Hydroxyurea for treatment of severe sickle cell anemia: a pediatric clinical trial. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. A multicenter randomized controlled clinical trial of Shosaiko-to in chronic active hepatitis. A comparative study to evaluate the effect of honey dressing and silver sulfadiazene dressing on wound healing in burn patients. DuoDERM hydroactive dressing versus silver sulphadiazine/Bactigras in the emergency treatment of partial skin thickness burns. Role of hydroxyurea during structured treatment interruptions. Oxybutynin chloride for geriatric urinary dysfunction: a double-blind placebo-controlled study. The efficacy of ursodeoxycholic acid and bezafibrate combination therapy for primary biliary cirrhosis: A prospective, multicenter study. Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis.
Hydroxyurea (HU) enhances the synthesis of fetal hemoglobin (HbF) and can improve the clinical course of some adult patients with sickle cell anemia (SCA). In a randomized trial, we studied the biologic effects and the clinical benefit of HU in children and young adults with severe SCA. Twenty-five patients (median age, 9 years) were randomized to receive either HU (at the initial dosage of 20 mg/kg/d) or a placebo for 6 months and were then switched to the other arm for the next 6 months. Among the 22 evaluable patients (median age, 8 years), significant increases in HbF and mean corpuscular volume occurred during the HU treatment period. The white blood cell and reticulocytes counts decreased significantly, but these changes were not clinically relevant. Sixteen of 22 patients (73%) experienced a complete disappearance of events requiring hospitalization. The number of days of hospitalization as well as the number of hospitalizations for patients on HU, as compared with those for the patients receiving placebo, were significantly reduced. We conclude that treatment with HU in children and young adults is feasible, well-tolerated, and improves the clinical course of SCA. The long-term effects of HU require further investigation. In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises.
                In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months.
                Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P < 0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P < 0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P < 0.001), and fewer underwent transfusions (48 vs. 73, P = 0.001). At the end of the study, the doses of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day. Treatment with hydroxyurea did not cause any important adverse effects.
                Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year. Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored. The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain. The efficacy of Shosaiko-to (SST) on 222 patients with chronic active hepatitis was studied in a double-blind multicenter clinical study. One hundred and sixteen patients received SST in a daily oral dose of 5.4 g for 12 weeks, followed by the same dose for a further 12 weeks. One hundred and six patients received a placebo containing 0.5 g of SST for 12 weeks, followed by a cross-over to SST for a further 12 weeks. Among the liver tests, serum AST and ALT values decreased significantly with the administration of SST. The difference of the mean value between the SST group and the placebo group was significant after 12 weeks. In patients with chronic active type B hepatitis, a tendency towards a decrease of HBeAg and an increase of Anti-HBe antibodies was also observed. No remarkable side effects were noticed. To compare the effect of honey dressing and silver-sulfadiazene (SSD) dressing on wound healing in burn patients. Patients (n=78) of both sexes, with age group between 10 and 50 years and with first and second degree of burn of less than 50% of TBSA (Total body surface area) were included in the study, over a period of 2 years (2006-08). After stabilization, patients were randomly attributed into two groups: 'honey group' and 'SSD group'. Time elapsed since burn was recorded. After washing with normal saline, undiluted pure honey was applied over the wounds of patients in the honey group (n=37) and SSD cream over the wounds of patients in SSD group (n=41), everyday. Wound was dressed with sterile gauze, cotton pads and bandaged. Status of the wound was assessed every third and seventh day and on the day of completion of study. Patients were followed up every fortnight till epithelialization. The bacteriological examination of the wound was done every seventh day. The mean age for case (honey group) and control (SSD group) was 34.5 years and 28.5 years, respectively. Wound swab culture was positive in 29 out of 36 patients who came within 8 hours of burn and in all patients who came after 24 hours. The average duration of healing in patients treated with honey and SSD dressing at any time of admission was 18.16 and 32.68 days, respectively. Wound of all those patients (100%) who reported within 1 hour became sterile with honey dressing in less than 7 days while none with SSD. All of the wounds became sterile in less than 21 days with honey, while tthis was so in only 36.5% with SSD treated wounds. The honey group included 33 patients reported within 24 hour of injury, and 26 out of them had complete outcome at 2 months of follow-up, while numbers for the SSD group were 32 and 12. Complete outcome for any admission point of time after 2 months was noted in 81% and 37% of patients in the honey group and the SSD group. Honey dressing improves wound healing, makes the wound sterile in lesser time, has a better outcome in terms of prevention of hypertrophic scarring and post-burn contractures, and decreases the need of debridement irrespective of time of admission, when compared to SSD dressing. The study compared DuoDERM Burn Pack Hydroactive Dressings (DHD) with silver sulphadiazine/Bactigras dressings (SSD/Bactigras) in the outpatient management of small partial skin thickness burns. Forty-eight patients were entered into the study, and randomly allocated into either the DHD or SSD/Bactigras group. Burn wounds were followed until complete re-epithelialization occurred. There were no statistical differences between the groups, either with respect to their composition or characteristics of healing in days, and patients' subjective responses to treatment. However, application was easier in the DHD group (93 per cent), compared with 71 per cent in the SSD/Bactigras group (P = 0.0009), and the SSD/Bactigras were easier to remove (96 per cent) versus DHD (66 per cent, P = 0.0004). Furthermore, the DHD group had significantly less dressing changes; a mean of three changes per subject in the DHD group compared with eight in the SSD/Bactigras group (P = 0.117). Two burn wounds became infected in the DHD group, and one in the SSD/Bactigras group. In this study both modalities were found to be equally suitable and effective for small partial skin thickness burns. Highly active antiretroviral therapies (HAART) represent a major advance in the treatment of HIV infection. Although with HAART a substantial suppression of viral replication can be obtained, eradication of the virus from the body cannot be achieved. Therefore, HIV-infected subjects have to be treated for the rest of their lives. Long term treatment will increase the frequency of: i) drug-related side effects; ii) onset of drug-resistant viral strains; iii) non-adherence of the patients to the treatment. Structured treatment interruptions (STI)-HAART might represent a feasible alternative and preliminary studies have shown that STI-HAART might induce immune control in patients treated in the early stage of infection. This regimen does not produce similar effects in patients treated during the chronic phase of the infection. However, there are some clinical data suggesting a possible role of hydroxyurea (HU) in inducing control of HIV replication in patients with established infection. In this manuscript in vitro and in vivo data indicating that HU might play a major role in the setting of STI-HAART will be presented. Twenty-four incontinent elderly institutionalized subjects with detrusor instability participated in a double-blind placebo-controlled trial of oxybutynin chloride. Patients were randomly assigned to oral oxybutynin 5 mg or placebo twice daily. Administration continued for 8 days; a 6-day washout period was followed by the alternative treatment. Incontinence was recorded using a bedside electronic monitor. Four subjects withdrew because of side-effects before completing the trial. There were no clinically significant differences between the oxybutynin and placebo treatments. Both groups experienced side-effects, of which dry mouth was the commonest. Thus, oxybutynin does not appear to be more effective than placebo for the treatment of incontinence in the presence of detrusor instability in elderly institutionalized people. Aim: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. Methods: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). Results: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. Conclusion: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis. 40 patients with idiopathic membranous glomerulonephritis were randomized to receive either no treatment or a regime of cyclophosphamide for 6 months, and warfarin and dipyridamole for two years. During the two years of the trial there was no significant deterioration in renal function in either group. A significantly greater improvement in urinary protein excretion was, however, observed at all time points in the treatment group. Plasma albumin was also significantly higher in the treatment group at 18 and 24 months. As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment.
While hydroxyurea appears both effective and safe in severely affected SS adults over a two-year period; further studies are required to elucidate its role in other patient groups and for other conditions.