The clinical impact of time to response in de novo accelerated-phase chronic myeloid leukemia

We aimed to describe the impact of time to response on the outcomes of 75 patients with accelerated-phase chronic myeloid leukemia (CML-AP) at diagnosis. Patients had at least 1 feature of AP: blasts ≥15% (n = 2), basophils ≥20% (n = 19), platelets <100 × 10⁹/L (n = 7), cytogenetic clonal evolution (n = 34), or more than one factor (n = 13). Thirty-three patients received imatinib; 42 received a second-generation tyrosine kinase inhibitor (2GTKI) (19 dasatinib and 23 nilotinib). We used chi-square and Kaplan-Meier analyses to determine the impact of various degrees of molecular and cytogenetic response at early time points (3 and 6 months) on rates of overall cytogenetic and molecular response, overall survival (OS), event-free survival (EFS), transformation-free survival (TFS), and failure-free survival (FFS). After a median follow-up of 96 months (range: 18-224 months), the overall rate of complete cytogenetic response was 79%, of major molecular response, 71%, and of molecular reponse (MR)4.5, 59%. Patients who achieved a major cytogenetic response (MCyR) (n = 49) at 3 months had significantly better 3-year OS (94% vs 75%; P = .002), TFS (98% vs 73%; P < .001), EFS (93% vs 42%; P < .001), and FFS (83% vs 25%; P < .001) rates than patients who did not have MCyR at 3 months. Most (67%) who eventually achieved sustained MR4.5 had achieved MCyR at 3 months. In de novo CML-AP, early response at 3 and 6 months is a strong determinant of long-term outcome.     

The Anti-Oxidant Effects of Ginger and Cinnamon on Spermatogenesis Dys-function of Diabetes Rats

Background

Diabetes rats have been linked to reproductive dysfunction and plant medicine has been shown to be effective in its treatment. Antioxidants have distinctive effects on spermatogenesis, sperm biology and oxidative stress, and changes in anti-oxidant capacity are considered to be involved in the pathogenesis of chronic diabetes mellitus. Ginger and cinnamon are strong anti-oxidants and have been shown to reduce oxidative stress in the long-term treatment of streptozotocin (STZ)-induced diabetes in animal models. The present study examined the influence of combined ginger and cinnamon on spermatogenesis in STZ-induced diabetes in male Wistar rats.

Materials and Methods

Animals (n = 80) were allocated randomly into eight groups, 10 each: Group 1: Control rats given only 5cc Normal saline (0.9% NaCl) daily;Group2: rats received ginger (100mg/kg/rat) daily; Group 3: rats received cinnamon (75mg/kg) daily; Group 4: rats received ginger and cinnamon, (100mg/kg/rat ginger and 75mg/kg cinnamon) daily; Group 5: Diabetic control rats received only normal saline. Group 6: Diabetic rats received 100mg/kg/day ginger; Group 7: Diabetic rats received 75mg /kg/ day cinnamon; Group 8: Diabetic rats received ginger and cinnamon (100mg/kg/day and 75mg/kg /day). Diabetes was induced with 55 mg/kg, single intra-peritoneal injection of STZ in all groups. At the end of the experiment (56th day), blood samples were taken for determination of testosterone, LH,FSH, total anti-oxidant capacity, and levels of malondialdehyde, SOD, Catalase and GPX. All rats were euthanized, testes were dissected out and spermatozoa were collected from the epididymis for analysis.

Results

Sperm numbers, percentages of sperm viability and motility, and total serum testosterone increased in ginger and cinnamon and combined ginger and cinnamon treated diabetic rats compared with control groups. Serum testosterone, LH and FSH were higher compared to control group and also serum anti-oxidants (TAC, SOD, GPX and catalase) all were increased at the end of treatment. Combined ginger and cinnamon showed more intense increase in all parameters compare to ginger and cinnamon alone. Most of the results were significant (P<0.05).

Conclusion

We concluded that combined ginger and cinnamon have significant beneficial effects on the sperm viability, motility, and serum total testosterone, LH,FSH and serum anti-oxidants'' level and could be effective for maintaining healthy sperm parameters and male reproductive function in diabetics.     

Sulfated zirconium oxide-decorated magnetite KCC-1 as a durable and recyclable adsorbent for the efficient removal of asphaltene from crude oil

Sulfated zirconium oxide (ZrO₂/SO₄²⁻) as a highly durable acidic reagent was immobilized on magnetite KCC-1 nanoparticles (Fe₃O₄@SiO₂/KCC-1@ZrO₂/SO₄²⁻ NPs), and the resulting hybrid was used as a highly efficient recyclable adsorbent for the adsorption and removal of asphaltene from crude oil. The presence of ZrO₂/SO₄²⁻ groups not only promotes the adsorption capacity, but also helps recycle the adsorbents without any significant efficiency loss arising from its high chemical resistance. The results showed an obvious synergistic effect between the magnetic core (Fe₃O₄ NPs), fibrous silica (KCC-1) and the sulfated zirconium oxide groups with high correlation for asphaltene adsorption. The effective parameters in asphaltene adsorption, including initial asphaltene concentration, catalyst concentration and temperature, were investigated. Maximum adsorption occurred in the presence of 0.7 g L⁻¹ of the adsorbent, at a concentration of 2000 mg L⁻¹ of asphaltene. The asphaltene adsorption by NPs follows a quasi-second order adsorption kinetics. Asphaltene adsorption kinetics were studied by Langmuir, Freundlich, and Temkin isotherms. The prominent advantage of the adsorbent is its ability to be recovered after each adsorption by acid treatment, so that no significant reduction in adsorbent adsorption activity was observed, which can be directly attributed to the presence of ZrO₂/SO₄²⁻ groups in the hybrid.

A new, efficient and recyclable hybrid based on immobilized sulfated zirconium oxide on magnetite fibrous silica (KCC-1) has been developed and utilized for the efficient adsorption and removal of asphaltene from crude oil.     

CO2 laser treatment for plantar warts in children: A case series

Several types of human papillomaviruses induce warts. Warts are one of the most common infections in childhood with a reported prevalence of up to 20%. Warts are divided clinically into genital and nongenital forms. Plantar warts are common nongenital warts. In this series, five pediatric cases treated with CO₂ laser for their plantar warts are presented. One patient was a known case of Hodgkin's lymphoma. Three of our patients had history of unsuccessful treatments with other modalities, while the other had received no previous treatment. CO₂ laser with continuous mode (focused and defocused) was used. In our cases, only one session was enough for clearance of the warts. All the patients were visited 1 week and 3 months after treatment to assess the efficacy and any possible recurrences. Follow‐up showed that all the patients remained in remission up to 3 months posttreatment with no adverse events.     

Correlation between creatinine clearance and Helicobacter pylori infection eradication with sequential and triple therapeutic regimens: A randomised clinical trial

Background and study aimsUraemic patients show susceptibility to gastrointestinal mucosal lesions and colonisation by Helicobacter pylori (HP). Antibiotic resistance constitutes a problem in treatment and bismuth preparations are toxic in uraemic patients. This study aimed to assess the correlation between creatinine clearance (CrCl) and eradication of HP infection with new sequential and standard triple therapeutic regimens.Patients and methodsA total of 120 HP-positive patients with renal function impairment and 60 control patients with HP infection were enrolled in this study. Patients were divided into four groups on the basis of CrCl and were randomly assigned to one of the two different regimens: A 14-day standard triple therapy with 20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid and a new sequential regimen with 20 mg omeprazole bid and 1000 mg amoxicillin bid both for 14 days, 500 mg ciprofloxacin bid for the first 7 days and 200 mg furazolidone bid for the last 7 days. Doses of amoxicillin, clarithromycin and ciprofloxacin were reduced to 50% in the cases of CrCl <30 mg dl^?1.ResultsOne hundred and sixty two out of 180 HP-positive patients (54.3% male, 51.6 ± 12.1 years) completed treatment in the four groups and were studied. According to renal function they were classified into group A (n = 39), haemodialysis (HD) patients; group B (n = 37), CrCl <30 mg dl^?1 without HD; group C (n = 36), CrCl between 30 and 60 mg dl^?1; and group D (n = 50), control subjects with CrCl >90 mg dl^?1. HP was successfully eradicated in 77.7% of patients with standard triple therapy and in 81.4% of patients with the sequential therapy. There was no significant difference among the study groups in the rate of HP-infection eradication with both regimens.ConclusionHP eradication rates did not differ with both sequential and standard therapeutic regimens in uraemic and non-uraemic patients. We, therefore, prefer the standard triple therapy due to its simplicity and reported.     

Melatonin effects on luteinizing hormone in postmenopausal women: a pilot clinical trial NCT00288262

Background  

In many mammals, the duration of the nocturnal melatonin elevation regulates seasonal changes in reproductive hormones such as luteinizing hormone (LH). Melatonin's effects on human reproductive endocrinology are uncertain. It is thought that the same hypothalamic pulse generator may both trigger the pulsatile release of GnRH and LH and also cause hot flashes. Thus, if melatonin suppressed this pulse generator in postmenopausal women, it might moderate hot flashes. This clinical trial tested the hypothesis that melatonin could suppress LH and relieve hot flashes.     

Phase I/II study of the mammalian target of rapamycin inhibitor everolimus (RAD001) in patients with relapsed or refractory hematologic malignancies.

PURPOSE: Everolimus (RAD001, Novartis), an oral derivative of rapamycin, inhibits the mammalian target of rapamycin (mTOR), which regulates many aspects of cell growth and division. A phase I/II study was done to determine safety and efficacy of everolimus in patients with relapsed or refractory hematologic malignancies. EXPERIMENTAL DESIGN: Two dose levels (5 and 10 mg orally once daily continuously) were evaluated in the phase I portion of this study to determine the maximum tolerated dose of everolimus to be used in the phase II study. RESULTS: Twenty-seven patients (9 acute myelogenous leukemia, 5 myelodysplastic syndrome, 6 B-chronic lymphocytic leukemia, 4 mantle cell lymphoma, 1 myelofibrosis, 1 natural killer cell/T-cell leukemia, and 1 T-cell prolymphocytic leukemia) received everolimus. No dose-limiting toxicities were observed. Grade 3 potentially drug-related toxicities included hyperglycemia (22%), hypophosphatemia (7%), fatigue (7%), anorexia (4%), and diarrhea (4%). One patient developed a cutaneous leukocytoclastic vasculitis requiring a skin graft. One patient with refractory anemia with excess blasts achieved a major platelet response of over 3-month duration. A second patient with refractory anemia with excess blasts showed a minor platelet response of 25-day duration. Phosphorylation of downstream targets of mTOR, eukaryotic initiation factor 4E-binding protein 1, and/or, p70 S6 kinase, was inhibited in six of nine patient samples, including those from the patient with a major platelet response. CONCLUSIONS: Everolimus is well tolerated at a daily dose of 10 mg daily and may have activity in patients with myelodysplastic syndrome. Studies of everolimus in combination with therapeutic agents directed against other components of the phosphatidylinositol 3-kinase/Akt/mTOR pathway are warranted.