Drug-Induced Erectile Dysfunction: Two Interesting Cases

Erectile dysfunction (ED) is the inability to achieve or maintain an erection that is required for satisfactory sexual performance, and affects a considerable proportion of men around the globe at least occasionally. Although roles for nonendocrine and endocrine pathways have been propose, presence of comorbidities, psychogenic factors may contribute to its development. Large number of published reports link many commonly prescribed drugs with sexual dysfunction. Many common drugs such asanti-hypertensive, anti-psychotic, and anti-histaminic are linked with iatrogenic ED. On the other hand, psychogenic ED may be wrongly perceived to be of iatrogenic origin. While dealing a subject with ED it is important for the clinicians to take a detailed medical, surgical, sexual and drug/substance abuse history. In this article, we have described two such cases which would reflect the importance of determining the cause of ED before initiating treatment.

Lamivudine plus tenofovir versus lamivudine plus adefovir for the treatment of hepatitis B virus in HIV-coinfected patients, starting antiretroviral therapy

Background: Combination of tenofovir disoproxil fumarate (TDF), lamivudine (3TC) and efavirenz (EFV) is preferred in the treatment of HIV/hepatitis B virus (HBV) coinfection. We postulated that a HBV active nucleoside reverse transcriptase (RT) inhibitor/nucleotide RT inhibitor backbone of adefovir dipivoxil (ADV) +3TC would be as effective as TDF +3TC for the Indian population. Objective: ADV + 3TC could be an alternative option for these HIV/HBV coinfected individuals, preserving the dually active TDF + 3TC as second-line nucleoside backbone following failure of the first-line ART. Materials and Methods: This randomised control trial (CTRI/2012/03/002471) was carried out at the ART Centre of Calcutta School of Tropical Medicine, India. Seventy-eight (39 on each arm) treatment-naïve HIV/HBV coinfected patients were randomised to receive either the combination of lamivudine + tenofovir + EFV or lamivudine + adefovir + zidovudine + EFV and followed up for 120 weeks. Results: Median age of the study participants was 36 years (21–62), majority were male (61/78; 78.2%) and heterosexually (39/78; 50%) infected. Baseline characteristics were identical in both arms. There was no statistically significant difference in median aspartate aminotransferase (37 vs. 29.5 U/L), alanine aminotransferase (ALT) (36 vs. 34.5 U/L), ALT normalisation rate (80 vs. 70%), AST to platelet ratio index (0.45 vs. 0.33), CD4 count (508 vs. 427 cells/mm3), HBV DNA suppression (81.8 vs. 70%), hepatitis B e antigen loss (9 vs. 5%), hepatitis B surface antigen seroclearance rate (6.06 vs. 18.75%) and death (3 vs. 3) at 120 weeks between TDF (n = 33) and ADV (n = 32), respectively. Conclusions: Adefovir plus lamivudine is an effective alternative of tenofovir plus lamivudine in long-term HBV treatment outcome in HIV/HBV coinfected patients.

Utility of Pap Smear Screening for Prevention of Cervical Cancer-A 3yrs Study from Rural Tripura-A Northeastern State of India

Background: Cancer cervix is a leading cause of mortality and morbidity among women worldwide. According to National Cancer Registry Program of India, cancers of cervix and breast are leading malignancies in Indian women. The morbidity and mortality could be significantly reduced with an active cervical smear screening programme. Objective: The study was done to evaluate the knowledge and attitudes of women about cervical smear testing, to establish a cervical smear screening program and to evaluate the cervical cytological abnormalities. It was done to determine the applicability, limitations and utility of this screening in a district hospital. Materials and Methods: A total of 287 married women were included in our study. Knowledge about Pap smear testing was determined through printed questionnaires. Pap smear screening was performed on every woman in our study group. Detailed clinical data and cytology reports were noted in a proforma. Results: About 92% women of our study group had never heard or undergone Pap smear screening before. Maximum number of patients was in 4th decade. Of the 287 smears, 276(96.16%) were adequate. Normal smear were 78(27.18%), inflammatory 168(58.54%), whereas epithelial cell abnormalities were seen in 26(9.05%) cases. The 26 abnormal cases comprised of 17(5.92%) cases with ASCUS, 5(1.74%) cases of LSIL, 1(0.35%) cases of HSIL, 3(1.04%) cases of squamous cell carcinoma. Conclusions: Epithelial cell abnormality in our study group was less than Western countries. There is poor knowledge about Pap smear screening. Pap smear study can be easily done through a chain built between the primary health care unit and district hospital and laboratory

Utility of Pap Smear Screening for Prevention of Cervical Cancer-A 3yrs Study from Rural Tripura-A Northeastern State of India

Background: Cancer cervix is a leading cause of mortality and morbidity among women worldwide. According to National Cancer Registry Program of India, cancers of cervix and breast are leading malignancies in Indian women. The morbidity and mortality could be significantly reduced with an active cervical smear screening programme. Objective: The study was done to evaluate the knowledge and attitudes of women about cervical smear testing, to establish a cervical smear screening program and to evaluate the cervical cytological abnormalities. It was done to determine the applicability, limitations and utility of this screening in a district hospital. Materials and Methods: A total of 287 married women were included in our study. Knowledge about Pap smear testing was determined through printed questionnaires. Pap smear screening was performed on every woman in our study group. Detailed clinical data and cytology reports were noted in a proforma. Results: About 92% women of our study group had never heard or undergone Pap smear screening before. Maximum number of patients was in 4th decade. Of the 287 smears, 276(96.16%) were adequate. Normal smear were 78(27.18%), inflammatory 168(58.54%), whereas epithelial cell abnormalities were seen in 26(9.05%) cases. The 26 abnormal cases comprised of 17(5.92%) cases with ASCUS, 5(1.74%) cases of LSIL, 1(0.35%) cases of HSIL, 3(1.04%) cases of squamous cell carcinoma. Conclusions: Epithelial cell abnormality in our study group was less than Western countries. There is poor knowledge about Pap smear screening. Pap smear study can be easily done through a chain built between the primary health care unit and district hospital and laboratory

Comparison of third generation ELISA and conventional nested RT-PCR for detection of HCV among hemodialysis patients.

Hepatitis C virus is one of the main cause of chronic hepatitis in developing countries. The current study was done to evaluate the efficacy of the third generation ELISA compared to nested RT- PCR for establishing the diagnosis of hepatitis C virus (HCV) in patients on hemodialysis. This descriptive, cross-sectional study was carried out on 237 Hemodialysis patients in Lucknow, Uttar Pradesh. The retrospective demographic data of the subjects was collected and the patient’s serum samples were analyzed by ELISA & RT-PCR for HCV. In the present study, of total 21 HCV positive either by ELISA or PCR 12 (57.14%) were positive for both RT-nested PCR and ELISA. Total four (19.05%) patients were positive for HCV by RT-nested PCR and negative by ELISA while five (23.81%) patients were negative for RT-nested PCR and positive for ELISA. PCR method is accredited as a specific and reliable method suitable for screening of HCV and is recommended for establishing exact and final diagnosis of these patients. However third generation ELISA assays have many advantages in the diagnostic setting including ease of automation, ease of use, relative cost-effectiveness, and low variability.

Copper induced oxidative stress in tea (Camellia sinensis) leaves.

Tea [Camellia sinensis L. (O.) Kuntze] is an economically important plantation crop of India but is prone to attack by several fungal pathogens. Copper based fungicides are being used for decades to control fungal diseases in tea which may lead to accumulation of copper in the soil. The biochemical responses to increasing concentrations of copper (50 to 700 µM) were investigated in the leaves of two cultivars of tea commonly grown in the Darjeeling hills. Exposure to excess Cu resulted in increased lipid peroxidation (level of TBARS increased from 3.5 µmol g-1 f.wt. in control to 12 µmol g-1 f.wt. in TS-520 plants exposed to 700 mM of Cu), reduced chlorophyll content (from 83.7 µg g-1 f.wt. in control to 22.5 µg g-1 f.wt. in TS-520 plants exposed to 700 µM of Cu), higher levels of phenolic compounds(total phenol content increased from 4.54 mg g-1 f.wt. in control to 5.79 mg g-1 f.wt. in TS-520 plants exposed to 400 µM of Cu) and an increase in peroxidase enzyme levels. Two new peroxidase isozymes (POD1 and POD2) were detected in plants exposed to Cu. In addition, biochemical responses in two tested cultivars, TS-462 and TS-520 differed significantly. TS-520 was found to be more sensitive to increasing concentrations of Cu. Superoxide dismutase activity increased progressively from 2.55 U mg-1 protein in control to 5.59 U mg-1 protein in TS-462 but declined from 4.75 U mg-1 protein in control to 3.33 U mg-1 protein in TS-520 when exposed to Cu concentrations higher than 400 µM. A sharp increase in the activity of ascorbate peroxidase (from 0.53 units in control to 2.37 units in plants exposed to 400 µM of Cu) was noticed at the 10th day of exposure in the more tolerant cultivar. On the other hand, catalase levels increased only marginally (from 8.4 to 10.1 units in TS 520 and 8.7 to 10.9 units in TS 462) in both the cultivars. From this study, it appears that Cu exposure led to the production of reactive oxygen species in the leaves resulting in significant lipid peroxidation. Tea plants try to mitigate this oxidative damage through accumulation of phenolic compounds and induction of antioxidant enzymes.

Influence of culture media and environmental factors on mycelial growth and sporulation of Lasiodiplodia theobromae (Pat.) Griffon and Maubl.

Lasiodiplodia theobromae, a common tea (Camellia sinensis) pathogen, usually does not sporulate or sporulates poorly in common media, which makes spore production difficult. In this study the effects of culture media, carbon source, nitrogen source, temperature, pH and light on mycelial growth and sporulation were evaluated. Among several carbon sources tested, glucose and sucrose were found superior for growth. Potassium nitrate supplemented media showed maximum growth amongst the tested inorganic nitrogen sources while peptone produced maximum growth among the tested organic nitrogen sources. Tea root extract supplemented potato dextrose agar medium was found to be the most suitable for mycelial growth and sporulation of L. theobromae. The fungus grow at temperatures ranging from 40 to 36 degrees C, with optimum growth at 28 degrees C and no growth was noted at 40 degrees C. There was no significant effect of different light period on growth of L. theobromae, but light enhanced sporulation. The fungus grow at pH 3.0-8.0 and optimum growth was observed at pH 6.0. Tea root extract supplemented potato dextrose agar medium with pH 6.0 was the most suitable for production of conidia of L. theobromae at 28 degrees C. Hence this media may be recommended for inoculum production for further studies.

Evaluation of conventional & serological methods for rapid diagnosis of cryptococcosis.

BACKGROUND & OBJECTIVE: Cryptococcosis is a chronic infective condition affecting the central nervous system. Unless diagnosed early and specific treatment instituted it can be fatal. There is an urgent need for a rapid and specific diagnostic tool for better management of the patients. Conventional methods such as culture and India ink are specific but cumbersome and time consuming. Serological methods of detection are rapid but have problems of false positivity and cross-reactivity with other micro-organisms. We carried out this study to compare and evaluate the conventional methods with serological methods of detection of cryptococcal meningitis. METHODS: A comparative evaluation of conventional methods (India ink and culture) with LAT (latex agglutination test) and EIA (enzyme immunoassay) was done in 127 CSF samples using culture and EIA as reference separately. RESULTS: India ink was positive for Cryptococcus in 72.4 per cent of the samples; 56 per cent were culture positive; LAT positive were 85 per cent and 79.5 per cent were positive by EIA. When culture was positive, all other tests were in agreement to it. However, when culture was negative there was significant difference between the pair of discordance of various diagnostic tests. Culture was 83.46 per cent in agreement to India ink, 76.3 per cent to EIA and 70.8 per cent to LAT. EIA was 92.9 per cent in agreement to India ink and LAT; 6.3 per cent showed false positive by LAT. INTERPRETATION & CONCLUSION: EIA is valuable in establishing diagnosis when culture is negative for cryptococcosis. EIA is more specific and has potential advantages over LAT as it gives clear discrimination of positive from negative results. Thus, EIA may be used as a simple, rapid, and reliable serological test for early detection of cryptococcal antigen in clinical samples like CSF in routine laboratories.

Histopathological changes in experimental cholera with a non toxigenic non- O1 non-O139 Vibrio cholerae strain isolated from Kolkata, India.

This study was conducted to understand the pathophysiological changes in experimental rabbit ileal loop model using the Vibrio cholerae strain non-O1non-O139, isolated as sole pathogen from clinically diagnosed cholera patients in Kolkata. Significant amount of haemorrhagic fluid accumulation was observed in all the test loops of rabbit model where the strain of V.cholerae was inoculated as compared to control loops. Microscopic examination of the accumulated fluid showed the presence of erythrocytes and pus cells. Histology revealed structural alteration of the villous epithelium with inflammatory cells infiltration in all the layers of the gut mucosa including the nerve plexus region. Preliminary observation with a haemagglutinin protease extracted from the non-O1 non-O139 strain, was also studied in different concentrations in the same animal model which showed similar type of macroscopic and microscopic response in the ileal loops as seen with the original strain. The results highlight that along with other pathways, inflammatory cells and the enteric neurons have an important role in the pathophysiology of diarrhoea and the isolated protease may be the probable virulence factor in initiating the disease process in this non-O1non-O139 strain induced cholera.

Isolation of Salmonella enterica serotypes from children with diarrhoea in Calcutta, India.

The prevalence of Salmonella enterica serotypes, antimicrobial susceptibility, and phage typing of serovers were studied. Clinical presentations of the infected cases were also examined. The study was carried out during August 1993-September 1996 in and around Calcutta, India. In total, 1,025 faecal samples from hospitalized diarrhoeal children were screened for enteropathogens. Four S. enterica serotypes were identified in 157 (15.3%) cases as a single pathogen. S. enterica serotype Typhimurium was detected in 110 (70%) cases. S. Seftenberg, S. Infantis, and S. Virchow were detected in 28 (17.8%), 14 (8.9%), and 5 (3.2%) cases respectively. S. Typhimurium was isolated from 11 (3.2%) non-diarrhoeal control children. All of these children had acute watery diarrhoea, and 5% of them had severe dehydration, 40% had some dehydration, and 55% had no dehydration. Vomiting, fever, and diffused pain in abdomen were the associated presentations of these children. Most (95%) of them recovered with oral rehydration therapy only and without any antibiotics. In-vitro susceptibility testing showed that 120 of the 121 S. Typhimurium strains isolated from cases and controls were resistant to the commonly-used drugs. Thirteen of the 121 strains were phage-typeable and belonged to the phage type 193. However, no clinical or epidemiological significance could be established with these typeable strains. The findings of the study indicate that diarrhoeagenic Salmonella is one of the major pathogens causing diarrhoeal diseases in eastern India.

Hepatitis and HIV infection during haemodialysis.

Viral hepatitis and human immunodeficiency virus (HIV) infection are important causes of mortality and morbidity in patients treated by haemodialysis (HD). Both are further promoted by the characteristic immunological dysfunction that develops in renal failure and interferes with the patient's ability to eliminate these viruses. The hepatotropic viruses A through G remain the causative agents in 60 to 80% of hepatitis. But, as far as HD is concerned, hepatitis B virus (HBV) and hepatitis C virus (HCV) are the two most important organisms responsible for almost all the patients' morbidity. In HD, both patients as well as staff are at a high risk of acquiring hepatitis B infection. The prevalence of HBV in the dialysis population in India is reported to range between 3.4% and 42%. The acute course of the infection is often anicteric and peak transaminase concentration is significantly less than in patients with normal renal function. Up to 60% of dialysis patients with HBV infection develop chronic hepatitis with persistence of hepatitis B surface antigen (HBsAg) and infectivity. The risk of transmission of HBV infection due to blood from one patient to another is mostly because of inadequate precautions taken by the dialysis staff. Combined therapy with interferon (6-10 million units) three times a week and lamivudine (100-300 mg/day) would be more effective in controlling viral replication. The most important modality for prevention of HBV infection is induction of immunity by hepatitis B vaccination. Administration of 40 microg doses at months 0, 1, 2 and 6 is the most rapid immunogenic schedule. The prevalence of HCV in HD patients ranges from 6% in the United Kingdom to 60% in Poland and Eastern Europe, 8-36% in North America. HD patients in different parts of India exhibit high anti-HCV positivity (12.1%, 45.2%, 33.3% and 41.9%) in various studies. The incidence and prevalence of HCV infection among patients on dialysis in developed countries are steadily declining because of (i) reduction in post-transfusion HCV infection, (ii) infection control measures to prevent nosocomial infection. Among HD patients with HCV infection, serum alanine aminotransferase (ALT, SGPT) levels are elevated in only 4 to 67% patients who are positive for anti-HCV, in only 12 to 31% patients with HCV RNA and only in one-third of those with biopsy proven hepatitis. Number of blood transfusion, duration of HD treatment, and mode of dialysis are important risk factors. Patient to patient transmission of HCV occurs in HD units by needle stick injury, breakdown in standard infection control practices, physical proximity to an infected patient, dialysis machines, dialysis membranes and HD ultrafiltrate and reprocessing of dialyser. The prevalence of HIV infection in dialysis populations varies according to different countries and geographic areas, 0% and 13% in 1990 and 1995 respectively. There was no evidence of transmission within the centre transmission, from patient to patient or patient to staff. Antiretroviral therapy is the corner-stone of the HIV infection in end stage renal disease (ESRD). Most commonly, zidovudine (AZT) has been used in these patients. Currently recommended dose of 200 mg three times a day is probably safe in these patients.

Detection of faecal leucocytes & erythrocytes from stools of cholera patients suggesting an evidence of an inflammatory response in cholera.

BACKGROUND & OBJECTIVES: Detection of faecal leucocytes and RBCs in stool samples of cholera patients has been reported in a small number of studies. This study extends these observations by examining stool samples of cholera patients in Calcutta. METHODS: Out of 1562 diarrhoeal stool samples, Vibrio cholerae was isolated in 266 cases. Stool samples obtained were examined microscopically within two hours of collection. RBCs and faecal leucocytes were examined by normal saline and methylene blue stain. Stool culture was performed using selective and differential media for isolation of V. cholerae. RESULTS: Among 266 cholera patients, RBCs was detected in 58 per cent and faecal leucocytes in 88 per cent respectively. The extent of the changes correlated with clinical severity. INTERPRETATION & CONCLUSION: This study showed the presence of RBCs and faecal leucocytes in stools of patients of cholera caused by V. cholerae 01 and 0139 which indicates some inflammatory changes in the gut mucosa. Further study is required to elucidate the inflammatory mechanism involved in the underlying process(es).

Value of faecal leucocyte count as an indicator of invasiveness in mucoid diarrhoea.

Importance of faecal leucocyte count as an indicator of invasiveness in mucoid diarrhoea was studied. A total of 290 faecal specimen, 170 from mucoid diarrhoea and 120 from watery diarrhoea were examined for faecal leucocyte count under high power field (hpf) from rural children below four years of age during the period from November 1992 to October 1995. Faecal leucocyte count > 10/hpf was noted in 45.9% of mucoid diarrhoea as against 19.2% of watery diarrhoea (p < 0.0001) samples. From faecal samples with > 10 faecal leucocyte count, invasive pathogens could be recovered in 19 (24.5%) to none of 23 patients with watery diarrhoea (p < 0.006 Fisher exact test). This sample test appears to be of value as an indicator of invasiveness in mucoid diarrhoea in the absence of culture facility.

Intestinal parasitism: a childhood problem in rural Bengal.

A study was undertaken to assess the parasitic infection rate in a rural community of West Bengal amongst children below four years of age suffering from gastrointestinal complaints. A total of 221 faecal samples were examined during November 1992 to April 1994. G. lamblia (17.2%) and E. histolytica (8.1%) were the predominant protozoas, whereas E. vermicularis (12.2%) and A. lumbricoides (8.1%) were found to be common amongst helminthic infection. A significantly lower infection rate was observed in children below one year (24.4 per cent) as compared to older age groups (66.4 per cent).

Comparative efficacy of furazolidone and nalidixic acid in the empirical treatment of acute invasive diarrhea: randomized clinical trial.

Efficacy of furazolidone and nalidixic acid was compared in a randomized trial involving 72 children with acute invasive diarrhea. Thirty six children received furazolidone (7.5 mg/kg/day) and 36 children received nalidixic acid (55 mg/kg/day). Clinical characteristics of the two treatment groups were comparable on admission. Of these, 34 children in furazolidone treated group and 29 children in nalidixic acid treated group completed the full course of treatment and were analyzed finally for clinical efficacy. Clinical cure was observed in 29(85.3%) children treated with furazolidone and 29(100.0%) children treated with nalidixic acid. Nalidixic acid treated group had statistically significantly higher cure rate (p = 0.039) as compared to furazolidone treated group. However, 85% cure rate in furazolidone treated group may be potentially useful for the treatment of acute invasive diarrhea because of decreasing efficacy of nalidixic acid against shigellosis in many countries.

Mechanism of action of an eukaryotic initiation factor-2 (eIF-2) associated 67 kDa glycoprotein (p67) and an eIF-2 kinase (dsI).

Mechanism of regulation of eIF-2 alpha-subunit phosphorylation by dsI and p67 was studied. The results are as follows: (1) At low dsI concentration, p67 protected equimolar concentration of eIF-2. (2) At high dsI concentration, dsI efficiently phosphorylated eIF-2 alpha-subunit even when equimolar concentrations of both p67 and eIF-2 were present. Significantly increased p67 concentration was necessary to protect eIF-2 alpha-subunit at high dsI concentration. (3) dsI was also phosphorylated as it phosphorylated eIF-2 alpha-subunit. p67 inhibited both eIF-2 alpha-subunit and dsI phosphorylation similarly. (4) Although the [32P]-labelled dsI formed during the reaction could be effectively chased upon subsequent addition of excess unlabelled eIF-2 and ATP, the [32P] labelled eIF-2 formed under identical conditions, retained most of the radioactivity. (5) dsI coimmunoprecipitated with three subunit eIF-2 and p67 inhibited this coimmunoprecipitation reaction. It has been proposed: Three subunit eIF-2 and free p67 are in equilibrium with eIF-2 bound to p67 and, eIF-2.p67 complex is resistant to dsI phosphorylation. Activated dsI is already phosphorylated. At high concentration, dsI(P) can bind to free three subunit eIF-2 and form eIF-2.dsI(P) complex. dsI(P) in this complex then transfers its phosphoryl residue to eIF-2 and forms eIF-2 alpha(P) in an irreversible reaction. In a subsequent reaction, unphosphorylated dsI is autophosphorylated using [gamma 32P]-ATP and the cycle continues. Inhibition of eIF-2 alpha-subunit phosphorylation by p67 blocks this phosphorylation cycle and consequent dsI phosphorylation.