Shock-wave lithotripsy: variance within UK practice.

The objectives of this study are to determine the current treatment policies of UK shock-wave lithotripsy centres. Fixed-site lithotripter centres in the UK were identified via the national Therapeutic Interventions for Stones of the Ureter (TISU) study (n = 25). Questionnaires were completed regarding current SWL protocols for each centre, including management of anticoagulation, use of antibiotics and analgesia, urine testing, pacemakers, and arterial aneurysms. Data were collected regarding service delivery. Responses were obtained for 21 centres. Most centres use the Storz Modulith (85.7 %). Wide variation was observed in clinical contraindications to SWL, with 47.6 % centres performing SWL in patients with an abdominal aortic aneurysm, 66.7 % performing SWL in patients with a pacemaker, and 66.7 % of centres not performing SWL in asymptomatic patients with a urine dipstick positive for nitrites and leucocytes. The management of anticoagulation pre- and post-SWL showed wide variation, with the omission of anticoagulation ranging from 0 to 10 days pre-SWL. Seventeen distinct analgesia regimens were reported and prophylactic antibiotics are routinely administered in 25.0 % of centres. Tamsulosin is prescribed to all patients in 20.0 % of centres and a further 15.0 % of centres routinely prescribe tamsulosin post-SWL of ureteric stones. The included centres undertake SWL a median of 4 days per week and treat a median of six patients per list. Emergency SWL is unavailable in 30.0 % of centres. This observational real-life study has identified a significant disparity in the delivery of SWL throughout the UK, despite high numbers of patients with renal and ureteric stones being treated with this modality. Further studies should address the key areas of controversy, including an assessment of technical training, and facilitate the development of national guidelines to ensure a high level of standardized care for SWL patients.

Integration of copy number and transcriptomics provides risk stratification in prostate cancer: A discovery and validation cohort study.

BACKGROUND: Understanding the heterogeneous genotypes and phenotypes of prostate cancer is fundamental to improving the way we treat this disease. As yet, there are no validated descriptions of prostate cancer subgroups derived from integrated genomics linked with clinical outcome. METHODS: In a study of 482 tumour, benign and germline samples from 259 men with primary prostate cancer, we used integrative analysis of copy number alterations (CNA) and array transcriptomics to identify genomic loci that affect expression levels of mRNA in an expression quantitative trait loci (eQTL) approach, to stratify patients into subgroups that we then associated with future clinical behaviour, and compared with either CNA or transcriptomics alone. FINDINGS: We identified five separate patient subgroups with distinct genomic alterations and expression profiles based on 100 discriminating genes in our separate discovery and validation sets of 125 and 103 men. These subgroups were able to consistently predict biochemical relapse (p = 0.0017 and p = 0.016 respectively) and were further validated in a third cohort with long-term follow-up (p = 0.027). We show the relative contributions of gene expression and copy number data on phenotype, and demonstrate the improved power gained from integrative analyses. We confirm alterations in six genes previously associated with prostate cancer (MAP3K7, MELK, RCBTB2, ELAC2, TPD52, ZBTB4), and also identify 94 genes not previously linked to prostate cancer progression that would not have been detected using either transcript or copy number data alone. We confirm a number of previously published molecular changes associated with high risk disease, including MYC amplification, and NKX3-1, RB1 and PTEN deletions, as well as over-expression of PCA3 and AMACR, and loss of MSMB in tumour tissue. A subset of the 100 genes outperforms established clinical predictors of poor prognosis (PSA, Gleason score), as well as previously published gene signatures (p = 0.0001). We further show how our molecular profiles can be used for the early detection of aggressive cases in a clinical setting, and inform treatment decisions. INTERPRETATION: For the first time in prostate cancer this study demonstrates the importance of integrated genomic analyses incorporating both benign and tumour tissue data in identifying molecular alterations leading to the generation of robust gene sets that are predictive of clinical outcome in independent patient cohorts.

Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair.

Many cancers display increased expression of histone deacetylases (HDACs) and therefore transcriptionally inactive chromatin, resulting in the downregulation of genes including tumour suppressor and DNA repair genes. Histone deacetylase inhibitors (HDACi) are a heterogeneous group of epigenetic therapeutics, showing promising anticancer effects in both pre-clinical and clinical settings, in particular the effect of radiosensitisation when administered in combination with radiotherapy. Radiotherapy remains one of the most common forms of cancer treatment, leading to cell death through the induction of DNA double-strand breaks (DSBs). Cells have developed mechanisms to repair such DSB through two major pathways: non-homologous end-joining and homologous recombination. Here, we explore the current evidence for the use of HDACi in combination with irradiation, focusing on the effects of HDACi on DNA damage signalling and repair in vitro. In addition, we summarise the clinical evidence for using HDACi with radiotherapy, a growing area of interest with great potential clinical utility.

Initial assessment of scaled-up sexually transmitted infection intervention in Himachal Pradesh under National AIDS Control Program - III.

OBJECTIVES: To assess the impact of scaled-up sexually transmitted infection (STI) intervention under National AIDS Control Program (NACP) III and to examine the profile of STI/RTI clinic (now named Suraksha Clinic) attendees. MATERIALS AND METHODS: A retrospective study by data analysis was done from April 2008 to March 2010. The scaled-up intervention comprised of (i) adopting enhanced syndromic approach, (ii) capacity building by appointing counselors and trainings of staff, (iii) strengthening STI/RTI clinics by provision of logistics and privacy by civil works, and (iv) supervisory support. The outcome which directly influenced service delivery was evaluated within this framework. RESULTS: Sixteen "Suraksha Clinics" have been remodeled, equipped with supplies and laboratory set up. A total of 64,554 clinic visits were reported of which 27,317 [42%] attended the clinics for index STI/RTI complaint(s). Majority of the clients (44%) were young, 25-44 years old. Male to female ratio was 1:1.8. In females, the commonest complaint was lower abdominal pain (25%) and vaginal discharge (33%), the commonest syndrome. Amongst laboratory-confirmed STIs, 305 (1.4%) attendees were positive for trichomoniasis, while bacterial vaginosis was corroborated in 230 (1.07%) patients with clue cells. Amongst antenatal women, 251 were reactive for syphilis (≥1:8 dilutions). 10,579 partners of index STI/RTI patients were notified and partner management was attained to the level of 99%. CONCLUSION: Preliminary results show increased utilization of STI clinical services, though laboratory services need further strengthening. Continued supportive supervision and capacity building will enable skill development and quality monitoring.

Robotic-assisted laparoscopic prostatectomy.

Prostate cancer remains a significant health problem worldwide and is the second highest cause of cancer-related death in men. While there is uncertainty over which men will benefit from radical treatment, considerable efforts are being made to reduce treatment related side-effects and in optimising outcomes. This article reviews the development and introduction of robotic-assisted laparoscopic radical prostatectomy (RALP), the results to date, and the possible future directions of RALP.

Mucocutaneous manifestations in 150 HIV-infected Indian patients and their relationship with CD4 lymphocyte counts.

Mucocutaneous findings in 150 HIV+ve cases (F, 79; M, 71) were evaluated over a one-year period. Mucocutaneous manifestations were seen in 96% with 2.9 mean number of dermatoses and mean cluster of differentiation (CD4) count of 196.33 cells/mm(3). The highest number of mean dermatoses, 3.29, was seen in individuals with severe immunosuppression. The most common mucocutaneous manifestation seen was candidiasis (35.33%), followed by seborrhoeic dermatitis (31.33%), oral pigmentation (29.33%), xerosis/ichthyosis (22.67%), pyodermas (22%), periodontitis (17.33%) and nail pigmentation (16.67%). Patient stratification according to the WHO immunological staging, according to CD4 counts, showed a statistically significant association (P < 0.05) for candidiasis, scabies, paronychia, oral pigmentation and diffuse hair loss. Nail and oral pigmentary changes, trichomegaly and subcutaneous fungal infections caused by dermatophytes were highlights of the study. Incidences of xerosis/ichthyosis, pyodermas, scabies and molluscum contagiosum reported in our study were higher and pruritic popular eruptions was lower than those in previous Indian studies. Cutaneous neoplasms were not seen in the present study.

An epitope-specific PCR test for diagnosis of Leishmania donovani infections.

The carboxy-terminal region of recombinant heat shock protein 70 of Leishmania donovani has been shown to have an immunodominant epitope. We designed a PCR assay using a new set of primers encompassing the gene sequence from 457bp to 927bp, which amplified a segment of the L. donovani genome in a species-specific manner. The assay was sensitive enough to detect 0.5pg of parasite DNA, which increased 10-fold (0.05pg) when an internal probe (583-609bp) was used in the Southern blot. The assay was able to detect parasite DNA from the liver and spleen of L. donovani-infected hamsters as well as lesion aspirates from parasitologically confirmed post-kala-azar dermal leishmaniasis (PKDL) and bone marrow aspirates from visceral leishmaniasis (VL) patients. No amplification was seen with axenically cultured promastigotes of L. infantum, L. tropica, L. major, L. mexicana, L. aethiopica or other intracellular organisms such as Entamoeba histolytica, Mycobacterium tuberculosis, Plasmodium vivax or human peripheral blood mononuclear cells. This PCR provides a specific tool for the diagnosis of VL and PKDL with simultaneous species identification.

Cutaneous sporotrichosis in Himachal Pradesh, India.

During the period 1990-2002 in Himachal Pradesh, India, 103 new patients with cutaneous sporotrichosis were detected. Lymphocutaneous and fixed cutaneous varieties were the most common and seen in 49% and 43% respectively. Chronic non-specific inflammation without granuloma formation was seen in 46% skin biopsy specimens, 29% showed acute or chronic inflammation and tuberculoid granuloma formation was seen in 25%. In 32% of cases Sporothrix schenckii growth was seen on Sabouraud glucose agar. A saturated solution of potassium iodide was used as first-line treatment and in 93% patients healing of lesions occurred in 4-32 weeks (average 8.7 weeks) without significant side-effects. Itraconazole, used in 12 patients, was highly effective in recommended doses. Rapid healing was seen with higher than previously used doses of fluconazole in one patient who also had unusual exacerbation of lesional inflammation with saturated solution of potassium iodide.

Epidemiology of a new focus of localized cutaneous leishmaniasis in Himachal Pradesh.

A new focus of localised cutaneous leishmaniasis has emerged along the Satluj River valley in the mountainous region of north west Himachal Pradesh. The main endemic region extends from Pooh subdivision of Kinnaur district to Kumarsain subdivision of Shimla district with adjoining Nirmand subdivision of Kullu District comprising 86 villages. The climate of the affected areas varies from temperate to subtropical. A total of 285 cases were recorded from 1988 to January, 2005. The age of these patients varied from 10 months to 75 years, with 63 children (<12Years), and a male to female ratio of 1: 0.9. The duration of disease was 15 days to 48 months with majority (85%) presenting between 1-6 months. The number of lesions varied from 1-8, and were mostly seen on exposed parts of the body. Morphologically, lesions were asymptomatic, dry, nodular or crusted nodulo-ulcerative plaques. Tissue smear positivity for amastigotes was 43%. The characterization of 14 strains of these Leishmania revealed presence of both Leishmania tropica (n=3) and Leishmania donovani (n=11). Identification of the 42 sandflies collected from the peridomestic environment of the patients, revealed Phlebotomus longiductus - 29, P. major 8, P. kandelaki 2, while 2 remained unidentified. The patients were treated with intralesional sodium stibogluconate and majority showed excellent response.

Effectiveness of fluoxetine in the treatment of skin-picking.

The case of an 18-year-old girl with skin-picking is reported. The patient used to pick at healthy skin and small skin lesions, leading to ulceration, hyperpigmentation and disfigurement. She recovered almost fully with fluoxetine. The implications of diagnosis and the need for early treatment are discussed.

Cutaneous sporotrichosis: an unusual clinico-pathologic and therapeutic presentation.

This report presents a number of unusual clinico-histopathologic and therapeutic features in a culture proven case of cutaneous sporotrichosis. These include lymphocutaneous sporotrichosis involving face; its dissemination in an otherwise healthy patient; its histology mimicking cutaneous cryptococcosis; two episodes of severe purulent inflammatory reaction bordering the lesion during therapy with saturated solution of potassium iodide; no therapeutic response to potassium iodide therapy and rapid healing of lesion with high-dose of fluconazole.

Orofacial conidiobolomycosis due to Conidiobolus incongruus.

We report here a patient of orofacial conidiobolomycosis presenting with classical centrofacial distribution described typically for Conidiobolus coronatus infection. The culture, however, showed C. incongruus. The mode of infection and its possible correlation with patient's occupation is also discussed.

A new focus of cutaneous leishmaniasis in Himachal Pradesh (India).

This paper highlights a new focus of cutaneous leishmaniasis (CL) in the temperate area of Himachal Pradesh (India), a previously non-endemic area. In this hospital-based study, 38 new cases of CL, acquired indigenously have been detected from 1988-2000. Of these, 26 were from Kinnaur district and 12 from adjoining areas of bordering districts situated along the river: Satluj. There were 18 males and 20 females. They were between 4-75 years of age and had the disease for one month to 2 years at the time of presentation. Face involvement was seen in majority of the patients. Nodulo-ulcerative plaque was the commonest lesion. Muco-cutaneous lesions were seen in four cases. Tissue smears and biopsies were positive for LD bodies in 61.7% and 29.4% cases respectively. Intralesional sodium stibogluconate produced a consistent therapeutic response. The possible mode of its introduction in the region is postulated. The reservoir of infection, identity of the vector at this altitude (9,002,900 meters above sea level) and the strain of leishmania, remain to be identified.

Trends in detection of new leprosy cases at two centres in Himachal Pradesh, India: a ten-year study.

An impressive decline in leprosy prevalence rate (PR) in all endemic districts of India is seen in the post-MDT era. However, the new case-detection rate, an important statistical indicator in leprosy control programmes, has not shown significant decline in spite of all efforts. In Himachal Pradesh, a decline in PR from 7.8 to 0.56/10000 between 1991 to 2000 is seen, and recently the State has won national acclaim for having achieved the goal of elimination of leprosy in all the districts. The vertical leprosy programme has been integrated into general health services of the state. An analysis of data from 1991 to 2000 of two leprosy control units of Himachal Pradesh, the Urban Leprosy Clinic in Shimla (ULC-S) and the District Leprosy Control Unit in Mandi (DLCU-M), showed no significant decline in the new cases detected. 277 and 271 new cases were detected at these centres respectively; these included 2.2% and 1.5% children of less than 14 years of age. Almost 75% of these cases were males and of MB type. A steadily increasing trend in the annual detection of new cases was seen at both the centres during the decade. The cases registered at DLCU-M were mainly indigenous to the district. At ULC-S, 45 migrant cases from other endemic areas-mainly from Nepal, Bihar, and Uttar Pradesh-had also contributed to the increased number of new cases. Other possible causes discussed for this higher new case detection, e.g. overdiagnosis, detection of backlog "hidden cases" and voluntary reporting of patients, do not differ from those seen in other parts of the country or the world.