Deferasirox-induced urticarial vasculitis in a patient with myelodysplastic syndrome

Abstract Deferasirox is an iron chelator agent used in the treatment of diseases with iron overload, such as thalassemia and myelodysplastic syndrome. Although the majority of adverse reactions of deferasirox involve gastrointestinal symptoms and increase in serum creatinine and transaminases, skin rashes, such as maculopapular and urticarial eruptions, have also been reported. This study reports a case of myelodysplastic syndrome with urticarial vasculitis due to deferasirox therapy. Drug eruption was been confirmed by means of a challenge test, together with histopathological and clinical findings. To the best of our knowledge, we report the first case of deferasirox-induced urticarial vasculitis. Physicians should be aware of the possibility of urticarial vasculitis on deferasirox therapy and the fact that the discontinuation of the drug generally results in improvement.

Análisis crítico de un artículo: La suspensión de inhibidores de la bomba de protones induciría síntomas de reflujo / Critically appraised article

Background & Aims: Rebound acid hypersecretion (RAHS) has been demonstrated after 8 weeks of treatment with a proton-pump inhibitor (PPI). IfRAHS induces acid-related symptoms, this might lead to PPI dependency and thus have important implications. Methods: A randomized, double-blind, placebo-controlled trial with 120 healthy volunteers was conducted. Participants were randomized to 12 weeks of placebo or 8 weeks of esomeprazole 40 mg/d followed by 4 weeks with placebo. The Gastrointestinal Symptom Rating Scale (GSRS) was filled out weekly. A score of >2 on 1 of the questions regarding heartburn, acid regurgitation, or dyspepsia was defined as a clinically relevant acid-related symptom. Results: There were no significant differences between groups in GSRS scores at baseline. GSRS scores for acid-related symptoms were significantly higher in the PPIgroup at week 10 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .023), week 11 (1.4 ± 1.4 vs 1.2 ± 0.9; P = .009), and week 12 (1.3 ± 1.2 vs 1.0 ± 0.3; P = .001). Forty-four percent (26/59) of those randomized to PPI reported >1 relevant, acid-related symptom in weeks 9-12 compared with 15% (9/59; P < .001) in the placebo group. The proportion reporting dyspepsia, heartburn, or acid regurgitation in the PPIgroup was 13 of 59 (22%) at week 10,13 of59 (22%) at week 11, and 12 of 58 (21%) at week 12. Corresponding figures in the placebo group were 7% at week 10 (P = .034), 5% at week 11 (P = .013), and 2% at week 12 (P = .001). Conclusions: PPI therapy for 8 weeks induces acid-related symptoms in healthy volunteers after withdrawal. This study indicates unrecognized aspects of PPI withdrawal and supports the hypothesis that RAHS has clinical implications.

A pilot study on the effect of telmisartan & ramipril on 24 h blood pressure profile & dipping pattern in type 1 diabetes patients with nephropathy.

Background & objectives: Angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have been used to normalize the blood pressure and the dipping pattern in patients with type 1 diabetes mellitus (T1DM) and nephropathy. However, there are no data on the effect of the dual blockade on the dipping pattern in these subjects. We therefore, carried out this study to evaluate the effect of administrating an ACEI followed by ARB in the optimum doses in T1DM patients with nephropathy on 24 h blood pressure (BP) profile and nocturnal dipping pattern. Methods: An open label interventional pilot study was done during a one year period involving 30 consecutive patients who were treated with telmisartan 80 mg (0800-1000 h) for eight weeks followed by addition of ramipril 10 mg (1200-1400 h) for the next eight weeks. Ambulatory BP, dipping pattern and albumin excretion rate were studied after each phase. Twenty patients were hypertensive and 10 patients had macro- and 20 patients had microalbuminuria. Results: Telmisartan produced a fall in the clinic BP by 4/1.3 mm Hg (P<0.05 and P<0.362, respectively), 2/1.9 mm Hg in the mean 24 h BP, 1.4/1.1 mm Hg in the day BP and 3.7/3 mm Hg in the trough BP. Addition of ramipril to telmisartan produced a further reduction of 6.3/5.9 mm Hg in the clinic BP (P<0.001 for both), 4.3/4.2 mm Hg in the mean 24 h BP (P<0.01 and P<0.0001, respectively), 5.8/3.9 mm Hg in the day BP (P<0.01 for both), 4.2/2.5 mm Hg in the trough BP, with a reduction of clinic SBP and DBP of 10.3/7.2 mm Hg from the baseline. Telmisartan restored normal systolic dipping pattern in 33.3 per cent of the nondippers (P<0.01) but addition of ramipril was not complimentary. Hyperkalamia (>5.5 mmol/l) was observed only in 2 patients towards the end of the study. Interpretation & conclusions: The dual blockade with telmisartan and ramipril had complimentary effect on lowering of the BP, however, similar beneficial effect on the nocturnal dipping was not observed. Further studies with large number of subjects with longer duration of follow-up are required to validate these observations.

[Effect of potassium benzoate on BALB/c mice placenta: a histopathological study]

The food additives, like sodium and potassium benzoate are used in many food products and drugs to prevent the growth of yeast and molds. There is no report about the histopathological effect of potassium benzoate. Placenta, has a critical role in embryonic development therefore this study was set up to evaluate the effects of potassium benzoate on placenta of BALB/c mice. 45 BALB/c female mice were allocated into two experimental [1, 2] and one control groups. Experimental groups received daily intraperitoneal injection of 280 and 560 mg/kg/body weight of potassium benzoate and control group received normal saline. All injections were done during 10 days before mating and 5th to 16th of gestational days [GD]. In GD 18 all placenta were removed via cesarean section. Macroscopic studies for morphological abnormalities were done and after measuring of placental weight and diameter, for microscopic studies the specimens were fixed and tissue passage were done. Tissue sections were stained with hematoxylin-eosin and histopathological changes were studied. Weight, diameter and percentage of agenesis of placenta in all groups were gathered. Data analyzed with using SPSS-11.5, ANOVA and Tukey tests. The mean weight and diameter of the placenta in both experimental groups 1 and 2 were significantly decreased compared to control group. Also atrophy of placenta in the experimental groups was increased significantly compared to the control group [P<0.05]. Comparison of weight and diameter between groups 1 and 2 was not significant. Percentage of placenta agenesis in the experimental groups was increased significantly compared to the control group [P<0.05]. Massive hemorrhage in labyrinth zone, fetal and maternal zones were seen in both experimental groups. This study showed that exposure of potassium benzoate during mice pregnancy cause morphological and histopathological changes of placenta, including decrease of weight and diameter, agenesis, hemorrhage and tissue disorders

A pilot study for evaluation of the efficacy and safety of telmisartan in reducing microalbuminuria in hypertensive patients with type 2 diabetes mellitus.

To evaluate efficacy and tolerability of telmisartan, an angiotensim II receptor blocker, in reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus, a prospective, open-label, non-comparative, assessor-blind, multicentric, pilot study was conducted in 60 eligible hypertensive patients with type 2 diabetes mellitus and microalbuminuria after obtaining their informed consent. The study was approved by the respective institutional review boards. Each patient received telmisartan 40 mg initially once daily for first 4 weeks which was titrated upwards to 80 mg once daily for the next 8 weeks. Blood pressure was assessed at the end of every 2 weeks and urinary albumin excretion and creatinine clearance were measured at baseline and after 12 weeks of therapy. Safety outcome measures included monitoring of physical examination, laboratory parameters and monitoring treatment-emergent adverse events. Fifty-five patients completed the study while 5 cases were lost to follow-up. The mean age of the patients was 48.27 years. Of the total patients 63.6% were males and 46.4% were females. At baseline the mean urinary albumin excretion rate was 131.81 +/- 38.82 mg/minute. A statistically significant (p < 0.05) reduction (32.96%) in urinary albumin excretion rate occurred after 12 weeks of therapy (118.36 +/- 37.22). The mean pre-study systolic blood pressure was 165.05 +/- 15.24 mmHg which was significantly (p < 0.05) reduced to 123.72 +/- 5.88 mmHg at the end of 12 weeks. At baseline the mean diastolic blood pressure was 103.55 +/- 9.84 mmHg which was significantly (p < 0.05) reduced to 84.71 +/- 8.54 mmHg. The JNC-VII goal of blood pressure below 130/80 was achieved in 34 (61.8%)of the 55 patients at the end of 12 weeks. Both fasting and postprandial blood sugar levels were well-controlled at the end of the study. Telmisartan was well tolerated with only 9.09% of the patients reported mild and transient adverse events like fatigue, dizziness, nausea and diarrhoea. No abnormalities were detected in the laboratory parameters. The results of this pilot study indicate that telmisartan is effective, safe and well tolerated while reducing microalbuminuria in adult Indian hypertensive patients with type 2 diabetes mellitus.

Comparison of the efficacy, safety and tolerability of telmisartan with losartan in Indian patients with mild to moderate hypertension: a pilot study.

A prospective, randomised, double-blind, parallel group study was carried out to compare the efficacy, safety and tolerability of telmisartan 40 mg once daily with losartan 50 mg once daily in Indian patients with mild to moderate hypertension. It had a placebo run-in period of 2 weeks followed by drug treatment (telmisartan 40 mg, once daily or losartan 50 mg once daily) for 8 weeks. Supine BP was assessed at the end of every 2 weeks. Tolerability and safety was assessed by physical examination, laboratory parameters and evaluation of adverse events. Treatment with telmisartan resulted in a significant reduction of SBP of 10.3% and 13.7% as compared to 6.6% and 10.6% in losartan group at the end of 6th and 8th weeks respectively. At the end of 6th and 8th weeks, the reduction was 14.3% and 18.1% among telmisartan which was significantly more as compared to 8.8% and 14.3% in losartan group respectively. The laboratory values were within normal limits. Both drugs were well tolerated. Telmisartan monotherapy in a dose of 40 mg once daily has a clinically better therapeutic effect as compared to losartan 50 mg and a good tolerability profile in patients with mild to moderate hypertension.

The efficacy and tolerability of an angiotensin II receptor blocker, telmisartan, in Thai patients with mild to moderate essential hypertension.

This open-labeled single-blinded study was performed to evaluate the efficacy and tolerability of telmisartan in the treatment of mild to moderate essential hypertension. Each patient was assigned to take a placebo for 4 weeks followed by once daily-titrated telmisartan (40-80 mg) for 8 weeks. "Office BP" and "24-hour ambulatory BP" measurements (24-h ABPM) were recorded as scheduled. Thirty-one patients (10 males: 21 females) with a mean age of 48.1 years were enrolled. The final SBP/DBP reductions of 14.6 +/- 14.2/9.9 +/- 6.2 mm Hg were obtained. Full response defined as office DBP reduction of > or = 10 mm Hg from baseline and/or DBP < 90 mm Hg was achieved in 73.3 per cent of cases. Excluding 5 cases of white coat HT diagnosed by 24-h ABPM, full response rate (DBP reduction of > or = 10 mm Hg from baseline and/or < 85 mm Hg) was 76 per cent. Trough to peak ratio and smoothness index for SBP/DBP were highly acceptable (0.75/0.76 and 0.97/1.01, respectively). There were 4 cases of adverse events (2 cases of dizziness, 1 case of headache, and 1 case of acute myocardial infarction).

Alteraciones en el coagulograma por el manejo de la encefalopatía hepática con benzoato de sodio / The effect of sodium benzoate on the coagulation test, in patients with hepatic encephalopathy

En un estudio longitudinal, comparativo al azar, se evaluó el efecto del benzoato de sodio (BS) sobre las pruebas de coagulación en un grupo de 10 sujetos con encefalopatía hepática severa, y se comparó con un grupo similar de 10 pacientes con encefalopatía hepática manejados con lactosa al 20 por ciento. En el grupo con BS, 8 sujetos fallecieron con agravamiento de la encefalopatía, 6 presentaron prolongación del tiempo parcial de tromboplastina (TTP) de 30" o más, no se registró modificación del tiempo de protrombina (TP). En el grupo que recibió lactosa hubo 3 defunciones (P=0.05), 1 sujeto presentó prolongación similar del TTP (P=0.025), 5 presentaron mejoría del mismo y tampoco hubo cambios del TP. Estos resultados sugieren que el BS prolonga el TTP y que la lactosa al 20 por ciento es una mejor opción que dicho fármaco en los pacientes con encefalopatía grave

Medicamentos ectoparasiticidas: risco e benefício / Ectoparasiticides drugs: risk and benefit

A escolha de produtos ectoparasiticidas para uso humano deve obedecer certos critérios, principalmente envolvendo a relaçäo risco-benefício, desde que muitos säo substâncias capazes de destruir formas de vida. As relaçöes adversas, os efeitos colaterais, a toxicidade, aliados a fatores como formulaçöes, interaçäo medicamentosa, incompatibilidades, freqüência das aplicaçöes e outras vias de penetraçäo orgânica devem ser avaliados. O trabalho se propöe a atualizar e revisar os dados farmacológicos e toxicológicos dos ectoparasiticidas mais freqüentemente utilizados para adequar a sua escolha