Neurometabolic disorders and dysfunction in autism spectrum disorders

The cause of autism remains largely unknown because it is likely multifactorial, arising from the interaction of biologic, genetic, and environmental factors. The specific role of metabolic abnormalities also is largely unknown, but current research may provide insight into the pathophysiologic underpinnings of autism, at least in some patients. We review a number of known neurometabolic disorders identified as having an autistic phenotype. We also discuss the possible involvement of mitochondrial disorders and dysfunction as well as a theory regarding an increased vulnerability to oxidative stress, by which various environmental toxins produce metabolic alterations that impair normal cellular function. Finally, we review various strategies for metabolic work-up and treatment. Accurate diagnosis of neurometabolic disorders and a broader understanding of underlying metabolic disturbance even in the absence of known disease have important implications both for individual patients and for research into the etiology of autism.     

Impact of Preoperative α-Fetoprotein Level on Disease-Free Survival After Liver Transplantation for Hepatocellular Carcinoma

Background

Preoperative α-fetoprotein (AFP) levels may have an influence on disease-free survival (DFS) of patients after liver transplantation for hepatocellular carcinoma (HCC) located on a cirrhotic liver.

Methods

Between 2000 and 2009, two groups were distinguished according to preoperative AFP level: normal-level group (<10?ng/ml) and increased-level group (>10?ng/ml). The increased-level group was further divided into three levels of preoperative AFP: 10–150, 150–500, and ≥500?ng/ml. DFS and recurrence rates were compared. All patients underwent transplantation using the preoperative 5/5 criteria.

Results

Of the 122 patients in this study, 63 had normal and 59 had increased preoperative AFP. There were no differences between the two groups concerning perioperative or pathologic data. Those with an increased preoperative AFP level had a significantly shorter 5-year DFS, and their recurrence rate was higher than that of the normal AFP group. The 5-year DFS and recurrence rates were 71 and 4?%, respectively, for those with normal AFP; 57 and 10?%, respectively, for those with AFP 10–150?ng/ml; 46 and 24?%, respectively, for those with AFP 150–500?ng/ml; and 28 and 62?%, respectively, for those with AFP ≥500?ng/ml.

Conclusions

This study shows the prognostic value of preoperative AFP levels on DFS after a liver transplant for HCC in a population of patients undergoing transplantation with the same preoperative criteria.     

Rituximab therapy for mixed cryoglobulinemia in seven renal transplant patients

Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have been achieved in hepatitis C virus-positive immunocompetent patients with rituximab, a human/mouse chimeric monoclonal antibody that specifically reacts with the CD20 antigen. Thus, this provides a rationale for the use of rituximab for type III cryoglobulin-related graft dysfunction in renal-transplant patients. Seven patients, of whom five were hepatitis C positive, developed renal function impairment long after transplantation, as well as de novo nephrotic syndrome (n = 5), severe hypertension (n = 5), nephritic syndrome (n = 1), and increased serum creatinine (n = 1). This type III cryoglobulinemia was associated with membranoproliferative glomerulonephritis and with thrombi within the glomeruli in one case. In addition to their baseline standard immunosuppressive medications, the patients were given weekly rituximab infusions: 375 mg/m(2) for 2 weeks in four cases, for 3 weeks in one case, and for 4 weeks in two cases. This treatment resulted in a dramatic improvement in all renal parameters, particularly a sustained remission of nephrotic syndrome in three cases, the disappearance of nephritic syndrome in one patient, and improved nephrotic syndrome in two cases, as well as a sustained clearance of cryoglobulins in six cases. However, it also resulted in severe infectious complications in two cases. We concluded that rituximab therapy is effective in cryoglobulin-related renal dysfunction in renal transplant patients but, due to chronic immunosuppression, this may be achieved at the expense of infectious complications.     

Viral infections after kidney transplantation

Chronic immunosuppression, required to maintain allograft function postorgan transplant, predisposes transplant patients to a variety of viral infections. These can occur at every stage of post-transplantation. Some infections, however, such as cytomegalovirus (CMV), Epstein Barr virus (EBV), or BK virus (BKV), tend to occur within months after transplantation. CMV infections can be easily prevented by prophylaxis therapy whereas EVB or BKV infections can be prevented by lowering (when possible) immunosuppression. Some viral infections can result in posttransplant lymphoproliferative disorders (EBV), Kaposi sarcoma (human herpes simplex virus type 8), or skin and/or cervical cancers (papillomavirus). Other viral infections, such as those due to influenza or para influenzae viruses, respiratory syncytial virus, or West nile fever virus, are mostly acquired through environmental spread. Thanks to modern laboratory technique, and a formidable antiviral armamentarium, viral infections in organ transplant patients i) can be easily detected at early stages, and ii) can be efficiently treated.     

Long-term,prolonged-release tacrolimus-based immunosuppression in de novo kidney transplant recipients: 5-year prospective follow-up of the ADHERE study patients

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m² at 6 months and 52.5 ± 23.0 ml/min/1.73 m² at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.     

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

1. Download : Download high-res image (301KB)
2. Download : Download full-size image

     

The electrocardiogram in patients with implanted cardiac pacemakers

In the submitted review the authors present electrocardiographic record of patients with atrial, ventricular and dual-chamber pacemakers. They also describe specially ECG findings in complications of cardiostimulation. Recommended procedures in these situation: changing pacemaker programme or electric cardioversion or surgical solution--reimplantation of pacemaker generator and/or lead or implantation of second lead.