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1.
Gac. méd. Méx ; 155(2): 191-195, mar.-abr. 2019. tab, graf
Article in Spanish | LILACS | ID: biblio-1286482

ABSTRACT

Resumen La enfermedad de Menkes es una patología neurodegenerativa y letal debida a mutaciones génicas de la enzima ATP-7A trasportadora de cobre; se manifiesta por síntomas neurológicos y alteraciones del tejido conectivo de severidad variable. El uso subcutáneo oportuno de histidinato de cobre (Cu-His) es determinante en la calidad de vida. Se reportan las primeras experiencias en México en la síntesis y uso seguro de Cu-His en tres casos en los que corroboramos hipocupremia e hipoceruloplasminemia. Bajo asesoramiento del Hospital for Sick Children, Toronto, Canadá, elaboramos una solución de 500 µg/mL. En los tres casos aplicamos 250 µg de Cu-His, sin efectos indeseables relevantes durante 30 días y observamos las siguientes determinaciones séricas de cobre (Cu en µg/L) y ceruloplasmina (Cp en mg/dL): caso 1, Cu días 0 y 30, 8 y 504 µg/L; Cp días 0 y 30, 4 y 10.75 mg/dL; caso 2, Cu días 0 y 30, < 50 y 502, µg/L; Cp días 0 y 30, 2 y 15 mg/dL; caso 3, Cu días 0 y 30, 3 y 84.2 µg/L; Cp días 0 y 30, 4 y 10.7 mg/dL. En México es posible la síntesis segura de Cu-His y tratar la enfermedad de Menkes, la cual debe ser intencionalmente buscada.


Abstract Menkes disease is a neurodegenerative and lethal pathology caused by gene mutations of the copper-transporting ATP-7A enzyme; it manifests itself by neurological symptoms and connective tissue changes of varying severity. Timely subcutaneous use of copper histidinate (Cu-His) is determinant for quality of life. We report the first experiences in Mexico on Cu-His synthesis and its safe use in 3 cases where hypocupremia and hypoceruloplasminemia were corroborated. With advice of the Hospital for Sick Children of Toronto Canada, we prepared a 500 µg/mL solution. In all three cases were 250 µg of Cu-His applied without relevant undesirable effects for 30 days. Serum copper (Cu, expressed in µg/L) and ceruloplasmin (Cp, in mg/dL) were determined: case 1, Cu days 0 and 30, 8 and 504 µg/L; Cp days 0 and 30, 4 and 10.75 mg/dL; case 2, Cu days 0 and 30, <50 and 502 µg/L; Cp days 0 and 30, 2 and 15 mg/dL; case 3, Cu days 0 and 30, 3 and 84.2 µg/L; Cp days 0 and 30, 4 and 10.7 mg/dL. In Mexico, it is possible to safely synthesize Cu-His and treat MD, which must be intentionally sought.


Subject(s)
Humans , Infant , Child, Preschool , Organometallic Compounds/administration & dosage , Quality of Life , Drug Compounding/methods , Histidine/analogs & derivatives , Menkes Kinky Hair Syndrome/drug therapy , Organometallic Compounds/adverse effects , Copper/blood , Pharmaceutical Solutions , Histidine/administration & dosage , Histidine/adverse effects , Mexico
2.
Rev. Soc. Bras. Med. Trop ; 51(3): 393-396, Apr.-June 2018. tab, graf
Article in English | LILACS | ID: biblio-957422

ABSTRACT

Abstract Visceral leishmaniasis is a systemic disease that is potentially severe and endemic in Brazil. It clinically manifests as fever, weight loss, swelling, hepatosplenomegaly, paleness, and edema. In this study, we discuss a case of a 1-year-old child diagnosed with refractory visceral leishmaniasis after being treated with liposomal amphotericin B in two distinct occasions. Considering the persistent clinical features and weak response to conventional treatment, a combination therapy with liposomal amphotericin B (ambisome), n-methylglucamine antimoniate (glucantime), and pentamidine isethionate was initiated, and response to treatment was good.


Subject(s)
Humans , Male , Infant , Organometallic Compounds/administration & dosage , Pentamidine/administration & dosage , Amphotericin B/administration & dosage , Leishmaniasis, Visceral/drug therapy , Meglumine/administration & dosage , Antiprotozoal Agents/administration & dosage , Drug Therapy, Combination , Meglumine Antimoniate
4.
Rev. chil. cir ; 70(3): 224-232, 2018. tab, graf, ilus
Article in Spanish | LILACS | ID: biblio-959375

ABSTRACT

Resumen Introducción La efectividad de la colonoscopia depende de múltiples factores, destacando la calidad de preparación intestinal y la tolerabilidad que tenga el paciente a la preparación administrada. Objetivo Comparar dos agentes de preparación intestinal, el polietilenglicol (PEG) y el picosulfato de sodiocitrato de magnesio (PSCM) en términos de efectividad y tolerabilidad de la preparación. Pacientes y Método Ensayo clínico aleatorizado en pacientes ambulatorios sometidos a colonoscopia en Clínica INDISA. Evaluando efectividad y tolerabilidad con el Boston Bowel Preparation Score (BBPS) y cuestionario de Lawrence [compuesto por escala Likert, dos preguntas cualitativas y escala visual análoga (EVA)], respectivamente. Resultados 189 pacientes, de los cuales 123 se aleatorizaron a PEG y 66 a PSCM. El BBPS en los pacientes que utilizaron PEG, la media fue 7,51 (DS 1,66) y con PSCM fue 7,12 (DS 1,71) (p = 0,111). Al analizar la tolerabilidad con escala Likert, la media con PEG fue 0,94 (DS 0,68) y con PSCM fue 0,63 (DS 0,61) (p = 0,0004). La EVA con PEG tuvo una media de 7,68 (DS 2,4) y con PSCM de 9,04 (DS 1,59) (p < 0,0001). Al preguntar ausentismo laboral, no hubo diferencias significativas en ambos grupos y al preguntar si ocuparía la misma preparación en una futura colonoscopia, hubo significancia estadística a favor del PSCM (p = 0,026). Conclusión No encontramos diferencias en la efectividad de preparación intestinal al comparar PEG y PSCM, sin embargo, el PSCM es mejor tolerado.


Introduction The effectiveness of colonoscopy depends on multiple factors, being two of the most important ones an adequate bowel preparation and the patient's tolerability to the preparation. Objectives Compare effectiveness and tolerability of two bowel preparation agents, polyethylene glycol (PEG) and sodium picosulfate/magnesium citrate (SPMC). Patients and Methods Randomized clinical trial on outpatients that went into colonoscopy in INDISA Clinic. We evaluated effectiveness and tolerability with Boston Bowel Preparation Score (BBPS) and Lawrence questionnaire [composed by Likert scale, two qualitative questions and Visual Analogue Scale (VAS) for pain], respectively. Results 189 patients, 123 were randomized to PEG and 66 to SPMC. BBPS average in patients in the PEG branch was 7.51 (SD 1.66) and for SPMC 7.12 (SD 1.71) (p = 0.111). Likert scale for evaluating tolerability average for PEG was 0.94 (SD 0.68) and for SPMC 0.63 (SD 0.61) (p = 0.0004). VAS scale for PEG had an average of 7.68 (SD 2.4) and for PSCM 9.04 (SD 1.59) (p < 0.0001). When we asked for workplace absenteeism, there were no significant differences between both groups and when we asked about using the same intestinal preparation in a future colonoscopy there was statistical significance in favor to SPMC (p = 0.026). Conclusions No differences were noted on effectiveness between the PEG and SPMC bowel preparations. Nevertheless, SPMC appeared to be better tolerated by patients.


Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Aged , Organometallic Compounds/administration & dosage , Polyethylene Glycols/administration & dosage , Cathartics/administration & dosage , Colonoscopy/methods , Citrates/administration & dosage , Picolines/administration & dosage , Preoperative Care/methods , Single-Blind Method , Surveys and Questionnaires , Patient Satisfaction
5.
Mem. Inst. Oswaldo Cruz ; 113(9): e180200, 2018. tab, graf
Article in English | LILACS | ID: biblio-955123

ABSTRACT

BACKGROUND Cutaneous leishmaniasis (CL) is a world-wide health problem which currently lacks effective, affordable and easy to use therapy. Recently, the meglumine antimoniate (MA) intralesional infiltration was included among the acceptable therapies for New World leishmaniasis. While this approach is attractive, there is currently little evidence to support its use in Americas. OBJECTIVES The aim of this study was to provide information about effectiveness and safety of a standardised MA intralesional infiltration technique for the treatment of CL. METHODS It is a single-arm phase II clinical trial conducted at a Brazilian referral centre. CL cases with parasitological confirmation presenting a maximum of three CL-compatible skin lesions were treated with weekly MA intralesional infiltration by using a validated technique, up to a maximum of eight infiltrations. RESULTS A total of 53 patients (62 lesions) were included. Overall, patients received a median of seven infiltrations (IQR25-75% 5-8) over a median treatment period of 43 days (IQR25-75% 28-52 days). The definitive cure rate at D180 was 87% (95% CI:77-96%). The majority of adverse events were local, with mild or moderate intensity. Bacterial secondary infection of the lesion site was observed in 13% of the treated patients, beside two intensity-three adverse events (hypersensitivity reactions).


Subject(s)
Humans , Organometallic Compounds/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , /therapeutic use , Injections, Intralesional , Antiprotozoal Agents/adverse effects
6.
Mem. Inst. Oswaldo Cruz ; 112(12): 838-843, Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-894858

ABSTRACT

BACKGROUND American tegumentary leishmaniasis (ATL) is a non-lethal parasitic disease that presents with cutaneous (CL) and mucosal (ML) clinical forms. ATL treatment aims at healing the lesions and preventing the development of the late mucosal form. Systemic meglumine antimoniate (MA) therapy with 10-20 mg Sb5+/kg/day is the first choice of treatment. However, alternative therapies using 5 mg Sb5+/kg/day or intralesional (IL) MA are the usual regimens at the National Institute of Infectious Diseases (NIID), Rio de Janeiro, Brazil. OBJECTIVES To evaluate lethality and the incidence of relapse and development of late ML in CL patients treated at NIID from 2001 until 2013. METHODS Data were recovered from records of all ATL patients diagnosed during that period. FINDINGS Out of 777 patients, 753 were treated with MA (96.9%). Of those, 89.1% received alternative therapy of 9.9% IL and 79.2% systemic 5 mg Sb5+/kg/day. Some patients required 1-3 additional courses of treatment, thus making a total of 997 courses; 85.2% of them were subjected to alternative therapies. Lethality was 0.1%, relapse incidence 5.8%, and late ML incidence 0.25%. As a final outcome for the 777 patients, 95.9% were cured, 0.1% died and 4.0% were not able to follow-up. MAIN CONCLUSIONS Alternative MA schedules resulted in low lethality without increase of relapse or late ML incidence.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Leishmaniasis, Cutaneous/mortality , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Injections, Intralesional/methods , Treatment Outcome
7.
Rev. Soc. Bras. Med. Trop ; 50(2): 269-272, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-842839

ABSTRACT

Abstract Although New World cutaneous leishmaniasis is not itself a life-threatening disease, its treatment with systemic antimonials can cause toxicity that can be dangerous to some patients. Intralesional meglumine antimoniate provides a viable, less toxic alternative. Herein, we describe an alternative treatment with subcutaneous intralesional injections of meglumine antimoniate into large periarticular lesions of three patients with cutaneous leishmaniasis and comorbidities. This treatment was safe, successful, and well tolerated. This case series suggests that intralesional meglumine antimoniate is an effective therapy for cutaneous leishmaniasis, even with periarticular lesions. This hypothesis should be tested in controlled clinical trials.


Subject(s)
Humans , Male , Female , Aged , Organometallic Compounds/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Antiprotozoal Agents/administration & dosage , Time Factors , Severity of Illness Index , Injections, Intralesional , Treatment Outcome , Meglumine , Middle Aged
8.
Rev. Soc. Bras. Med. Trop ; 49(6): 774-776, Dec. 2016. graf
Article in English | LILACS | ID: biblio-1041383

ABSTRACT

Abstract INTRODUCTION: Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. METHODS Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. RESULTS The technique is described in detail sufficient to enable replication. CONCLUSIONS: The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.


Subject(s)
Humans , Organometallic Compounds/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Antiprotozoal Agents/administration & dosage , Injections, Intralesional/standards , Meglumine Antimoniate
9.
Int. j. morphol ; 34(3): 918-922, Sept. 2016. ilus
Article in English | LILACS | ID: biblio-828963

ABSTRACT

Lead acetate is a chemical compound. Sources of human exposure to this metal include many foods, drinking water and dust. The aim of this study was to determine the immunohistochemical and histopathological changes on the face skin after lead acetate application. Wistar Albino rats (180-200 g body weight) were divided into a controlled and lead acetate-exposed group. Rats received lead acetate at 500 ppm in their drinking water for 60 days. Both groups were fed with the same standard food, but lead acetate was added to the drinking water. During the experimental period, blood samples were drawn from the abdominal aorta of the anesthetised animals. At the end of exposure, body weight and blood lead levels were measured. Sections of rat facial skin were examined histopathological and immunohistochemical. In the group treated with lead acetate, minimal to slight multifocal hydropic degeneration of basal cell layer, depending on the thinning of the epidermis, the cellular degeneration in the dermis and a increase in the number of necrotic cells was observed in sebaceous glands of the hair follicle hemorrhage. The immunohistochemical results of the present work demonstrated an increase in Proliferating cell nuclear antigen (PCNA) immunoreactivity in skin specimens from lead acetate treated animals. Vimentin immunoreactivity was very dense in hair follicle of the subepidermal region. It was also strongly stained around the myoepithelial cells surrounding sebaceous and stromal cells.


El acetato de plomo es un compuesto químico. Las fuentes de exposición humana a este metal incluyen una gran variedad de alimentos, agua potable y el polvo. El objetivo fue determinar los cambios inmunohistoquímicos e histopatológicos en la piel de la cara después de la aplicación de acetato de plomo en ratas Wistar albinas (180 a 200 g de peso corporal) las que fueron divididas en un grupo control y otro expuesto al acetato de plomo. Las ratas expuestas recibieron acetato de plomo en dosis de 500 ppm en el agua que bebían durante 60 días. Ambos grupos fueron alimentados con el mismo pellet estándar. Durante el período experimental, se extrajeron muestras de sangre desde la parte abdominal de la aorta con los animales anestesiados. Al final de la exposición, se midió el peso corporal y los niveles de plomo en la sangre. Secciones de piel de la cara se examinaron y estudiaron con procediminetos histopatológicos e inmunohistoquímicos. En el grupo expuesto, se observó una degeneracion hidrópica multifocal desde mínima a ligera de la capa de células basales; dependiendo del adelgazamiento de la epidermis, se observó degeneración celular en la dermis y un aumento en el número de células necróticas en las glándulas sebáceas de folículos pilosos hemorrágicos. Los resultados inmunohistoquímicos demostraron un aumento de inmunoreactividad al antígeno nuclear de células en proliferación (PCNA) en las muestras de piel de los animales tratados con acetato de plomo. La inmunoreactividad a vimentina fue muy densa en los folículos pilosos de la región subepidermal. También se observó una fuerte tinción alrededor de las células mioepiteliales que rodean las células sebáceas y estromales.


Subject(s)
Animals , Rats , Organometallic Compounds/administration & dosage , Skin/drug effects , Skin/pathology , Immunohistochemistry , Rats, Wistar
10.
Mem. Inst. Oswaldo Cruz ; 111(8): 512-516, Aug. 2016. tab, graf
Article in English | LILACS | ID: lil-789001

ABSTRACT

Although intralesional meglumine antimoniate (MA) infiltration is considered an option for cutaneous leishmaniasis (CL) therapy and is widely used in the Old World, there have been few studies supporting this therapeutic approach in the Americas. This study aims to describe outcomes and adverse events associated with intralesional therapy for CL. This retrospective study reviewed the experience of a Brazilian leishmaniasis reference centre using intralesional MA to treat 31 patients over five years (2008 and 2013). The median age was 63 years (22-86) and the median duration time of the lesions up to treatment was 16 weeks. In 22 patients (71%), intralesional therapy was indicated due to the presence of contraindications or previous serious adverse events with systemic MA. Other indications were failure of systemic therapy or ease of administration. Intralesional treatment consisted of one-six infiltrations (median three) for a period of up to 12 weeks. The initial (three months) and definitive (six months) cure rates were 70.9% and 67.7%, respectively. Most patients reported mild discomfort during infiltration and no serious adverse events were observed. In conclusion, these results show that the intralesional MA efficacy rate was very similar to that of systemic MA treatment, and reinforce the need for further studies with adequate design to establish the efficacy and safety of this therapeutic approach.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Antiprotozoal Agents/adverse effects , Injections, Intralesional , Leishmaniasis, Cutaneous/pathology , Meglumine/adverse effects , Organometallic Compounds/adverse effects , Retrospective Studies , Treatment Outcome
11.
Mem. Inst. Oswaldo Cruz ; 111(3): 147-154, Mar. 2016. tab, graf
Article in English | LILACS | ID: lil-777370

ABSTRACT

The polar hydroethanolic extract from Selaginella sellowii(SSPHE) has been previously proven active on intracellular amastigotes (in vitro test) and now was tested on hamsters infected with Leishmania (Leishmania) amazonensis (in vivo test). SSPHE suppressed a 100% of the parasite load in the infection site and draining lymph nodes at an intralesional dose of 50 mg/kg/day × 5, which was similar to the results observed in hamsters treated with N-methylglucamine antimonate (Sb) (28 mg/Kg/day × 5). When orally administered, SSPHE (50 mg/kg/day × 20) suppressed 99.2% of the parasite load in infected footpads, while Sb suppressed 98.5%. SSPHE also enhanced the release of nitric oxide through the intralesional route in comparison to Sb. The chemical fingerprint of SSPHE by high-performance liquid chromatography with diode-array detection and tandem mass spectrometry showed the presence of biflavonoids and high molecular weight phenylpropanoid glycosides. These compounds may have a synergistic action in vivo. Histopathological study revealed that the intralesional treatment with SSPHE induced an intense inflammatory infiltrate, composed mainly of mononuclear cells. The present findings reinforce the potential of this natural product as a source of future drug candidates for American cutaneous leishmaniasis.


Subject(s)
Animals , Cricetinae , Male , Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Plant Extracts/chemistry , Selaginellaceae/chemistry , Administration, Oral , Antiprotozoal Agents/isolation & purification , Biflavonoids/analysis , Chromatography, High Pressure Liquid , Drainage , Foot/parasitology , Glycosides/chemistry , Infusions, Intralesional , Leukocytes, Mononuclear/parasitology , Macrophages/parasitology , Meglumine/administration & dosage , Nitric Oxide/analysis , Organometallic Compounds/administration & dosage , Parasite Load , Plant Extracts/administration & dosage , Solvents , Tandem Mass Spectrometry
12.
Gut and Liver ; : 494-501, 2015.
Article in English | WPRIM | ID: wpr-149100

ABSTRACT

BACKGROUND/AIMS: We investigated whether sodium picosulfate with magnesium citrate (SPMC) plus bisacodyl compares favorably with conventional polyethylene glycol (PEG) with respect to bowel cleansing adequacy, compliance, and safety. METHODS: We performed a multicenter, prospective, single-blinded study in outpatients undergoing daytime colonoscopies. Patients were randomized into a split preparation SPMC/bisacodyl group and a conventional split PEG group. We compared preparation adequacy using the Boston bowel preparation scale (BBPS), ease of use using a modified Likert scale (LS), compliance/satisfaction level using a visual analogue scale (VAS), and safety by monitoring adverse events during the colonoscopy between the two groups. RESULTS: A total of 365 patients were evaluated by intention to treat (ITT) analysis, and 319 were evaluated by per protocol (PP) population analysis (153 for SPMC/bisacodyl, 166 for PEG). The mean total BBPS score was not different between the two groups in both the ITT and PP analyses (p>0.05). The mean VAS score for satisfaction and LS score for the ease of use were higher in the SPMC/bisacodyl group (p<0.001). The adverse event rate was lower in the SPMC/bisacodyl group than in the PEG group (p<0.05). CONCLUSIONS: The SPMC/bisacodyl treatment was comparable to conventional PEG with respect to bowel preparation adequacy and superior with respect to compliance, satisfaction, and safety.


Subject(s)
Adult , Aged , Cathartics/administration & dosage , Citrates/administration & dosage , Citric Acid/administration & dosage , Colon/drug effects , Colonoscopy , Drug Combinations , Drug Therapy, Combination/methods , Female , Humans , Intention to Treat Analysis , Laxatives/administration & dosage , Male , Middle Aged , Organometallic Compounds/administration & dosage , Patient Compliance , Patient Satisfaction , Picolines/administration & dosage , Polyethylene Glycols/administration & dosage , Preoperative Care/methods , Single-Blind Method , Young Adult
13.
Korean Journal of Radiology ; : 1029-1037, 2015.
Article in English | WPRIM | ID: wpr-163300

ABSTRACT

OBJECTIVE: To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. MATERIALS AND METHODS: This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (K(trans)) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. RESULTS: P792 group showed a more prominent decrease in K(trans) and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. CONCLUSION: Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.


Subject(s)
Animals , Antineoplastic Agents/therapeutic use , Benzophenones/therapeutic use , Disease Models, Animal , Heterocyclic Compounds/administration & dosage , Liver Neoplasms/drug therapy , Magnetic Resonance Imaging , Male , Organometallic Compounds/administration & dosage , Rabbits , Reproducibility of Results , Valine/analogs & derivatives
14.
Rev. Soc. Bras. Med. Trop ; 47(6): 756-762, Nov-Dec/2014. tab, graf
Article in English | LILACS | ID: lil-732985

ABSTRACT

Introduction Parenteral antimony-based compounds are still the standard of care for cutaneous leishmaniasis (CL) treatment in many countries, despite their high toxicity. Previous studies showed that oral azithromycin could be an option for CL treatment. The aim of this study was to evaluate efficacy and safety of oral azithromycin (AZ) for CL treatment compared with injectable meglumine antimoniate (MA). Methods This was a randomized, open-label, 2-arm, non-inferiority clinical trial. Treatment-naïve patients with localized CL were treated with MA (15mg/kg/day up to 1,215mg) or AZ (500mg/day) during 20 consecutive days. The primary efficacy end point was a CL cure 90 days after treatment completion. The analysis was performed with intention-to-treat (ITT) and per protocol (PP) analyses. After an anticipated interim analysis, the study was interrupted due to the high failure rate in the azithromycin group. Results Twenty-four volunteers were included in each group. The MA group had a higher cure rate than the AZ group with the ITT and PP analyses, which were 54.2% versus 20.8% [relative risk (RR) 1.97; 95% confidence intervals (95%CI) 1.13-3.42] and 72.2% versus 23.8% (RR 3.03; 95%CI 1.34-6.87), respectively. No unexpected adverse events were observed. Conclusions ...


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Anti-Bacterial Agents/administration & dosage , Antiprotozoal Agents/administration & dosage , Azithromycin/administration & dosage , Early Termination of Clinical Trials , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Administration, Oral , Brazil , Time Factors , Treatment Failure
15.
Mem. Inst. Oswaldo Cruz ; 109(4): 420-427, 03/07/2014. tab, graf
Article in English | LILACS | ID: lil-716312

ABSTRACT

Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.


Subject(s)
Animals , Male , Antimony/analysis , Antiprotozoal Agents/pharmacokinetics , Meglumine/pharmacokinetics , Organometallic Compounds/pharmacokinetics , Antiprotozoal Agents/administration & dosage , Dose-Response Relationship, Drug , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Rats, Wistar , Time Factors , Tissue Distribution
16.
Rev. Inst. Med. Trop. Säo Paulo ; 56(4): 361-362, Jul-Aug/2014. graf
Article in English | LILACS | ID: lil-716423

ABSTRACT

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.


Relatamos caso de paciente de 42 anos atendida em centro de referência em leishmanioses no Rio de Janeiro, Brasil, apresentando lesão de leishmaniose cutânea no antebraço direito. Iniciado tratamento com baixa dose de antimoniato de meglumina (AM) intramuscular (5 mg Sb5+/kg/dia), houve melhora após 28 dias, porém com desenvolvimento de eczema generalizado. Após 87 dias, notou-se piora da lesão. A paciente recusou o tratamento com anfotericina B. Infiltrou-se AM na lesão em duas sessões, resultando em eczema local com bolhas. Entretanto, 20 dias depois, tanto a úlcera quanto o eczema regrediram. A administração intralesional do AM deve ser utilizada com cautela em pacientes com hipersensibilidade cutânea a este fármaco.


Subject(s)
Adult , Female , Humans , Antiprotozoal Agents/adverse effects , Drug Eruptions/drug therapy , Eczema/chemically induced , Leishmaniasis, Cutaneous/drug therapy , Meglumine/adverse effects , Organometallic Compounds/adverse effects , Antiprotozoal Agents/administration & dosage , Eczema/drug therapy , Injections, Intralesional , Injections, Intramuscular , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage
17.
Rev. Inst. Med. Trop. Säo Paulo ; 56(4): 291-296, Jul-Aug/2014. tab
Article in English | LILACS | ID: lil-716424

ABSTRACT

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.


O desfecho favorável ao tratamento de uma enfermidade é influenciado pela adesão à terapia. Objetivamos avaliar fatores associados à adesão ao tratamento dos pacientes incluídos em ensaio clínico de equivalência entre o esquema de tratamento padrão e alternativos com antimoniato de meglumina (AM) no tratamento da leishmaniose cutânea (LC) no estado do Rio de Janeiro. Entre 2008 e 2011, 57 pacientes com LC foram entrevistados através de questionário para coleta de dados socioeconômicos. Para monitorização da adesão foram utilizados os seguintes métodos: contagem de ampolas excedentes, cartão de acompanhamento, teste de Morisky e teste de Morisky modificado (sem a pergunta referente ao horário). Observou-se adesão de 82,1% (devolução de ampolas), 86,0% (cartão de acompanhamento), 66,7% (teste de Morisky) e 86,0% (teste de Morisky modificado). Houve forte concordância entre o método contagem de ampolas e cartão de acompanhamento, bem como teste de Morisky modificado. Verificou-se associação significativa entre maior adesão ao tratamento e baixa dose de AM, bem como com menor número de pessoas dormindo no mesmo quarto. Recomendamos a utilização do teste de Morisky modificado na avaliação da adesão ao tratamento da LC com AM por ser método simples e com bom desempenho quando comparado aos outros testes.


Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antiprotozoal Agents/administration & dosage , Leishmaniasis, Cutaneous/drug therapy , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Patient Compliance/statistics & numerical data , Socioeconomic Factors
18.
Article in English | WPRIM | ID: wpr-184381

ABSTRACT

OBJECTIVE: To compare the effect of imaging time delay on the MR detection of intracerebral metastases using single dose gadobutrol. MATERIALS AND METHODS: Twenty-one patients with intracerebral metastases underwent contrast-enhanced MR with three-dimensional T1-weighted sequence at 1 minute, 5 minutes and 10 minutes after a single dose injection of gadobutrol. One hundred index metastatic lesions (1 to 30 mm; median, 7 mm) were chosen for the analysis. For the qualitative analysis, lesion conspicuity were assessed on a 1 (worst) to 5 (best) scale of the index lesions by an expert reader. For the quantitative analysis, signal intensity (SI) of enhancing lesions and normal parenchyma was measured to determine the contrast rate (CR, %) ([postcontrast SI lesion - postcontrast SI white matter] x 100 / postcontrast SI white matter) and the enhancement rate (ER, %) ([postcontrast SI lesion - baseline SI gray matter] x 100 / baseline SI gray matter). Statistical comparisons were made between three different time delays. RESULTS: Lesion conspicuity did not differ significantly among the three time delays (p = 0.097). Although the SI, CR and ER of lesions did not reveal any significant difference between 1 minute and 5 minutes delayed images, both the 1 minute and 5 minutes delayed images showed significantly higher CRs of lesions compared with the 10 minutes delayed images (p = 0.004 and p = 0.001, respectively). CONCLUSION: With single dose gadobutrol, imaging time delay did not have an effect on lesion conspicuity. Both 1-minute and 5-minute-delayed imaging after gadobutrol injection appears to be effective for the detection of intracerebral metastases.


Subject(s)
Adult , Aged , Aged, 80 and over , Brain Neoplasms/diagnosis , Contrast Media/administration & dosage , Female , Humans , Image Enhancement/methods , Magnetic Resonance Imaging/methods , Male , Middle Aged , Observer Variation , Organometallic Compounds/administration & dosage , Time Factors
19.
Article in English | WPRIM | ID: wpr-105915

ABSTRACT

Bowel preparation is essential for successful colonoscopy examination, and the most important factor is the bowel preparation agent used. However, selection of a bowel preparation agent invariably involves compromise. Originally, bowel preparation was performed for radiologic and surgical purposes, when the process involved dietary limitations, cathartics, and enemas, which had many side effects. Development of polyethylene glycol (PEG) solution led to substantive advancement of bowel preparation; however, despite its effectiveness and safety, the large volume involved, and its salty taste and unpleasant odor reduce compliance. Accordingly, modified PEG solutions requiring consumption of lower volumes and sulfate-free solutions were developed. Aqueous sodium phosphate is more effective and better tolerated than PEG solutions; however, fatal complications have occurred due to water and electrolyte shifts. Therefore, aqueous sodium phosphate was withdrawn by the US Food and Drug Administration, and currently, only sodium phosphate tablets remain available. In addition, oral sulfate solution and sodium picosulfate/magnesium citrate are also available, and various studies have reported on adjunctive preparations, such as hyperosmolar or stimulant laxatives, antiemetics, and prokinetics, which are now in various stages of development.


Subject(s)
Administration, Oral , Cathartics/administration & dosage , Citrates/administration & dosage , Citric Acid/administration & dosage , Colonic Diseases/diagnosis , Colonoscopy , Humans , Organometallic Compounds/administration & dosage , Phosphates/administration & dosage , Picolines/administration & dosage , Polyethylene Glycols/administration & dosage
20.
Rev. Soc. Bras. Med. Trop ; 46(6): 669-677, Nov-Dec/2013. tab, graf
Article in English | LILACS | ID: lil-698068

ABSTRACT

We aimed to assess and synthesize the information available in the literature regarding the treatment of American tegumentary leishmaniasis in special populations. We searched MEDLINE (via PubMed), EMBASE, LILACS, SciELO, Scopus, Cochrane Library and mRCT databases to identify clinical trials and observational studies that assessed the pharmacological treatment of the following groups of patients: pregnant women, nursing mothers, children, the elderly, individuals with chronic diseases and individuals with suppressed immune systems. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The available evidence suggests that the treatments of choice for each population or disease entity are as follows: nursing mothers and children (meglumine antimoniate or pentamidine), patients with renal disease (amphotericin B or miltefosine), patients with heart disease (amphotericin B, miltefosine or pentamidine), immunosuppressed patients (liposomal amphotericin), the elderly (meglumine antimoniate), pregnant women (amphotericin B) and patients with liver disease (no evidence available). The quality of evidence is low or very low for all groups. Accurate controlled studies are required to fill in the gaps in evidence for treatment in special populations. Post-marketing surveillance programs could also collect relevant information to guide treatment decision-making.


Subject(s)
Aged , Child , Female , Humans , Pregnancy , Antiprotozoal Agents/administration & dosage , Evidence-Based Medicine , Leishmaniasis, Cutaneous/drug therapy , Amphotericin B/administration & dosage , Chronic Disease , Immunocompromised Host , Meglumine/administration & dosage , Organometallic Compounds/administration & dosage , Pentamidine/administration & dosage , Phosphorylcholine/administration & dosage , Phosphorylcholine/analogs & derivatives , Risk Factors
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