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Initial Dose (initial + dose)
Selected AbstractsClinical Pharmacology of OxymorphonePAIN MEDICINE, Issue 2009Howard S. Smith MD ABSTRACT Oxymorphone (14-hydroxydihydromorphinone) is primarily a potent ,-opioid receptor agonist with oral immediate-release (IR) and extended-release (ER) formulations approved in the United States in 2006. The oral oxymorphone formulations are roughly three times more potent than oral morphine. It is more lipophilic than morphine and, thus, may more easily cross the blood-brain barrier because it differs from morphine having a ketone-group substituent at the C-6 position. Oxymorphone IR is indicated for the relief of moderate,to severe pain, while oxymorphone ER is indicated for persistent pain. Initial doses (opioid-naïve) are 10,20 mg every 4,6 hours (IR) and 5 mg every 12 hours (ER). Oxymorphone was found not to have any clinically significant cytochrome (CYP)3A4, CPY2C9, or CYP2D6 interactions, thus limiting its potential for causing some of the more common drug,drug interactions via the CYP450 system. The common adverse effects of oxymorphone are consistent with those commonly seen with other opioid, including nausea/vomiting, constipation, pruritis, pyrexia, somnolence, and sedation. [source] Topiramate Loading for Refractory Status Epilepticus in ChildrenEPILEPSIA, Issue 6 2006M. Scott Perry Summary:,Purpose: To describe three cases of refractory status epilepticus (RSE) in children responsive to topiramate (TPM). Methods: Patients with SE refractory to therapeutic doses of at least two antiepileptic medications were given TPM, 10 mg/kg/d, for 2 consecutive days, followed by maintenance doses of 5 mg/kg/d. Results: This protocol has been used in three cases of RSE at our institution. In each case, SE was aborted within 21 h of the initial dose of TPM. Two patients avoided pharmacologic coma, and one was rapidly weaned from continuous benzodiazepine infusion. Conclusions: Our experience indicates that TPM loading can be effective in the treatment of RSE in children. [source] Early Intervention With Almotriptan Improves Sustained Pain-free Response in Acute MigraineHEADACHE, Issue 10 2003Ninan T. Mathew MD Objective.,To determine whether treatment of migraine with almotriptan, when pain intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates compared with treatment when pain intensity is moderate or severe. Methods.,This was a post hoc analysis derived from an open-label, multicenter, long-term study of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who met International Headache Society criteria for migraine with or without aura were eligible. Patients were instructed to take a single dose of almotriptan 12.5 mg at the onset of a migraine attack. Rescue medication could be taken if migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5 mg could be taken if head pain recurred within 24 hours of the initial dose. Patients reported the intensity of pain at baseline and at 1 and 2 hours postmedication using a 4-point scale: no pain, mild, moderate, or severe pain. They also reported recurrence of pain (return of moderate or severe pain within 2 to 24 hours of taking the study medication) and use of rescue medication. Rescue medication consisted of supplemental analgesics taken for pain relief at 2 to 24 hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue medications. Based on these patient-reported end points, sustained pain-free rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and no use of rescue medication, were calculated. Results.,A higher proportion of migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with attacks of moderate or severe intensity (7.5%) (P < .001). Two-hour pain-free rates also were significantly higher with mild intensity pain (76.9%) compared to moderate or severe intensity (43.9%) (P < .001). In addition, recurrence rates and use of rescue medication were reduced when attacks were treated during mild pain. Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P < .001), and use of rescue medication was 9.4% for mild pain versus 17.2% for moderate or severe pain (P < .001). Sustained pain-free rates were nearly twice as high when attacks were treated during mild intensity pain (66.6%) compared with attacks treated during moderate or severe pain (36.6%) (P < .001). Conclusion.,Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity improves 1- and 2-hour pain-free and sustained pain-free responses. [source] Medium-term results of oral tacrolimus treatment in refractory inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Siew C. Ng MRCP Abstract Background: This study aimed to evaluate the efficacy of oral tacrolimus in patients with inflammatory bowel disease (IBD) refractory to conventional therapy, including azathioprine, 6-mercaptopurine, and infliximab. Methods: Retrospective review of all patients with IBD treated with oral tacrolimus was undertaken. Tacrolimus was administered at an initial dose of 0.05 mg/kg twice daily, aiming for serum trough levels of 5,10 ng/mL. We evaluated clinical response, a retrospective estimated Crohn's disease activity index (CDAI) for Crohn's disease (CD), modified Truelove-Witts index for ulcerative colitis (UC), and modified pouch disease activity index (mPDAI) for pouchitis. Patients had been monitored clinically for benefit and side effects and by whole blood tacrolimus level approximately every 4 weeks for the duration of treatment. Clinical remission was defined as an estimated CDAI <150 (CD), an inactive disease score on the Truelove-Witts index (UC), and mPDAI <5 (pouchitis). Results: Twelve patients with CD, six with UC, and one with pouchitis, all resistant to previous therapies, were treated for a median of 5 months. After 4 weeks 10 CD (83%), four UC (67%) patients, and one pouchitis patient had a clinical response. There was a median reduction of the estimated CDAI of 108 points (range 35,203; P = 0.002) and stool frequency of three per day at week 4. Remission was achieved in 42% (5/12) of CD and 50% (3/6) of UC patients at the end of follow-up. Side effects included temporary elevated creatinine (n = 1), tremor (n = 3), arthralgia (n = 1), insomnia (n = 1), and malaise (n = 1). Four patients discontinued treatment due to side effects. Conclusion: Oral tacrolimus is well tolerated and effective in patients with refractory IBD in the short- to medium-term. Further controlled, long-term evaluation is warranted. (Inflamm Bowel Dis 2007) [source] Acute febrile neutrophilic dermatosis (Sweet's syndrome) with nodular episcleritis and polyneuropathyINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2002Taizo Kato MD A 56-year-old Japanese housewife presented with multiple erythematous lesions in association with ocular hyperemia and pain in the right upper and lower extremities, including the hands and feet. These symptoms were preceded by a sore throat with persistent fever higher than 38.5 °C for about 1 week. Dermatologic examination showed tender, dull-red, erythematous lesions, measuring 1,2 cm in diameter, located predominantly on the forehead, cheeks, auricular region, neck, forearm, hands, and feet. A biopsy specimen obtained from an erythematous lesion on the right forearm revealed prominent edema in the papillary dermis and remarkable inflammatory cell infiltration throughout the entire dermis (Fig. 1). The infiltrate predominantly consisted of neutrophils and nuclear dust without signs of vasculitis. In routine examination, the leukocyte count was 15,000/mL (normal range, 4000,8000/mL) with severe neutrophilia (80%). The C-reactive protein (CRP) level was 17.65 mg/dL (normal range, < 0.5 mg/dL) and the anti-streptolysin (ASLO) level was 611 IU/mL (normal range, < 166 IU/mL). In human leukocyte antigen (HLA) testing, HLA-A2, -B39, -B35, -Cw2, and -Cw7 were positive, and HLA-B51, -B54, and -Cw1 were negative. Figure Figure 1 . Histologic picture showing a dermal infiltrate of neutrophils Ocular hyperemia was caused by episcleritis forming a nodule and surrounding congestion of the superficial episcleritic vessels at the central portion of the sclera (Fig. 2). The patient suffered from pain once an hour, continuing for about 3 min, at the lateral portion of the right upper and lower extremities, as well as the right small finger. Neurologic examination demonstrated moderate or slight muscle weakness in the extremities. Hand grasping powers were 9 and 7 kg on the right and left, respectively. The patient was right-handed. Dysesthesia and paresthesia were also observed on the hands and feet. The deep tendon reflexes were preserved, however, even in the distal portion of the upper and lower limbs. In addition, essential tremor localized to the neck was recognized. Magnetic resonance imaging did not show any episodes of transient abnormal signal intensity in the central nervous system. Figure 2. Nodular episcleritis (right eye). Telangiectasia of winding vessels with nodular elevation was observed at the upper portion of the sclera The patient was treated with prednisolone (initial dose of 30 mg/day) and intravenous injection of cefazolin sodium (2 g/day for 5 days). Almost complete regression of the ocular and neurologic manifestations, as well as the skin lesions, was achieved in 2 weeks. Prednisolone was reduced gradually and suspended after 4 weeks. Leukocyte and neutrophil counts, CRP, and ASO returned to normal on suspension of therapy. Slight paresthesia remained in the right small finger even after stopping steroid. There was no recurrence at follow-up 6 months later. [source] Cortisol response to two different doses of intravenous synthetic ACTH (tetracosactrin) in overweight catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2000J. P. Schoeman Fifteen middle-aged to older, overweight cats attending a first-opinion clinic were investigated to rule out hyperadrenocorticism as a cause of their weight problem, using two different protocols for the adrenocortlcotropic hormone (ACTH) stimulation test. The cats received intravenous synthetic ACTH (tetracosactrin) at an initial dose of 125 ,g; a second test was performed between two and three weeks later, using a dose of 250 vg intravenously. The mean basal serum cortisol concentration was 203 nmol/litre (range 81 to 354 nmol/litre). The highest mean serum cortisol concentration occurred at 60 minutes following the 125 ,g dose and at 120 minutes following the 250 ,g dose. There was, however, no statistically significant difference between these peak cortisol concentrations attained using either dose of tetracosactrin. A significantly higher mean serum cortisol concentration was attained after the higher dose at the 180 minutes time point, indicating a more prolonged response when compared with the lower dose. The cats were followed up for one year after the initial investigations and none were found to develop hyperadrenocorticism during this time. [source] AN OPEN STUDY OF RILUZOLE VERSUS RILUZOLE PLUS GABAPENTIN IN AMYOTROPHIC LATERAL SCLEROSISJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2000V Palma A randomised open study has been carried out to evaluate the efficacy of riluzole versus riluzole plus gabapentin in 50 patients (23 males, 27 females) affected by amyotrophic lateral sclerosis (ALS), who received the diagnosis according to El Escorial WFN criteria. At baseline, the mean age of the patients was 58.8 ± 11.7 years and the mean disease duration was 11.4 ± 5.9 months. Twenty patients had bulbar and 30 spinal onset. Twenty-eight patients were randomly assigned to riluzole (100 mg/day) and 22 to riluzole plus gabapentin at the initial dose of 300 mg/day, slowly increased to 1800 mg/day. Informed consent was obtained in all cases. Before treatment, each patient underwent neurological examination, Appel rate scale, pulmonary function tests, electromyography, and transcranial magnetic stimulation. Clinical examination and electrophysiologic tests were repeated at three-month intervals. Over the course of the trial, 4 patients (8%) were lost to follow-up and 16 (32%, 9 in the riluzole and 7 in the riluzole plus gabapentin group) died. The mean age at death was 65.0 ± 6.5 years after a mean disease duration of 20.8 ± 7.9 months (range 13,36). There was no significant difference in response to treatment when severity and duration of the disease were compared in the two groups. [source] Effects of Intravenously Administrated Omeprazole on Gastric Juice pH and Gastric Ulcer Scores in Adult HorsesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2006Frank M. Andrews The study was performed to evaluate the efficacy of omeprazole powder in sterile water, administered intravenously, on gastric juice pH in adult horses with naturally occurring gastric ulcers. Omeprazole (0.5 mg/kg, IV) was administered once daily for 5 days to adult horses with gastric ulcers. Gastric juice was aspirated through the biopsy channel of an endoscope and pH was measured before and 1 hour after administration of omeprazole on day 1, and then before and after administration of omeprazole on day 5. Gastric ulcer scores were recorded on day 1 before administration of omeprazole and on day 5, 23 hours after the 4th daily dose. Gastric juice pH and ulcer scores were compared between the times. When compared with the pre-injection value (2.01 ± 0.42), mean ± SD gastric juice pH was significantly higher when measured 1 hour after administration of the initial dose (4.35 ± 2.31), and before (5.27 ± 1.74) and 1 hour after (7.00 ± 0.25) administration of omeprazole on day 5. Nonglandular gastric ulcer number score significantly decreased from a mean ± SD of 3.2 ± 0.80 to 2.0 ± 1.1, but nonglandular gastric ulcer severity score remained the same. Few glandular ulcers were seen in the study, and scores did not change. Because of its potent and long duration of action on gastric juice pH, this intravenous formulation of omeprazole may show promise for treatment of equine gastric ulcer syndrome (EGUS) in horses with dysphagia, gastric reflux, or other conditions that restrict oral intake of omeprazole paste.a Aspiration of gastric juice and measurement of pH can be of use to determine whether the desired pH > 4.0 has been reached after omeprazole treatment. [source] Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North AmericaJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2007J. A. WREN Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0,112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8,14.0% compared with 3.0,3.9% for placebo (P = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs. [source] Mycophenolate mofetil in combination with reduction of calcineurin inhibitors for chronic renal dysfunction after liver transplantation,LIVER TRANSPLANTATION, Issue 12 2006Georges-Philippe Pageaux The purpose of the study was to introduce mycophenolate mofetil (MMF) in liver transplant recipients with renal dysfunction to decrease calcineurin inhibitor (CNI) dosages without increasing rejection risk. In this prospective, multicenter, randomized study, chronic CNI-related renal dysfunction was defined by an increase in serum creatinine with values >140 ,mol/L and <300 ,mol/L. Patients were randomized in 2 groups. Study group: combination of MMF (2 to 3 g/day) and reduced dose of CNI ,50% of initial dose; control group: no MMF, but with the ability to reduce CNI doses, but not below 75% of initial dose. Fifty-six patients were included, 27 in the study group and 29 in the control group. In the study group, there was a significant decrease in serum creatinine values, from 171.7 ± 24.2 ,mol/L at day 0 to 143.4 ± 19 ,mol/L at month 12 and a significant increase in creatinine clearance, from 42.6 ± 10.9 mL/min to 51.7 ± 13.8 mL/min. No rejection episode was observed in the study group. In the control group, there was no improvement of renal function, assessed by the changes in serum creatinine values, from 175.4 ± 23.4 ,mol/L at day 0 to 181.6 ± 63 ,mol/L at month 12, and in creatinine clearance, from 42.8 ± 12.8 mL/min to 44.8 ± 19.7 mL/min. The differences between the 2 groups were significant: P = 0.001 for serum creatinine, and P = 0.04 for creatinine clearance. In conclusion, the introduction of MMF combined with the reduction of at least 50% of CNI dose allowed the renal function of liver transplant recipients to significantly improve at 1 year, without any rejection episode and without significant secondary effects. Liver Transpl 12:1755,1760, 2006. © 2006 AASLD. [source] Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: A randomized, double-blind trialACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2004G. Dierking Background: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. Methods: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. Results: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53,88) mg to 43 (28,60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. Conclusion: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups. [source] Randomized trial comparing primidone initiation schedules for treating essential tremorMOVEMENT DISORDERS, Issue 2 2002Padraig O'Suilleabhain MB Abstract Early side effects are common when primidone is used to treat essential tremor, with as many as one-third of patients failing to tolerate the tablets. Lower doses can be prescribed initially using a suspension formulation. We suspected suspension initiation would result in fewer early side effects, allow better acclimatization, and improve compliance. Forty patients with essential tremor were randomized to begin primidone treatment using either 2.5 mg doses in the suspension form or 25 mg doses in the tablet form. Doses gradually increased over 3 weeks to 150 mg/day. This was a double-blind, double-dummy trial. Medication cessation due to side effects was designated the primary end-point. Four patients in the suspension group and two in the tablet group dropped out due to early side effects, resulting in a relative risk of 1.9 (95% confidence interval 0.4 to 9.2). Side effects in the first 48 hours of treatment were equally common, affecting seven subjects in each group. Treatment benefits were the same in both groups. We concluded that use of a very low initial dose and a graduated titration schedule in suspension formulation did not appear to improve primidone tolerability. If anything, compliance tended to be worse when compared with the tablet formulation, though the study was under-powered to reject the null hypothesis of equivalence. © 2002 Movement Disorder Society. [source] Safety and Efficacy of Intrathecal Baclofen Infusion by Implantable Pump for the Treatment of Severe Spinal Spasticity: A Spanish Multicenter StudyNEUROMODULATION, Issue 4 2000J Vidal MD Objective. To assess long-term efficacy, safety and functional benefit of intrathecal baclofen for severe spinal spasticity. Materials and Methods. This prospective multicenter study was performed in two stages: the first one consisted of an intrathecal bolus injection of baclofen, and the second of a continuous intrathecal baclofen infusion by means of an implantable pump. The sample consisted of 72 adult patients with severe spinal spasticity. Sixty-four were implanted and followed for 36 months. Muscular tone, spasms, and functional scales were evaluated before and periodically after administration of the drug, with a follow-up period of 36 months. Results. A very significant decrease in tone and spasms was observed in all cases (p < 0.001). Tolerance appeared during the first 12 months, increasing doses from a mean initial dose of 83.2 ,g (range 25,200 ,g) to a mean final dose of 270 ,g (range 25,800 ,g). Later on, efficacy remained stable, except in cases of mechanical problems of the infusion system. [source] (231) Use of Transmucosal Fentanyl in Non-Malignant, Chronic PainPAIN MEDICINE, Issue 3 2001Forest Tennant Transmucosal fentanyl (TF) has recently become available for treatment of breakthrough pain in cancer patients who are already tolerant to opioids. In addition to cancer patients, there is a growing number of chronic pain patients who regularly use and are tolerant to opioids and require a breakthrough opioid for adequate pain control. This pilot study was done to determine if TF is effective and acceptable to non-malignant, chronic pain patients who are opioid tolerant and require a breakthrough opioid(s) for pain control. Sixty patients with chronic, non-malignant pain who were maintained on a long-acting opioid and who required breakthrough pain control were given TF in an initial dose of 400 or 600 mcg per single, transmuscosal administration. Among the study group 35 (58.3%) experienced chronic pain due to injuries to the spine and 25 (41.7%) were due to medical conditions other than cancer. After at least three months of usage, patients were asked if they desired to continue TF and the reason(s) why they believed it to be effective. Fifty-eight (96.7%) of these subjects perceived that TF was an effective breakthrough opioid and desired to continue it. The single, effective dosage ranged from 800 to 1600 mcg per administration, and the number of separate monthly dosages ranged from 2 to 360. The majority of patients used TF only for emergency, pain purposes but others preferred TF as their major breakthrough opioid and ceased use of other short-acting opioids including injectable meperidine. Reported reasons for widespread patient acceptance included TF's fast action, fewer bed-bound days, increased energy, decreased use of other opioids, less depression, and fewer emergency room visits. This pilot study indicates that TF is effective and desired as a preferential opioid for breakthrough pain by a high percentage of chronic, non-malignant pain patients. [source] A single versus multiple doses of dexamethasone in infants wheezing for the first timePEDIATRIC PULMONOLOGY, Issue 9 2008Suzanne Schuh MD Abstract Rationale: Corticosteroid therapy is not routinely recommended in true bronchiolitis. However, since bronchiolitis and the first asthma attack are impossible to distinguish, some infants with the first wheezing episode receive corticosteroids. Optimal duration of corticosteroid therapy in this scenario is unknown. This study compared efficacy of multiple administrations and a single dose of dexamethasone in bronchiolitis. Methods: In this randomized double blind trial, previously healthy outpatients 2,23 months of age with bronchiolitis and Respiratory Disease Assessment Instrument (RDAI) score 6 or more received 1 mg/kg of oral dexamethasone in the Emergency Department. Prior to discharge at 4 hr they were randomized to either 4 daily doses of dexamethasone 0.15 mg/kg or placebo equivalent. Primary outcome was the proportion of subsequent hospitalizations or prescribed trials of bronchodilator/corticosteroid therapy for dyspnea by day 6 in the groups. Secondary outcomes were changes in the RDAI to day 6, and proportions with unscheduled visits by days 6 and 28. Results: The rate of primary outcome in the single dose group (SDG, N,=,64) was 9/64 or 14.1% versus 7/61 or 11.5% in the multiple dose group (MDG, N,=,61) [95% CI 0.09; 0.14]. Twelve (18.8%) children in the SDG had unscheduled medical visits by day 6 versus 11 (18.0%) children in the MDG [95% CI 0.13; 0.14]. On day 6 the RDAI decreased from 9.5,±,2.1 to 2.1,±,2.4 in the SDG and from 9.8,±,2.2 to 1.6,±,2.3 in the MDG [95% CI 0.36; 2.06]. Between days 7,28, 24/64 (37.5%) SDG infants returned for care versus 20/61 (32.8%) of the MDG [95% CI 0.12; 0.21]. Conclusions: Our study suggests that, in outpatients with bronchiolitis who receive dexamethasone, continuation of this agent beyond the initial dose does not provide significant benefit. Pediatr Pulmonol. 2008; 43:844,850. © 2008 Wiley-Liss, Inc. [source] Oral administration of tacrolimus in the presence of jejunostomy after liver transplantationPEDIATRIC TRANSPLANTATION, Issue 3 2001Toshimichi Hasegawa Abstract: The feasibility of oral administration of tacrolimus in the presence of an intestinal stoma after liver transplantation (LTx) has not been adequately demonstrated. A 10-month-old girl underwent LTx with biliary reconstruction using a Roux-en Y loop. She developed intestinal perforation and underwent a jejunostomy at 40,50 cm distal to the jejunojejunostomy of the Roux-en Y loop on day 8 post-LTx. Tacrolimus was given twice daily via a nasogastric tube or orally; the initial dose of tacrolimus was 0.10 mg/kg/day. Until the time of intestinal perforation, the trough level of tacrolimus ranged from 13.0 to 19.6 ng/mL. The dose-normalized trough concentration (DNTC) of tacrolimus ranged from 130 to 196 ng.kg.daypermg.mL (control: 80,145 ng.kg.daypermg.mL). For a 2-week period when the patient was septic, the tacrolimus dose was reduced to 0.05 mg/kg/day, with a subsequent trough level of 3.6,5.1 ng/mL (DNTC: 72,102 ng.kg.daypermg.mL). After 3 weeks, the dose was increased to 0.175 mg/kg/day with the disappearance of infection; the trough level ranged from 8.5 to 9.7 ng/mL with a peak level of 26.3 ng/mL (DNTC: 48.5,55.4 ng.kg.daypermg.mL). After the initiation of oral feeding, the dose was slightly increased to 0.20 mg/kg/day with the trough level ranging from 8.1 to 9.8 ng/mL (DNTC: 40.5,49 ng.kg.daypermg.mL). After closure of the jejunostomy, the dose of tacrolimus was reduced to 0.075 mg/kg/day to maintain the same trough level (7.9,9.1 ng/mL) and the DNTC ranged from 105 to 121 ng.kg.daypermg.mL. In conclusion, oral administration of tacrolimus may achieve the therapeutic level, even in the presence of jejunostomy after LTx, although the bioavailability is decreased. [source] Effectiveness of Amitriptyline Versus Cough Suppressants in the Treatment of Chronic Cough Resulting From Postviral Vagal Neuropathy,THE LARYNGOSCOPE, Issue 12 2006Anita Jeyakumar MD Abstract Objective: The objective of this prospective, randomized, controlled study (N = 28) was to evaluate the effectiveness of amitriptyline versus cough suppressants in the treatment of chronic cough resulting from postviral vagal neuropathy. Methods: Patients were selected based on a clinical history consistent with postviral vagal neuropathy and a history of an antecedent upper respiratory tract infection. All patients had been tried on antireflux medication (proton pump inhibitors) and had a negative chest x-ray before presentation. All were nonsmokers without a history of asthma. Patients on angiotensin-converting enzyme inhibitors were excluded from the study. All patients completed a pretreatment, validated cough-specific quality-of-life (QOL) survey. Patients were randomized by chart numbers to either 10 mg amitriptyline at bedtime or 10 to 100 mg/5 mL, 10 mL codeine/guaifenesin every 6 hours standing dose while awake. Both groups were instructed to complete 10 days of therapy and then asked to subjectively rate the reduction in the frequency and severity of their cough by 100%, 75%, 50%, 25%, or 0% as well as completing the posttreatment cough QOL questionnaire. Those patients experiencing a 75% to 100% reduction were recorded as having a complete response, 25% to 50% a partial response, and 0% as having no response. Final results and the cough QOL survey were recorded and used for statistical analysis. Results: A majority of patients in the amitriptyline group achieved a complete response on the initial dose of 10 mg. None of the codeine/guaifenesin group achieved a complete response. The data were analyzed using a logistic regression model, and amitriptyline was found to be a highly significant predictor of a greater than 50% response when compared with codeine/guaifenesin (P = .0007). The same data were analyzed using a proportional odds model and similar results were noted. Conclusions: Chronic cough can have a profound impact on the psychosocial function of patients. The most common causes of a persisting cough in the absence of infection or chronic smoking are laryngopharyngeal reflux, asthma, particularly the cough variant, allergy, rhinosinusitis, bronchitis, and medications, in particular angiotensin-converting enzyme inhibitors. Currently, there are few effective treatments for cough with an acceptable therapeutic ratio and more selective drugs with a more favorable side effect profile are needed. This is this first prospective, randomized, controlled study comparing the effectiveness of amitriptyline versus codeine/guaifenesin for select cases of chronic cough resulting from suspected postviral vagal neuropathy. [source] The Use of Bivalirudin for Cardiopulmonary Bypass Anticoagulation in Pediatric Heparin-Induced Thrombocytopenia PatientsARTIFICIAL ORGANS, Issue 8 2010Richard Gates Abstract Infants with heparin-induced thrombocytopenia (HIT) represent a challenging and high-risk group of patients when they require cardiopulmonary bypass (CPB). Bivalirudin offers many potential pharmacologic advantages over other nonheparin anticoagulants for such patients. We describe our protocol for the use of bivalirudin in a 5-month-old infant undergoing stage 2 Norwood for hypoplastic left heart syndrome. The patient was a 5- month-old, 6-kg infant who developed HIT after a bowel resection complicating initial Norwood stage 1. After sternotomy and dissection had been redone, the child received an initial dose of bivalirudin of 1.0 mg/kg and 0.5 mg/kg 5 min later. The CPB circuit was primed with 50 mg/kg bivalirudn/400 cc volume. With the initiation of CPB, a continuous infusion of 2.5 mg/kg bivalirudin was begun. Activated clotting time (ACT) was targeted for over 400 s, with an examination prior to bypass and each 15 min thereafter. Bivalirudin was discontinued with separation from bypass and during modified ultrafiltration (MUF). The ACT was 286 s after the initial 1 mg/kg bolus and 597 s after the second 0.5 mg/kg bolus and initiation of CPB. At a rate of 2.5 mg/kg/min, ACT ranged between 461 and 597 s. At the completion of MUF, the ACT was 316 s. The ACT was 214 s 20 min after MUF. No clots were noted in the CPB circuit, and good hemostasis was achieved within 10 min after MUF was completed. Incision to closure time was 160 min; time from completion of MUF to sternal closure was 30 min. Post-MUF, 60 cc of processed cell saver blood was reinfused, and no clotting factors were required. Chest tube output was 10, 10, 3, and 4 ccs, respectively, at hours 1,4 post operation. Bivalirudin provides effective anticoagulation in infants requiring CPB in the presence of HIT. Bivalirudin's efficacy is effectively monitored by ACT, and, after CPB, its short half-life and ability to be ultrafiltered facilitate the ability to achieve hemostasis in a timely fashion. [source] Regulatory mechanisms of intestinal iron absorption,Uncovering of a fast-response mechanism based on DMT1 and ferroportin endocytosisBIOFACTORS, Issue 2 2010Marco T. Núñez Abstract Knowledge on the intestinal iron transport process and the regulation of body iron stores has greatly increased during the last decade. The liver, through the sensing of circulating iron, is now recognized as the central organ in this regulation. High iron levels induce the synthesis of hepcidin, which in turn decreases circulating iron by inhibiting its recycling from macrophages and its absorption at the intestine. Another mechanism for the control of iron absorption by the enterocyte is an active Iron Responsive Element (IRE)/Iron Regulatory Protein (IRP) system. The IRE/IRP system regulates the expression of iron uptake and storage proteins thus regulating iron absorption. Similarly, increasing evidence points to the transcriptional regulation of both divalent metal transporter 1 (DMT1) and ferroportin expression. A new mechanism of regulation related to a phenomenon called the mucosal block is starting to be unveiled. The mucosal block describes the ability of an initial dose of ingested iron to block absorption of a second dose given 2,4 h later. Here, we review the mechanisms involved in the expression of DMT1 and ferroportin, and present recent evidence on the molecular components and cellular processes involved in the mucosal block response. Our studies indicate that mucosal block is a fast-response endocytic mechanism destined to decrease intestinal iron absorption during a high ingest of iron. [source] Pharmacokinetics and safety of oral almotriptan in healthy male volunteersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2004J. McEwen Abstract Almotriptan (LAS 31416) is a new, oral, specific 5-hydroxytryptamine1B/1D receptor agonist for the treatment of migraine. The pharmacokinetics and safety of a range of oral doses were assessed in 23 healthy male volunteers. Peak plasma concentrations were reached between 1.5 and 4 h after dosing. The maximum plasma concentration and area under the curve showed dose proportionality over the dose range 5,200 mg. The elimination half-life was constant at approximately 3 h across all dose levels. A substantial proportion of the initial dose was excreted in urine (27%,39%) during 12 h post-dose and the main excretory product was unchanged drug. Three major urinary metabolites were detected, all of which were pharmacologically inactive. The most common events following almotriptan administration were headache, tiredness and mild nausea. Nine events (18%) were classed as probably related to almotriptan and these were all at the highest dose level of 200 mg. The maximum tolerated dose of almotriptan was, therefore, determined as 150 mg. In conclusion, almotriptan is well tolerated following single, oral doses up to 150 mg and has predictable pharmacokinetics. Copyright © 2004 John Wiley & Sons, Ltd. [source] Randomised controlled trial comparing the efficacy of same-day administration of mifepristone and misoprostol for termination of pregnancy with the standard 36 to 48 hour protocolBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 2 2007J Guest Objective, To determine the efficacy of oral mifepristone followed by vaginal misoprostol 6 hours later compared with the standard 36- to 48-hour regimen for medical termination of pregnancy. Design, Single centre, two arm, parallel, open randomised controlled trial. Setting, Medical termination service at a teaching hospital. Sample, Four hundred and fifty women undergoing medical termination of pregnancy at up to 63 days of gestation. Methods, Eligible women were randomised to receive mifepristone 200 mg orally followed by vaginal misoprostol 800 micrograms either 6 hours (n= 225) or 36,48 hours (n= 225) later. All participants were invited to attend for a follow-up pelvic ultrasound scan within 7 days following the misoprostol administration. For those women in whom products of conception remained at the follow-up ultrasound scan, expectant management ensued with weekly follow-up ultrasound scans until the termination was complete. They could elect to undergo an evacuation of uterus at any stage following the scan. Those women with a nonviable gestation sac at the follow-up scan were offered a further dose of vaginal misoprostol 800 micrograms or suction termination of pregnancy. Women with a continuing pregnancy were managed with surgical termination. Main outcome measure, Successful medical abortion defined as no requirement for medical or surgical intervention beyond the initial dose of misoprostol. Results, One hundred and sixty-five women (79%) in the 6-hour group and 197 women (92%) in the 36- to 48-hour group had a successful termination at first follow-up ultrasound or presumed on the basis of other considerations (those not seen for ultrasound but deemed successful by negative pregnancy test, products passed on ward or long-term assessment of notes). Twenty-two women (10%) in the 6-hour regimen required up to three further ultrasound scans after 7 days following the mifepristone administration in order to ensure that the termination process was complete. None of these women required a suction evacuation of uterus. In the 36- to 48-hour regimen, ten (5%) women had up to two further ultrasound scans to confirm a complete termination without the need for a surgical evacuation of uterus. Therefore, the overall successful termination rate in the 6-hour regimen was 89% (187/210) compared with 96% (207/215) in the 36- to 48-hour regimen (relative risk = 0.92, 95% CI 0.84,0.98). Repeat administration of misoprostol or surgical treatment was required in 23 women (11%) in the 6-hour group and 8 women (4%) in the 36- to 48-hour group. A viable pregnancy was found in five women (2%) in the 6-hour group and in three women (1%) in the 36- to 48-hour group. Conclusions, Oral mifepristone 200 mg followed by vaginal misoprostol 800 micrograms after 6 hours is not as effective at achieving a complete abortion compared with the 36- to 48-hour protocol. [source] Phase II study of pentostatin in advanced T-cell lymphoid malignanciesCANCER, Issue 2 2004Update of an M. D. Anderson Cancer Center series Abstract BACKGROUND The goal of the current study was to assess the toxicity, safety, and efficacy of pentostatin in patients with T-cell lymphoid malignancies. METHODS Patients were eligible if they had biopsy-proven T-cell lymphoma or leukemia and failure to respond to previous therapy or an expected complete response rate to conventional therapy of < 20%. Pentostatin was administered at an initial dose of 3.75 or 5.0 mg/m2 by intravenous bolus daily over a consecutive 3-day period every 3 weeks. RESULTS Forty-two of 44 patients enrolled in the study were evaluable. The median age of the patients was 62 years (range, 38,86 years). Patients received a median of 3 previous therapies (range, 0,10 previous therapies). Of these patients, 32 (76%) had mycosis fungoides/Sézary syndrome and 10 patients (24%) had other T-cell leukemias or lymphomas. The overall response rate was 54.8% (complete remission, 6 patients [14.3%]; partial remission, 17 patients [40.5%]). Durable responses were observed mainly in patients with Sézary syndrome or peripheral T-cell lymphoma. The median follow-up period for surviving patients was 20 months (range, 1,83+ months). The median duration of response was 4.3 months (range, 1,61 months). The most common toxicities were neutropenia, nausea, and CD4 suppression. A transient early ,flare' of disease was observed in some responders. CONCLUSIONS At these doses, pentostatin was reasonably well tolerated and is an effective drug for the treatment of T-cell lymphomas. Cancer 2004;100:342,9. © 2003 American Cancer Society. [source] A phase II study of gemcitabine and docetaxel therapy in patients with advanced urothelial carcinomaCANCER, Issue 9 2003Barbara J. Gitlitz M.D. Abstract BACKGROUND The objectives of the current study were to evaluate the safety and efficacy of gemcitabine plus docetaxel in patients with unresectable (Stage T4 or , N1) metastatic or locally advanced transitional cell carcinoma (TCC) of the urothelial tract. METHODS A total of 27 patients were enrolled in the current multisite study, which was performed within the University of California-Los Angeles Community Oncology Research Network. The first 10 patients in the study received 800 mg/m2 of gemcitabine intravenously on Days 1, 8, and 15 of a 28-day treatment cycle. In addition, on Day 1, the first 10 patients received 80 mg/m2 of docetaxel intravenously after completion of the gemcitabine infusion. Because of dose-limiting toxicity (neutropenia), the initial dose of docetaxel was reduced to 60 mg/m2 for the remaining patients who entered the study (n = 17 patients). RESULTS Neutropenia was the most common adverse event that occurred in patients at the Grade 3 level (in 10 of 27 patients; 37.0%) and the Grade 4 level (in 6 of 27 patients; 22.2%). There were no other adverse events at the Grade 4 toxicity level. Twenty-five of 27 patients (92.6%) completed more than 1 cycle of combination therapy and were evaluated for antitumor responses. The frequency of objective clinical responses was 33.3% (9 of 27 patients). Complete responses to therapy were observed in 2 of 27 patients (7.4%), and partial responses were observed in 7 of 27 patients (25.9%). The median duration of response was 20 weeks (range, 12+ weeks to 152 weeks). The median survival duration was 52 weeks (range, 12 weeks to 160+ weeks). Four of 27 patients (14.8%) remained alive at the time of the current data analysis. CONCLUSIONS The results of the current study suggested that combination therapy with gemcitabine and docetaxel was an effective treatment for patients with unresectable (Stage T4 or , N1) metastatic or locally advanced TCC of the urothelial tract. Gemcitabine plus docetaxel appeared to be tolerated well, and treatment-related toxicities were limited to hematologic toxicities. Because cisplatin-containing regimens are contraindicated for patients with impaired renal function, the gemcitabine plus docetaxel combination may prove to be an effective and well tolerated treatment option for these patients. Cancer 2003. © 2003 American Cancer Society. [source] Head circumference and linear growth during the first 3 years in treated congenital hypothyroidism in relation to aetiology and initial biochemical severityCLINICAL ENDOCRINOLOGY, Issue 1 2004Sze May Ng Summary aims, To determine the head circumference and linear growth in children with congenital hypothyroidism (CH) during the first 3 years of life in relation to the aetiology of CH and initial biochemical severity of thyroid function. methods, We examined the head circumference and linear growth of 125 patients with CH from diagnosis up to 3 years of age. All infants had radionuclide scans prior to treatment. Patients were categorized into athyreosis, ectopia and dyshormonogenesis. Occipito-frontal circumference (OFC) SD, length SD, initial plasma TSH, initial plasma thyroxine (T4) and age of suppression of plasma TSH were compared between the groups. Multiple linear regression analysis was used to determine factors affecting OFC SD at 3 years of age. results, There were 125 children in the study: athyreosis (n = 34), ectopia (n = 73) and dyshormonogenesis (n = 18). No difference was found in gestation, birth weight, age of starting L-T4 and initial dose of L-T4 in mcg/kg/day between groups. Confirmatory plasma total T4 at diagnosis was significantly lower for athyreosis when compared with ectopia and dyshormonogenesis. Median values for confirmatory TSH were significantly lower in dyshormonogenesis compared with the other two groups. At diagnosis, OFC were similar in all three groups. Children with athyreosis showed significantly larger OFCs compared with ectopia and dyshormonogenesis from 1 to 3 years. Length SD was within 1 SD of normal population standards at diagnosis and did not differ between the three groups throughout the 3 years. Spearman's correlation for OFC SD at 3 years of age showed a significant negative correlation with initial confirmatory plasma T4 (r = ,0·35, P = 0·01). Multivariate analysis for OFC SD at 3 years of age showed confirmatory T4 as the only independent risk factor. conclusion, Children with athyreosis showed significantly larger OFC from 1 to 3 years of age compared with ectopia and dyshormonogenesis, independent of linear growth. Our data shows that initial confirmatory T4 at diagnosis is an independent factor influencing head growth in the first 3 years of life. [source] A multicentre, open-label, randomized comparative study of tigecycline versus ceftriaxone sodium plus metronidazole for the treatment of hospitalized subjects with complicated intra-abdominal infectionsCLINICAL MICROBIOLOGY AND INFECTION, Issue 8 2010S. Towfigh Clin Microbiol Infect 2010; 16: 1274,1281 Abstract Tigecycline (TGC) has demonstrated clinical efficacy and safety, in comparison with imipenem/cilastatin in phase 3 clinical trials, for complicated intra-abdominal infection (cIAI). The present study comprised a multicentre, open-label, randomized study of TGC vs. ceftriaxone plus metronidazole (CTX/MET) for the treatment of patients with cIAI. Eligible subjects were randomized (1:1) to receive either an initial dose of TGC (100 mg) followed by 50 mg every 12 h or CTX (2 g once daily) plus MET (1,2 g daily), for 4,14 days. The primary endpoint was the clinical response in the clinically evaluable (CE) population at the test of cure (TOC) assessment. Of 473 randomized subjects, 376 were CE. Among these, clinical cure rates were 70.4% (133/189) with TGC vs. 74.3% (139/187) with CTX/MET (95% CI ,13.1 to 5.1; p 0.009 for non-inferiority). Clinical cure rates for subjects with Acute Physiological and Chronic Health Evaluation II scores ,10 were 56.8% (21/37) with TGC vs. 58.3% (21/36) with CTX/MET. The microbiologic response was similar between the two treatment arms, with microbiological eradication at TOC achieved in 68.1% (94/138) of TGC-treated subjects and 71.5% (98/137) of CTX/MET-treated subjects. ( The most frequently reported adverse events (AEs) for both treatment arms were nausea (TGC, 38.6% vs CTX/MET, 27.7%) and vomiting (TGC, 23.3% vs CTX/MET, 17.7%). Overall discontinuation rates as a result of an AE were 8.9% and 4.8% in TGC- and comparator-treated subjects, respectively. The results obtaned in the present study demonstrate that TGC monotherapy is non-inferior to a combination regimen of CTX/MET with respect to treating subjects with cIAI. [source] Early intervention with second-generation antipsychotics in first-episode psychosis: results of an 8-week naturalistic studyEARLY INTERVENTION IN PSYCHIATRY, Issue 1 2010Richard C. Josiassen Abstract Objective: The objective was to compare short-term effectiveness of aripiprazole with three other second-generation antipsychotics (SGAs) in the treatment of first-episode psychosis. Method: In a naturalistic, ,single-blind' design, 60 subjects experiencing their first psychotic episode were treated for 8 weeks with aripiprazole (n = 19), risperidone (n = 16), olanzapine (n = 14) or quetiapine (n = 11). Medication and dosing decisions were made by treating psychiatrists, constrained to once-a-day dosing, low initial doses and no clozapine. Weekly ratings were obtained using the Positive and Negative Syndrome Scale (PANSS), Simpson-Angus Rating Scale and Barnes Akathasia Rating Scale. Weight and vital signs were also collected weekly. Results: The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged. Conclusions: Early intervention with low doses of four SGAs led to rapid symptom reduction in first-episode psychotic patients with severe psychopathology. Although no clear medication advantages were observed in the short term, longer duration studies with larger samples will be required for determining efficacy, rates of compliance, relapse prevention and diminished incidence of extrapyramidal signs and symptoms. [source] The BCH Epidural System, a safe system for epidural infusion analgesia in childrenPEDIATRIC ANESTHESIA, Issue 9 2002N. Llewellyn Epidural infusions in children are usually delivered by syringe drivers because of the lower volumes of local anaesthetic solutions used in children rather than in adult practice. Recently concern has arisen both via the media and anecdotally over a number of adverse events associated with intravenous administration of bupivacaine. We have designed and validated a system that should significantly reduce the possibility and incidence of this adverse effect. (1) [ The system is based on the reversal of the standard luer-lock system. ] A female 60 cc syringe is connected to a reversed 150 cm infusion line that is connected to a male epidural filter. The filter connects with standard epidural infusion catheters. The reversal of the luer-lock system requires that devices are also available for the initial doses of local anaesthetic, for the preparation of the epidural infusion syringe and for administration of rescue boluses of local anaesthetic. With this system it is extremely unlikely that the epidural syringe or infusion catheter can be connected to an intravenous line. It is also less likely that intravenous drugs may be connected to the epidural filter. [source] CANCER INPATIENTS MORPHINE USAGE: A NEW ENGLAND AREA SURVEYAUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 4 2003John Trollor ABSTRACT:,This is a one year study of the use of morphine in cancer patients in 10 inpatient facilities in the New England Area Health Service in the north-west of New South Wales. The study explored 170 admissions relating to 122 patients, most of whom were cared for by their general practitioners. The use of morphine in these cancer patients was compared with the recommendations made by the expert working group of the European Association of Palliative Care.1 Those items which matched the recommendations included the initial doses for new users of morphine and the subcutaneous route being the preferred parenteral route. The data in this study differed from the recommendations in that only half of the patients received the immediate release morphine when first given oral morphine, only 43% had orders for immediate release oral morphine for breakthrough pain (with a variable frequency) and a significant number of orders for parenteral and immediate release oral morphine for breakthrough pain were outside the recommended doses (100% and 86.2%, respectively). Written orders for immediate release oral and parenteral morphine involved a dose range in significant numbers while only 30% of patients had orders for parenteral morphine for breakthrough pain. There was a low use of fixed interval variable dose (FIVD) morphine charts despite these being available in most facilities. (See summary Appendix A.) [source] Alemtuzumab as treatment for residual disease after chemotherapy in patients with chronic lymphocytic leukemiaCANCER, Issue 12 2003Susan M. O'Brien M.D. Abstract BACKGROUND The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy. METHODS Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment. RESULTS The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow-up of 18 months. Six patients remained in disease remission between 24,38 months after therapy. Infusion-related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1,2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein,Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin. CONCLUSIONS Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated. Cancer 2003;98:2657,63. © 2003 American Cancer Society. [source] A novel therapeutic paradigm to treat congenital hypothyroidismCLINICAL ENDOCRINOLOGY, Issue 1 2008Sarah Mathai Summary Objective, To determine the effectiveness of a novel therapeutic paradigm to treat congenital hypothyroidism (CH) incorporating variable initial doses of L-T4 based on the underlying aetiology and frequent monitoring, up to 2 years of age. Design, Retrospective cohort study. Patients, Infants with primary CH diagnosed by newborn screening. Measurements, Treatment with L-T4 suspension initiated at 10, 12 and 15 µg/kg/day for dyshormonogenesis, ectopia and athyreosis, respectively. Serum TSH and free T4 (FT4) levels monitored weekly during the first 4 weeks, at 6 weeks, thereafter monthly during the first 2 years. Dose changes were made to keep FT4 level in upper half of the normal range. Results, Sixty-nine infants; 17 had dyshormonogenesis, 35 ectopia and 17 athyreosis. Seventy-eight percent of subjects normalized FT4 levels within 7 days of treatment and 100% within 14 days. TSH levels normalized in 26% of infants within 7 days and in 92% by 21 days. Supraphysiological levels of FT4 were noted in 28% of infants, for a maximum of 2 weeks. 48% infants needed one dose adjustment and 30% needed at least two in the first month. In 52 infants over the first 2 years, mean FT4 levels were consistently in the upper half of the normal range. Two or more dose adjustments every 3 months were made 57 times in the first year as compared to 19 times in the second year. Conclusions, A variable initial dose paradigm based on aetiology with frequent testing and using T4 suspension rapidly normalizes FT4 levels without producing persistent hyperthyroxinaemia. [source] | |||||||||||||||||||||||||