Conclusion. Although the mortality and morbidity of acute corrosive gastric injuries is high, the key to improve the survival is early identification of perforation, maintenance of nutrition and control of sepsis.

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.

Flagella promote Escherichia coli K1 association with and invasion of human brain microvascular endothelial cells.

Escherichia coli containing the K1 capsule is the leading cause of gram-negative meningitis, but the pathogenesis of this disease is not completely understood. Recent microarray experiments in which we compared the gene expression profile of E. coli K1 associated with human brain microvascular endothelial cells (HBMEC) to the gene expression profile of E. coli K1 not associated with HBMEC revealed that there was a threefold increase in the expression of the fliI gene, encoding an ATP synthase involved in flagellar synthesis and motility, in HBMEC-associated E. coli. In this study, we examined the role of flagella in E. coli K1 association with and invasion of HBMEC by constructing isogenic DeltaflhDC, DeltafliI, DeltafliC, and DeltacheW mutants that represented each class of flagellar genes. Mutations that affected the flagellum structure and flagellum formation (DeltaflhDC, DeltafliI, and DeltafliC) resulted in significant defects in motility, as well as in HBMEC association and invasion, compared to the characteristics of the wild-type strain when preparations were examined with or without centrifugation. Transcomplementation with the corresponding genes restored the levels of these mutants to the levels of the parent strain. These findings suggest that the HBMEC association and invasion defects of the mutants are most likely related to flagella and less likely due to their motility defects. This conclusion was supported by our demonstration that the cheW mutant was not motile but was able to associate with and invade HBMEC. In addition, purified recombinant flagellin reduced the association of the wild-type strain with HBMEC by approximately 40%, while it had no effect on the fliC mutant's association with HBMEC. Together, these findings indicate that flagella promote E. coli K1 binding to HBMEC.

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.

A study on trend of relapse in leprosy and factors influencing relapse.

A retrospective analysis of data pertaining to the rural field operation area of the Central Leprosy Teaching and Research Institute, Chengalpattu, Tamil Nadu, was carried out to determine the magnitude of relapse after MDT and its significance with other variables. The study included 3248 leprosy patients who have successfully completed treatment during 1987-2003, of whom 2892 were PB and 356 MB cases. A total of 58 cases of relapse was reported which gives a crude cumulative relapse rate of 1.78% for the 16-year period of follow-up and the rates for PB and MB were 1.9% and 0.84% respectively. With respect to PB cases, 68% of relapses were reported in the first 3 years of RFT. The person-year relapse rate was highly significant with regard to the number of skin lesions (p<0.0002) and nerve involvement (p<0.0002). The person-year relapse rate did not differ significantly between PB and MB leprosy, male and female, and child and adult cases. RFT year cohort relapse rate reveals that the introduction of MB-MDT regimen for PB leprosy had resulted in the reduction of relapses among PB cases after 1998. The relapse rate with reference to the time gap after RFT reveals that relapse declines with passage of time after RFT. The risk of relapse was very low in both PB and MB leprosy which fact emphasizes that proper counselling about signs and symptoms of relapse during RFT is adequate to combat the problem. A majority of relapses occurred in the first three years after RFT. The number of skin lesions and involvement of nerves were the main risk factors for relapse.

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.