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Divided Doses (divided + dose)
Selected AbstractsLow-Dose Topiramate Versus Lamotrigine in Migraine Prophylaxis (The Lotolamp Study)HEADACHE, Issue 3 2007Praveen Gupta MD Objective.,To assess the efficacy and safety of topiramate and lamotrigine for prophylaxis in patients with frequent migraine as compared to each other and to placebo. Methods.,Sixty patients with frequent migraine (more than 4 attacks per month) from the headache clinic at a tertiary referral centre in India were randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1 month each in 2 divided doses in 4 phases in a crossover manner with a washout period of 7 days in between. Primary efficacy measure was responder rate (50% decrease in mean migraine frequency/intensity). Secondary efficacy measures included reduction in mean monthly frequency, intensity, duration, rescue medication use, migraine associated symptoms, and adverse events. Statistical analysis.,Analysis was on intention to treat basis. Data were analyzed as correlated data. Generalized estimation equation was used to compute overall mean standard deviation and 95% confidence intervals for each of the outcome variables. Bonferroni's correction done for multiple comparisons. P value of <.017 was taken as significant. Results.,Fifty-seven patients comprised the intent-to-treat population. Four patients withdrew from the study at various phases, none because of the side effects. Responder rate for frequency was significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and versus lamotrigine (63% vs 46 %, P= .02). For intensity of headache also a responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus lamotrigine (50% vs 41%, P= .01) was observed. Topiramate showed statistically significant benefits (P < .017) in most of the secondary efficacy measures while lamotrigine was beneficial for reduction in headache frequency, and migraine associated symptoms. Adverse events were similar. Conclusion.,Low-dose topiramate is efficacious in migraine prophylaxis as compared to both placebo and lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency; however, longer trials are required to establish its efficacy on the intensity and frequency of migraine. [source] Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot studyINFLAMMATORY BOWEL DISEASES, Issue 5 2009Hien Q. Huynh MD Abstract Background: Ulcerative colitis (UC) is a form of inflammatory bowel disease (IBD) that has periods of exacerbated symptoms and periods that are symptom-free. The treatment of active UC with probiotic bacteria could possibly induce remission. We evaluated the clinical efficacy and safety profile of probiotic preparation VSL#3 in the treatment of mild to moderate acute UC in the pediatric population. Methods: Eighteen eligible patients between the ages of 3,17 with mild to moderate acute UC received open-label VSL#3 daily in 2 divided doses for 8 weeks. The disease activity pre- and post-VSL#3 therapy was assessed by the simple clinical colitis activity index (SCCAI); Mayo ulcerative colitis endoscopic score; inflammatory markers: erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP); serum cytokine profiling; and rectal tissue microbial profiling done at baseline and at week 8. Results: Thirteen patients completed 8 weeks of VSL#3 treatment and 5 patients were withdrawn due to lack of improvement. Remission (defined as SCCAI ,3) was achieved in 56% of children (n = 10); response (decrease in SCCAI ,2, but final score ,5) in 6% (n = 1); and no change or worsening in 39% (n = 7). Post-VSL#3 treatments demonstrated a bacterial taxonomy change in rectal biopsy. The VSL#3 was well tolerated in clinical trials and no biochemical and clinical adverse effects attributed to VSL#3 were identified. Conclusions: Treatment of pediatric patients diagnosed with mild to moderate UC with VSL#3 resulted in a remission rate of 56% and a combined remission/response rate of 61%. (Inflamm Bowel Dis 2008) [source] Acyclovir-induced neuropsychosis successfully recovered after immediate hemodialysis in an end-stage renal disease patientINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2007Hung-Hsu Yang MD A 70-year-old man developed herpes zoster over the right L5,S2 region for 3 days and was admitted for acyclovir therapy. He had a medical history of rectal cancer status post-colostomy and end-stage renal disease undergoing thrice weekly hemodialysis. Without a prior loading dose, acyclovir 500 mg (7.7 mg/kg) daily was given intravenously in two divided doses. On the third dosage, the patient became confused and agitated and developed insomnia. Within the following 24 h, delirium, visual and auditory hallucinations, disorientation to place and time, as well as impaired recent memory occurred. At the same time, a transient low grade fever (38 °C) was noted but resolved spontaneously after ice pillow (Fig. 1). Figure 1. The clinical and treatment course of the patient The etiology was vigorously explored. He had no history of any neurological or psychiatric disorders. Drug history was reviewed, but no other medications besides acyclovir were currently being used. Physical examination revealed neither meningeal signs nor focal neurological deficits. Serum blood urea nitrogen, glucose, and electrolytes were within normal limits except for an elevated creatinine level at 6.2 and 5.7 mg/dl (before and after neuropsychotic symptoms, respectively). Complete blood count with differentiation was also unremarkable. Cerebrospinal fluid examination was not possible as the patient's family refused the lumbar puncture. Moreover, an electroencephalograph study and head computed tomography scan disclosed no abnormalities. Acyclovir-induced neurotoxicity was suspected. Therefore, acyclovir was discontinued. Subsequently, serum acyclovir and CMMG were checked by enzyme-linked immunosorbent assay. Serum acyclovir level was 1.6 mg/l (normal therapeutic level, 0.12,10.8 mg/l) and CMMG level was 5 mg/l. Emergent hemodialysis (4-h/session) was given; the neuropsychotic symptoms, including agitation, delirium, and visual and auditory hallucinations, greatly abated after the second session. The patient fully recovered after three consecutive days of hemodialysis; the serum was rechecked and revealed that the acyclovir level was below 0.5 mg/l and the CMMG level was undetectable. At the same time, his herpetic skin lesions resolved well. [source] Successful treatment of extensive muscle calcification in a patient with primary idiopathic polymyositis with diltiazemINTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006Yasser EMAD Abstract A 25-year-old female patient with documented diagnosis of polymyositis developed extensive muscle calcification in the left thigh muscles with overlying skin induration one year after her disease onset, despite well controlled myositis. Plain X-ray of the left femur and hip revealed extensive calcification involving the periarticular soft tissue shadows around the left hip and left upper thigh. The patient received diltiazem 90 mg/day in divided doses and follow-up plain X-ray study after 6 months of treatment revealed almost complete resolution of the muscle calcifications. [source] Acute Interaction of Baclofen in Combination With Alcohol in Heavy Social DrinkersALCOHOLISM, Issue 1 2009Suzette M. Evans Background:, There is growing evidence that gamma-amino butyric acid-B receptor agonists may be effective in the treatment of alcohol abuse or dependence. The primary goal of this study was to determine the safety of baclofen in combination with alcohol consumption in heavy drinkers. In addition, the effects of baclofen alone, and in combination with alcohol, on subjective effects, cognitive performance effects, as well as alcohol craving, were assessed. Methods:, Eighteen non-treatment-seeking heavy social drinkers (mean of 28 drinks per week), who did not meet the criteria for alcohol dependence participated. All individuals were tested using a double-blind double-dummy design with six 2-day inpatient phases. Baclofen (0, 40, and 80 mg) was administered 2.5 hours before alcohol (1.5 g/l body water or approximately 0.75 g/kg) or placebo beverages, given in 4 divided doses every 20 minutes. Results:, Baclofen, either alone or in combination with alcohol, produced only modest increases in heart rate and blood pressure and no adverse effects were reported. Baclofen did not increase positive subjective effects (e.g., Stimulant effects, Drug Liking) but did increase sedation and impair performance. Even though both baclofen and alcohol impaired performance, for the most part performance was not impaired to a greater extent when baclofen was combined with alcohol. Among this population of nondependent drinkers, baclofen did not alter alcohol craving or alcohol-induced positive subjective effects. Conclusions:, Baclofen alone has minimal abuse liability in heavy social drinkers, and baclofen is relatively well tolerated and safe when given in combination with intoxicating doses of alcohol. [source] Glucose production pathways by 2H and 13C NMR in patients with HIV-associated lipoatrophy,MAGNETIC RESONANCE IN MEDICINE, Issue 4 2004Brian C. Weis Abstract Patients with HIV taking protease inhibitors were selected for the presence (five subjects) or absence (five subjects) of lipoatrophy. Following an overnight fast, subjects were given oral 2H2O in divided doses (5 mL/kg body water), [U- 13C3] propionate (10 mg/kg), and acetaminophen (1000 mg). Glucose (from plasma) or acetaminophen glucuronide (from urine) were converted to monoacetone glucose for 2H NMR and 13C NMR analysis. The fraction of plasma glucose derived from gluconeogenesis was not significantly different between groups. However, flux from glycerol into gluconeogenesis relative to glucose production was increased from 0.20 ± 0.13 among subjects without lipoatrophy to 0.42 ± 0.12 (P < 0.05) among subjects with lipoatrophy, and the TCA cycle contribution was reduced. Lipoatrophy was associated with an abnormal profile of glucose production as assessed by 13C and 2H NMR of plasma and urine. Magn Reson Med 51:649,654, 2004. Published 2004 Wiley-Liss, Inc. [source] Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trialPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 1 2010Edgardo Abalos Summary Abalos E, Merialdi M, Wojdyla D, Carroli G, Campodónico L, Yao S-E, Gonzalez R, Deter R, Villar J, Van Look P. Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trial. Paediatric and Perinatal Epidemiology 2010; 24: 53,62. Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth. [source] Efficacy of prednisolone in children hospitalized for recurrent wheezingPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 4 2007Tuomas Jartti Data on the efficacy of corticosteroids on respiratory picornavirus-induced wheezing are limited. To determine whether prednisolone is effective in rhinovirus- or enterovirus-induced recurrent wheezing, we conducted a controlled trial comparing oral prednisolone (2 mg/kg/day in three divided doses for 3 days) with placebo in hospitalized wheezing children and studied post hoc virus-specific efficacy in early wheezing (<3 episodes, reported elsewhere) and in recurrent wheezing (,3 episodes). Virus-negative children where excluded. Our primary endpoint was the time until children were ready for discharge. Secondary endpoints included oxygen saturation and exhaled nitric oxide during hospitalization, duration of symptoms, blood eosinophil count, and impulse oscillometry 2 wk after discharge, and occurrence of relapses during the following 2 months. Virus-specific effects were analyzed with interaction analysis in a multivariate regression model. During the study period, 661 patients were hospitalized, 293 randomized, and 59 were accepted in this analysis (mean age 2.6 yr, s.d. 1.3). Prednisolone did not significantly decrease the time until ready for discharge in all patients (prednisolone vs. placebo, medians, 18 vs. 24 h, p = 0.11). However, prednisolone decreased the time until ready for discharge in children with picornavirus infection (respectively, 12 vs. 24 h, p = 0.0022) and more specifically, in children with enterovirus infection (6 vs. 35 h, p = 0.0007). In the secondary endpoints, prednisolone decreased the duration of cough and dyspnea in rhinovirus-affected children (p = 0.033 for both). Prospectively designed clinical trial is needed to test the hypothesis that prednisolone reduces symptoms in picornavirus-affected wheezing children. [source] A phase 2 trial of all- trans -retinoic acid in combination with interferon-,2a in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology Branch, NCI and Children's Oncology Group StudyPEDIATRIC BLOOD & CANCER, Issue 5 2007Peter C. Adamson MD Abstract Background The combination of the antiproliferative and differentiation-inducing effects of retinoids together with the antiproliferative, immunostimulatory, and differentiation-potentiating effects of interferon-, (IFN-,) were the basis for the development of this combination in pediatric patients with refractory neuroblastoma or Wilms tumor. Procedure A phase 2 trial of all- trans -retinoic acid (ATRA), administered orally at a dose of 90 mg/m2/day in three divided doses for 3 consecutive days per week, and IFN-,2a, administered subcutaneously daily at a dose of 3,×,106 U/m2/day for 5 consecutive days per week, in 4 week cycles was performed. A two-stage design was used for each disease stratum. Results Seventeen patients (16 evaluable) with neuroblastoma, median age 9 years, and 15 patients (14 evaluable) with Wilms tumor, median age 6 years, were enrolled. Overall, the combination was well tolerated, with headache being the most common toxicity observed. There were no complete or partial responses. The median number of cycles administered was 1 (range 1,9). Four patients with neuroblastoma had stable disease for 12 or more weeks. Conclusions The combination of ATRA and IFN-,2a was inactive in children with relapsed or refractory neuroblastoma and Wilms tumor. The lack of activity with this combination in children with refractory neuroblastoma is similar to the disappointing phase 2 results of single agent 13- cis -retinoic-acid (13cRA) and does not support further development of ATRA for children with relapsed neuroblastoma. Pediatr Blood Cancer 2007;49:661,665. © 2006 Wiley-Liss, Inc. [source] Correlation of IMPDH1 Gene Polymorphisms with Subclinical Acute Rejection and Mycophenolic Acid Exposure Parameters on Day 28 after Renal TransplantationBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010Hideaki Kagaya The correlations with subclinical acute rejection, IMPDH1 polymorphisms and MPA exposure on day 28 post-transplantation were investigated in 82 Japanese recipients. Renal transplant recipients were given combination immunosuppressive therapy consisting of tacrolimus and 1.0, 1.5 or 2.0 g/day of MMF in equally divided doses every 12 hr at designated times. There were no significant differences in the incidence of subclinical acute rejection between IMPDH1 rs2278293 or rs2278294 polymorphisms (p = 0.243 and 0.735, respectively). However, in the high MPA night-time exposure range (AUC >60 ,g·h/ml and C0 , 1.9 ,g/ml), there was a significant difference in the incidence of subclinical acute rejection between IMPDH1 rs2278293 A/A, A/G and G/G genotypes (each p = 0.019), but not the IMPDH1 rs2278294 genotype. In the higher daytime MPA exposure range, patients with the IMPDH1 rs2278293 G/G genotype also tended to develop subclinical acute rejection. In patients with the IMPDH rs2278293 A/A genotype, the risk of subclinical acute rejection episode tends to be low and the administration of MMF was effective. The risk of subclinical acute rejection for recipients who cannot adapt in therapeutic drug monitoring (TDM) of MPA seems to be influenced by IMPDH1 rs2278293 polymorphism. The prospective analysis of IMPDH1 rs2278293 polymorphism as well as monitoring of MPA plasma concentration after transplantation might help to improve MMF therapy. [source] A randomized study of docetaxel and dexamethasone with low- or high-dose estramustine for patients with advanced hormone-refractory prostate cancerBJU INTERNATIONAL, Issue 3 2006THOMAS NELIUS OBJECTIVE To test the combination of docetaxel with two different doses of estramustine in patients with hormone-refractory prostate cancer (HRPC), to improve response rates and to lower side-effects, as docetaxel-based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival. PATIENTS AND METHODS In all, 72 patients with metastatic HRPC were randomly assigned to receive docetaxel (70 mg/m2 intravenously, on day 2 every 21 days) and estramustine (3 × 280 mg/day oral starting 1 day before docetaxel, for 5 consecutive days) for arm A, or estramustine (3 × 140 mg/day oral starting 1 day before docetaxel, for 3 consecutive days) for arm B. Premedication with oral dexamethasone at a total daily dose of 16 mg, in divided doses twice a day was administered in arm A on day 1,5 and in arm B on day 1,3. Initially, six cycles were administered. Chemotherapy was restarted after a significant increase in prostate-specific antigen (PSA) level. Patients were monitored for any measurable PSA response and toxicity. RESULTS Between the arms there was no statistically significant difference in time to progression and overall survival. However, treatment B had less treatment-related toxicity than A. Independent prognostic variables were baseline factors like PSA level, haemoglobin level, Eastern Cooperative Oncology Group performance status, and bone pain at presentation. CONCLUSIONS In this randomized phase II study the combination of docetaxel and estramustine had substantial activity in HRPC, with a significant incidence of severe toxicity, both haematological and not. Nevertheless, treatment-related toxicity was predictable and manageable. There was no better effect with a higher dose of estramustine with docetaxel than for a lower dose. There was a slight tendency to higher toxicity for high-dose estramustine but this was not statistically significant. The present results support the assertion that estramustine is not necessary in docetaxel-based treatment regimens. [source] Comparison of the efficacy and safety of miconazole 50-mg mucoadhesive buccal tablets with miconazole 500-mg gel in the treatment of oropharyngeal candidiasis,CANCER, Issue 1 2008A prospective, comparative, multicenter, neck cancer, phase III trial in patients treated with radiotherapy for head, randomized, single-blind Abstract BACKGROUND. Topical antifungal treatments are recommended but rarely used as first-line therapy for oropharyngeal candidiasis (OPC) in patients with cancer. Miconazole Lauriad 50-mg mucoadhesive buccal tablet (MBT) Loramyc reportedly delivered rapid and prolonged, effective concentrations of miconazole in the mouth. The objective of the current study was to compare MBT with miconazole 500-mg oral gel (MOG) in patients with head and neck cancer. METHODS. Two hundred eighty-two patients with head and neck cancer received a 14-day treatment of either single-dose MBT or MOG administered in 4 divided doses. The primary endpoint was clinical success at Day 14, and secondary endpoints included clinical success at Day 7, clinical cure, improvement in clinical symptoms, mycologic cure, recurrence rate, and safety. RESULTS. The success rate was statistically not inferior (P < .0001) in the MBT population to the rate observed in the MOG group (56% vs 49%, respectively; P < .0001). After adjustment for the extent of lesions and salivary secretions, a trend toward superiority was observed in favor of MBT (P = .13), particularly among patients with multiple lesions (P = .013). Results for secondary endpoints were comparable to those observed for the primary endpoint. Compliance with MBT was excellent, and >80% of patients completed treatment. Both treatments were safe. CONCLUSIONS. The success rate of MBT Loramyc was significantly not inferior to that of MOG in the treatment of cancer patients with OPC; and, after adjusting for prognostic variables, it was more effective than MOG. MBT was well tolerated and, thus, may be recommended as first-line treatment in cancer patients who have OPC as an alternative to systemic antifungal agents. Cancer 2008. © 2007 American Cancer Society. [source] Treatment of advanced colorectal carcinoma with oxaliplatin and capecitabineCANCER, Issue 3 2004A Phase II trial Abstract BACKGROUND The current study was designed to evaluate the antitumor activity and toxicity of capecitabine and oxaliplatin in previously untreated patients with advanced colorectal carcinoma. The primary endpoint of the study was to determine the objective response rate, and a secondary endpoint was to measure the time to disease progression. METHODS A 2-stage trial was planned with an accrual goal of 35 patients. The treatment included oxaliplatin given at a dose of 130 mg/m2 on Day 1 of each 3-week cycle. Initially, capecitabine at a dose of 2000 mg/m2/day in 2 divided doses was given on Days 1,14 of each cycle, but this was reduced to a dose of 1500 mg/m2/day because of toxicity. Patients were followed by computed tomography scans every two cycles to evaluate treatment response, and toxicity was monitored. RESULTS The first 13 patients on the trial received the higher dose of capecitabine. Although 5 responses (38.5%) were noted, 5 patients were hospitalized with diarrhea and dehydration. This toxicity led to a decrease in the dose of capecitabine to 1500 mg/m2/day and an additional 35 patients were treated. At the lower dose, the partial response rate was 37.1% (95% confidence interval [95% CI], 21.5,55.1%). The estimated median progression-free survival was 6.9 months (95% CI, 4.4,8.2 months). At the lower dose, four patients were hospitalized with diarrhea/dehydration (with one death reported), one with febrile neutropenia, and one with ventricular fibrillation. Overall, Grade (according to version 2.0 of the National Cancer Institute Common Toxicity Criteria) 3-4 diarrhea was reported to develop in 20% of those patients treated at the capecitabine dose of 1500 mg/m2/day compared with 62% of patients treated at the dose of 2000 mg/m2/day. CONCLUSIONS The combination of oxaliplatin and capecitabine is an active and convenient regimen for the treatment of patients with advanced colorectal carcinoma and should be compared with other front-line regimens as therapy for disease. Cancer 2004. © 2003 American Cancer Society. [source] Activity of interferon-, and isotretinoin in patients with advanced, refractory lymphoid malignanciesCANCER, Issue 3 2004Apostolia-Maria Tsimberidou M.D., Ph.D. Abstract BACKGROUND Interferon-, (IFN-,) and retinoids have shown nonoverlapping toxicity and each has shown antitumor activity in patients with lymphoma. The aim of the current study was to assess the toxicity, safety, and efficacy of IFN-, combined with isotretinoin in patients with advanced, refractory lymphoid malignancies. METHODS Adults with biopsy-proven advanced lymphoid malignancy were treated. Patients with compromised bone marrow function (platelet counts as low as 30 × 109/L) were eligible. Treatment was comprised of IFN-, at a starting daily dose of 3 mega units subcutaneously and isotretinoin orally starting at a dose of 1 mg/kg daily in 2 divided doses. RESULTS Forty-four patients were evaluable. Their median age was 57 years (range, 18,82 years). Eighteen patients had advanced cutaneous T-cell lymphoma, 6 patients had peripheral T-cell lymphoma, 14 patients had Hodgkin disease, and 6 patients had a variety of other lymphoid malignancies. Patients with Hodgkin disease had received a median of 6 previous therapies (range, 3,12 therapies) and patients with other lymphoid malignancies had received a median of 4 previous therapies (range, 1,9 therapies). The median duration of treatment was 4 months (range, 0.25,38 months). The overall response rate was 38.6% (complete response in 5 patients [11.3%] and partial response in 12 patients [27.3%]). The median response duration was 3 months (range, 1,95+ months). The most common toxicities were low-grade fever, flu-like symptoms, and fatigue (IFN-, effects); dry mouth and skin and hypertriglyceridemia (cis-retinoic acid effects); and thrombocytopenia (which generally occurred in patients with low baseline platelet counts). CONCLUSIONS IFN-, and isotretinoin combination therapy had antitumor activity and was well tolerated in heavily pretreated patients with lymphoid malignancies. Cancer 2004. © 2003 American Cancer Society. [source] Glucocorticoid replacement is associated with hypertriglyceridaemia, elevated glucose and higher non-HDL cholesterol and may diminish the association of HDL cholesterol with the ,629C>A CETP promoter polymorphism in GH-receiving hypopituitary patientsCLINICAL ENDOCRINOLOGY, Issue 3 2008Robin P. F. Dullaart Summary Objectives, The effect of glucocorticoid substitution on the prevalence of metabolic syndrome components (NCEP ATP III criteria) and serum lipid levels was determined in GH-replaced hypopituitary patients. As glucocorticoid replacement is associated with a pronounced decrease in plasma cholesteryl ester transfer protein (CETP) activity, we also tested associations of HDL cholesterol with the ,629C>A CETP promoter polymorphism in subjects with and without ACTH deficiency. Design and patients, In a university setting, we retrieved protocolized clinical and laboratory data from 165 adult hypopituitary patients, who had received GH for 1 year. Results, After adjustment for age, sex and smoking, non-HDL cholesterol (P = 0·05) and triglycerides (P = 0·004) were higher, but HDL cholesterol was not decreased in 117 glucocorticoid (mainly cortisone acetate in two divided doses) receiving subjects compared to 48 ACTH-sufficient subjects. The prevalence of elevated plasma glucose and/or diabetes (P = 0·04) and hypertriglyceridaemia (P = 0·005), but not of other metabolic syndrome components, was higher in glucocorticoid-replaced subjects. HDL cholesterol was higher in ,629 A allele carriers compared to ,629CC homozygotes in ACTH-sufficient subjects (P = 0·04), but not in glucocorticoid-treated subjects (P = 0·13). Multiple linear regression analysis demonstrated that only in ACTH-sufficient subjects, HDL cholesterol was independently related to this CETP gene variation (P = 0·03). Conclusions, In GH- and glucocorticoid-replaced hypopituitary patients, serum non-HDL cholesterol and triglycerides are higher and the prevalence of hyperglycaemia is increased, but HDL cholesterol is not decreased. Conventional glucocorticoid replacement appears to diminish the association of HDL cholesterol with a common CETP gene variation. [source] Why is the management of glucocorticoid deficiency still controversial: a review of the literatureCLINICAL ENDOCRINOLOGY, Issue 5 2005Anna Crown Summary All endocrinologists would like to make glucocorticoid replacement therapy for their hypoadrenal patients as physiological as possible. Many would like the reassurance of a method of monitoring such treatment to confirm that they are achieving this aim. Advances in our knowledge of the normal physiology are relevant to our attempts to do this. The cortisol production rate in normal subjects is lower than was previously believed. The normal pattern of glucocorticoid secretion includes both a diurnal rhythm and a pulsatile ultradian rhythm. Glucocorticoid access to nuclear receptors is ,gated' by the 11-,-hydroxysteroid dehydrogenase enzymes, which interconvert active cortisol and inactive cortisone. Such complexities make the target of physiological glucocorticoid replacement therapy hard to achieve. The available evidence suggests that conventional treatment of hypoadrenal patients may result in adverse effects on some surrogate markers of disease risk, such as a lower bone mineral density than age-sex matched controls, and increases in postprandial glucose and insulin concentrations. Although the quality of life of hypoadrenal patients may be impaired, there is no evidence of an improvement on higher doses of steroids, although quality of life is better if the hydrocortisone dose is split up, with the highest dose taken in the morning. Thus the evidence suggests that most patients may safely be treated with a low dose of glucocorticoid (e.g. 15 mg hydrocortisone daily) in two or three divided doses, with education about the appropriate action to take in the event of intercurrent illnesses. [source] Apparent low absorbers of cyclosporine microemulsion have higher requirements for tacrolimus in renal transplantationCLINICAL TRANSPLANTATION, Issue 4 2007Andrew A. House Abstract:, Bioavailability and exposure of cyclosporine microemulsion and tacrolimus in renal transplantation are governed by many complex factors. Failure to achieve therapeutic two-h post-dose (C2) levels despite adequate doses of cyclosporine ("low absorbers") may merit conversion to tacrolimus. We compared tacrolimus dose requirements in "low absorbers" (n = 15) with a random control group of de novo tacrolimus patients (n = 14). Low absorbers failed to reach target C2 despite increasing dose from 10.1 to 16.2 mg/kg/d. At conversion the mean C2 was 969 ng/mL (95% CI: 684,1255; target 1700 ng/mL). Low absorbers tended to be younger, heavier, and diabetic. Despite a similar initial tacrolimus dose (0.17,0.18 mg/kg/d), low absorbers required a much higher daily dose to achieve target; 0.25 vs. 0.16 mg/kg/d (p = 0.016). Furthermore, daily maintenance tacrolimus remained much higher in low absorbers at three wk (0.22 vs. 0.13 mg/kg/d, p = 0.012). Although not statistically significant, this group experienced an acute rejection rate of 33%, compared with 21% in the control group. Patients treated with cyclosporine as initial immunosuppression who fail to reach target C2 levels in a timely fashion are at risk for impaired bioavailability of tacrolimus. Based on our data, a starting dose of 0.25 mg/kg/d in divided doses may be warranted for low absorbers converting to tacrolimus; however, we encourage larger studies with formal pharmacokinetic analysis in this population. [source] | ||||||||||