Discovery of Novel Dimeric Pyridinium Bromide Analogues Inhibits Cancer Cell Growth by Activating Caspases and Downregulating Bcl-2 Protein.

Flexible dimeric substituted pyridinium bromides with primary and tertiary amines are prepared by conventional and solvent-free methods. The formation of compounds 2 and 4 is much easier than that of compounds 1 and 3 because of the benzyl carbon which is more electropositive than the primary alkyl carbon. The newly synthesized dimeric pyridinium compounds are optimized using DFT and B3LYP 6-31 g(d,p). The in vitro antiproliferative activity is studied in lung (A549) and breast cancer cell lines (MDA-MB 231). Among the four compounds, 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 showed potent anticancer activity when compared to the standard drug 5-fluorouracil. 1,1'-(1,3-Phenylene bis(methylene)bis 2-aminopyridinium bromide 4 is not toxic to normal cell lines 3T3-L1 and MRC-5 cell lines. Also, 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4-induced apoptosis in cancer cell lines is examined using AO/EB and Hoechst staining, which is further supported by cell cycle analysis. Western blot analysis showed that 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 induces apoptosis through the extrinsic apoptotic pathway by upregulating caspase 3 and caspase 9. This compound also downregulates intrinsic apoptotic proteins, including Bcl-2, Bcl-x, and Bad. From the present study results, it is confirmed that 1,1'-(1,3-phenylene bis(methylene)bis 2-aminopyridinium bromide 4 has potent anticancer activity when compared to other compounds.

Outcomes of surgical interventions for the treatment of limbal stem cell deficiency.

Background & objectives: In the current scenario, with availability of different surgical procedures for limbal stem cell deficiency (LSCD), there exists no common consensus as to the standardization of the management protocol for the same. In addition, there also exists diversity in the views about the clinical diagnosis, ancillary investigations and clinical parameters. The objective of the present study was to evaluate the reported outcomes of surgical interventions for the management of LSCD. Methods: A systematic review of published literature on limbal stem cell transplantation (LSCT) was performed using Ovid Medline, Embase and PubMed for a duration of 2009 to 2019. Original studies including prospective, retrospective case series and randomized controlled trials, articles in English language, articles with access to full text and studies with more than or at least 10 patients were included in this review. Data related to clinical and visual outcomes were evaluated, and pool estimates of different surgeries were calculated using random-effects model and individually using Pearson's Chi-square test. Results: A total of 1133 abstracts were evaluated. Finally, 17 studies were included for the analysis. Among these 17 studies, direct limbal lenticule transplantation was performed in five studies, of which autologous tissue from the fellow eye [conjunctival limbal autograft (CLAU)], allograft from a cadaver/live donor [keratolimbal allograft (KLAL)/conjunctival limbal allograft (CLAL)] and combination of CLAU plus KLAL were done in one, three and one studies, respectively. The ex vivo expanded cultivated limbal epithelial transplantation (CLET) was reported in six studies and simple limbal epithelial transplantation (SLET) in four studies. Two were comparative studies comparing CLET and CLAL (living-related CLAL) with cadaveric KLAL, respectively. Outcome analysis of the included studies showed significant heterogeneity. Calculated pool rate for various types of surgeries was calculated. The pool estimate for CLAL was 67.56 per cent [95% confidence interval (CI), 41.75-93.36; I2=83.5%, P=0.002]. For KLAL, this value was 63.65 per cent (95% CI, 31.38-95.91; I2=92.4%, P=0.000). Pool estimate for CLET was 78.90 per cent (95% CI, 70.51-87.28; I2=73.6%, P=0.001). Corresponding values for SLET were 79.08 per cent (95% CI, 74.10-84.07; I2=0.0%, P=0.619). CLAU and combination of CLAU plus KLAL were done in one study each; hence, statistical analysis could not be done. The functional outcome in terms of gain in visual acuity post-operatively was better in KLAL (P<0.005) and SLET group as compared to CLET group. Interpretation & conclusions: The present analysis suggests that though the anatomical success rates were almost identical between SLET, CLET, CLAL, and KLAL procedures, the functional success rates were better following KLAL and SLET procedures as compared to CLET. Decision for LSCT for cases of ocular burns based on either clinical judgement of the surgeon or individual diagnosis remains a suitable option.

Ultrasound liver elastography for the detection of liver fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy: A cross-sectional study.

BACKGROUND: Long-term low-dose methotrexate therapy is associated with liver fibrosis. Although liver biopsy is the gold standard for detecting fibrosis, it is an invasive procedure associated with morbidity and mortality risks. Hence noninvasive imaging techniques such as transient elastography (TE) and shear wave elastography (SWE) have been studied to measure liver stiffness. AIMS: To assess the utility of TE and SWE in detecting fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. METHODS: A cross-sectional prospective study was undertaken on 54 patients with psoriasis and reactive arthritis who had received ≥1.5 g of methotrexate. Various clinical and biochemical [fibrosis 4 index (FIB4), aspartate-transaminase-to-platelet ratio index (APRI)] parameters were calculated and liver stiffness measurement (LSM) was done with TE and SWE. The degree of steatosis was measured using controlled attenuation parameter (CAP). Liver biopsy was done when indicated and was interpreted by a pathologist blinded to clinical and imaging results. RESULTS: Fifty four patients with a mean age of 40.3 years and a male-to-female ratio of 5:1 were included. The mean cumulative methotrexate dose was 3.04 g. The median FIB4, APRI, and gamma-glutamyl transpeptidase-to-platelet ratio values were 0.75, 0.23, and 0.15, respectively. The median LSM for TE and SWE was 5.3 and 7.32 kPa, respectively. SWE and TE showed a weak positive correlation (r = 0.26, P = 0.053). The mean CAP was 217 dB/m (area under the receiver operating characteristic = 0.70). In the 19 of 26 cases whose liver biopsies could be assessed, only 4 (21%) showed F1 fibrosis (Ishak staging). The median LSM on SWE was significantly higher in patients with a cumulative methotrexate dose ≥ 4 g when compared with those with a dose <4 g (9.85 vs 7.1, P = 0.02). Other parameters did not correlate with TE and SWE. LIMITATIONS: The small sample size and the low number of cases with significant fibrosis on histopathology were the major limitations of this study. CONCLUSION: Histologically detectable LF is uncommon in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. Both TE and SWE are good at detecting the absence of fibrosis in these patients. In our study, SWE and TE values did not correlate with clinical, biochemical, or histopathological parameters.

Peptide-based therapeutics: quality specifications, regulatory considerations, and prospects.

Exquisite selectivity, remarkable efficacy, and minimal toxicity are key attributes inherently assigned to peptides, resulting in increased research interest from the pharmaceutical industry in peptide-based therapeutics (PbTs). Pharmacopoeias develop authoritative standards for PbT by providing standard specifications and test methods. Nevertheless, a lack of harmonization in test procedures adopted for PbT in the latest editions of Pharmacopoeias has been observed. Adoption of a harmonized monograph could increase further the interest of the global pharmaceutical industry in PbTs. Here, we provide an overview of pharmacopoeial methodologies and specifications commonly observed in PbT monographs and highlight the main differences among the pharmacopoeias in terms of the active pharmaceutical ingredients that they focus on. We also address the prospects for PbTs to mature as a new therapeutic niche.

Fluoride-associated ultrastructural changes and apoptosis in human renal tubule: a pilot study.

The susceptibility of the kidneys to fluoride toxicity can largely be attributed to its anatomy and function. As the filtrate moves along the complex tubular structure of each nephron, it is concentrated in the proximal and distal tubules and collecting duct. It has been frequently observed that the children suffering from renal impairments also have some symptoms of dental and skeletal fluorosis. The findings suggest that fluoride somehow interferes with renal anatomy and physiology, which may lead to renal pathogenesis. The aim of this study was to evaluate the fluoride-associated nephrotoxicity. A total of 156 patients with childhood nephrotic syndrome were screened and it was observed that 32 of them had significantly high levels ( p ≤ 0.05) of fluoride in urine (4.01 ± 1.83 ppm) and serum (0.1 ± 0.013 ppm). On the basis of urinary fluoride concentration, patients were divided into two groups, namely group 1 (G-1) ( n = 32) containing normal urine fluoride (0.61 ± 0.17 ppm) and group 2 (G-2) ( n = 32) having high urine fluoride concentration (4.01 ± 1.83 ppm). Age-matched healthy subjects ( n = 33) having normal levels of urinary fluoride (0.56 ± 0.15 ppm) were included in the study as control (group 0 (G-0)). Kidney biopsies were taken from G-1 and G-2 only, who were subjected to ultrastructural (transmission electron microscopy) and apoptotic (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling) analysis. Various subcellular ultrastructural changes including nuclear disintegration, chromosome condensation, cytoplasmic ground substance lysis, and endoplasmic reticulum blebbing were observed. Increased levels of apoptosis were observed in high fluoride group (G-2) compared to normal fluoride group (G-1). Various degrees of fluoride-associated damages to the architecture of tubular epithelia, such as cell swelling and lysis, cytoplasmic vacuolation, nuclear condensation, apoptosis, and necrosis, were observed.

A study of the histopathology of palmo-plantar psoriasis and hyperkeratotic palmo-plantar dermatitis.

BACKGROUND AND OBJECTIVES: Palmo-plantar psoriasis and dermatitis show several overlapping clinical features. We undertook this retrospective study to elucidate and compare the histological findings in these two dermatoses. MATERIALS AND METHODS: Biopsies of 31 clinically diagnosed cases of palmo-plantar psoriasis and 24 cases of hyperkeratotic palmo-plantar dermatitis, with concomitant presence of representative lesions at other body sites, were retrieved and analysed. RESULTS: Histologically, confluent parakeratosis, suprapapillary thinning and dermal edema were observed in significantly greater number of palmo-plantar psoriasis biopsies while an inflammatory infiltrate confined to the papillary dermis only, was a significant feature in palmo-plantar dermatitis. The two conditions could not be differentiated on the basis of features like focal parakeratosis, presence of neutrophils and fibrin globules in the stratum corneum, hypogranulosis, acanthosis, spongiosis, rete ridge pattern, or vascularity. CONCLUSION: Histopathology of palmo-plantar psoriasis and dermatitis can have several overlapping features. In our study, we found only few features as strong pointers towards psoriasis.

Does sleep quality affects the immediate clinical outcome in patients undergoing coronary artery bypass grafting: A clinico-biochemical correlation.

OBJECTIVE: Poor sleep quality is emerging as high prevalence among the patients suffering from cardiometabolic disturbances. The vascular polypeptide endothelin 1 (ET-1) is involved in many of the health disorders. However, its potential involvement in patients having poor sleep quality along with cardiovascular problem is limited. The present study was formulated to conduct a prospective analysis of the relationship between ET-1 and in hospital outcome in sleep disorder patients undergoing routine coronary artery bypass grafting (CABG). METHODS: A total of 156 patients were enrolled and divided into two groups based on the Pittsburg Sleep Quality Index (PSQI) of ≤5 (Group I, n = 101) or >5 (Group II, n = 55). Blood sample was collected before anesthesia induction (ET-1a) and at 48 h (ET-1b) to analyze the plasma ET-1 and blood sugar level. The patients were monitored for any intraoperative adverse events and postoperative complications during their hospital stay. RESULTS: Both groups were comparable in relation to age, sex, incidence of smoking and alcohol consumption. The distribution of comorbid conditions was also similar in both groups. The ET-1 level was higher in Group II than Group I before anesthesia induction as well as 48 h postoperatively (4.5 ± 1.75 vs. 10.61 ± 9.3, P = 0.001; 2.08 ± 1.3 vs. 8.3 ± 9.86, P = 0.0001, respectively). The Group II patients had a longer duration of mechanical ventilation (14.6 ± 12.05 vs. 10.1 ± 8.19, P = 0.001), Intensive Care Unit stay (2.08 ± 0.95 vs. 2.7 ± 1.45, P = 0016) and hospital stay (5.98 ± 1.73 vs. 7.8 ± 3.66, P = 0.0001, respectively). The high number of patients from Group II required inotrope and intra-aortic balloon pump support while compared with Group I (P ≤ 0.05 in each). The overall postoperative complication rate was significantly higher among patients with PSQI of >5 (Group II) except the rate of infection and neurological complications which was similar among both group of patients. The postoperative in hospital mortality was nil in Group I and 3.6% in Group II (P = 0.05). There was a strong relationship between PSQI and ET-1 at both the time points. CONCLUSION: Poor sleep quality associated with a higher incidence of adverse perioperative events in patients undergoing elective CABG. There exists a potential link between poor sleep quality and ET-1 in these groups of patients.

Cytotoxic and pro-apoptotic activities of leaf extract of Croton bonplandianus Baill. against lung cancer cell line A549.

The acetone extract (AcE) of the Croton bonplandianus Baill., an exotic weed of the Euphorbiaceae family was studied for cytotoxicity, apoptosis, cell cycle arrest in A549 cell line and antioxidant capacities using MTT assay, acridine orange/ethidium bromide (AO/EB staining), cell cycle analysis and DPPH radical scavenging assay respectively. Based on the cytotoxic activity, the extract was tested for the apoptotic effect using AO/EB and Hoechst 33258 staining. The apoptosis was characterized by chromatin condensation and DNA fragmentation. Further, to determine the stage of cell death, cell cycle analysis was performed by flow cytometry and AcE was found to arrest G2/M phase in a dose dependent manner. The number of cells in G2/M phase increases with concurrent accumulation of cells in sub G0/G1phase indicates the induction of apoptosis at G2M phase. The free radical scavenging activity of the AcE against DPPH was considerably significant. The cytotoxic, apoptotic and antioxidant effect of the AcE could be well correlated with the presence of potent free radical scavenging secondary metabolites such as phenols (43 ± 0.05 µg/mL), flavonoids (3.5 ± 0.07 µg/mL) and tannin (0.36 ± 0.1 µg/mL). Our study has shown that A549 cells were more sensitive to AcE with an IC50 of 15.68 ± 0.006 µg/mL compared to the standard drug 2.20 ± 0.008 µg/mL (cisplatin). The results suggest that Croton bonplandianus could serve as a potential source of alternative therapeutic agent for treating cancer. Further research is required to isolate the active principle compound and determination of its anticancer property.

Tumour morphology after neoadjuvant chemotherapy as a predictor of survival in serous ovarian cancer: an experience from a tertiary care centre in India.

Serous ovarian cancer is the most common malignant ovarian tumour. Traditional management consists of surgical resection with postoperative chemotherapy. Currently neoadjuvant chemotherapy is offered to patients with advanced stage disease. The present study aims to analyse the histomorphological alterations in serous ovarian cancer following neoadjuvant chemotherapy. Correlation of these morphological alterations with survival is also presented here. Serous ovarian cancers from 100 advanced stage cases were included; 50 were treated with pre-surgery chemotherapy. Semi-quantitative scoring was used to grade the alterations in tumour morphology. Survival data was correlated with the final morphological score. Tumour morphology was significantly different in cases treated with neoadjuvant chemotherapy (CT group) as compared to cases with upfront surgery. The CT group cases showed more fibrosis, calcification, and infiltration by lymphocytes, plasma cells, foamy and hemosiderin-laden macrophages. The residual tumour cells had degenerative cytoplasmic changes with nuclear atypia. Patients with significant morphological response had a longer median survival, although it did not attain statistical significance in the current study. With the increasing use of neoadjuvant chemotherapy in management, the pathologist needs to be aware of the altered morphological appearance of tumour. Further studies are required to establish a grading system to assess the tissue response which can be helpful in predicting the overall therapeutic outcome and the prognosis of patients.

Health Related Quality of Life in Indian Children with Cystic Fibrosis.

OBJECTIVE: This study was devised to translate Cystic Fibrosis Questionnaire-Revised to Hindi and administer it to Indian children and adolescents diagnosed with cystic fibrosis. DESIGN: Cross-sectional study. SETTING: This study was carried out in cystic fibrosis patients attending Pediatric Chest Clinic of a tertiary-care hospital in Northern India from July 2012 to December 2012. PARTICIPANTS: 45 children (6-13 years) and their parents, and 14 adolescents. Patients with unstable health in the past two weeks were excluded. INTERVENTION: Cystic Fibrosis Questionnaire- Revised translated in Hindi was administered. Clinical evaluation and scoring, throat swab cultures and spirometry were also done during the same visit. MAIN OUTCOME MEASURES: Health Related Quality of Life scores were the primary measures, and clinical scores, swab cultures and spirometry were secondary measures. RESULTS: Cronbachs alpha ranged from 0.020-0.863.The Factor analysis indicated that most test-items correlated more with competing scales than the intended scales. Convergence between self and proxy-rating was found to be dependent on the domain. The Cystic Fibrosis Questionnaire- Revised scores correlated well with clinical scores (r=0.65,P=0.011), Pseudomonas spp culture data and pulmonary function tests. There was an inverse relation between Health Related Quality of Life scores and age at diagnosis (r=-0.339, P=0.02). CONCLUSIONS: Hindi versions of Cystic Fibrosis Questionnaire- Revised: Child, Adolescent and Parents instruments will act as an important step towards data on Health Related Quality of Life of Indian patients with cystic fibrosis.

Therapeutic monoclonal antibodies and the need for targeted pharmacovigilance in India.

A growing number of innovative mAb therapeutics are on the global market, and biosimilar versions have now also been approved, including in India. Although efficacy and safety is demonstrated prior to approval, targeted pharmacovigilance is essential for the identification and assessment of risk for any mAb products. We analyzed the ADR data related to mAbs reported to the NCC-PvPI through the spontaneous reporting system Vigiflow during April 2011 to February 2014 to identify mAbs with the highest number of ADR including fatal/serious ADR. Only 0.72% reports were related to mAbs. Although 15 mAbs are approved in the country, only 6 mAbs were reported through Vigiflow. Rituximab was highly reported, and no fatal/serious ADR related to any mAbs were reported during the study period. Our study shows that PvPI is effective and robust system in the detection and assessment of risks associated with the use of mAbs.

Tissue biomarkers in prognostication of serous ovarian cancer following neoadjuvant chemotherapy.

Serous ovarian cancer (SOC) is a significant cause of morbidity and mortality in females with poor prognosis because of advanced stage at presentation. Recently, neoadjuvant chemotherapy (NACT) is being used for management of advanced SOC, but role of tissue biomarkers in prognostication following NACT is not well established. The study was conducted on advanced stage SOC patients (n = 100) that were treated either conventionally (n = 50) or with NACT (n = 50), followed by surgery. In order to evaluate the expression of tissue biomarkers (p53, MIB1, estrogen and progesterone receptors, Her-2/neu, E-cadherin, and Bcl2), immunohistochemistry and semiquantitative scoring were done following morphological examination. Following NACT, significant differences in tumor histomorphology were observed as compared to the native neoplasms. MIB 1 was significantly lower in cases treated with NACT and survival outcome was significantly better in cases with low MIB 1. ER expression was associated with poor overall survival. No other marker displayed any significant difference in expression or correlation with survival between the two groups. Immunophenotype of SOC does not differ significantly in samples from cases treated with NACT, compared to upfront surgically treated cases. The proliferating capacity of the residual tumor cells is less, depicted by low mean MIB1 LI. MIB 1 and ER inversely correlate with survival.

Synthesis, vibrational and quantum chemical investigations of hydrogen bonded complex betaine dihydrogen selenite.

The molecular complex of betaine with selenious acid namely, betaine dihydrogen selenite (C(5)H(13)NO(5)Se, BDHSe) was synthesised by the reaction of betaine and SeO(2) in a 1:1:1 solution of isopropanol, methanol and water. Crystals were grown from this solution by cooling to 253 K for few days. The complex was formed without accompanying proton transfer from selenious acid molecule to betaine. The complete vibrational assignments and analysis of BDHSe have been performed by FTIR, FT-Raman and far-infrared spectral studies. More support on the experimental findings was added from the quantum chemical studies performed with DFT (B3LYP) method using 6-311++G(**), 6-31G(**), cc-pVDZ and 3-21G basis sets. The structural parameters, energies, thermodynamic parameters and the NBO charges of BDHSe were determined by the DFT method. The (1)H and (13)C isotropic chemical shifts (δ ppm) of BDHSe with respect to TMS were also calculated using the gauge independent atomic orbital (GIAO) method and compared with the experimental data. SHG experiment was carried out using Kurtz-Perry powder technique. The efficiency of second harmonic generation for BDHSe was estimated relatively to KDP: d(eff)=0.97 d(eff) (KDP).

Persistent renin-angiotensin system activation after anti-reflux surgery and its management.

PURPOSE: To study renin-angiotensin system activation and the role of angiotensin-converting enzyme inhibition (ACE-I) after anti-reflux surgery. MATERIAL AND METHODS: Thirty nine children underwent anti-reflux surgery for high grades of primary VUR. Plasma renin activity (PRA), urinary microalbumin, renal scars, split renal function (SRF), glomerular filtration rate (GFR), serum creatinine, blood pressure and episodes of breakthrough urinary tract infection were monitored in the early (5.9 ± 3.9; range 3-9 months) and late (27.1 ± 6.5; range 15-36 months) postoperative phase, before and after therapy with ACE-I (mean period 13.6 ± 2.5; range 10-24 months). RESULTS: The early postoperative improvement in renal parameters (rise in SRF and GFR by 11.2% and 7.3%, respectively, and fall in PRA by 68.8%), was not sustained subsequently (minimal improvement in SRF, 7.4%, and GFR, 0.14%, was accompanied by a rise in PRA by 92.3%). After ACE-I therapy, improvement was noted in SRF and GFR by 0.5% and 7.5%, respectively, and there was a fall in urinary microalbumin by 52.3%. CONCLUSIONS: Significant down regulation of rennin-angiotensin system activation and the accompanying improvement in renal function seen early after surgery is not sustained during follow up. ACE-I aids renal recovery.

Current knowledge and future direction of research on soy isoflavones as a therapeutic agents.

Isoflavones, the most abundant phytoestrogens in Soy beans, are structurally similar to 17beta-estradiol. The antioxidant property of the soy isoflavones, namely, genistein and daidzein is well established in different experimental models and also in clinical studies. The compounds have been found effective in the management of diabetes by acting on peroxisome proliferator-activated receptors. It reduces the risk of coronary heart disease by reducing the level of low-density lipoprotein and triglycerides. Soy isoflavones have the potential in the treatment of osteoporosis to act on osteoclasts further to inhibit tyrosine kinase. Among the soy isoflavones, genistein is the potential compound found effective in the treatment of cancer by acting on androgen receptor further to inhibit tyrosine kinases. In this article, various aspects of the diverse biological activities of soy isoflavones and their potential clinical implications with mechanism of action, especially in the treatment and prevention of diabetes, cardiovascular diseases, cancer, osteoporosis, neuroprotection, and also future area of research on soy isoflavones are reviewed and discussed.

Intravenous dexamethasone vs methylprednisolone pulse therapy in the treatment of acute endothelial graft rejection.

PURPOSE: To study the outcome of therapy for acute endothelial graft rejection with an intravenous (i.v.) pulse of dexamethasone vs methylprednisolone, in addition to topical corticosteroids. METHODS: Records of 98 eyes of 99 patients treated for endothelial graft rejection with a single i.v. pulse of dexamethasone or methylprednisolone in addition to topical steroids, between January 1999 and June 2004, were retrospectively reviewed. Baseline characteristics such as surgery-rejection interval, time taken to consult after onset of symptoms, history of failed grafts, extent of stromal vascularization, best-corrected visual acuity (BCVA) and corneal thickness at the time of presentation were noted. Main outcome measures following treatment for rejection included improvement in BCVA, change in corneal thickness, and reversal of graft rejection. RESULTS: Fifty-one patients were treated with i.v. methylprednisolone and 47 with i.v. dexamethasone, in addition to topical steroids. Both groups were found to be comparable with respect to baseline parameters, that is, time taken to present, history of failed grafts, extent of stromal vascularization, BCVA, and graft thickness. Graft rejection could be successfully reversed in 72.3% cases in the dexamethasone group and 49% in the methylprednisolone group (P=0.018). A significant improvement in visual acuity was recorded following treatment in both groups, with a better outcome in the dexamethasone group (P=0.012). Post-treatment pachymetry values were lower than pretreatment values in both groups, with significantly lower final pachymetry in the dexamethasone group (P=0.017). No adverse effects were observed. CONCLUSION: I.v. pulse therapy with dexamethasone may be used as an effective alternative to methylprednisolone in reversing acute endothelial graft rejection.

Nutritional status of patients with Crohn's disease.

BACKGROUND AND AIM: Malnutrition is a common feature in patients with Crohn's disease (CD), which leads to frequent infections and poor prognosis. In view of the rising incidence of CD in India we planned this study to assess the nutritional status of patients with CD. METHODS: Nutritional status of 112 patients (mean age 35.9 [SD 11.7] years; 61 men) with CD was assessed by anthropometric, dietary and biochemical parameters. Patients were considered malnourished if 3 or more anthropometric parameters (% ideal body weight [IBW], % tricep skin fold [TSF], %mid upper arm circumference [MUAC], and % mid arm muscle circumference [MAMC], body mass index [BMI]) were abnormal. Dietary intake was assessed by a 24-hour dietary recall along with a semi-quantitative food frequency method. Eighty volunteers were taken as healthy controls (HC). RESULTS: At the time of assessment, 77 patients were in remission and 35 had active disease. The values of BMI, MUAC, TSF and mid arm fat area (MAFA) in patients were significantly lower than those in healthy controls. MAMC and mid arm muscle area (MAMA) of patients and controls were comparable. TSF (Rem vs HC = 10.4 [2.8-71] vs 16 [3-41]) and MAFA (Rem vs HC = 1236 [240-7757] vs 1858 [322-5650]) of the patients in the remission phase were significantly lower than those of healthy controls; the remaining parameters were comparable. There was no difference in the dietary intake of patients in the remission and active phases, and healthy controls. The percentage energy fulfillment of the patients was lower than that of healthy controls. Twenty-nine of 35 (82.8%) patients in the active and 30 of 77 (38.9%) patients in the remission phase were malnourished (OR 7.5, 95% CI 2.8-20.4). The overall prevalence of malnutrition was 52.6% among patients. CONCLUSION: The percentage of malnourished patients in the active and remission phases of the disease was 82.8% and 38.9%, respectively, possibly due to low percentage energy fulfillment.

Plasma renin activity for monitoring vesicoureteric reflux therapy: mid-term observations.

OBJECTIVE: To study plasma renin activity (PRA) as an early marker for monitoring treatment of vesicoureteric reflux (VUR). PATIENTS AND METHODS: Fifty-nine children (35 males and 24 females), mean age 43.3+/-26.5 (range 4.5-89) months, with various grades (I-V) of primary VUR were enrolled. PRA, renal scars, split renal function (SRF), glomerular filtration rate (GFR), serum creatinine, blood pressure and episodes of breakthrough urinary tract infection were monitored at regular intervals. Surgery was performed as per currently accepted criteria. PRA values were used for post-hoc analysis of results. RESULTS: Thirty-eight children (64.4%) underwent anti-reflux surgery during the mean follow up of 17.1+/-3.1 months; 21 (35.6%) continued on non-operative follow up. Rise in PRA up to the time of surgery was seen in all patients. It normalized after surgery in 86%, and reduced but plateaued at a higher level than normal in 13.8% in the surgical group. While improvement in SRF and GFR was seen only in 2/38 (5.2%) and 12/38 (31.6%), respectively, blood pressure stabilized in 30.7% and serum creatinine showed inconsistencies. In non-operatively managed cases, improvement in SRF was seen in only one case and GFR in 14.2% of cases. However, 80.9% children showed a progressive rise in PRA throughout the period of non-operative follow up. CONCLUSION: Current end points of non-operative management already cause irreversible renal damage by the time surgery is indicated. Our results suggest that serial measurement of plasma renin activity may help in better stratification of patients with moderate to high grade (III-V) VUR with respect to management and prognosis.

Effects of butorphanol and fentanyl on cerebral pressures and cardiovascular hemodynamics during tunneling phase for ventriculoperitoneal shunt insertion.

PURPOSE: Subcutaneous tunneling for ventriculoperitoneal shunt insertion is the most painful step of this surgery. It is associated with intense hemodynamic response, may influence the intracranial pressure, and thus may worsen the existing intracranial pathology. The purpose of this report is to evaluate the commonly used opioid fentanyl, along with butorphanol, an agonist-antagonist compound. METHODS: Twenty adult patients undergoing ventriculoperitoneal shunt surgery were induced with fentanyl 2-mcg.kg(-1) and thiopentone 4-5 mg.kg(-1). Intubation followed the administration of rocuronium 1 mg.kg(-1). All patients were put on mechanical ventilation to maintain end-tidal carbon dioxide levels of 32 +/- 2 mmHg. Anesthesia was maintained with isoflurane in N2O and O2 (MAC 1.0 +/- 0.2). Routine monitoring, arterial blood pressure and intracranial pressures were measured. Three minutes prior to the tunneling phase, patients received either fentanyl 1 mcg.kg(-1) or butorphanol 1 mg in a randomized manner. Thereafter hemodynamic and intracranial pressure changes were noted during tunneling and each minute in the post-tunneling period for 5 minutes. The duration of the tunneling phase was also noted. Data were presented as number (proportion) or mean +/- SD/median (range) as appropriate. Statistical analysis was done using Wilkoxon ranksum test and the repeated measures of ANOVA. The value of p < 0.05 was considered significant. RESULTS: A significant rise in the intracranial pressure and cerebral perfusion pressure along with the hemodynamic parameters was noted during the tunneling phase in both groups. The changes were of longer clinical duration in the butorphanol group. CONCLUSION: Butorphanol must be used with caution in neurosurgical patients. The ventricular end of the shunt catheter should preferably be put before the tunneling phase to avoid rise in intracranial pressure.