Long-term efficacy of single-dose radiofrequency-induced heat therapy vs. intralesional antimonials for cutaneous leishmaniasis in India.

BACKGROUND: Radiofrequency-induced heat therapy (RFHT) has been found to be safe and effective against cutaneous leishmaniasis (CL) in the short term, but its long-term efficacy is unclear. OBJECTIVES: To compare the long-term efficacy of RFHT vs. intralesional sodium stibogluconate (SSG) injections in the treatment of CL in India. METHODS: One hundred patients with a confirmed diagnosis of CL were randomly assigned in a 1 : 1 ratio to receive topical RFHT for 30-60 s or seven intralesional injections of SSG (50 mg cm(-2) of lesion). Improvement and recurrence were monitored every 15 days after the initiation of treatment for 4 months and then at 5, 6, 9, 12 and 18 months post-treatment; the rates of complete cure were compared. RESULTS: Lesions were healed in 47 out of 50 patients (94%) in the RFHT group and in 46 out of 50 patients (92%) in the SSG group at week 12. Time to complete healing was comparable in the two groups. At 6 months post-treatment, cure rates in the RFHT and SSG groups were 98% [95% confidence interval (CI) 94-100%] and 94% (95% CI 86-100%), respectively. Age, sex and lesion size or number had no effect on cure rates. No relapse of infection was recorded in cured patients in either group up to 12-18 months after initiation of treatment. Skin biopsies of cured lesions in eight out of eight (100%) patients from the RFHT group and three of three from the SSG group at 12 months showed minimal fibrosis and were negative for Leishmania tropica by polymerase chain reaction test. CONCLUSIONS: A single application of RFHT is safe, cosmetically acceptable and effective in inducing a long-term cure of CL.

Efficacy of short-duration (twice weekly) intralesional sodium stibogluconate in treatment of cutaneous Leishmaniasis in India.

BACKGROUND: Cutaneous leishmaniasis (CL) is caused by Leishmania major and L. tropica in the old world. Bikaner, the 'Thar Desert', situated in the north-western corner of India, is an endemic pocket for CL caused by L. tropica. Skin lesions of CL heal slowly, causing disfiguring scars if remaining untreated. Current recommended treatment for CL comprises systemic administration of sodium stibogluconate (SSG) for 2-3 weeks. Five to seven injections of SSG intralesionally have also been found to be effective. OBJECTIVES: To determine the efficacy of a short-duration, twice-weekly intralesional SSG treatment for CL. METHODS: Two hundred and twenty patients with CL having 298 lesions were included in the present study. They were divided into groups A and B (110 patients each). Patients were treated with five to seven intralesional injections of SSG in doses of 50 mg cm(-2) of lesion either once (group A) or twice (group B) weekly. Improvement was recorded at 6, 8, 10, 12, 16, 20 and 24 weeks and the rate of complete cure was compared. RESULTS: Complete cure rate at 6, 8 and 10 weeks was higher (20%, 57% and 73%, respectively) in group B as compared with group A (12%, 36% and 62%, respectively). The differences in cure rates at these time points were statistically significant (P < 0.05). The complete cure rate at 24 weeks was similar in both groups (96% in group B and 92% in group A). The remaining 4% and 8% of patients in groups B and A were 'nonresponders', respectively. No major side-effects were observed in either group. In all cured cases, there were no relapses reported up to 2 years after treatment. CONCLUSIONS: A short-duration, twice-weekly intralesional SSG treatment for CL accelerates cure and is highly effective and well tolerated.

Nail Changes Caused by Chemotherapy among Cancer Patients: A Cross-Sectional Study of Northwest Rajasthan.

BACKGROUND: The nail changes caused by chemotherapy in cancer patients are difficult to assess and often overlooked by clinician. The present study was undertaken to study nail changes caused by various chemotherapeutic agents and various drug protocols most commonly associated with them. MATERIALS AND METHOD: Five hundred patients with malignancies receiving chemotherapy in the oncology ward and skin outpatient department were screened in this cross-sectional observational study from November 2018 to October 2019. RESULTS: Nail changes due to chemotherapy were observed in 37.6% patients. The most common condition observed was melanonychia (84.04%), followed by half and half nails (6.91%), erythronychia (5.31%), longitudinal grooves (2.12%), leukonychia (2.12%), Mees' lines (1.59%), Beau's lines (0.53%), pitting (0.53%), and subungual hyperkeratosis (0.53%). The usual protocol to cause melanonychia was platinum analogues + taxanes based combinations, half and half nails by platinum analogues + taxanes + 5 fluorouracil (5FU) based polypharmacy, and erythronychia by cisplatin-based adjuvants. CONCLUSION: The knowledge of the nail changes caused by chemotherapy will help in counseling of already worried patients with malignancy. It will also improve patient compliance and enrich the clinicians' knowledge pertaining to chemotherapy-induced nail changes.

Comparison of Efficacy of Two Different Concentrations of Intralesional Amphotericin B in the Treatment of Cutaneous Leishmaniasis; A Randomized Controlled Trial.

INTRODUCTION: Cutaneous leishmaniasis is a vector borne disease caused by Leishmania major and Leishmania tropica. Bikaner is an endemic pocket for cutaneous leishmaniasis caused by Leishmania tropica. MATERIALS AND METHODS: A prospective study was done to evaluate the efficacy of different concentrations of intralesional amphotericin B as a treatment modality for cutaneous leishmaniasis in Bikaner, Rajasthan, India from January 2016 to June 2017. Fifty patients were randomized into two groups, A and B. Twenty-five patients from group A, received intralesionl amphotericin B (2.5 mg/ml) 0.5 ml/cm2, weekly for 8 weeks. Another group of 25 patients were treated by intralesional amphotericin B (5.0 mg/ml) weekly for same period. The cases were followed-up for response, side effects, and recurrence of disease. RESULTS: The results at the end of 8 weeks, showed complete response in 18 (72%) patients, partial response in 5 (20%) and 2 (8%) patients were non responders in group A. In group B, complete response was observed in 14 (56%), partial response in 7 (28%) patients and 4 (16%) patients did not show response. The difference was statistically insignificant (P > 0.05). No side effects were observed in both groups. CONCLUSION: The difference between the efficacy of 5 mg/ml and 2.5 mg/ml concentrations of Amphotericin B injections was found to be statistically insignificant. So, weekly injections of amphotericin B looks promising, however, larger sample size is required to assess the efficacy of both concentrations in the treatment of cutaneous leishmaniasis.

Effect of altitude on football performance.

Altitude will impact football performance through two separate and parallel pathways related to the hypobaric (physical) and hypoxic (physiological) components of terrestrial altitude: (a) the decrease in partial pressure of oxygen reduces maximal oxygen uptake and impairs "aerobic" performance by reducing maximal aerobic power, increasing the relative intensity of any given absolute level of work, and delaying recovery of high-energy phosphates between high-intensity "interval" type efforts; (b) the decrease in air density reduces air resistance which will facilitate high-velocity running, but will also alter drag and lift thereby impairing sensorimotor skills. These effects appear to have their greatest impact very early in the altitude exposure, and their physiological/neurosensory consequences are ameliorated by acclimatization, though the extent of restoration of sea level type performance depends on the absolute magnitude of the competing and living altitudes.

A double blind, randomised placebo controlled trial of rifampicin with omeprazole in the treatment of human cutaneous leishmaniasis.

BACKGROUND & OBJECTIVES: This study was conducted on 50 patients of Anthroponotic cutaneous leishmaniasis (oriental sore) to assess the efficacy of rifampicin and omeprazole through a double blind, randomised placebo control study. METHODS: The diagnosis of Anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica was done by demonstration of Leishmania tropica (LT) bodies from the painless, dry ulcerative lesion. Each patient was assessed clinically in the beginning of the study, at the end of 2,4 and 6 weeks and all observations were compared in both the groups. Twenty-five patients received rifampicin with omeprazole (Group A) whereas other 25 patients received placebo (Group B) for a period of six weeks. RESULTS: Altogether 23 cases in group Aand 21 cases in group B completed the study. About 16 (69.7%) cases in group A and 3 (14.29%) cases in group B had complete healing, whereas 3 patients (13.04%) of group A and 4 patients (19.05%) of group B had partial response and 4 patients (17.93%) of group A and 14 patients (66.67%) of group B had no response at the end of study. The difference of two groups was statistically highly significant (p < 0.00025). All patients tolerated the drug and placebo very well and no side effect was reported. INTERPRETATION & CONCLUSION: In our opinion rifampicin and omeprazole is a highly effective, less toxic and cheaper alternative for the management of cutaneous leishmaniasis.

Amoebiasis cutis in HIV positive patient.

Protozoan infections of the skin, particularly cutaneous amoebiasis, are rare in HIV-positive patients. We report a case of amoebiasis cutis in an HIV-positive truck driver with a history of frequent unprotected sexual exposures. He presented with multiple painful ulcers and sinuses with purulent discharge, necrotic slough and scarring in the perianal and gluteal region for the last 2 years. He was positive for HIV-1 and -2. Cutaneous biopsy revealed numerous Entamoeba histolytica in the trophozoite form, in addition to an inflammatory infiltrate and necrotic debris. He responded well to oral metronidazole and chloroquine. Amoebiasis cutis should be considered in the differential diagnosis of perianal ulcers, particularly in HIV-positive patients.

Divalproex sodium in the management of post-herpetic neuralgia: a randomized double-blind placebo-controlled study.

BACKGROUND: Post-herpetic neuralgia is difficult to treat. Divalproex sodium (valproic acid and sodium valproate in molar ratio 1:1) has been used successfully in the management of various painful neuropathies. AIM: To study the effectiveness and safety of divalproex sodium in the management of post-herpetic neuralgia. DESIGN: Randomized double-blind placebo-controlled trial. METHODS: We enrolled 48 consecutively attending out-patients with post-herpetic neuralgia, out of whom three were excluded (two had insufficient pain, one withdrew consent). Quantification of pain was by Short Form-McGill pain questionnaire (SF-MPQ), visual analogue scale (VAS), present pain intensity score (PPI) and 11 point Likert scale (11 PLS) at the beginning of the study, after 2 weeks, 4 weeks and at the end of the study (8 weeks). We also assessed patients' global impression of change by questionnaire at the end of the study. RESULTS: After 8 weeks treatment with 1000 mg/day divalproex sodium, there was significant reduction in pain: SF-MPQ, 20.47 +/- 2.29 to 11.90 +/- 6.52 (p < 0.0001); PPI 4.0 +/- 0.52 to 1.95 +/- 1.29 (p < 0.0001); VAS 70.17 +/- 9.21 to 31.27 +/- 29.74 (p < 0.0001) and 11 PLS 6.97 +/- 0.73 to 3.63 +/- 2.34 (p < 0.0001) in comparison to placebo (means +/- SEM). The 'global impression of change' questionnaire showed much or moderate improvement in pain in 58.2% of patients receiving divalproex vs. 14.8% of those receiving placebo. The drug was well tolerated by all patients, except one who developed severe vertigo after 10 days of treatment. DISCUSSION: Divalproex sodium provides significant pain relief in patients of post-herpetic neuralgia, with very little incidence of adverse reactions. These data provide a basis for longer trials in a larger group of patients.

The role of rifampicin in the management of cutaneous leishmaniasis.

We assessed the efficacy of rifampicin in the treatment of cutaneous leishmaniasis (oriental sore) using a double-blind placebo-controlled study. We studied 46 patients with cutaneous leishmaniasis, of whom 23 received rifampicin (group A) and another 23 received placebo (group B) for a period of 4 weeks. Each patient was assessed clinically for size of lesion, type of lesion, duration of lesion, number of lesions, and distribution of lesions, initially, and at the end of 1 week, 2 weeks and 4 weeks. Biochemical tests including enzyme studies were done to detect any toxic effects of the drug. Group A patients received rifampicin 1200 mg/day in two divided doses and group B patients received two doses of an identical placebo capsule. Seventeen (73.9%) of the 23 patients receiving rifampicin had complete healing. Two (8.6%) had partial healing and four (17.3%) showed no response, whereas out of 23 patients receiving placebo one patient (4.3%) showed complete healing, eight (34.7%) patients showed partial healing and 14 (60. 98%) patients showed no healing or exacerbation of lesion. The difference was statistically significant in favour of response to rifampicin. This dose of rifampicin was well-tolerated and no side-effects were seen in any patient. In cases of cutaneous leishmaniasis where injectable treatment is not feasible or not acceptable, as in cases of multiple lesions, rifampicin is a better alternative oral treatment. It is simple to administer, cheap, more effective and less toxic than other available oral drugs, and well-tolerated by patients.

Preclinical assessment of hypocrellin B and hypocrellin B derivatives as sensitizers for photodynamic therapy of cancer: progress update.

Hypocrellins are perylenequinone pigments with substantial absorption in the red spectral region and high singlet oxygen yield. They are available in pure monomeric form and may be derivatized to optimize properties of red light absorption, tissue biodistribution and toxicity. In vitro screening of synthetic derivatives of the naturally occurring compound, hypocrellin B (HB), for optimal properties of cyto-(dark) toxicity and phototoxicity resulted in selection of three compounds for preclinical evaluation: HBEA-R1 (ethanolaminated HB), HBBA-R2 (butylaminated HB) and HBDP-R1 [2-(N,N-dimethylamino)-propylamine-HB]. Extinction coefficients at 630 nm (epsilon 630) are 6230, 6190 and 4800, respectively; and 1O2 quantum yields, phi, 0.60, 0.32 and 0.42. Intracellular uptake is essentially complete within 2 h (HBEA-R1, HBBA-R2) and 20 h (HBDP-R1). Greatest uptake is associated with lysosomes and Golgi. The HBEA-R1 and HBBA-R2 elicit phototoxicity in vitro primarily via the type II mechanism, with some type I activity under stringently hypoxic conditions. Transcutaneous phototherapy with HBEA-R1 permanently ablates EMT6/Ed tumors growing in the flanks of Balb/c mice, with minimal cutaneous effects. The HBBA-R2 does not elicit mutagenic activity in strains TA98 and TA100 of Salmonella typhimurium. Further development of selected hypocrellin derivatives as photosensitizers for photodynamic therapy is warranted.

Genetic activity of diethylstilbestrol in Saccharomyces cerevisiae: enhancement of mutagenicity by oxidizing agents.

Diethylstilbestrol (DES), a synthetic estrogen, is known to cause cancer in humans and experimental animals. Although it has been established that DES can induce unscheduled DNA synthesis, sister-chromatid exchange, and cell transformation in various short-term tests, the efforts to demonstrate its mutagenic activity in bacterial and mammalian systems have largely failed. It has been shown that DES can covalently bind to DNA after being oxidized either chemically, in the presence of iodine and hydrogen peroxide, or metabolically, by mammalian cells in tissue culture and also in the presence of rat-liver microsomes. We studied genetic activity of DES in growing cultures of the strains XV185-14C and D5 of S. cerevisiae in the presence and absence of oxidizing agents, namely, iodine and hydrogen peroxide. We demonstrated that DES alone exhibits a weak mutagenic response in the strain XV185-14C. On the other hand, the treatment of cells with DES in the presence of iodine or hydrogen peroxide plus ferrous sulfate induced a large increase in the frequency of induced mutations in strain XV185-14C and mitotic recombination and gene conversion in strain D5. This enhancement in the genetic activity of DES in our test assays in the presence of chemical oxidative systems indicates that DES undergoes oxidation to produce a genetically active metabolite.

Genetic activity in Saccharomyces cerevisiae and thin-layer chromatographic comparisons of medical grades of pyrvinium pamoate and monopyrvinium salts.

The pamoate, chloride, and iodide salts of pyrvinium, a cyanine dye with anthelmintic properties, were studied in a diploid mitotic recombination and gene conversion assay system (strain D5 of Saccharomyces cerevisiae) and a haploid yeast reversion assay (strain XV185-14C). With the use of a thin-layer chromatographic (TLC) detection technique, samples of pyrvinium pamoate from several sources were found to contain different numbers and quantities of impurities. All samples of pyrvinium pamoate and the monopyrvinium salts were recombinogenic in strain D5 and mutagenic in strain XV185-14C; the degree of genetic activity varied among the tested medical grades of pyrvinium pamoate. Monopotassium pamoate was found to be genetically inactive in both strains. Light-catalyzed degradation did not enhance the genetic activity of pyrvinium in either of the yeast strains; the degraded samples were not mutagenic.

Safrole, eugenol and methyleugenol induce intrachromosomal recombination in yeast.

Deletion of an integrated plasmid, a specific type of intrachromosomal recombination, was evaluated for inducibility with the phenylpropenes safrole, eugenol and methyleugenol in the yeast Saccharomyces cerevisiae. These phenylpropenes are found in food products, spices, pharmaceuticals and clove cigarettes. Safrole and eugenol are known carcinogens in animals and methyleugenol is a suspected carcinogen. These phenylpropenes are not detectable by the Ames assay and most other short-term tests used currently in predictive carcinogenesis. Like safrole, which has been shown to be nonmutagenic with the Ames assay, eugenol and methyleugenol were found to be nonmutagenic with the Ames assay. In contrast, with the yeast assays which screen for intra- and inter-chromosomal recombination in logarithmic phase cultures, all 3 compounds gave a positive dose-related response. These results demonstrate further that the yeast system can be modified easily to detect various genetic endpoints and that it deserves serious consideration as a test system for predictive carcinogenesis.

Modulation in cytochrome P-420 and P-450 content in Saccharomyces cerevisiae according to physiological conditions and genetic background.

The diploid strain D5 of Saccharomyces cerevisiae, relative to other strains of yeast, has a large amount of cytochrome P-450 present during the logarithmic phase of growth and a low amount of cytochrome P-420. As the stationary phase of growth is approached, an increasing intensity of absorbance is observed at 420 nm. If the cells are suspended in buffer during mid-logarithmic growth, the absorbance at 450 nm disappears and absorbance at 420 nm is increased after the cells have been held in buffer for 24 h. At late logarithmic growth, the absorbance at 450 nm is still retained after the cells have been held in buffer for 24 h. Within 44 h of the time of harvest, the absorbance at 450 nm disappears completely and the absorbance at 420 nm is intense. Cytoplasmic petite variants of strain D5 have less of both cytochromes P-450 and P-420 than does the grande D5 strain; the absorbances at 450 and 420 nm are retained up to 96 h when the cells are held in buffer. Haploid spores of strain D5 exhibit absorbances at 450 and 420 nm during the logarithmic phase of growth, and these absorbances are retained after the cells are held in buffer for 24 h. An hypothesis is proposed which states that cytochrome P-450 is the membrane-bound form and cytochrome P-420 is free in the cytosol; the cytochromes interconvert and are active in either state until the associated enzymes disassociate.

Hypopigmented lesions in early leprosy--a clinical and histological study.

26 Patients of leprosy presenting with hypopigmented lesions were divided on morphological grounds into 3 Sub groups, Group I (9 patients) with well-defined single patch with moderate to complete sensory loss; Group II (8 patients) with single ill-defined lesion having partial sensory loss; and Group III (9 patients) having multiple hypo-pigmented patches with mild to moderate sensory loss. Epidermal atrophy was a conspicuous histological finding in all groups. Only patients in Group I showed epitheloid cells in dermal infiltrate with erosion of epidermis in one case. This group may be labelled as maculoanesthetic leprosy. Patients in Group II and III showed mononuclear cell infiltrate in dermis, around neurovascular bundles and appendages. They were histologically consistent with indeterminate leprosy. Follow-up biopsy after six to eight months of treatment showed healing of the lesion of reduction in the infiltrate in most cases.

Congenital naevoid psoriasis.

A 1 1/2sub - year-old child who had typical linear psoriatic plaques since birth is being reported.

Crusted scabies in a patient of systemic sclerosis.

A case of Norwegian (crusted) scabies is reported in a patient suffering from systemic sclerosis.

Localised cutaneous blastomycosis : Response to fluconazole.

A case of atypical cutaneous blastomycosis is reported. Patient responded to oral fluconazole 200 mg per day given for 9 months.