Role of nonoperative treatment in managing degenerative tears of the medial meniscus posterior root

BACKGROUND: Tears of the medial meniscus posterior root can lead to progressive arthritis, and its management has no consensus. The aim of our study was to evaluate the effect of supervised exercise therapy on patients with medial meniscus posterior root tears. MATERIALS AND METHODS: Between January 2005 and May 2007, 37 patients with this tear verified by magnetic resonance imaging (MRI) and osteoarthritis grade 1–2 by radiographic examination were treated by a short course of analgesics daily for up to 6 weeks and then as required during follow-up, as well as a 12-week supervised exercise program followed by a home exercise program. Final analysis was performed for 33 patients, average age 55.8 (range 50–62) years and average follow-up of 35 (range 26–49) months. Patients were followed up at 3, 6, and 12 months and yearly thereafter using the Lysholm Knee Scoring Scale, Tegner Activity Scale (TAS), and visual analog scale (VAS). The analysis was performed using one-way analysis of variance (ANOVA) and Pearson’s correlation coefficient to determine the relationship between Lysholm score and body mass index (BMI). RESULTS: Patients showed an improvement in Lysholm score, TAS, and VAS, which reached maximum in 6 months and later was accompanied by a decline. However, scores at the final follow-up were significantly better than the pretherapy scores. There was also a progression in arthritis as per Kellgren and Lawrence radiographic classification from median 1 preintervention to median 2 at the final follow-up. A correlation between BMI and Lysholm scores was seen (r = 0.47). CONCLUSION: Supervised physical therapy with a short course of analgesics followed by a home-based program results in symptomatic and functional improvement over a short-term follow-up; however, osteoarthritis progression continues and is related to BMI

AmBisome Monotherapy and Combination AmBisome-Miltefosine Therapy for the Treatment of Visceral Leishmaniasis in Patients Coinfected With Human Immunodeficiency Virus in India: A Randomized Open-Label, Parallel-Arm, Phase 3 Trial.

BACKGROUND: Visceral leishmaniasis (VL) in patients with human immunodeficiency virus (HIV) presents an increasingly important patient cohort in areas where both infections are endemic. Evidence for treatment is sparce, with no high-quality studies from the Indian subcontinent. METHODS: This is a randomized, open-label, parallel-arm, phase 3 trial conducted within a single hospital in Patna, India. One hundred and fifty patients aged ≥18 years with serologically confirmed HIV and parasitologically confirmed VL were randomly allocated to 1 of 2 treatment arms, either a total 40 mg/kg intravenous liposomal amphotericin B (AmBisome; Gilead Pharmaceuticals) administered in 8 equal doses over 24 days or a total 30 mg/kg intravenous AmBisome administered in 6 equal doses given concomitantly with a total 1.4 g oral miltefosine administered through 2 daily doses of 50 mg over 14 days. The primary outcome was intention-to-treat relapse-free survival at day 210, defined as absence of signs and symptoms of VL or, if symptomatic, negative parasitological investigations. RESULTS: Among 243 patients assessed for eligibility, 150 were recruited between 2 January 2017 and 5 April 2018, with no loss to follow-up. Relapse-free survival at day 210 was 85% (64/75; 95% CI, 77-100%) in the monotherapy arm, and 96%, (72/75; 90-100%) in the combination arm. Nineteen percent (28/150) were infected with concurrent tuberculosis, divided equally between arms. Excluding those with concurrent tuberculosis, relapse-free survival at day 210 was 90% (55/61; 82-100%) in the monotherapy and 97% (59/61; 91-100%) in the combination therapy arm. Serious adverse events were uncommon and similar in each arm. CONCLUSIONS: Combination therapy appears to be safe, well tolerated, and effective, and halves treatment duration of current recommendations. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry India (CTRI/2015/05/005807; the protocol is available online at https://osf.io/avz7r)

Congener specific distribution of polychlorinated dibenzo-p-dioxins and dibenzo-p-furans in ambient air particulates (less than PM10) in Delhi, India

Polychlorinated dibenzo-<em>p</em>-dioxins (PCDDs) and polychlorinated dibenzo-<em>p</em>-furans (PCDFs) are unintentionally formed during inefficient combustions and as a by-product. Due to their resistance to degradation and their toxic effect on health, PCDD/Fs are listed by the Stockholm Convention as persistent organic pollutants (POPs). Once released into the atmosphere, most of them are adsorbed to air particles and transported away from sources in atmosphere. India signed the Stockholm Convention India agreeing thereby to reduce and eliminate the use of POPs. The German agency for Technical Cooperation helped develop facilities for monitoring POPs at a national level in Delhi. This paper presents the data generated during a training assignment for Central Pollution Control Board officials at the German laboratory. Air borne particulate matter (&lt;PM₁₀) was collected from 6 different locations in Delhi, India and analyzed in a German laboratory for 17 congeners of PCDD/Fs. The concentrations of &Sigma;PCDD/Fs ranged between 1720-9010 fg m^-3 (mean 5559 fg m^-3) and their toxic equivalency values ranged from 67 to 460 fg I-toxic equivalent quantities (TEQ) m^-3, with an average of 239 fg I-TEQ m^-3 which was lower than the ambient air standards. The dominant congeners were octachlorinated dibenzo-p-dioxin (OCDD), octachlorinated dibenzo-p-furans (OCDF), 1,2,3,4,6,7,8-heptachlorinated dibenzo- p-furans, and 1,2,3,4,6,7,8-heptachlorinated dibenzo-p-dioxin. The contributions of individual homologs for &Sigma;PCDDs/Fs I-TEQ was in the order of OCDD (31%)&gt;HCDF (21%)&gt;hexachlorodibenzofurans (13%)=OCDF (13%)&gt; HCDF (12%) and other individual congeners contribute less than 5%. High chlorinated congeners contributed with more than 80% for &Sigma;PCDD/Fs I-TEQ. Rough estimates of tolerable daily intake (TDI) shows low health risk of exposure to &Sigma;PCDD/Fs with inhalation of 0.098 pg I-TEQ kg¹day¹ for adult and 0.152 pg TEQ kg^-1day^-1 for children, which is much lower than World Health Organization recommended TDI for dioxins

Assessment of quality of life in patients with post kalaazar dermal leishmaniasis

Abstract Background Post kala-azar dermal leishmaniasis (PKDL) is a dermatological disorder caused by protozoal parasite Leishmania donovani. PKDL cases are thought to be a reservoir of parasites and may increase cases of visceral leishmaniasis. The disease is not life threatening but cosmetic disfigurement associated with it may impair the patients’ quality of life. This study aimed to assess the health related quality of life in patients with post kalaazar dermal leishmanasis for the first time. Methods A total of 92 PKDL cases and 96 healthy participants filled out the questionnaires. The Dermatology Life Quality Index (DLQI) and SF 36 questionnaire were used to assess the quality of life. Data on socio-demographic and clinical features were also collected. The collected data were analyzed by using SPSS software (version 16), Student’s t-test, analysis of variance (ANOVA) was applied for comparison of means. Results PKDL patients experienced very large impact on their quality of life. The mean score of DLQI was 11.41. Highest impact was found in symptoms and feelings and lowest impact was observed for personal relationship domain. Patients below 20 years age group found to have lower quality of life. There was a significant difference in mean DLQI scores with regard to age and severity of lesions (P  0.05). Conclusion PKDL significantly impaired the patient’s quality of life. Further studies to assess the impact of treatment on quality of life in these patients are recommended

Intracellular zinc flux causes reactive oxygen species mediated mitochondrial dysfunction leading to cell death in Leishmania donovani.

Leishmaniasis caused by Leishmania parasite is a global threat to public health and one of the most neglected tropical diseases. Therefore, the discovery of novel drug targets and effective drug is a major challenge and an important goal. Leishmania is an obligate intracellular parasite that alternates between sand fly and human host. To survive and establish infections, Leishmania parasites scavenge and internalize nutrients from the host. Nevertheless, host cells presents mechanism like nutrient restriction to inhibit microbial growth and control infection. Zinc is crucial for cellular growth and disruption in its homeostasis hinders growth and survival in many cells. However, little is known about the role of zinc in Leishmania growth and survival. In this study, the effect of zinc on the growth and survival of L.donovani was analyzed by both Zinc-depletion and Zinc-supplementation using Zinc-specific chelator N, N, N', N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) and Zinc Sulfate (ZnSO4). Treatment of parasites with TPEN rather than ZnSO4 had significantly affected the growth in a dose- and time-dependent manner. The pre-treatment of promastigotes with TPEN resulted into reduced host-parasite interaction as indicated by decreased association index. Zn depletion resulted into flux in intracellular labile Zn pool and increased in ROS generation correlated with decreased intracellular total thiol and retention of plasma membrane integrity without phosphatidylserine exposure in TPEN treated promastigotes. We also observed that TPEN-induced Zn depletion resulted into collapse of mitochondrial membrane potential which is associated with increase in cytosolic calcium and cytochrome-c. DNA fragmentation analysis showed increased DNA fragments in Zn-depleted cells. In summary, intracellular Zn depletion in the L. donovani promastigotes led to ROS-mediated caspase-independent mitochondrial dysfunction resulting into apoptosis-like cell death. Therefore, cellular zinc homeostasis in Leishmania can be explored for new drug targets and chemotherapeutics to control Leishmanial growth and disease progression

Advanced case of PKDL due to delayed treatment: A rare case report.

Post-kala-azar dermal leishmaniasis (PKDL) is clinical outcome of visceral leishmaniasis (VL) and is thought to be the potential reservoir of parasite. Miltefosine (MF) is the only oral drug existing for treatment of post-kala-azar dermal leishmaniasis (PKDL). Increased miltefosine tolerance in clinical isolates of Leishmania donovani has been reported and is one of the major concerns in the treatment of PKDL. Here, we report a highly ulcerated PKDL case that was successfully cured after miltefosine treatment

Conversion of asymptomatic infection to symptomatic visceral leishmaniasis: A study of possible immunological markers.

IntroductionPresence of asymptomatic individuals in endemic areas is common. The possible biomarkers in asymptomatic individuals once they get exposed to infection as well as following conversion to symptomatic disease are yet to be identified.We identified asymptomatic Visceral leishmaniasis (VL) infection amongst rK39+sorted direct agglutination test positive (DAT+) endemic healthy population and confirmed it by quantitative PCR(qPCR).The immunological determinants such as Adenosine deaminase (ADA), Interferon gamma (IFN-γ), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 10 (IL-10)were examined to predict probable biomarkers for conversion to symptomatic VL.MethodsSample size was 5794 healthy individuals from VL endemic region. Antibody tests(DAT &rK39) were performed and later a qPCR assay was employed using kDNA specific primers and probes. Immunological biomarkers examined were ADA level by ADA-MTP kit and quantitative cytokines(IFN-γ, IL-10 and TNF-α) by ELISA.Results120 asymptomatic individuals of 308 rK39 sero-positives were DAT positive comprising of 56 with previous history and 64 with no history of VL. RT-PCR confirmed asymptomatic VL in 42 sero-positives. These were followed up through repeated qPCR and evaluation of immunological determinants. We observed10 symptomatic cases converted from a total of 42 asymptomatic individuals identified at base-line. The level of ADA, IL-10 and IFN-γ remained consistently high in asymptomatic cases and amongst these, ADA and IL-10 but not IFN-γ remained higher at the development of clinical symptoms into active VL. On the contrary, there was no significant change in the mean concentration of TNF-α at both stages of the disease.DiscussionWe surmise from our data that considerable proportion of asymptomatic cases can be a reservoir and may play a crucial role in transmission of visceral leishmaniasis in endemic areas. The data also suggests that ADA and IL-10 can serve as a potential biomarker during the conversion of asymptomatic into symptomatic VL

Reversibility in proliferation of <i>L</i>. <i>donovani</i> after TPEN treatment.

<p>Parasites were treated with 15 μM TPEN for 24 and 48 hr and then re-inoculated into fresh medium. Cell density was determined at 24 hr interval by counting with haemocytometer. Cell proliferation in untreated and treated parasites was also monitored. Bar represents mean and standard error of three independent experiments. * P< 0.05, **P< 0.001, ns Not significant; as compared between different time points in treated promastigotes by Student’s t test.</p