Individualized Mycophenolate Mofetil Dosing Based on Drug Exposure Significantly Improves Patient Outcomes After Renal Transplantation

Efficacy and safety of mycophenolate mofetil (MMF) may be optimized with individualized doses based on therapeutic monitoring of its active metabolite, mycophenolic acid (MPA). In this 12-month study, 137 renal allograft recipients from 11 French centers receiving basiliximab, cyclosporine A, MMF and corticosteroids were randomized to receive either concentration-controlled doses or fixed-dose MMF. A novel Bayesian estimator of MPA AUC based on three-point sampling was used to individualize doses on posttransplant days 7 and 14 and months 1, 3 and 6. The primary endpoint was treatment failure (death, graft loss, acute rejection and MMF discontinuation). Data from 65 patients/group were analyzed. At month 12, the concentration-controlled group had fewer treatment failures (p = 0.03) and acute rejection episodes (p = 0.01) with no differences in adverse event frequency. The MMF dose was higher in the concentration-controlled group at day 14 (p < 0.0001), month 1 (p < 0.0001) and month 3 (p < 0.01), as were median AUCs on day 14 (33.7 vs. 27.1 mg*h/L; p = 0.0001) and at month 1 (45.0 vs. 30.9 mg*h/L; p < 0.0001). Therapeutic MPA monitoring using a limited sampling strategy can reduce the risk of treatment failure and acute rejection in renal allograft recipients 12 months posttransplant with no increase in adverse events.     

Endovascular treatment (EVT) of acute traumatic lesions of the descending thoracic aorta--7 years' experience.

OBJECTIVES: To present a single centers' 7-year experience in the endovascular treatment of acute traumatic lesions of the descending thoracic aorta (ATL of the DTA). MATERIALS & METHODS: Between March 1999 and December 2006, 34 consecutive acute traumatic lesions of the descending aorta (23 men, mean age 44 years) were treated endovascularly. Stentgrafts used were TAG Excluder, Zenith TX2 and Talent. In 23 patients the Left Subclavian Artery (LSA) was covered. Mean procedural duration was 20 to 75 minutes. RESULTS: Exclusion of the rupture site was achieved in all cases with no conversion to open surgery. Overall 30-day mortality was 8.8%. Two patients died on post operative day (pod) 1 and one on pod 22 from cranial injuries. No death or neurological deficit related to the endovascular treatment was reported. Four type I endoleaks required treatment either by balloon reexpansion (n=2) or by additional stentgraft implantation (n=2). In two patients the stentgraft collapsed totally several days postoperatively. Two patients required secondary surgical procedures (iliac access complication and revascularisation of the left subclavian artery n=1). The average follow-up was 43.8 months (1-93 months). No stentgraft related abnormality has been subsequently documented. CONCLUSIONS: The endovascular treatment of ATL of the DTA may offer the best means of therapy in a polytrauma patient.     

Perforation of a retrocaecal appendix presenting clinically as a right lumbar abscess.

Presentations of acute appendicitis represent an ongoing challenge to surgeons. This case of retrocaecal perforated appendicitis presented clinically as a right lumbar abscess, with the concomitant new diagnosis of type 2 diabetes mellitus in a 66-year-old male. This case emphasises the importance of an abdominal CT scan in any patient presenting with unusual sepsis near the abdomen.     

Usefulness of PCR Strategies For Early Diagnosis of Chagas'' Disease Reactivation and Treatment Follow-Up in Heart Transplantation

Heart transplantation (HTx) is a useful therapy for end‐stage Chaga? cardiomyopathy; however, Chagas reactivation remains a mayor complication. Parasitological methods offer poor diagnostic sensitivity, and use of more sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary. In the present study, reactivation incidence and PCR usefulness for early reactivation diagnosis, as well as for treatment response evaluation during follow‐up, were analyzed using Strout parasite detection test, in 10 of 222 consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and miniexon genes (SL‐DNA, 200 parasite/10 mL) were performed to compare parasite burdens between samples. No patients received prophylactic antiprotozoal therapy (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean period of 71.6 days; positive Strout results were observed in most cases presenting clinical manifestations. kDNA‐PCR was positive 38–85 days before reactivation, whereas SLDNA‐PCR became positive only 7–21 days later, revealing post‐HTx parasitic load enhancement present prior to clinical reactivation development. Reactivations were successfully treated with benznidazole and generated negative PCR results. Results observed in this study indicate the value of PCR testing for an early diagnosis of Chagas reactivation as well as for monitoring treatment efficacy.     

Subtotal resection of clavicle for chronic, recurrent, multifocal osteomyelitis in children

Chronic, recurrent, multifocal osteomyelitis (CRMO) is an obscure disease of bone, occurring in children. It appears to be an inflammatory condition with no obvious microbiological cause. Current treatments of antibiotics and anti-inflammatory medication appear to have limited success. This case report looks at two separate cases of CRMO where partial resection of the affected bone—the clavicle—leads to complete resolution of symptoms and regrowth of the excised bone.     

Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Pulmonary hypertension in patients with pulmonary fibrosis awaiting lung transplant.

Pulmonary hypertension (PH) may complicate idiopathic pulmonary fibrosis (IPF) but the prevalence of PH in IPF remains undefined. The present authors sought to describe the prevalence of PH in IPF. The lung transplant registry for the USA (January 1995 to June 2004) was analysed and IPF patients who had undergone right heart catheterisation (RHC) were identified. PH was defined as a mean pulmonary arterial pressure ((Ppa)) > or =25 mmHg and severe PH as a (Ppa) >40 mmHg. Independent factors associated with PH were determined. Of the 3,457 persons listed, 2,525 (73.0%) had undergone RHC. PH affected 46.1% of subjects; approximately 9% had severe PH. Variables independently associated with mild-to-moderate PH were as follows: need for oxygen, pulmonary capillary wedge pressure (P(pcw)) and forced expiratory volume in one second (FEV(1)). Independent factors related to severe PH included the following: carbon dioxide tension, age, FEV(1), P(pcw), need for oxygen and ethnicity. A sensitivity analysis in subjects with P(pcw) <15 mmHg did not appreciably alter the present findings. Pulmonary hypertension is common in idiopathic pulmonary fibrosis patients awaiting lung transplant, but the elevations in mean pulmonary arterial pressure are moderate. Lung volumes alone do not explain the pulmonary hypertension. Given the prevalence of pulmonary hypertension and its relationship with surrogate markers for quality of life (e.g. activities of daily living), future trials of therapies for this may be warranted.     

Definition, epidemiology and natural history of COPD.

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for alpha(1)-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.     

Congenital dextrocardia complicated by hypertension,coronary artery disease and myocardial infarction

The case record of a seventy-three year old man with congenital dextrocardia and situs inversus viscerum complicated by hypertension, coronary artery disease and myocardial infarction is presented. Electrocardiographic recordings of the limb leads, with and without reversal of the arm lead wires, and of the precordial leads of the V series derived from both right and left chest areas are presented. In this instance the electrocardiographic findings in precordial leads taken over the right chest point to fresh anteroseptal infarction; those leads recorded from the left chest were not informative. This serves to emphasize the fact that precordial leads should be recorded from the right side of the chest rather than the left in order that the exploring precordial electrode may overlie the area of cardiac damage, and thus manifest maximal changes in the electrocardiogram. We agree that the electrocardiogram may best be interpreted by application of the usual criteria to the limb leads taken with the arm lead wires reversed although in this case the limb leads yielded no information of diagnostic significance.