Antifungal Agents ; therapeutic use ; Humans ; Infant ; Meningitis, Cryptococcal ; drug therapy ; Pyrimidines ; adverse effects ; therapeutic use ; Triazoles ; adverse effects ; therapeutic use ; Voriconazole

OBJECTIVETo investigate the efficacy of letrozole for delaying bone maturation and increasing predicted adult height in boys with idiopathic central precocious puberty (ICPP) who have a bone age above 13 years and a short stature, and its adverse effects.

METHODSTwenty ICPP boys with a bone age above 13 years and a short stature were randomly divided into letrozole treatment (n=10) and control groups (n=10). The letrozole treatment group received oral letrozole [2.5 mg/(m(2)·d), Qd] for 6 months, while the control group received no treatment and was observed periodically. Bone age, growth rate, height standard deviation (SD) score, predicted adult height SD score, sexual maturity, and levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone, testosterone (T), estradiol (E2), progesterone (P), and androstenedione (ASD) were measured. The letrozole-related adverse reactions were evaluated.

RESULTSAfter 6 months of treatment, both groups had a significantly increased bone age, but the letrozole group had a significantly slowed increase in bone age compared with the control group (13.82 ± 0.23 years vs 14.47 ± 0.30 years; P<0.05); compared with the control group, the letrozole group had a significantly increased predicted adult height SD score (-1.69 ± 0.26 vs -1.91 ± 0.35; P<0.05) and a significantly increased T level (4.9 ± 0.9 nmol/L vs 4.4 ± 0.8 nmol/L; P<0.05). There was no significant difference in testicular volume between the two groups. The treatment led to no significant changes in growth rate, Tanner stage, and levels of FSH, LH, P, E2 and ASD in the two groups, and there was no significant difference in these indices between the two groups. No adverse reactions were observed during letrozole treatment.

CONCLUSIONSLetrozole delays bone maturation and increases predicted adult height in ICPP boys with a bone age above 13 years and a short stature, and it causes no obvious adverse reactions.

Adolescent ; Aromatase Inhibitors ; therapeutic use ; Body Height ; drug effects ; Bone Development ; drug effects ; Gonadal Steroid Hormones ; blood ; Humans ; Male ; Nitriles ; adverse effects ; therapeutic use ; Puberty, Precocious ; blood ; drug therapy ; Testis ; drug effects ; pathology ; Triazoles ; adverse effects ; therapeutic use

BACKGROUNDLiver transplantation is the most effective treatment for end-stage liver diseases; however, infections after transplantation can seriously affect the patient's health. The aim of this research was to investigate the diagnosis and treatment of fungal infection following liver transplantation.

METHODSClinical data for 232 liver transplant patients at risk of fungal infection were examined for the presence of fungus in the blood, fluid, sputum, urine and stools of patients and by chest or abdominal CT scans. Patients diagnosed with a fungal infection were treated with Fluconazole or, if this was not effective, Voriconazole or Amphotericin B. Immunosuppressive therapy was also reviewed.

RESULTSThirty-seven of 232 (15.9%) patients were diagnosed with a fungal infection, which occurred 4 to 34 days post-transplantation. Candida infections were diagnosed in 23 cases (62.2%) and Aspergillus infections in 12 cases (32.4%). Twenty-one cases were effectively treated with Fluconazole, 11 cases with Voriconazole, and two cases with Amphotericin B; however, three cases were not effectively treated with any of the antifungal agents. Overall, treatment was effective in 91.9% of patients.

CONCLUSIONSFungal infection has a significant influence on survival rate after liver transplantation. Imaging studies, and pathogenic and biopsy examinations can diagnose fungal infections, which can be effectively treated with antifungal agents such as Fluconazole, Voriconazole or Amphotericin B.

Adult ; Amphotericin B ; therapeutic use ; Antifungal Agents ; therapeutic use ; Female ; Fluconazole ; therapeutic use ; Humans ; Liver Transplantation ; adverse effects ; Male ; Mycoses ; diagnosis ; drug therapy ; etiology ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Voriconazole

PURPOSE: Posaconazole is a second-generation triazole with a broad spectrum. However, there is a lack of data to support a significant role for posaconazole in the treatment of invasive fungal infection (IFI), especially in Korea. Until recently, posaconazole was available only through the Korean Orphan Drug Center. This study was designed to review the use of posaconazole at a single-center in Korea. MATERIALS AND METHODS: Data from patients who received posaconazole treatment at Catholic Blood and Marrow Transplantation Center were retrospectively reviewed between January 2007 and September 2012. RESULTS: A total of 11 cases (3 males and 8 females, median age 52 years) received posaconazole. Five patients were given the drug for mucormycosis, two for invasive aspergillosis, and four for unspecified IFI for which galactomannan (GM) assays were negative. The treatment duration ranged from 4-250 days. Three patients received posaconazole for management refractory IFI, two for intolerance of previous antifungal therapy, and six for long-term maintenance treatment. The overall successful response rate to posaconazole was 55% (six of eleven patients). Five of eleven patients died during the study period. However, only one death was attributed to the progression of IFI. None of the patients discontinued posaconazole therapy due to adverse events. CONCLUSION: Posaconazole is an attractive oral antifungal agent for salvage treatment of IFI, particularly upon diagnosis of mucormycosis or in cases in which mucormycosis cannot be ruled out due to a negative GM.
Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Female ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Mucormycosis/drug therapy ; Mycoses/*drug therapy ; Republic of Korea ; Salvage Therapy/adverse effects ; Triazoles/adverse effects/*therapeutic use

Many Korean patients with transfusion-induced iron overload experience serious clinical sequelae, including organ damage, and require lifelong chelation therapy. However, due to a lack of compliance and/or unavailability of an appropriate chelator, most patients have not been treated effectively. Deferasirox (DFX), a once-daily oral iron chelator for both adult and pediatric patients with transfusion-induced iron overload, is now available in Korea. The effectiveness of deferasirox in reducing or maintaining body iron has been demonstrated in many studies of patients with a variety of transfusion-induced anemias such as myelodysplastic syndromes, aplastic anemia, and other chronic anemias. The recommended initial daily dose of DFX is 20 mg/kg body weight, taken on an empty stomach at least 30 min before food and serum ferritin levels should be maintained below 1000 ng/mL. To optimize the management of transfusion-induced iron overload, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the general consensus on iron overload and the Korean data on the clinical benefits of iron chelation therapy, and developed a Korean guideline for the treatment of iron overload.
Anemia, Aplastic/therapy ; Benzoates/therapeutic use ; Blood Transfusion/*adverse effects ; Chelation Therapy/*methods ; Humans ; Iron Chelating Agents/*therapeutic use ; Iron Overload/*therapy ; Myelodysplastic Syndromes/therapy ; Pyridones/therapeutic use ; Republic of Korea ; Triazoles/therapeutic use

During the last five decades, long-term therapy with immunosuppressive agents such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has enhanced both patient survival and renal survival in patients with diffuse proliferative lupus nephritis. Nevertheless, severe side effects such as infectious complications remain the main cause of morbidity and mortality. Central nervous system aspergillosis is uncommon but life-threatening in lupus patients. In this single-patient case study, carotid aneurysm with sphenoidal sinusitis was suspected when severe epistaxis occurred during cyclophosphamide pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae, indicating aspergillosis. Three months after stopping voriconazole treatment, two cerebral aneurysms that were revealed on MR images were successfully removed by aneurysmal clipping. The patient remained alive at one-year follow-up with lupus nephritis in remission. The rarity and high mortality of aspergillus-related fungal aneurysms have led to most cases being recognized postmortem. However, such aneurysms must be diagnosed early to prevent fatal complications by performing appropriate management such as surgical procedure or endovascular intervention.
Antifungal Agents/therapeutic use ; Female ; Humans ; Immunosuppressive Agents/adverse effects ; Intracranial Aneurysm/drug therapy/*etiology/surgery ; Lupus Nephritis/*complications/drug therapy ; Middle Aged ; Neuroaspergillosis/drug therapy/*etiology/surgery ; Pyrimidines/therapeutic use ; Stents ; Surgical Instruments ; Triazoles/therapeutic use

OBJECTIVETo study the effectiveness and safety of deferasirox (DFX) in the treatment of iron overload in children with β-thalassemia major.

METHODSTwenty-four β-thalassemia major children with iron overload who received regular blood transfusion were randomly enrolled. The serum feritin (SF) levels were measured in the patients after different doses of DFX treatment. The DFX treatment-related adverse events were observed. The values of cardiac MRI T2* and liver MRI T2* were compared between the patients receiving DFX treatment for 5 years and the patients treated with deferoxamine and deferiprone.

RESULTSThe patients with iron overload did not respond to DFX at the initial dose of 20-30 mg/kg•d. However, the SF level decreased significantly after the dose of DFX increased to 30-40 mg/kg•d (U=58, P<0.01). Serum liver transaminase elevation was the most common adverse effect, followed by non-progressive elevation in serum creatinine level. The mean SF level was significantly lower (1748±481 ng/mL vs 3462±1744 ng/mL; P<0.05), in contrast, the liver MRI T2* value was significantly higher (8.5±2.9 ms vs 2.7±1.9 ms; P<0.01) in patients receiving DFX treatment for 5 years than in the controls. There were no significant differences in the cardiac MRI T2* value between the two groups.

CONCLUSIONSDFX can reduce SF levels in a dose-dependent manner in children with β-thalassemia major. It can significantly lower liver iron overload but not cardiac overload. Serum liver transaminase elevation and non-progressive elevation in serum creatinine level are major adverse effects in DFX treatment.

Adolescent ; Adult ; Benzoates ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Dose-Response Relationship, Drug ; Female ; Ferritins ; blood ; Humans ; Iron Chelating Agents ; adverse effects ; therapeutic use ; Iron Overload ; drug therapy ; Male ; Transfusion Reaction ; Triazoles ; adverse effects ; therapeutic use ; beta-Thalassemia ; blood ; complications ; therapy

INTRODUCTIONBecause invasive fungal infections cause significant morbidity and mortality in liver transplant recipients, the use of antifungal prophylaxis, and the early empirical use of antifungal agents, is widespread on liver transplant units. The new-generation azoles such as voriconazole and the echinocandins have been welcome additions to the antifungal armamentarium. These agents have become the leading options for prophylaxis in liver transplant units, despite the absence of strong data for their efficacy in this setting.

CLINICAL PICTUREWe report two recipients of living-donor liver transplants who became infected/colonised with fungi resistant to an echinocandin and the azoles after exposure to these agents. One patient developed trichosporonosis while on caspofungin and the other became infected/ colonised with Candida glabrata that was resistant to voriconazole and posaconazole.

CONCLUSIONWe report these to highlight some of the consequences of using the newer antifungal agents.

Adult ; Antifungal Agents ; therapeutic use ; Drug Resistance, Fungal ; Echinocandins ; therapeutic use ; Fatal Outcome ; Female ; Fluconazole ; therapeutic use ; Humans ; Lipopeptides ; Liver Transplantation ; adverse effects ; immunology ; Male ; Middle Aged ; Mycoses ; drug therapy ; prevention & control ; Pyrimidines ; therapeutic use ; Triazoles ; therapeutic use ; Trichosporonosis ; drug therapy ; prevention & control ; Voriconazole ; Young Adult

In the two decades since AZT was first approved for clinical use in 1987, 24 additional antiretroviral agents have been approved. They include 7 nucleoside analogs, a nucleotide analog and 4 non-nucleoside reverse transcriptase inhibitors, 10 protease inhibitors, 2 entry inhibitors and an integrase inhibitor. More than 20 investigational agents are currently being studied in clinical trials. Highly active antiretroviral therapy (HAART), which involves a combination of anti-HIV-1 drugs, is extremely effective in suppressing HIV-1 replication and increasing CD4+ number and results in substantial reductions in HIV-1-related morbidity and mortality. In last 20 years, much has been learned about resistance to antiretroviral drugs, drug interactions and metabolic complications of antiviral drug use. Drugs are now selected on the basis of resistance tests and on the risk of specific drug complications in individual patients. As a result, decisions about the therapy of HIV/AIDS have become personalized and are made on a patient-by-patient basis. With appropriate medical management, a person with HIV-1 now has the possibility of a nearly normal life expectancy.
Anti-HIV Agents ; adverse effects ; pharmacology ; therapeutic use ; Antiretroviral Therapy, Highly Active ; Cyclohexanes ; chemistry ; pharmacology ; therapeutic use ; Drug Resistance, Viral ; HIV Envelope Protein gp41 ; chemistry ; therapeutic use ; HIV Fusion Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Infections ; drug therapy ; HIV Integrase Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Protease Inhibitors ; chemistry ; pharmacology ; therapeutic use ; HIV Reverse Transcriptase ; chemistry ; pharmacology ; therapeutic use ; HIV-1 ; drug effects ; physiology ; Humans ; Molecular Structure ; Peptide Fragments ; chemistry ; therapeutic use ; Pyrrolidinones ; chemistry ; pharmacology ; therapeutic use ; Raltegravir Potassium ; Saquinavir ; chemistry ; pharmacology ; therapeutic use ; Triazoles ; chemistry ; pharmacology ; therapeutic use ; Virus Replication ; drug effects ; Zidovudine ; chemistry ; pharmacology ; therapeutic use

Multiple RBC transfusions inevitably lead to a state of iron overload before and after high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT). Nonetheless, iron status during post-SCT follow-up remains unknown. Therefore, we investigated post-SCT ferritin levels, factors contributing to its sustained levels, and organ functions affected by iron overload in 49 children with high-risk neuroblastoma who underwent tandem HDCT/autoSCT. Although serum ferritin levels gradually decreased during post-SCT follow-up, 47.7% of the patients maintained ferritin levels above 1,000 ng/mL at 1 yr after the second HDCT/autoSCT. These patients had higher serum creatinine (0.62 vs 0.47 mg/mL, P = 0.007) than their counterparts (< 1,000 ng/mL). Post-SCT transfusion amount corresponded to increased ferritin levels at 1 yr after the second HDCT/autoSCT (P < 0.001). A lower CD34+ cell count was associated with a greater need of RBC transfusion, which in turn led to a higher serum ferritin level at 1 yr after HDCT/autoSCT. The number of CD34+ cells transplanted was an independent factor for ferritin levels at 1 yr after the second HDCT/autoSCT (P = 0.019). Consequently, CD34+ cells should be transplanted as many as possible to prevent the sustained iron overload after tandem HDCT/autoSCT and consequent adverse effects.
Antigens, CD34/metabolism ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Benzoic Acids/therapeutic use ; Blood Transfusion/*adverse effects ; Child ; Child, Preschool ; Creatinine/blood ; Ferritins/blood ; Follow-Up Studies ; Humans ; Infant ; Iron Chelating Agents/therapeutic use ; Iron Overload/*etiology ; Neuroblastoma/drug therapy/*therapy ; Retrospective Studies ; Risk Factors ; *Stem Cell Transplantation ; Transplantation, Autologous ; Triazoles/therapeutic use