Abnormal coagulation and enhanced fibrinolysis due to lysinuric protein intolerance associates with bleeds and renal impairment.

INTRODUCTION: Lysinuric protein intolerance (LPI), a rare autosomal recessive transport disorder of cationic amino acids lysine, arginine and ornithine, affects intestines, lungs, liver and kidneys. LPI patients may display potentially life-threatening bleeding events, which are poorly understood. AIMS: To characterize alterations in haemostatic and fibrinolytic variables associated with LPI. METHODS: We enrolled 15 adult patients (8 female) and assessed the clinical ISTH/SSC-BAT bleeding score (BS). A variety of metabolic and coagulation assays, including fibrin generation test derivatives, clotting time (CT) and clot lysis time (CLT), thromboelastometry (ROTEM), and PFA-100 and Calibrated Automated Thrombogram (CAT), were used. RESULTS: All patients had mild-to-moderate renal insufficiency, and moderate bleeding tendency (BS 4) without spontaneous bleeds. Mild anaemia and thrombocytopenia occurred. Traditional clotting times were normal, but in contrast, CT in fibrin generation test, and especially ROTEM FIBTEM was abnormal. The patients showed impaired primary haemostasis in PFA, irrespective of normal von Willebrand factor activity, but together with lowered fibrinogen and FXIII. Thrombin generation (TG) was reduced in vitro, according to CAT-derived endogenous thrombin potential, but in vivo TG was enhanced in the form of circulating prothrombin fragment 1 and 2 values. Very high D-dimer and plasmin-α2-antiplasmin (PAP) complex levels coincided with shortened CLT in vitro. CONCLUSIONS: Defective primary haemostasis, coagulopathy, fibrin abnormality (FIBTEM, CT and CLT), low TG in vitro and clearly augmented fibrinolysis (PAP and D-dimer) in vivo were all detected in LPI. Altered fibrin generation and hyperfibrinolysis were associated with the metabolic and renal defect, suggesting a pathogenetic link in LPI.

Effect of Sildenafil Citrate on Pulmonary Arterial Systolic Pressure and Sub-maximal Exercise Capacity in Chronic Obstructive Pulmonary Disease.

Background Pulmonary hypertension (PH) often complicates Chronic Obstructive Pulmonary Disease (COPD). Sildenafil reduces pulmonary arterial pressure associated with multitude of diseases. Objective To evaluate the use of Sildenafil in Pulmonary Hypertension associated with COPD. Method This randomized control study enrolled 72 patients: 61 completed the study. Thirtypatients with COPD received Sildenafil 25 mg thrice daily and 31 patients with COPD received optimal medical therapy for four weeks. Symptom assessment and dyspnoea grading was done with modified Borg scale and Modified Medical Research Council (MMRC) grade. The functional assessment was done with WHO functional classification. The estimation of pulmonary arterial systolic pressure and six minute walking distance was done before and after four weeks of the administration of therapy in both groups. Adverse reaction profiling was done for Sildenafil. The primary outcomes were the changes in pulmonary arterial systolic pressure and six minute walk test. The secondary outcomes were change in modified Borg scale for dyspnoea, MMRC grading and WHO functional class. Result The mean decrease in pulmonary arterial systolic pressure in Sildenafil group was significant as compared to controls (9.87+7.84 mmHg Vs 5.93+7.44 mmHg, P=0.048). The mean increase in six minute walk distance was significantly more in cases as compared to controls (48.13+25.79 m Vs 32.59+32.96 m,P=0.047). The changes in modified Borg scale was not significant (1.20+1.92 to 1.55+1.23; P=0.401). There was significant changes in MMRC grade (p=0.037). There was no significant change in WHO functional class after four weeks (p=0.071). Conclusion Sildenafil marginally decreased pulmonary arterial systolic pressure and increased six minute walk distance in COPD patients. It improved MMRC grading without affecting modified Borg's Scale and WHO functional class.

Asymptomatic throat carriage rate and antimicrobial resistance pattern of Streptococcus pyogenes in Nepalese school children.

BACKGROUND: Streptococcus pyogenes or Group A streptococcus (GAS) causes several suppurative and non suppurative infections. In addition to pharyngitis and skin infections, GAS are also the causative agent of post-streptococcal infection syndromes such as acute rheumatic fever (ARF) and post-streptococcal glumerulonephritis (PSG). GAS frequently colonises in the throat of an asymptomatic person. Pharyngeal carriage rates of GAS among healthy school children vary with geographical location and seasons. OBJECTIVES: We carried out this preliminary study to determine the throat carriage rate and antimicrobial resistance trend of Streptococcus pyogenes or Group A streptococcus (GAS) among the Nepalese school children. MATERIALS AND METHODS: Four schools situated at different locations of Kathmandu valley were included in the study. Throat swabs from 350 students of age group 5-15 years were collected, immediately transported to the laboratory and were processed for S. pyogenes following standard microbiological procedures. Antimicrobial susceptibility testing of the isolates was performed by Kirby Bauer disc diffusion method following CLSI guidelines. RESULTS: S. pyogenes was isolated from 10.9% (38/350) of the screened children. The GAS colonisation rate was statistically insignificant (P>0.05) with sex and age sub-groups, although the rate was slightly higher among girls and age sub-group 9-12 years. No significant difference in carrier rate was observed among different schools (P>0.05). All isolates were susceptible to azithromycin. No resistance was detected for penicillin and its derivative antibiotic ampicillin. Highest resistance rate was observed for cotrimoxazole (71.0%) followed by chloramphenicol (7.8%), ciprofloxacin (5.2%) and erythromycin (5.2%). CONCLUSION: Antibiotic resistant GAS isolated from asymptomatic Nepalese school children is a public health concern. When screened and appropriately treated with antibiotics, carriers can be prevented from spreading of streptococcal infections in the school environment and the community. Preventing cross infections would ultimately reduce the incidence of life-threatening sequelae which are debilitating and difficult to treat. It is recommended to conduct regular screening and GAS surveillance in schools, and maintain rational use of antibiotics to minimise GAS carriage/infections and resistance.

Detection of human papillomavirus infection in tissue blocks by in situ hybridization as compared with a polymerase chain reaction procedure.

Tissue blocks from 25 cases of condyloma and/or dysplasia were used for human papillomavirus typing with DNA in situ hybridization, compared with the very sensitive polymerase chain reaction. Only one of these cases was negative with both methods: a case of vaginal "koilocytosis." Polymerase chain reaction, as expected, was the more sensitive method, positive in 24 cases, with seven double infections. In situ hybridization was positive in 18 cases, with only two detected double infections. There was excellent agreement between the two methods in typing results. In all cases in situ hybridization showed a positive reaction in areas of koilocytosis and/or dysplasia.

Early equatorial cataracts in workers exposed to trinitrotoluene.

Twelve workers (nine men and three women with a mean age of 39.5 +/- 8.9 years) with occupational exposure to trinitrotoluene had a mean duration of exposure of 6.8 +/- 4.7 years. The general physical findings were minimal, but ophthalmologic examinations showed bilateral peripheral cataracts in six of the 12 workers. Cataracts were visible only with maximal mydriasis and were continuous or annular opacities at the equator. The cataracts did not interfere with visual acuity or visual fields. Only one worker with and one without cataracts had increased serum alanine aminotransferase and bilirubin levels, possibly associated with trinitrotoluene exposure.

Refractive error profile--a clinical study.

AIM: To study the distribution of refractive error in different ethnic groups of Nepal. METHODS: A total of 1276 new eye patients between 5-35 years of age were included in this study after a thorough eye examination consisting of vision test, anterior and posterior segment eye examination including the investigative procedures whenever needed to rule out any systemic and ocular diseases. Thereafter, the patients were subjected to rigorous streak retinoscopic refraction. RESULTS: Out of 1276 eye patients examined 51.33 % patients are males and 48.66 % are females. The ethnic distribution of refractive error shows that there are 32.44% Newars; 27.50% Brahmins; 21.63% Chhetriyas; 12.14% Gurungs, Magars, Rais, Limbus, Tamangs, Sunuwars; and 6.26% Madhesias. Out of 414 Newar patients, 14.00% patients are myopic; 29.71% hyperopic; and 56.28% astigmatic. In 351 Brahmin patients, 14.81% patients are myopic; 49.85% hyperopic; and 35.32% astigmatic. In 276 Chhetry patients, 13.40% patients are myopic; 48.18% hyperopic; and 38.40% astigmatic. Out of 155 Gurungs, Magars, Rais patients, 11.61% are myopic; 52.90% hyperopic; and 35.48% astigmatism. Out of 80 Madhesias patients, 11.25% are myopic; 37.50% hyperopic; and 51.25 % astigmatic. CONCLUSION: Thus, a refractive error profile is drawn up in Nepalese population.