Multidrug Treatment Research Articles

Survival time and influencing factors in multidrug-resistant tuberculosis patients in Wuhan, 2006-2014

Objective: To investigate the survival time of multidrug-resistant tuberculosis (MDR-TB) patients and the influential factors in Wuhan. Methods: The relevant information were collected from TB management information system, cause of death reporting system and medical records by trained doctors. The univariate and multivariate Cox proportional hazards model were applied to analyze the factors affecting survival time of patients. Results: A total of 552 patients with MDR-TB were included in the analysis. After the diagnosis of MDR-TB, the cumulative survival rates from the first year to the third year were 0.94, 0.88, and 0.80, respectively. The mortality density of MDR-TB patients was 6.52/100 person-years, and the median survival time was (89.52±1.85) months. Kaplan-Meier analysis showed that the cumulative survival rate of the standardized treatment group was significantly higher than that of the non-standardized treatment group (Log rank=101.070, P<0.001). Compared with the patients aged <30 years, the HR of the patients aged 30-years and ≥60 years were 2.987 (95%CI: 1.268-7.036), 4.957 (95%CI: 1.942-12.653). Compared with the patients with the education level of high school and above, the HR of the patients with education level of junior high school/primary school and below were 1.908 (95%CI: 1.152-3.160), 1.681(95%CI: 1.033-2.735). Compared with the patients without diabetes, the HR of the patients with diabetes was 1.961(95%CI: 1.347-2.854). Compared with the patients without other serious diseases, the HR of the patients with other serious diseases was 2.597 (95%CI: 1.820-3.706). Compared with the patients who had been treated less than one time, the HR of the patients having previous treatment with more than 2 times was 1.611 (95%CI: 1.077-2.409). Compared with patients receiving standard MDR regimen treatment, the HR of the patients receiving no standard MDR regimen treatment was 3.155 (95%CI: 2.132-4.670). Conclusions: The cumulative survival rate of MDR-TB patients without standard treatment was significantly lower than that of patients with standard treatment. Older age, low educational level, diabetes mellitus, other serious diseases, more than two times treatment in the past, and receiving no multi-drug resistance regimen treatment were the risk factors affecting the survival of MDR-TB patients.

Antibacterial effect of TiO2 :Cu:Ag thin coatings on Pseudomonas strain measured by microbiological and ATP assays.

The aim of this study is to investigate the antimicrobial properties of nanocomposite thin TiO2 :Cu:Ag films on Pseudomonas putida as a natural isolate and an opportunistic pathogen. Several different methods were used to compare the antibacterial effect of thin TiO2 :Cu:Ag layers obtained by radiofrequency magnetron sputter deposition against P. putida: optical density of the bacterial suspension, most probable number of survived cells, dehydrogenase activity inhibition, scanning electron microscopy images, atomic flame absorption spectroscopy, and adenosine triphosphate (ATP) luminescent assay. Optical density measurements and most probable plate count were in agreement and showed a strong bactericidal effect of the as-deposited and only bacteriostatic effect of the annealed coatings with the same metal content on tested bacteria. As the metal quantity in the medium rises during the first hour of the experiment, it could be suggested that this is the main reason for cell death. ATP-luminescent assay showed up to 18-fold reduction of the signal. It was compared with other microbiological and biochemical assays to prove the strong antibacterial effect of nanocomposite thin TiO2 :Cu:Ag coatings with the possibilities of medical applications. Protection of medical devices against infections is a significant current challenge raised by an increasing number of medical devices-associated infections and microbial resistance to conventional antibiotic and multidrug treatments. Deposition of antimicrobial coatings is one of the current approaches to mitigate the problem.

WS03.08 Panel - Emerging Therapies - Immunotherapy

WS03.08 Panel - Emerging Therapies - Immunotherapy

Delamanid Central Nervous System Pharmacokinetics in Tuberculous Meningitis in Rabbits and Humans.

Central nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low MIC (1 to 12 ng/ml) against Mycobacterium tuberculosis It is used for the treatment of pulmonary MDR-TB, but pharmacokinetic (PK) data for DLM in the central nervous system (CNS) of patients with TBM are not available. In the present study, we measured DLM concentrations in the brain and cerebrospinal fluid (CSF) of six rabbits with and without experimentally induced TBM receiving single-dose DLM. We report the steady-state CSF concentrations from three patients receiving DLM as part of multidrug treatment who underwent therapeutic drug monitoring. Drug was quantified using liquid chromatography-tandem mass spectrometry. In rabbits and humans, mean concentrations in CSF (in rabbits, 1.26 ng/ml at 9 h and 0.47 ng/ml at 24 h; in humans, 48 ng/ml at 4 h) were significantly lower than those in plasma (in rabbits, 124 ng/ml at 9 h and 14.5 ng/ml at 24 h; in humans, 726 ng/ml at 4 h), but the estimated free CSF/plasma ratios were generally >1. In rabbits, DLM concentrations in the brain were 5-fold higher than those in plasma (means, 518 ng/ml at 9 h and 74.0 ng/ml at 24 h). All patients with XDR-TBM receiving DLM experienced clinical improvement and survival. Collectively, these results suggest that DLM achieves adequate concentrations in brain tissue. Despite relatively low total CSF drug levels, free drug may be sufficient and DLM may have a role in treating TBM. More studies are needed to develop a fuller understanding of its distribution over time with treatment and clinical effectiveness.

Predicting the impact of household contact and mass chemoprophylaxis on future new leprosy cases in South Tarawa, Kiribati: A modelling study.

BackgroundThe country of Kiribati is a small Pacific island nation which had a new case detection rate of 191 per 100,000 in 2016, and is one of the few countries yet to reach the WHO leprosy elimination goal. Chemoprophylaxis of household contacts of new cases, or to the whole population in a highly endemic areas have been found to be effective in reducing new case rates. This study investigated the potential impact of different chemoprophylaxis strategies on future cases in South Tarawa, the main population centre of Kiribati.MethodologyThe microsimulation model SIMCOLEP was calibrated to simulate the South Tarawa population and past leprosy control activities, and replicate annual new cases from 1989 to 2016. The impact of six different strategies for delivering one round of single dose rifampicin (SDR) chemoprophylaxis to household contacts of new cases and/or one or three rounds of SDR to the whole population was modelled from 2017 to 2030.Principal FindingsOur model predicted that continuing the existing control program of high levels of public awareness, passive case detection, and treatment with multidrug treatment would lead to a substantial reduction in cases but this was less effective than all modelled intervention scenarios. Mass chemoprophylaxis led to a faster initial decline in cases than household contact chemoprophylaxis alone, however the decline under the latter was sustained for longer. The greatest cumulative impact was for household contact chemoprophylaxis with three rounds of mass chemoprophylaxis at one-year intervals.ConclusionsThe results suggest that control of leprosy would be achieved most rapidly with a combination of intensive population-based and household chemoprophylaxis. These findings may be generalisable to other countries where crowding places social contacts as well as household contacts of cases at risk of developing leprosy.

THE EFFECT OF VIRGIN COCONUT OIL AGAINST SKIN TREATMENT OF LEPROSY PATIENTS

Objective: Leprosy is a major cause of permanent disability among infectious diseases. The important parts of the human body that is disturbed in leprosy patients are the skin and peripheral nerves. Multidrug therapy treatment can kill leprosy germs, but previous existing defects cannot be eliminated. The purpose of this study was to determine the effectiveness of virgin coconut oil (VCO) in improving the skin of lepers.&#x0D; Methods: The methods of this research used a pre- and post-test of the control group of 50 people respondents which consisted of the treatment group of VCO and control group of original coconut oil. All treatment and control groups of respondents were given once per day for 1 month based on non-probability sampling.&#x0D; Results: The results showed that there was a significant effect of VCO on the skin of leprosy patients with a statistical value p=0.000 (α=0.001). This was also supported by the observation of the patient’s skin which all of patients experience changed in the results of the assessment of the skin after VCO administration intervention. This relates to lauric acid content in coconut oil which can reduce skin moisture levels.&#x0D; Conclusion: Based on the results of this study can be concluded that VCO is effective in improving the skin of lepers. VCO can be used as an alternative intervention in skin care for leprosy patients and to prevent further disability. Therefore, it is important for leprosy patients to obtain information about the use of VCO in the care and moisture of the skin.

Multidrug use positively correlates with high-risk prescriptions in the Japanese elderly: a longitudinal study

BackgroundThere is a lack of evidence that multidrug use triggers adverse events. Therefore, the main purpose of this study was to clarify the relationship between the total number of drugs and number of high-risk prescriptions administered to Japanese elderly patients.MethodsUsing hospital electronic medical records (EMR), we evaluated the prescriptions of outpatients aged 65 years or older. We defined prescriptions of potentially inappropriate medications (PIMs) and overlapping prescription of drugs with the same mechanism of action (DSAs) as high-risk prescriptions. We analyzed the relationship among total number of drugs and high-risk prescriptions. In addition, we performed a secondary research to determine whether the hospitalization rate and concomitant medication contents differ depending on the high-risk prescriptions.ResultsData for 13,630 outpatients were analyzed. A significant positive correlation between the numbers of total drugs and PIMs was found. The prescription frequency of individual PIMs rose as the total number of prescription drugs increased. The odds ratio (OR) of overlapping DSAs was significantly higher in patients using 5 or more drugs. In addition, there were significantly more prescriptions of laxatives among patients with overlapping prescriptions of anticholinergic drugs. The use of almost all PIMs was not an independent risk factor for hospitalization; instead, the number of PIMs was an independent risk factor for hospitalization [OR 1.18 (95% CI, 1.12–1.26)].ConclusionsThe number of PIMs and overlapping DSAs were high in patients receiving multidrug treatment. To avoid adverse events and hospitalization, it might be useful to review prescriptions and consider the number of PIMs and overlapping DSAs.

Alternative Leprosy Treatment Using Rifampicin Ofloxacin Minocycline (ROM) Regimen – Two Case Reports

Abstract Introduction. Leprosy is a disease that predominantly affects the skin and peripheral nerves, resulting in neuropathy and associated long-term consequences, including deformities and disabilities. According to the WHO classification, there are two categories of leprosy, paucibacillary (PB) and multibacillary (MB). The standard treatment for leprosy employs the use of WHO MDT (Multi Drug Treatment) regimen, despite its multiple downsides such as clofazimine-induced pigmentation, dapsone-induced haematological adverse effects, poor compliance due to long therapy duration, drug resistance, and relapse. Multiple studies and case reports using ROM regimen have reported satisfactory results. Nevertheless, there are still insufficient data to elucidate the optimum dosage and duration of ROM regimen as an alternative treatment for leprosy. Previous experience from our institution revealed that ROM regimen given three times weekly resulted in a satisfactory outcome. Case Reports. We report two cases of leprosy treated with ROM regimen from our institution. The first case was PB leprosy in a 64-year-old male who presented with a single scaly plaque with erythematous edge on the right popliteal fossa. Sensibility examination showed hypoesthesia with no peripheral nerve enlargement. Histopathological examination confirmed Borderline Tuberculoid leprosy. ROM regimen was started three times weekly for 6 weeks and the patient showed significant clinical improvement at the end of the treatment with no reaction or relapse until after 6 months after treatment. The second case was MB leprosy in a 24-year-old male patient with clawed hand on the 3rd-5th phalanges of the right hand and a hypoesthetic erythematous plaque on the forehead. Histopathology examination confirmed Borderline leprosy. The patients received ROM therapy 3 times a week with significant clinical improvement after 12 weeks. Conclusion. ROM regimen given three times weekly for 6 weeks in PB leprosy and 12 weeks in MB leprosy resulted in a significant clinical improvement. Thus, ROM regimen could be a more effective, safer, faster alternative treatment for leprosy.

Oro-facial manifestations in lepromatous leprosy patients in Central India: clinical findings from a cross-sectional study.

To clinically evaluate the oro-facial manifestations in lepromatous leprosy patients undergoing multidrug therapy in Central India. Two hundred patients from 2 leprosy treatment centers in Central India who satisfied the diagnostic criteria set by the WHO (2006-2010) committee on leprosy were included in the study. To avoid bias, only patients who started the multi-drug treatment regimen less than 1year ago were included. All the patients were examined for the presence of oral and facial manifestations. To confirm that the oro-facial manifestations were not due to HIV co-infection, serological diagnostic tests including ELISA, Immunocomb, and Tri-dot were performed. Majority of the patients (n = 189) exhibited oral (n = 145) and/or facial (n = 147) manifestations. The most common oral lesions were found to be fissuring and depapillation of the tongue followed by fibrosis and loss of uvula. Among the facial manifestations, facial skin lesions and loss of eyebrows were most prevalent followed by sagging of facial skin and facies leonine. The facial manifestations of leprosy are quite common, readily recognizable, and relatively specific to the disease. Thus, the presence of facial manifestations, especially with co-existing oral lesions must prompt the clinician to mandate further investigations to confirm the diagnosis. As evidenced by the present study, facial manifestations and oral lesions are an integral part of leprosy. In addition to being a diagnostic parameter, facial manifestations and oral lesions could potentially be used to monitor the disease progression and treatment outcome.

Type I IFNs and M. bovis BCG vaccine: The sword to target germinal centers and unlock humoral immunity in leprosy

Leprosy is a still a serious human health problema in developed countries. Environmental and genetic factors are playing a key role in the chronic course of the disease, resistance versus susceptibility. The multidrug treatment is not effective for all infected individuals; “cured” individuals mostly show relapses of neurological disordes and potential as the same as not cured can present physical and deformed constrainst. The unsolved puzzle in leprosy is that clinic spectrum depends of the host immune response.and thus, the outcome of the immune response. In the present review we intended to describe some aspects of the immunotherapy, based on type I IFNs and M. bovis BCG vaccine as a strategy such as sword to target germinal centers, either for the generation or for the enhancement and thus, throughout key signals delivered by folicular CD4+ T cells, and controlled by folicular regulatory CD4+ T cells, B cell differentiation into plasmacytoid cells be highly promoted the induction of protective high affinity neutralyzing antibodies to unlock humoral immunity, protective toward M. leprae infected individuals.

Abstract 3669: Defining an ELAVL1-Musashi 2 signaling cascade in neuroblastoma tumorigenesis

Abstract Background: Patients with high-risk neuroblastoma endure an extremely intense, multidrug treatment regimen and yet, approximately half of them die, thus mandating a better approach to this cancer. Our laboratory is investigating the overarching hypothesis that RNA binding proteins (RBPs), which play key roles in balancing self-renewal, differentiation, and cell proliferation, are deregulated in neuroblastoma, and drive oncogenic signaling networks. Therefore, RBPs may constitute novel targets for therapeutic development. In this work, we focus on Musashi 2 (MSI2), an RBP that has been shown to play a critical role in the maintenance of stem cell populations and in the formation of aggressive tumors, notably in acute myeloid leukemia and in colon cancer. The role of MSI2 in neuroblastoma, however, has not been assessed and is the focus of this investigation. Methods: To test this hypothesis, we used in silico analysis of neuroblastoma gene expression datasets annotated with clinical parameters. Additionally, we used shRNAs to manipulate transcripts of interest in neuroblastoma cells and measured effects on cell proliferation, cell cycle status, and apoptosis. Results: Gene expression profiling revealed that MSI2 is robustly expressed in neuroblastoma cell lines, tumors, and patient derived xenografts, within both the MYCN and non-MYCN amplified context. Immunoblotting in a representative panel of lines confirmed the expression of MSI2 at the level of protein. High MSI2 expression was associated with more advanced stages of neuroblastoma across multiple independent datasets and was correlated with worse survival. Depletion of MSI2 using four independent shRNAs led to 2 to 3-fold decreased proliferation across four cell lines that was due in part to increased apoptosis. Another RBP, ELAVL1, is also expressed within neural lineages, and has been shown to regulate MSI1 expression. We hypothesized that ELAVL1 might similarly promote MSI2 expression and we demonstrated that, ELAVL1 depletion led to decreased MSI2 expression. Conclusions: MSI2 is robustly expressed in multiple models of neuroblastoma and appears to drive increased proliferation and survival. Currently, we are investigating the functional interplay between ELAVL1 and MSI2 providing a foundation for designing strategies to target the ELAVL1-MSI2 interaction for therapeutic effect. Citation Format: Selma M. Cuya, Adeiye Pilgrim, Komal Rathi, DongDong Chen, Robert Schnepp. Defining an ELAVL1-Musashi 2 signaling cascade in neuroblastoma tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3669.

Co-delivery of Doxorubicin and Afatinib with pH-responsive Polymeric Nanovesicle for Enhanced Lung Cancer Therapy

Drug-resistance and drastic side effects are two major issues of traditional chemotherapy which may result in trail failure even death. Nanoparticle-mediated multidrug combination treatment has been proven to be a feasible strategy to overcome these challenges. In the present study, amphipathic block polymer of methoxyl poly(ethylene glycol)-poly(aspartyl(dibutylethylenediamine)-co-phenylalanine) (mPEG-P(Asp(DBA)-co-Phe)) was synthesized and self-assembled into pH-responsive polymeric vesicle. The vesicle was utilized to co-deliver cancer-associated epidermal growth factor (EGFR) inhibitor of afatinib and DNA-damaging chemotherapeutic doxorubicin hydrochloride (DOX) for enhanced non-small-cell lung cancer (NSCLC) therapy. As evaluated in vitro, the pH-responsive design of nanovesicle resulted in a rapid release of encapsulated drugs into tumor cells and caused enhanced cell apoptosis. In addition, in vivo therapeutic studies were conducted and the results evidenced that the co-delevery of DOX and afatinib using pH-sensitive nanovector was a promising strategy for NSCLC treatment.

Cutaneous nontuberculous mycobacteria infections: A retrospective case series of 78 patients from the Texas Gulf Coast region

The incidence of cutaneous nontuberculous mycobacteria (NTM) infections is increasing. These infections are a diagnostic and therapeutic challenge. We investigated the clinical features, diagnosis, and management of cutaneous NTM infections. A retrospective case series studied 78 patients from a Gulf Coast tertiary referral center diagnosed with cutaneous NTM infection by culture or stain of a skin biopsy specimen. A history of trauma, procedure, or environmental exposure was common. The mean time between the initial evaluation and diagnosis was 12weeks. Only 15% of acid-fast bacillus-positive cultures had a positive acid-fast bacillus smear, and only 43% of those accompanied by skin biopsy specimen had a positive Fite stain. Immunosuppressed patients were more likely to have a positive Fite stain. Treatment included surgery and multiple antibiotics. Immunosuppressed patients and Mycobacterium abscessus group infections were more likely to have persistent disease. M chelonae and M abscessus isolates were indistinguishable and therefore were reported together. Five cases were not confirmed by culture. Even with clinical suspicion, the diagnosis of NTM infection can be difficult. Results of acid-fast bacillus smears and special stains are frequently negative. Antibiotic resistance is common. Multidrug treatment is often required, and surgical therapy may be needed.

Knowledge and self-care practice of leprosy patients at ALERT Hospital, Ethiopia

Introduction: In addition to multi-drug treatment, patient self-care practice is crucial for the successful treatment of the disease. This study assessed the knowledge and self-care practices of leprosy patients at ALERT leprosy referral hospital in Ethiopia. Methods: A total of 424 leprosy patients were interviewed using pre-tested structured questionnaires. The questionnaires included core points such as sociodemographic characteristics, knowledge of leprosy and self-care practices. Bloom’s cut off point was used to describe the knowledge and self-care practices of the respondents and statistical significance was assessed at 95% confidence interval with 5% of level of significance. Results: The knowledge score of the respondents was poor for 276 (65.1%) and good for 148 (34.9%). The level of knowledge varied significantly with respect to age group (p &lt; 0.01), sex (p &lt; 0.01), marital status (p = 0.003), educational status (p &lt; 0.01) and income (p &lt; 0.01). About 77.4% of interviewed patients had poor self-care practices and only 22.6 of patients had a good self-care practice score (p &lt; 0.01). Age (p &lt; 0.002), previous disability due to leprosy (p &lt; 0.01), knowledge of leprosy (p = 0.038) and income (P = 0.028), were significantly associated with poor selfcare practice. Conclusion: Although leprosy treatment, disability prevention and rehabilitation programs have been run in the country for decades, poor leprosy self-care practice and poor leprosy knowledge has been confirmed in this study. Therefore, the leprosy program should re-visit its strategy and mode of delivery to improve the leprosy knowledge and leprosy self-care practices of patients.

Pharmacology of dipeptidyl peptidase-4 inhibitors and its use in the management of metabolic syndrome: a comprehensive review on drug repositioning.

Despite advances in our understanding of metabolic syndrome (MetS) and the treatment of each of its components separately, currently there is no single therapy approved to manage it as a single condition. Since multi-drug treatment increases drug interactions, decreases patient compliance and increases health costs, it is important to introduce single therapies that improve all of the MetS components. We conducted a PubMed, Scopus, Google Scholar, Web of Science, US FDA, utdo.ir and clinicaltrial.gov search, gathered the most relevant preclinical and clinical studies that have been published since 2010, and discussed the beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors to prevent and treat different constituent of the MetS as a single therapy. Furthermore, the pharmacology of DPP-4 inhibitors, focusing on pharmacodynamics, pharmacokinetics, drug interactions and their side effects are also reviewed. DPP-4 inhibitors or gliptins are a new class of oral anti-diabetic drugs that seem safe drugs with no severe side effects, commonly GI disturbance, infection and inflammatory bowel disease. They increase mass and function of pancreatic β-cells, and insulin sensitivity in liver, muscle and adipose tissue. It has been noted that gliptin therapy decreases dyslipidemia. DPP-4 inhibitors increase fatty oxidation, and cholesterol efflux, and decrease hepatic triglyceride synthase and de novo lipogenesis. They delay gastric emptying time and lead to satiety. Besides, gliptin therapy has anti-inflammatory and anti-atherogenic impacts, and improves endothelial function and reduces vascular stiffness. The gathered data prove the efficacy of DPP-4 inhibitors in managing MetS in some levels beyond anti-diabetic effects. This review could be a lead for designing new DPP-4 inhibitors with greatest effects on MetS in future. Introducing drugs with polypharmacologic effects could increase the patient's compliance and decrease the health cost that there is not in multi-drug therapy. Graphical abstract ᅟ.

Ursodeoxycholic acid attenuates hepatotoxicity of multidrug treatment of mycobacterial infections: A prospective pilot study.

Tuberculosis (TB) remains a global health problem. The application of rifampicin-based regimens for antimycobacterial therapy is hampered by its marked hepatotoxicity which results in poor adherence and may contribute to prolonged therapy or treatment failure. The purpose of this prospective investigation was to evaluate the hepatoprotective effectiveness of oral ursodeoxycholic acid (UDCA) (250-500 mg TID) administered to TB- or non-TB mycobacterial (NTM)-infected patients with drug-induced hepatotoxicity and ongoing therapy. Study population: During 2009-2017, 27 patients (11 women, 16 men, aged 19-90 years; median age 44 years, 16 Caucasians, 10 Africans, 1 Asian) out of 285 patients with active TB (24/261) or NTM infections (3/24) treated at our TB Center developed clinically relevant hepatotoxicity. Oral UDCA was administered to treat hepatotoxicity. Twenty-one out of 27 patients (77.8%) showed normalization of elevated enzymes (alanine transferase and aspartate aminotransferase), alkaline phosphatase, and bilirubin while continuing TB treatment and 5 patients demonstrated a significant reduction of liver enzymes (18.5%). No change was observed in 1 patient (3.7%). Drug dose was not reduced in all patients; they all showed radiological and clinical improvement. There were no significant side effects. Oral administration of UDCA to TB patients developing anti-TB drug-induced liver injury may reverse hepatotoxicity in adults.

Laparoscopic Transperitoneal Nephrectomy in Non-functioning Severe Hydronephrotic Kidneys With or Without Renal Stone.

AimTo investigate the effects of the additional presence of nephrolithiasis on the results of laparoscopic simple nephrectomy in patients with severe hydronephrotic non-functional kidneys.Patients and methodsA total of 43 patients in whom severe hydronephrosis had been determined on spiral computerized tomography, who had a renal function of lower than 10% according to the dimercaptosuccinic acid (DMSA) renal scintigraphy, and who had undergone a laparoscopic simple nephrectomy due to persistent renal pain and/or recurrent urinary tract infection and/or unresolved hypertension with multidrug treatment, were included in the study. The patients were divided into two groups based on the presence of renal stone as those with stone formation (Group 1) and those without stone formation (Group 2). The groups were compared with regard to the patients’ demographic characteristics, operation durations, pre- and postoperative hemoglobulin and creatinine levels, percentage of change of postoperative hemoglobulin levels, complications, transfusion requirements, and durations of hospitalization.ResultsOverall, there were 43 patients including 19 patients in Group 1 and 24 patients in Group 2. Although the durations of operations, the durations of hospitalization, and the rates of change of hemoglobulin were higher in the patients in Group 1, these differences were not statistically significant. Postoperative complications were observed in 21 (48.8%) of the 43 patients. Postoperative complications were observed in 13 patients in Group 1 and in eight patients in Group 2. This difference was determined to be statistically significant (p<0.01).ConclusionsWe observed that except for the postoperative complication rates, the laparoscopic nephrectomy results in patients with severe hydronephrotic non-functional kidneys with or without stone were similar.

Recent Advancement in the Diagnosis and Treatment of Leprosy.

Many of the tropical diseases are neglected by the researchers and medicinal companies due to lack of profit and other interests. The Drugs for Neglected Diseases initiative (DNDi) is established to overcome the problems associated with these neglected diseases. According to a report published by the WHO, leprosy (Hansen's disease) is also a neglected infectious disease. A negligible amount of advancements has been made in last few decades which includes the tools of diagnosis, causes, treatment, and genetic studies of the bacterium (Mycobacterium leprae) that causes leprosy. The diagnosis of leprosy at earlier stages is important for its effective treatment. Recent studies on vitamin D and its receptors make leprosy diagnosis easier at earlier stages. Skin biopsies and qPCR are the other tools to identify the disease at its initial stages. Until now a specific drug for the treatment of leprosy is not available, therefore, Multi-Drug Therapy (MDT) is used, which is hazardous to health. Besides Mycobacterium leprae, recently a new bacterium Mycobacterium lepromatosis was also identified as a cause of leprosy. During the last few years the genetic studies of Mycobacterium leprae, the role of vitamin D and vitamin D receptors (VDR), and the skin biopsies made the treatment and diagnosis of leprosy easier at early stages. The studies of micro RNAs (miRNAs) made it easy to differentiate leprosy from other diseases especially from tuberculosis. Leprosy can be distinguished from sarcoidosis by quantitative study of reticulin fibers present in skin. The treatment used until now for leprosy is multi-drug treatment. The complete genome identification of Mycobacterium leprae makes the research easy to develop target specified drugs for leprosy. Rifampicin, identified as a potent drug, along with other drugs in uniform multi-drug treatment, has a significant effect when given to leprosy patients at initial stages. These are effective treatments but a specific drug for leprosy is still needed to be identified. The current review highlights the use of modern methods for the identification of leprosy at its earlier stages and the effective use of drugs alone as well as in combination.

Myocardial Perfusion Abnormalities in Young and Premenopausal Women with Systemic Lupus Erythematosus, Detected with 99MTC MIBI Myocardial Perfusion Scintigraphy - Prevalence and Correlation with Proatherogenic Factors.

Atherosclerosis in young and premenopausal women with systemic lupus erythematosus (SLE) is frequent, premature and progressive. Although asymptomatic or with atypical clinical presentation, the patients are at high risk of cardiac events. Aim of this study is to estimate the risk profile for atherogenesis and the prevalence of myocardial perfusion abnormalities with 99mTc myocardial perfusion scintigraphy (MPS) in young and premenopausal women. Sixty female patients, aged 30-72 years (divided into two subgroups - patients under 45 years of age and patients over 45 years), diagnosed with SLE for over of 5 years, in active phase of the disease were analyzed for disease activity scores (SLEDAI), the immunologic status of the disease (ANA and a-DNA antibodies in the serum), procoagulant tendency (antiphospholipid antibodies-APhL and lupus-anticoagulant-LAC), the activity of the inflammatory process (hsCRP), the anti-SLE therapeutic approach and the presence of traditional risk factors for atherosclerosis (BMI, smoking, hypertension, hyperlipidemia, diabetes, and familial history for the CAD). Using one-day Dipyridamol - Rest 99mTc SPECT Gated MPS SPECT the extent, severity and reversibility of myocardial perfusion abnormalities were estimated, along with summed scores at stress, rest and summed difference scores and left ventricle volumes and ejection fraction. Abnormal MPS SPECT were detected in 27/60 or in 45% of patients, with one vessel affection of 66.7% (18/27pts) of LAD and 14.8% (4/27pts) o RCA and with two vessel disease of LAD/RCA in 2/27 pts (7.4%) and LAD/Cx in 3/27pts (11.1%). Myocardial perfusion abnormalities were equally prevalent in subgroups of patients younger than 45 years (44,4%) and in patients older than 45 years (45.5%) (ns). The subgroups did not differ significantly concerning the extent of perfusion abnormalities (9,8±3.2% of LV myocardial mass vs. 9,8±7.1%,ns), their severity (with predominance of mild perfusion defects, 48,6% vs. 51,3%,ns) and reversibility (reversible in 41.3% and 58.6%, ns). The differences between the summed scores of severity and the extent of ischemia in the two subgroups were statistically nonsignificant. Younger patients had significantly higher end-diastolic, end-systolic and stroke volumes during stress and rest conditions, compared to older patients (p<0,01) although there were no differences in systolic function, which was not affected in either of the groups as expressed threw ejection fraction. Although nonsignificant, younger patients had higher values of hsCRP and higher procoagulant activity (positive aPhL, LAC) while they were with more active disease activity, with higher SLEDAI score compared to older patients (p=0.028). Higher SLEDAI score and LV volumes, especially EDV at stress were identified as predictor of abnormal MPS in younger groups and more aggressive multidrug anti SLE treatment as predictor of normal MPS. The prevalence and characteristics of myocardial perfusion abnormalities in young SLE are equal as the same in older SLE patients, which indicates the presence of premature, accelerated atherosclerosis in young cohort of patients with SLE. Younger SLE patients with pure disease control (higher SLEDAI score, less aggressive treatment, high hsCRP values and pronounced procoagulant tendency) should undergo screening for myocardial perfusion abnormalities s using 99mTc MIBI MPS).

Female genital tuberculosis: Revisited.

Female genital tuberculosis (FGTB) is caused by Mycobacterium tuberculosis (rarely Mycobacterium bovis and/or atypical mycobacteria) being usually secondary to TB of the lungs or other organs with infection reaching through haematogenous, lymphatic route or direct spread from abdominal TB. In FGTB, fallopian tubes are affected in 90 per cent women, whereas uterine endometrium is affected in 70 per cent and ovaries in about 25 per cent women. It causes menstrual dysfunction and infertility through the damage of genital organs. Some cases may be asymptomatic. Diagnosis is often made from proper history taking, meticulous clinical examination and judicious use of investigations, especially endometrial aspirate (or biopsy) and endoscopy. Treatment is through multi-drug antitubercular treatment for adequate time period (rifampicin, isoniazid, pyrazinamide, ethambutol daily for 60 days followed by rifampicin, isoniazid, ethambutol daily for 120 days). Treatment is given for 18-24 months using the second-line drugs for drug-resistant (DR) cases. With the advent of increased access to rapid diagnostics and newer drugs, the management protocol is moving towards achieving universal drug sensitivity testing and treatment with injection-free regimens containing newer drugs, especially for new and previously treated DR cases.