Association of proton pump inhibitors with renal dysfunction: a cross-sectional study

Background: Proton pump inhibitors are the most frequently prescribed class of medications for prescription and over-the-counter, and the data suggest that comorbidities, polypharmacy, self-medication, no clear indications and duration beyond the recommended guidelines PPIs use are associated with renal dysfunction. Aim was to study the proportion of renal dysfunction among patients using oral PPIs and determine the association between the duration of oral PPIs use and the severity of renal dysfunction. Methods: The data collection of 250 patients was done at the time of contact, which included demographic profiles, complete medical history, physical examination, and laboratory investigation in this study. For analysis, name of oral PPIs used, duration and dosage of oral PPIs therapy, laboratory values of serum blood urea, serum creatinine, eGFR, and serum electrolytes parameters have been considered. Results: Amongst 250 patients with PPIs used for a week, 23 patients showed mildly reduced kidney function (p=0.000), PPIs used for >1 to 2 weeks, 29 patients showed grade 2 kidney function (p=0.001), while PPIs used for >2-3 weeks only two patients showed grade 3 kidney function (p=0.44). Patients aged >50 years in all groups showed grade 2 renal function, regardless of the duration of PPIs use. Increasing age, males, rural, smoking, and alcoholics were the risk factors for renal dysfunction. PPIs use significantly impacts eGFR. Conclusions: Collectively, this study found a significant association between PPIs use and renal dysfunction. PPIs used for >2 weeks in elderly patients have shown a 4?fold increased risk of developing renal dysfunction.

Chronic postthoracotomy pain in transapical transcatheter aortic valve replacement

Objective: Chronic postthoracotomy pain (CPTP) is a persistent, occasionally debilitating pain lasting >2 months following thoracic surgery. This study investigates for the first time the prevalence and clinical impact of CPTP in patients who have undergone a transapical transcatheter aortic valve replacement (TA-TAVR). Design: This was a single-institution, prospective observational survey and a retrospective chart review. Setting: The study was conducted in the University Hospital. Participants: Patients. Materials and Methods: A survey of 131 participants with either a previous TA TAVR or transfemoral (TF) TAVR procedure was completed. A telephone interview was conducted at least 2 months following TAVR; participants were asked to describe their pain using the Short-Form McGill Pain Questionnaire. Measurements and Main Results: Odds ratio (OR) was calculated using the proportions of questionnaire responders reporting “sensory” descriptors in the TA-TAVR versus the TF-TAVR groups. Results were then compared to individual Kansas City Cardiomyopathy Questionnaire (KCCQ12) scores and 5-min walk test (5MWT) distances. A total of 119 participants were reviewed (63 TF, 56 TA). Among TA-TAVR questionnaire responders (n = 16), CPTP was found in 64.3% of participants for an average duration of 20.5-month postprocedure (OR = 10, [confidence interval (CI) 95% 1.91–52.5];P = 0.003). TA-TAVR patients identified with CPTP had significant reductions in 5MWT distances (−2.22 m vs. 0.92 m [P = 0.04]) as well as trend toward significance in negative change of KCCQ12 scores OR = 18.82 (CI 95% 0.85–414.99;P = 0.06) compared to those without CPTP. Conclusions: CPTP occurs in patients undergoing TA-TAVR and is possibly associated with a decline quality of life and overall function.

Larvicidal activity of few select indigenous plants of North East India against disease vector mosquitoes (Diptera: Culicidae)

Mosquitoes are the vectors of several life threatening diseases like dengue, malaria, Japanese encephalitis and lymphatic filariasis, which are widely present in the north-eastern states of India. Investigations on five local plants of north-east India, selected on the basis of their use by indigenous communities as fish poison, were carried out to study their mosquito larvicidal potential against Anopheles stephensi (malaria vector), Stegomyia aegypti (dengue vector) and Culex quinquefasciatus (lymphatic filariasis vector) mosquitoes. Crude Petroleum ether extracts of the roots of three plants viz. Derris elliptica, Linostoma decandrum and Croton tiglium were found to have remarkable larvicidal activity; D. elliptica extract was the most effective and with LC50 value of 0.307 μg/ml its activity was superior to propoxur, the standard synthetic larvicide. Half-life of larvicidal activity of D. elliptica and L. decandrum extracts ranged from 2-4 days.

Comparison of tolterodine with standard treatment in pediatric patients with non-neurogenic dysfunctional voiding/over active bladder : A systematic review.

To examine the efficacy, safety and tolerability of tolterodine in children with overactive bladder in comparison with standard treatment i.e. oxybutynin as demonstrated in randomized clinical trials and other studies. A systematic search was done to screen the studies evaluating the effect of tolterodine in children with nonneurogenic overactive bladder. Results of studies were pooled and compared. Efficacy was determined from micturition diaries and dysfunctional voiding symptoms score. Safety and tolerability were assessed from the reported treatment emergent adverse events. A total of six randomized clinical trials and 11 other studies of tolterodine in children with urinary incontinence were included in the present systematic review. The dose of tolterodine used in different settings ranged from ‘0.5 to 8 mg/day’ instead of ‘0.5 to 8 mg/kg per day’ and the duration of studies ranged from 2 weeks to 12 months. Both extended and immediate release preparations of tolterodine were shown to have comparable efficacy and tolterodine proved to have comparable efficacy with better tolerability than oxybutynin in these studies. It can be concluded that tolterodine is efficacious in treatment of urinary incontinence in children. Moreover, its efficacy is comparable to oxybutynin, the most commonly prescribed anticholinergic in this condition, while having better tolerability. Hence, it can be considered as first line therapy for the treatment of urinary incontinence in children.

Effect of esomeprazole on pharmacokinetics of phenytoin in rabbits.

Esomeprazole is commonly prescribed proton pump inhibitor for gastritis and peptic ulcer disease. Most of the time in clinical practice, phenytoin and esomeprazole are prescribed for patients of generalized seizures with concomitant peptic ulcer. Hence there are chances of drugdrug interaction because of modulations of isoenzymes CYP2C9 and CYP2C19, are involved in metabolism of phenytoin and esomeprazole. But it is important to maintain the therapeutic level of phenytoin in plasma for effective seizures control. So, the aim of the study was to determine the effect of esomeprazole on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin, 30 mg/kg/day per oral was given daily for 14 days. On day 15, blood samples were taken at various time intervals between 0-24 hours. In esomeprazole-phenytoin group, phenytoin was administered for seven days as mentioned earlier and from day 8th onward, esomeprazole 2.8 mg/kg along with phenytoin 30 mg/kg/day was administered till 14th days and blood samples were drawn as above on 15th day. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In esomeprazole-phenytoin group, there was a significant increase of t½el than phenytoin alone group and significant increase in AUC0-24 was also observed in the esomeprazole and phenytoin treated group. These results suggest that esomeprazole alters the pharmacokinetics of phenytoin. Confirmation of these results in further clinical studies will warrant changes in phenytoin dose or frequency when esomeprazole is co-administered.

Concomitant occurrence of cemento-ossifying fibroma and adenomatoid odontogenic tumor with bilateral impacted permanent canines in the mandible.

Adenomatoid odontogenic tumor (AOT) is an uncommon, benign and slow growing odontogenic tumor, which is usually located in an anterior region of the maxilla without pain. Cemento-ossifying fibroma (COF) is a relatively rare benign tumor of the jaw. Here we present 2 lesions presenting in unusual forms, follicular variant of AOT in the mandible and COF associated with impacted canine in the mandible, occurring concomitantly in the same patient. Both lesions presented classic histopathologic features.

Mosquito biodiversity of Dibru-Saikhowa biosphere reserve in Assam, India.

Entomological surveys were conducted for three consecutive years in core and buffer zone of the Dibru-Saikhowa biosphere reserve in pre monsoon, monsoon and post-monsoon seasons. A total of 52 species of mosquitoes under eleven genera have been detected. The genus Anopheles (18 species) was the predominant followed by Culex, Aedes, Mansonia, Armigeres, Mimomyia, Ochlerostatus, Malaya, Toxorhynchites, Ficalbia and Aedeomyia. The buffer zone of the forest reserve where human habitations are there exhibited the presence of maximum number of species (49 species under 10 genera) in comparison to core zone (42 species under 10 genera). In buffer zone, maximum numbers of species (38) were recorded in monsoon season followed by post- monsoon (35 species) and Pre-monsoon season (34 species). Whereas in core zone, maximum number of species were collected in post monsoon season followed by pre monsoon season and monsoon season. In Core and buffer zone, the maximum species were recorded from the ground pool habitat and slow flowing stream respectively. Among the disease vectors, the potential Japanese encephalitis vectors incriminated in India were very much prevalent. This study provides the list of available mosquito species recorded for the first time in the Dibru-Saikhowa biosphere reserve.

Effect of Manuka honey and sulfasalazine in combination to promote antioxidant defense system in experimentally induced ulcerative colitis model in rats.

Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced colonic inflammation and all the biochemical parameters were significant compared to control and MH alone treated group. Combination therapy showed additive effect of the MH which restored lipid peroxidation and improvement of antioxidant parameters. Morphological and histological scores were significantly reduced in combination groups. In inflammatory model of colitis, oral administration of MH (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of Manuka honey with sulfasalazine in colitis.

Effect of propofol in altering pentylenetetrazol induced seizure threshold in rats.

The present study was undertaken to evaluate the role of propofol in altering pentylenetetrazol induced seizure threshold in rats. Total 42 Wistar rats were used to evaluate different parameters (onset of action, duration of seizure, seizure severity score and number of seizure) following propofol injection. The present results showed that there was significant reduction in the time required for onset of seizure in propofol treated groups following PTZ treatment. If treated with propofol alone (2 and 5 mg/kg), there was no significant difference as compared to controls. In seizure severity score assessment, there was no significant difference with various doses of propofol alone treated groups, but the difference was observed in propofol (2 and 5 mg/kg) treated groups following PTZ treatment. Duration of seizure also significantly increased in propofol (5 mg/kg) treated group, but at 2 mg/kg of propofol treatment, no significant difference was observed. The present results showed that propofol ameliorate seizure threshold and caused prolongation of duration of seizure. However, further study and trials are needed to confirm the present results.

Ataxia and deafness in a young male: an unusual aetiology.

We report here a case of 18 year old male with tremors of hands, deafness, tendency to fall while walking, drowsiness and double vision of total duration 1(1/2) years. He had internuclear ophthalmoplegia, broken saccades, hypertonia and hyperreflexia of all four limbs, intention tremors, signs of gait and limb ataxia. Pupillary reactions and fundus examination were normal and signs of meningeal irritation or sensory neurological deficit were absent. MRI head and cervical spine with gadolinium enhancement revealed demyelination as evident from multiple oblong foci isointense on T1-weighted images and hyperintense on T2-weighted and fluid attenuated inversion recovery sequences in corpus callosum, sub-cortical white matter, right thalamus, pons and periaqueductal region of midbrain. Ill-defined linear hyperintense signals were observed in cervical spinal cord. No skeletal abnormality was noted in the skull or cervical spine. Oligoclonal bands were present in the cerebrospinal fluid. Brainstem auditory evoked potentials were abnormal, although visual evoked potentials were in normal range. A diagnosis of primary progressive multiple sclerosis (PPMS) was made fulfilling the revised criteria as laid down. In view of its presentation, it is a unique case of PPMS from India.

Visceral leishmaniasis masquerading as chronic liver disease.

We report a patient with fever, progressive jaundice and abdominal distension, having marked pallor, icterus, ascites and hepatosplenomegaly. Investigations revealed pancytopenia and deranged liver functions. Doppler study revealed portal hypertension and endoscopy showed grade II oesophageal varices. Liver biopsy suggested leishmanial hepatitis and bone marrow demonstrated multiple LD bodies. Diagnosis of "visceral leishmaniasis with leishmanial hepatitis with portal hypertension" was made. The case is being reported because of its rarity apart from it being an unusual presentation of kala-azar.

Drug-induced kidney diseases.

Drug-induced kidney disease constitutes an important cause of acute renal failure and chronic kidney disease in present day clinical practice. Different classes of drugs, by virtue of immunological mechanisms or direct toxicity initiate certain stereotyped renal responses. For most patients suffering from drug-induced nephropathy common risk factors which precipitate the adverse effects include: old age, volume -depleted state, pre-existing renal dysfunction and coexisting use of other nephrotoxins. Although it is impossible to present all the drugs causing renal disease, a few prototype drugs are mentioned. In a case of undiagnosed renal disease a possibility of drug-induced renal failure should be kept as the prompt removal of the drug and supportive management can reverse the renal dysfunction to a large extent.

Effect of losartan on albuminuria, peripheral and autonomic neuropathy in normotensive microalbuminuric type 2 diabetics.

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are emerging as effective agents for preventing microvascular complications of diabetes. Losartan (angiotensin II antagonist) has an antihypertensive efficacy equivalent to ACE inhibitors, however its role in microvascular complications is not yet known. MATERIAL AND METHODS: We studied the efficacy of losartan (50 mg once daily for 12 weeks) on albuminuria, peripheral and autonomic neuropathy in 25 normotensive microalbuminuric type 2 diabetics who were asymptomatic for neuropathy. RESULTS: Mean age was 46.6 +/- 4.34 years with the average duration of diabetes being 8.1 +/- 1.54 years. Albuminuria improved significantly from 54 +/- 9.35 mg/L to 32.8 +/- 25 mg/L (Paired student's t-test, P=0.0005) after therapy. Autonomic neuropathy was observed in 64% while 76% had peripheral neuropathy; but there was no improvement with losartan. The duration of diabetes had a negative correlation with autonomic neuropathy. It also had a similar negative correlation with median and common peroneal nerve motor conduction velocities (Pearson's correlation coefficient, r = -0.53, P<0.01 and r = -0.56, P<0.01 respectively) implying that autonomic and peripheral neuropathy worsen as a diabetic ages. However, no correlation existed between albuminuria and autonomic or peripheral nerve function. CONCLUSION: Autonomic and peripheral neuropathy are highly prevalent in normotensive microalbuminuric diabetic patients. Losartan remarkably improves albuminuria but a similar benefit in autonomic or peripheral neuropathy is not seen over 12 weeks. The future may see a defining role for losartan in microvascular complications in normotensive diabetics.

Mediastinitis presenting as pyrexia of unknown origin.

A 55 year old female was admitted as a case of pyrexia of unknown origin (PUO) of 2 months duration. She had developed throat ache, progressive dysphagia for both solids and liquids, dry cough and retrosternal pain for one week. Examination revealed fever, tachycardia, tachypnoea and a soft tissue warm tender, erythematous, non-fluctuant swelling in lower anterior neck with chest findings suggestive of bilateral pleural effusion. Plain X-rays of the neck and chest strengthened the clinical suspicion of cellulitis of lower neck with bilateral pleural effusion. CT scan confirmed the radiologic findings and also revealed pericardial effusion and thickening; small mediastinal lymphadenopathy and mediastinitis. Patient responded to parenteral antibiotics (ceftriaxone and metronidazole) and hydrocortisone with complete resolution in 10 days.

Genes encoding chimeras of Neurospora crassa erg-3 and human TM7SF2 proteins fail to complement Neurospora and yeast sterol C-14 reductase mutants.

The human gene TM7SF2 encodes a polypeptide (SR-1) with high sequence similarity to sterol C-14 reductase, a key sterol biosynthetic enzyme in fungi, plants and mammals. In Neurospora and yeast this enzyme is encoded by the erg-3 and erg24 genes respectively. In an effort to demonstrate sterol C-14 reductase activity for SR-1 we constructed six recombinant genes coding for chimeras of the Neurospora erg-3 and SR-1 protein sequences and tested them for complementation of the Neurospora erg-3 mutant. To our surprise, all the chimeras failed to complement erg-3. A few of the chimeric proteins were also tested against the yeast erg24 mutant, but again there was no complementation. We discuss some reasons that might account for these unexpected findings.

Homeotic regeneration of eye in amphibian tadpoles and its enhancement by vitamin A.

After removal of both the lateral eyes of external gill stage tadpoles of the toad Bufo melanostictus, the pineal organ gets transformed into a median eye. This type of transformation occurs in tadpoles of both control and vitamin A treated groups. However, vitamin A increases the likelihood of homeotic regeneration (57% in the control group and 71% in the vitamin A treated group). Histological studies showed that the newly transformed median eye developed from the pineal organ. The pineal eye so developed possessed all components of a normal eye such as a retina, sensory cells and lens.

Lens regeneration in mice under the influence of vitamin A.

The effect of vitamin A has been studied on lens regeneration in young (7 days old) as well as adult mice. A longitudinal slit was made under local anesthesia in the cornea over the lens. The lens was extracted intact through the incision. Intraperitonial injection of vitamin A (0.05 ml of 30 IU/ml in young and 0.05 ml of 50 IU/ml in adult) was given to the operated animals. Vitamin A was found to induce lens regeneration in not only young but also in adult mice. Regenerated lenses were similar in shape, size, transparency and histological features to normal intact lenses.

Adenosquamous carcinoma of colon.

Primary adenosquamous carcinoma of the colon is an aggressive entity. We report a 41-year-old man with a combination of adenocarcinoma and squamous cell carcinoma of the cecum, treated by right hemicolectomy and ileo-transverse anastomosis. Postoperatively he received adjuvant chemotherapy. However, the tumor recurred at the original site within two months and thereafter the patient was lost to follow up.

Risk factors of malaria in the fringes of an evergreen monsoon forest of Arunachal Pradesh.

BACKGROUND: The forested hilly and foothill regions of north-east India are highly endemic for malaria and have a distinct epidemiological pattern. Nearly half the reported cases of malaria are from these areas. A knowledge of the risk factors in this eco-geographic entity may be helpful in formulating a specific control strategy. Hence, we conducted a community-based epidemiological study in a hilly, forested terrain of Arunachal Pradesh and examined different socio-demographic factors to identify those predisposing to the occurrence of malaria, especially Plasmodium falciparum infection, in such areas. METHODS: Four epidemiological surveys were carried out during 1997 in 7 villages located at the fringes of a forest (total population: 1177) under Nompong Primary Health Centre of Changlang district, Arunachal Pradesh. Blood slides were collected randomly from the inhabitants, irrespective of their fever status, ensuring at least 50% coverage. One hundred and thirty-four microscopically confirmed Plasmodium falciparum cases were identified and 536 controls were randomly selected from the list of uninfected inhabitants. Relevant socio-demographic information was obtained from both cases and controls. The data were analysed by simple and multiple logistic regression using the unconditional maximum likelihood method. RESULTS: Factors which were found to be strongly associated with Plasmodium falciparum malaria on univariate analysis were age, ethnicity, village of residence and accessibility to the nearest health care facility. However, in multiple regression analysis, after controlling for the effects of confounding variables, the only risk factor identified was accessibility to the nearest health care facility (adjusted odds ratio: 4.5; 95% CI: 1.8-11.3; p < 0.0001 for those at a distance of 2-8 km and adjusted odds ratio: 11.1; 95% CI: 4.1-30.0; p < 0.0001 for those > 8 km away). CONCLUSION: Distance, particularly non-motorable distance, from the place of residence to the nearest health care facility was a major risk factor for malaria in this hilly forested terrain. This indicates the need for special efforts to detect cases early and institute treatment promptly in such areas of the north-eastern region, so as to reduce the morbidity and mortality of malaria.