In Vivo Evaluation of 5-ASA Colon-Specific Tablets Using Experimental-Induced Colitis Rat Animal Model.

Colonic drug delivery is intended not only for local treatment in inflammatory bowel disease (IBD) but also for systemic delivery of therapeutics. Intestinal myeloperoxidase (MPO) determination could be used to estimate the average level of inflammation in colon as well as to determine the efficacy of drugs to be used in the treatment of inflammatory bowel diseases or study the specificity of dosage forms to be used for colonic targeting of anti-inflammatory drugs. Colonic prodrug sulfasalazine (SASP) gets metabolized to give 5-aminosalicylic acid (5-ASA), which is the active portion of SASP. However, when given orally, 5-ASA is absorbed in upper part of gastrointestinal tract (GIT) and not made available in colon. In the present study, colon-targeted delivery of 5-ASA was achieved by formulating tablets with two natural polymers namely guar gum and pectin using compression coating method. Colonic specificity of 5-ASA tablets (prepared using guar gum and pectin as polymers) was evaluated in vitro using simulated fluids mimicking in vivo environment as well as in vivo method using chemically (2,4,6-trinitrobenzenesulfonic acid and acetic acid)-induced colitis rat model. Both colon-specific formulations of 5-ASA (guar gum and pectin) were observed to be more effective in reducing inflammation in chemically induced colitis rat models when compared to colon-specific prodrug sulfasalazine as well as conventional 5-ASA administered orally.

Pulmonary complications in the non-HIV immunocompromised patient.

The incidence of non-HIV immunocompromised patients is increasing. This is primarily due to improved immunosuppressive regimes for autoimmune diseases and also increases in stem cell transplantation. Pulmonary complications are a major cause of morbidity and mortality in these patients. Imaging is frequently used to assess these complications and to streamline therapies, as microbiological and/or pathological diagnosis can often be difficult, invasive, or protracted. This review provides the reader with a structured approach to interpret the imaging findings and differentiate between different infective and non-infective complications in these patients.

A practical approach to bladder preservation with hypofractionated radiotherapy for localised muscle-invasive bladder cancer.

Bladder preservation with trimodality treatment (TMT) is an alternative strategy to radical cystectomy (RC) for the management of localised muscle invasive bladder cancer (MIBC). TMT comprises of transurethral resection of the bladder tumour (TURBT) followed by radiotherapy with concurrent radiosensitisation. TMT studies have shown neo-adjuvant chemotherapy with cisplatin-based regimens is often given to further improve survival outcomes. A hypofractionated radiotherapy regimen is preferable due to its non-inferiority in local control and late toxicities. Radiosensitisation can comprise concurrent chemotherapy (with gemcitabine, cisplatin or combination fluorouracil and mitomycin), CON (carbogen and nicotinomide) or hyperthermic treatment. Radiotherapy techniques are continuously improving and becoming more personalised. As the bladder is a mobile structure subject to volumetric changes from filling, an adaptive approach can optimise bladder coverage and reduce dose to normal tissue. Adaptive radiotherapy (ART) is an evolving field that aims to overcome this. Improved knowledge of tumour biology and advances in imaging techniques aims to further optimise and personalise treatment.

Isolation and characterization of a Pseudomonas sp. strain IITR01 capable of degrading α-endosulfan and endosulfan sulfate.

AIM: To isolate bacteria capable of degrading endosulfan (ES) and the more toxic ES sulfate and to characterize their metabolites. METHODS AND RESULTS: A Pseudomonas sp. strain IITR01 capable of degrading α-ES and toxic ES sulfate was isolated using technical-ES through enrichment culture techniques. No growth and no degradation were observed using ß-ES. Thin-layer chromatography and gas chromatography-mass spectrum analysis revealed the disappearance of both α-ES and ES sulfate and the formation of hydroxylated products ES diol, ether and lactone. We show here for the first time the formation of aforementioned metabolites in contrast to ES hemisulfate yielded by an Arthrobacter sp. Metabolism of α-ES and endosulfate was also observed using the crude cell extract of IITR01. The molecular mass of protein induced during the degradation of α-ES and sulfate as substrate was found to be approximately 150 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). CONCLUSION: We describe characterization of bacterium capable of degrading α-ES and ES sulfate but not ß-ES. Genetic investigation suggests that a gene nonhomologous to the reported esd may be present in the strain IITR01. SIGNIFICANCE AND IMPACT OF THE STUDY: This study describes toxic ES degradation by a Pseudomonas species that may be utilized for the bioremediation of the industrial soils contaminated with ES residues.

Studies on antidermatophytic activity of waste leaves of Curcuma longa L.

During antidermatophytic screening of some essential oils, Curcuma longa L. exhibited the strongest antifungal activity, completely inhibiting the mycelial growth of ringworm, caused by the fungi- Microsporum gypseum and Trichophyton mentagrophytes. The essential oil from leaves of Curcuma longa was fungicidal at 2.5 µl/ml at which it tolerated heavy doses of inoculum. The fungicidal activity of the oil was thermostable up to 80 °C and self life up to 24 months in storage. The oil also showed a broad fungitoxic spectrum, inhibiting the mycelial growth of other fungi, viz., Epidermophyton floccosum, M. nanum, T. rubrum, T. violaceum. Moreover, up to 5 % concentration it did not exhibit any adverse effect on mammalian skins. The oil has been formulated in the form of an ointment, 1 % w/v and subjected to topical testing on patients of the Out Patient Department (OPD) at Moti Lal Nehru Medical College, Allahabad. Patients were selected on the basis of KOHpositive results and diagnosed tenia corporis. After the second week of treatment, all patients were KOH- negative. At the end of medication, 75 % of patients recovered completely while 15 % showed significant improvement from the disease. The ointment thus, can be exploited commercially after ongoing successful clinical trials. Relationship of the dermatophytes to the toxicity of the oil vis-a-vis phylogeny using molecular data of the pathogens have also been discussed.

Extra precision glide docking, free energy calculation and molecular dynamics studies of 1,2-diarylethane derivatives as potent urease inhibitors.

For the latter half of the twentieth century, most medical professionals considered bacterial infection to be a primary cause of gastrointestinal ulcers in human beings. In 1994, the World Health Organization (WHO) recognized Helicobacter pylori, the bacterium most closely linked to ulcer development, as a type I carcinogen. Biological research has shown that there is a positive correlation between the number of species in the Helicobacter genus and the number of medical conditions associated with Helicobacter infection, both of which are increasing rapidly. N-Benzylaniline derivatives, frequently used in industrial manufacturing, are being considered as a strong candidate for ongoing drug modeling in search of novel therapies. The basic goal behind this study was to determine the potency of experimentally proved data, and to determine favorable substituents to enhance potency, and thereafter to support this finding through theoretical modification of the existing base skeleton by addition of suitable substituents. Ligands were investigated thoroughly by paying attention to the urease-inhibitory properties present in the selected series. Initially, docking was performed on ligands with protein to produce efficient docking poses. Molecular dynamics (MD) simulations were also performed to precisely understand the interactions between ligands and proteins. Thereafter, MM-GBSA was used in order to validate the methods and results. Good interaction was observed with amino acids Arg338, Ala169, Asp223, His322, and Asn168. This study also revealed that the electron rich hydroxyl group (-OH) substituent plays an important role during bond formation. In addition, various hydrogen bonds, ionic bonds, and pi-pi stacking bonds make significant contributions towards urease inhibition. Therefore, further research utilizing electron-rich moieties may lead to novel and efficacious urease inhibitors.

Bilateral retinoblastoma in early infancy: a case report.

Retinoblastoma is the most common primary intraocular tumour of childhood. Though congenital, it is not diagnosed at birth, and is usually seen between 1-2 years of age. We here report a case of bilateral retinoblastoma with early presentation at the age of one month.

A comparison of morphologic and angiographic findings in long-term internal mammary artery and saphenous vein bypass grafts.

Internal mammary artery grafts are currently considered the conduits of choice for myocardial revascularization. Comparisons of long-term morphologic changes in internal mammary artery grafts and saphenous vein grafts and correlation with premortem angiography have not been reported. Eighteen internal mammary artery and 15 saphenous vein grafts that had been in place for 12 to 118 months (mean 56) in 18 patients were removed either surgically or at necropsy and examined histologically. Premortem angiograms were performed within 1 month of histologic study in 15 of these patients. Fibrointimal proliferation was more frequent in internal mammary artery than in saphenous vein grafts 8 [( 44%] of 18 versus 4 [27%] of 15; p = NS). In contrast, atherosclerosis was common in saphenous vein grafts but was extremely rare in internal mammary artery grafts (10 of 15 versus 1 of 18; p = 0.01). A good correlation was noted between the degree of narrowing estimated by angiographic and histologic measurements in both internal mammary artery grafts (d = 0.90) and saphenous vein grafts (d = 0.71). Accelerated atherosclerosis did not occur in internal mammary artery grafts, but was common in saphenous vein grafts. Fibrointimal proliferation was commonly associated with graft narrowing in internal mammary artery grafts and may be an important factor in late graft closure. This study also confirms that internal mammary artery grafts have greater longevity compared with saphenous vein grafts.

Induction-intubation response--smokers vs non-smokers--.

BACKGROUND AND OBJECTIVES: Tobacco smoking has been established to be a hazardous activity. Changing social attitude is bringing a decline in tobacco consumption but a significant proportion of patients presenting for surgery still continues to smoke, putting themselves at risk of perioperative complications. We evaluated induction-intubation response in 40 male patients (ASA-I) divided into two groups of 20, each consisting of smokers and non-smokers. METHODS: All patients received standard premedication and general anesthesia. Heart rate, blood pressure and rate-pressure product were measured prior to induction, just before intubation and at 1, 3, 5 and 10 minutes after intubation. Continuous electrocardiography (EKG lead II) monitoring was done. Carboxyhemoglobin and total hemoglobin were estimated at the time of securing venous access. Arterial blood gases were analysed 5 minutes before and after the tracheal intubation. RESULTS: Incidence of arrhythymias (30%) was higher in smokers compared to non-smokers (10%). Mean carboxyhemoglobin (COHb) level in smokers was 3.81 +/- 2.17 gdL(-1) as compared to 2.95 +/- 1.33 gdL(-1) in non-smokers. Four patients who continued to smoke till the day of surgery had higher COHb levels (8.2, 5.9, 6, 8.8 gdL(-1)). PaO2 and PaCO2 levels were comparable in both groups. CONCLUSIONS: During induction-intubation period, heart rate; systolic, diastolic and mean arterial pressure and rate-pressure product showed more pronounced fluctuations in smokers than in non-smokers (p < 0.05).

Safety of implantation of a cardioverter-defibrillator without general anesthesia in an electrophysiology laboratory.

Implantable cardioverter-defibrillators (ICDs) have conventionally been implanted in an operating room under general anesthesia. This study was performed to evaluate ICD implantation without general anesthesia by 2 electrophysiologists in an electrophysiology laboratory. Between February and September 1994, 27 consecutive patients (22 men and 5 women, mean age 59 +/- 15 years) who underwent ICD implantation by 2 electrophysiologists were included in this study. Fourteen patients received biphasic waveform ICDs, and the remaining 13 had monophasic waveform devices. All patients received local anesthesia and intravenous sedation for implantation. Implantation was successful in 23 of 27 patients at first attempt (11 of 11 with biphasic and 12 of 16 with monophasic waveform ICDs, respectively). Of 4 patients in whom implantation was initially unsuccessful, 3 subsequently received biphasic devices and 1 had improved defibrillation threshold ( < or = 26 J) on repeat testing after amiodarone withdrawal. Mean implantation time was 128 +/- 51 minutes, with 132 +/- 35 minutes under sedation. Patients who received biphasic versus monophasic waveform ICDs had no significant differences in mean sedation or implantation time. Minor complications occurred in 2 patients (7%): 1 minor abdominal pocket hematoma and 1 incision-site cellulitis. Mean time from implantation to discharge was 2.5 +/- 2.1 days. During late follow-up (n = 23; mean 12.4 +/- 5.8 weeks), all devices were functioning appropriately. In conclusion, this report demonstrates that ICD implantation can be successfully and safely performed by a team of 2 electrophysiologists using local anesthesia and intravenous sedation.(ABSTRACT TRUNCATED AT 250 WORDS)

Hamartoma of mature cardiac myocytes.

The clinical and pathological findings of three patients with hamartomas of mature cardiac myocytes resembling localized hypertrophic cardiomyopathy are presented. Hypertrophic cardiomyopathy is manifest by a poorly demarcated area of cardiac hypertrophy, microscopically demonstrating myofiber disarray and intramural coronary thickening. Localized, nonencapsulated masses of hypertrophied cardiac myocytes in locations other than the left ventricle or ventricular septum have not been reported. The clinical and pathological data of three patients with localized hamartomas were retrospectively retrieved. The patients were 9, 22, and 28 years old, respectively; none had a known family history of heart disease or cardiomyopathy. Two patients had cardiac arrhythmias: one patient died suddenly, and one patient had the Wolff-Parkinson-White syndrome. The third patient was asymptomatic. Two patients treated surgically had single masses in the right atrium and right ventricle, respectively. The patient who died suddenly had multiple discrete masses throughout the atrial and ventricular myocardium, including the left ventricular free wall. None of the three patients had septal asymmetry suggestive of hypertrophic cardiomyopathy. Histologically, there were discrete but unencapsulated nodules of marked myocyte hypertrophy with disorganization, focal scarring, and thickened intramural arteries. There was no myocyte vacuolization suggestive of cardiac rhabdomyoma. Ultrastructurally, the myocytes showed abundant and disorganized myofilaments and normal intercellular junctions. Hamartoma of mature cardiac myocytes is a previously undescribed cardiac tumor that shares some features of hypertrophic cardiomyopathy and rhabdomyoma, but is currently best considered a separate entity.

Plasma insulin and growth hormone during antarctic residence.

Circulatory levels of insulin and growth hormone (GH) were estimated in nine tropical euglycemic men in New Delhi and during the first week of every month of stay in Dakshin Gangotri, Antarctica. Prolonged residency in Antarctica did not alter GH levels because mean GH values during Austral summer and Austral winter were not significantly different from the New Delhi values. Compared with GH, the insulin levels during March, April, and June were found to be significantly lower than the New Delhi values. In Antarctica, the insulin levels in March, April, May, June, July, and August were also found to be significantly lower than the December values. This decline in insulin in Antarctica might be important in increasing substrate availability for heat production by facilitating lipolysis and hepatic glucose output.

Identification of a contact depigmenting agent in Indian bindi.

INTRODUCTION: Bindis, which Indian women apply on their foreheads, occasionally depigment the skin. METHODS: We analysed the adhesive on bindi samples using thin layer chromatography, infrared spectrophotometry, high performance liquid chromatography and patch tested 15 patients with bindi depigmentation, 10 normal individuals and 14 patients with vitiligo. RESULTS: The bindi adhesive contained about 80% paratertiary butyl phenol-a depigmenting agent with a marked irritant action. Hypersensitivity to the agent did not occur. CONCLUSIONS: Para-tertiary butyl phenol causes depigmentation after bindi application on the forehead and we suggest that the use of this agent as an adhesive be banned.

Sleep deprivation in anaesthetists : effect on cognitive functions.

Sleep deprivation is one of the various stress factors which may affect the efficiency of an anaesthitist. Cognitive functions play a vital role in safe anaesthetic practice. To assess the effect of sleep deprivation on cognitive functions, forty anaesthesia residents were tested using various tests in two planned situations. 'Situation I' comprised of non sleep deprived state and 'Situation II' was the sleep deprived state defined as 'less than 4 hours of sleep in the last 24 hours'. The tests used were Trail making task, Digit symbol test, Letter comparison test and Standard progressive matrices. There was a statistically significant decrease in the performance scores after sleep deprivation. It is concluded that acute sleep deprivation adversely affects cognitive functions.

Cerebral and cardiovascular haemodynamics with vecuronium as an intubating agent in neurosurgical patients.

The effects of vecuronium and pancuronium, administered for muscle relaxation prior to endotracheal intubation, on intracranial pressure and systemic haemodynamics were compared in 20 patients undergoing supratentorial surgery. The patients were randomly divided into two groups of 10 patients each depending upon the muscle relaxant used. Patients in group I received pancuronium (0.15 mg kg-1) following thiopentone induction while patients in group II were given vecuronium (0.15 mg kg-1) for intubation. Intracranial pressure, heart rate, mean systolic and diastolic blood pressures, central venous pressure, nasopharyngeal temperature and arterial blood gases were monitored at 3 minutes before induction, 1 and 3 minutes after thiopentone and relaxant intubation and 4, 6, 8 and 10 minutes after intubation. Induction of anaesthesia resulted in a small but significant fall in intracranial pressure in both the groups at 1 and 3 minutes (p < 0.05). The rise in intracranial pressure at intubation was significantly higher in group I patients (26.4 ñ 3.2 mm Hg) compared to group II patients (14 ñ 2.8 mm Hg). A significantly greater degree of rise in heart rate, and systolic and mean arterial pressure was observed in group I patients as compared to group II patients.

Computer--aided drug interaction retrieval programme.

A drug interaction database has been created to include information on drug interactions based both on the generic and trade names of drugs. The database has approximately one thousand records that provide the information on drug-drug, food, smoke, alcohol interactions and a message to briefly describe the particulars of drug interactions. The computer programme was designed using Dbase III plus commands, to readily identify potentially significant interactions in a prescription. The computer outputs may be used to alert the physicians in time to take precautions and hence to reduce the incidences of adverse effects associated with drug interactions. This would result in reduction in hospital stay as well as reducing costs of medical care. This is urgently needed in public as well as private hospitals.

Clinical profile and electrodiagnostic study of peripheral neuropathy.

A clinical analysis and electrophysiological study was performed in 40 cases of peripheral neuropathy. Motor nerve conduction velocity (MNCV) and electromyography (EMG) were also recorded in 20 healthy volunteers. Twelve cases were of diabetic neuropathy (DN), nine of Guillain-Barre syndrome (GBS), eight of idiopathic, six of leprous, three of toxic neuropathy and one each of acute intermittent porphyria (AIP) and carcinomatous neuropathy. The onset was insidious in a majority of the cases (70%), the presenting symptom being paraesthesia (27.5%). A variable sensory loss was the commonest finding (77.5%). Two patients each had evidence of cranial nerve involvement and affection of urinary bladder and bowel. In both DN and GBS there was a significant reduction in the MNCV especially in the peroneal nerves. In DN 41.6% had evidence of decreased motor unit potentials and 16.6% showed spontaneous fibrillatory activity. For GBS these figures were 77.7% and 8.3% respectively. The peripheral nerve involvement was variable in leprosy and the EMG was normal in all, but one case.

Clinico-histopathological concordance in leprosy.

Histopathological examination of biopsies from 111 patients with clinically diagnosed leprosy was carried out in order to observe the clinico-histopathological correlation. Clinical diagnosis was based on Ridley and Jopling (R-J) classification and World Health Organization (WHO) classification. The concordance rate between the two clinical classifications was 73.8%. Sections were stained with haematoxylin and eosin (H&E) and Ziehl-Neelsen's (Z-N) stains. The histological classification was as per the R-J criteria. Skin biopsy showed evidence of leprosy in 104 cases (93.69%). Overall concordance was observed in 58.6% (R-J) and 85.6% (WHO classification). The kappa test, when applied, showed significant agreement between clinical and histopathological diagnosis (z=11.775; P<0.001). Individual subtypes showed variable concordance rates which were again higher using WHO classification. When some of the subtypes were combined, the concordance rate was 83.02% for TT+BT; 72.58% for BT+BB+BL; 73.91% for BL+LL; 80.77% for BL+HL and 100% for LL+HL. (See Introduction for definitions of abbreviations.) The present study highlights the importance of histopathological examination for exact subtyping of leprosy, so as to facilitate the institution of accurate mode of therapy and regular follow-up of patients to prevent undesirable complications.

Antispermatozoal antibodies in leprosy with special reference to their morphological patterns.

Sixty two male patients with polar leprosy--38 lepromatous and 24 tuberculoid types were investigated for the presence of antispermatozoal antibodies with special reference to their morphological patterns. Antibodies were detected by three different immunological techniques. Sperm agglutination was found to be the most sensitive. The incidence of antibodies was higher in patients with lepromatous leprosy and was directly proportional to the duration of the disease in both types of leprosy. Morphologically, head-to-head type of agglutination was observed in 50 percent of the patients, mixed in 41.7 percent and tail-to-tail type in 8.3 percent. There was no correlation between the number of ENL attacks and the incidence of anti-bodies. In polar tuberculoid leprosy patients the histological findings of testicular biopsy indicated cell mediated tissue damage occurring in a non-infective form.

Evaluation of audiovestibular status in leprosy.

One hundred twenty five cases of lepromatous leprosy and 25 cases of tuberculoid leprosy were investigated for audiovestibular status. Impaired hearing was detected in 52 percent and vestibular hypofuction in 7.2 per cent of lepromatous cases. Conductive deafness was due to eustachian tube catarrh secondary to atrophic rhinitis associated with the disease. The perceptive deafness and vestibular hypofuction were due to end organ lesion probably due to E.N.L. reaction. The vestibulococlear nerve involvement was considered to be unlikely. In tuberculoid leprosy derangement in hearing was not observed in any cases.