Comparison of Manning, Rome I, II, and III, and Asian diagnostic criteria: Report of the Multicentric Indian Irritable Bowel Syndrome (MIIBS) study

Background

Attempts to diagnose and subtype irritable bowel syndrome (IBS) by symptom-based criteria have limitations, as these are developed in the West and might not be applicable in other populations.

Objectives

This study aimed to compare different criteria for diagnosing and subtyping of IBS in India.

Method

Manning's and the Rome I, II, and III criteria as well as the Asian criteria were applied to 1,618 patients (from 17 centers in India) with chronic lower gastrointestinal (GI) symptoms with no alarm features and negative investigations.

Results

Of 1,618 patients (aged 37.5 [SD 12.6] years; 71.2 % male), 1,476 (91.2 %), 1,098 (67.9 %), 649 (40.1 %), 849 (52.5 %), and 1,206 (74.5 %) fulfilled Manning's, Rome I, II, and III, and the Asian criteria, respectively. The most common reason for not fulfilling the criteria was absence of the following symptoms: “more frequent stools with onset of pain,” “loose stool with onset of pain,” “relief of pain with passage of stool,” “other abdominal discomfort/bloating,” and, in a minority, not meeting the duration criterion of 3 months/12 weeks. By stool frequency, constipation-predominant IBS (<3 stools/week) was diagnosed in 319 (19.7 %), diarrhea-predominant IBS (>3 stools/day) in 43 (2.7 %), and unclassified in 1,256 (77.6 %). By Bristol stool form, constipation, diarrhea, and unclassified were diagnosed in 655 (40.5 %), 709 (43.8 %), and 254 (15.7 %) patients, respectively. By their own perception, 462 (28.6 %), 541 (33.4 %), and 452 (27.9 %) patients reported constipation-predominant, diarrhea-predominant, and alternating types, respectively.

Conclusion

By Manning's and the Asian criteria, a diagnosis of IBS was made frequently among Indian patients with chronic functional lower GI symptoms with no alarm features; the Rome II criteria gave the lowest yield. By the stool frequency criteria, a majority of patients had unclassified pattern, unlike by the stool form and patients' perception of their symptoms.     

Randomized Cluster Crossover Trials for Reliable,Efficient, Comparative Effectiveness Testing: Design of the Prevention of Arrhythmia Device Infection Trial (PADIT)

Randomized clinical trials are a major advance in clinical research methodology. However, there are myriad important questions about the effectiveness of treatments used in daily practice that are not informed by the results of randomized trials. This is in part because of important limitations inherent in the methodology of randomized efficacy trials which are performed with tight control of inclusion, exclusion, treatment, and follow-up. This approach enhances evaluation of clinical efficacy (performance in controlled situations) but increases complexity and is not well suited to test clinical effectiveness (performance under conditions of actual use). The cluster crossover trial is a new concept for efficient comparative effectiveness testing. Deep tissue infection occurs in 2% of patients after arrhythmia device implantation, usually requires system extraction, and increases mortality. There is variation in antibiotic prophylaxis used to reduce implanted device infections. To efficiently evaluate the comparative effectiveness of antibiotic strategies now in use, we designed a cluster crossover clinical trial, which randomized implanting centres to 1 of 2 prophylactic antibiotic strategies, which became the standard care at the centre for 6 months, followed by crossover to the other strategy, rerandomization, and second crossover. This method greatly reduces trial complexity because it aligns study procedures with usual clinical care and increases generalizability. Pilot studies have tested the feasibility and an 10,800-patient trial, funded by the Canadian Institutes of Health Research, is now under way. The cluster crossover randomized trial design is well suited to efficiently test comparative effectiveness of existing treatments where there is variability of practice, clinical equipoise, and minimal risk.     

TIE2-expressing monocytes regulate revascularisation of the ischaemic limb

BackgroundMonocytes (CD14+ cells) expressing the receptor TIE2 are a highly angiogenic subset that are pivotal to neovascularisation in the tumour environment. We hypothesised that TIE2-expressing monocytes (TEMs) are also important in neovascularisation of ischaemic tissues.MethodsFlow cytometry was used to quantify circulating TEMs in 40 patients with critical limb ischaemia (20 age-matched and 20 healthy controls). RT-PCR was used to confirm TIE2 expression in FACS-sorted TEMs. ELISA was used to measure circulating levels of the TIE2 ligand angiopoietin 2 (ANG2). Mice were subjected to hindlimb ischaemia and TEMs quantified. In an additional study, haemopoietic stem/progenitor cells, isolated from Pgk-rtTA-miR-126T transgenic mice, were transduced ex vivo with a TRE-miR-Tie2-OFP lentiviral vector and used to reconstitute lethally irradiated mice. These mice were treated with alternate daily doses of doxycycline to silence Tie2 expression on TEMs, and hindlimb ischaemia (HLI) was induced. Conversely, bone-marrow-derived macrophages (BMDMs) were enforced to express Tie2 using a Pgk-Tie2 lentivirus and delivered into the ischaemic hindlimb. Recovery of ischaemia was measured with laser Doppler.FindingsFlow cytometry revealed a ten-fold higher number of circulating TEMs in patients with critical limb ischaemia than in matched controls (mean 3·52% [SE 0·28] vs 0·39 [0·09], p<0·0001). Revascularisation or amputation resulted in a fall in TEM numbers to control levels (p<0·005). Analysis by RT-PCR confirmed TIE2 mRNA expression in TEMs. Circulating ANG2 levels were two-fold higher in patients with critical limb ischaemia than in controls (mean 4354 pg/mL [SE 661] vs 1973 [247], p<0·05). Circulating CD115+/Tie2+ monocyte numbers were higher following hindlimb ischaemia in mice than in sham controls (p<0·05) and Tie2 expression was upregulated in CD45+/CD11b+/F4/80+ macrophages isolated from ischaemic hindlimbs (p<0·05). Tie2 gene knockdown in TEMs inhibited neovascularisation of the ischaemic hindlimb (p<0·0001). Delivery of Tie2-expressing BMDMs into the ischaemic limb accelerated the recovery of blood flow compared with treatment with control BMDMs.InterpretationOur studies suggest that TEMs are mobilised following ischaemia and contribute to the revascularisation of ischaemic tissue, and that TIE2 is important for the proangiogenic functios of TEMs. TEMs may represent a promising, novel therapeutic target for cell therapy in critically ischaemic tissues.FundingBritish Heart Foundation and Royal College of Surgeons of England.     

Nitration of N-methyl-D-aspartate receptor subunits following in vitro dephosphorylation of cerebral cortical membranes of newborn piglets.

Previous studies have shown that activity of the cerebral N-methyl-D-aspartate (NMDA) receptor is modified by receptor nitration and phosphorylation. Since the sites for tyrosine phosphorylation and nitration are on adjacent carbon atoms, the present study tested the hypothesis that in vitro dephosphorylation of the NR1, NR2A and NR2B subunits of the NMDA receptor increases receptor nitration by peroxynitrite in cortical membranes of newborn piglets. To test this hypothesis, cerebral cortical P(2) membranes were prepared from normoxic and hypoxic newborn piglets and divided into dephosphorylated and non-dephosphorylated control groups. Dephosphorylation was performed in vitro by incubation with protein tyrosine phosphatase 1B and confirmed by immunoprecipitation with antiphosphotyrosine antibody. Dephosphorylated and non-dephosphorylated samples were nitrated with 0.5 mM peroxynitrite. Nitration was measured by immunoprecipitating with agarose-conjugated anti-nitrotyrosine antibody followed by Western blot analysis using specific anti -NR1, -NR2A and -NR2B primary antibodies. The data demonstrate that nitration of the NR1, NR2A and NR2B subunits of the NMDA receptor increases following dephosphorylation in both normoxic and hypoxic animals, however increase is much higher in hypoxic animals. We conclude that dephosphorylation at the site adjacent to the nitration site (ortho-position) on tyrosine residues of the NMDA receptor enhances nitration. Since in vitro nitration of the NMDA receptor increases the affinity of the glutamate recognition site and the receptor ion channel, we speculate that tyrosine dephosphorylation of the NMDA receptor will remove steric hindrance and facilitate nitration of tyrosine residues resulting in increased ion-channel activation in the hypoxic newborn brain.     

Endoscopic versus external approach dacryocystorhinostomy: A comparative analysis

Background:

Dacryocystorhinostomy (DCR) consists of creating a lacrimal drainage pathway to the nasal cavity to restore permanent drainage of previously obstructed excreting system.

Aim:

To compare the result and advantages of both endonasal endoscopic and external DCR regarding the patency rate, patient compliance and complications.

Study Design:

Prospective non-randomized comparative study.

Materials and Methods:

Study was conducted for 16 months duration in a teaching hospital with 50 cases of endoscopic and 30 cases of external DCR with a follow-up of minimum 6 months. Data regarding surgical outcome and complications were analysed and compared using χ² test.

Results:

Total 72 patients were included in the study with six having bilateral involvement, out of which 20 were male and 52 were female. The mean age for endoscopic and external DCR was 33.6 years and 46.0 years, respectively. Right eye (63.8%) was involved more commonly than left eye (36.2%). Epiphora was the commonest presenting symptom (63.7%). Mean duration of surgery was much lengthier in external (mean 119.6 minutes) than endoscopic (mean 49.0 minutes) DCR. Bleeding was the most common immediate postoperative complication seen in 33.3% and 10.0% of external and endoscopic DCR cases, respectively. Primary surgical success rate was 90% and 96.7% for endoscopic and external DCR, respectively (P = 0.046). Among the endoscopic DCR group, four patients underwent revision surgery giving a total successful surgical outcome of 98% at third month of follow-up. However, at 6 month of follow-up, success rate was 92% for endoscopic DCR and 93.3% for external DCR. The difference was not statistically significant (P = 0.609).

Conclusion:

Intranasal endoscopic DCR is a simple, minimally invasive, day care procedure and had comparable result with conventional external DCR.     

Development and Validation of a Precise,Single HPLC Method for the Determination of Tolperisone Impurities in API and Pharmaceutical Dosage Forms

A novel, sensitive, stability-indicating HPLC method has been developed for the quantitative estimation of Tolperisone-related impurities in both bulk drugs and pharmaceutical dosage forms. Effective chromatographic separation was achieved on a C18 stationary phase with a simple mobile phase combination delivered in a simple gradient programme, and quantitation was by ultraviolet detection at 254 nm. The mobile phase consisted of a buffer and acetonitrile delivered at a flow rate 1.0 ml/min. The buffer consisted of 0.01 M potassium dihydrogen phosphate with the pH adjusted to 8.0 by using diethylamine. In the developed HPLC method, the resolution between Tolperisone and its four potential impurities was found to be greater than 2.0. Regression analysis showed an R value (correlation coefficient) of greater than 0.999 for the Tolperisone impurities. This method was capable of detecting all four impurities of Tolperisone at a level of 0.19 μg/mL with respect to the test concentration of 1000 μg/mL for a 10 µl injection volume. The tablets were subjected to the stress conditions of hydrolysis, oxidation, photolysis, and thermal degradation. Considerable degradation was found to occur in base hydrolysis, water hydrolysis, and oxidation. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 100%. The established method was validated and found to be linear, accurate, precise, specific, robust, and rugged.     

Interactions of herbal extract combinations against free radical scavenging activity

Herbal medicines are often combinations of herbal extracts that are assumed to have additive or synergistic effects. This investigation compared the effect of individual herbal extracts with combinations of extracts on antioxidant activity by 1,1-diphenyl picryl hydrazyl (DPPH) method and showed the additive or synergistic effects by studying interactions between herbal extracts in combination. Curcuma longa Linn. (Zingiberaceae), Bacopa monneira Linn. Penn. (Scrophulariaceae), Zingiber officinale Rosc. (Zingiberaceae) and Emblica officinalis Gaertn. (Euphorbiaceae) were collected and used to prepare the extracts. Effects of the extracts on DPPH scavenging activity were estimated quantitatively by a UV-spectrophotometeric method. Combinations of two herbal extracts of the four active extracts and their interactions were tested by the DPPH method. Each extract significantly scavenges the free radical activity in a dose-dependent manner. The active extracts of Curcuma longa, Bacopa monneira, Zingiber officinale and Emblica officinalis were tested as two-extract combinations. Curcuma longa and Bacopa monneiera, when combined, showed additive effect with a trend towards synergistic effect, whereas Curcuma longa and Emblica officinalis together were additive. The four extracts together were significantly (p?≤?0.01) more effective than the two-by-two combinations and the individual extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use.     

Granulocyte-colony stimulating factor improves Parkinson's disease associated with co-morbid depression: An experimental exploratory study

Introduction:

The present study was designed to evaluate the effect of granulocyte-colony stimulating factor (G-CSF) in the treatment of Parkinson''s disease (PD), the second most common neurodegenerative disease characterized by muscle and movement disorder, often associated with depression. PD is very difficult to treat. Hence, the present study was aimed to evaluate the effect of G-CSF in PD associated with depression.

Materials and Methods:

Adult Wistar male rats weighing about 180-250 g were selected and divided into five groups in parallel designed method namely; control group (n = 5); sham operated group (n = 5); Vehicle group (n = 5); G-CSF group (70 μg/kg, s.c.) (n = 5) and L-DOPA group (n = 5). The rats were treated with 6-hydroxydopamine (6-OHDA) on day 0 and then treatment was continued for 14 day of L-DOPA/carbidopa, whereas G-CSF (70 μg/kg, s.c.) was given from day 1 to 6. Thereafter, adhesive removal and forced swim tests were conducted to evaluate the behavioral outcome of G-CSF treatment. The finding was correlated and analyzed with Nissl staining findings for the final conclusion.

Results:

The behavioral parameters were assessed and found to be ameliorate the symptoms of Parkinson''s and reduced the depression like behavior in PD. The histological findings were supported the behavioral findings and showed pathological improvement.

Conclusion:

As a preliminary work, the present study first time suggested that G-CSF have a potential role in PD and associated depression.KEY WORDS: 6-hydroxydopamine, depression, forced swim test, granulocyte-colony stimulating factor, Parkinson''s disease     

Neutrophilic eccrine hidradenitis: A new culprit-carbamazepine

Neutrophilic eccrine hidradenitis (NEH) is a distinctive dermatosis occurring in patients with malignancy or undergoing chemotherapy. This disorder is characterized by a neutrophilic infiltrate around the eccrine glands and secretory coils, and is associated with necrosis. It must be distinguished from infections, drug eruptions, malignancies or other forms of skin diseases. As it is a self-limiting condition, establishing the diagnosis will avoid unnecessary investigations and treatment. Here we report a case of NEH in a 40-year-old woman suspected to be due to carbamazepine.KEY WORDS: Adverse cutaneous drug reaction, carbamazepine, neutrophilic eccrine hidradenitis