Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia

Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged < or = 45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7 micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.     

Pharmaceutical management of decompensated heart failure syndrome in children: Current state of the art and a new approach

Prompt initiation of appropriate and intensive treatment in children with decompensated heart failure is crucial to avoid irreversible end-organ dysfunction. Initial management of these children includes transfer to the pediatric cardiac intensive care unit, basic hemodynamic monitoring, and establishment of intravenous access. Inotropic support should be instituted peripherally before obtaining central venous and arterial access. The team should be prepared for emergent intubation and initiation of mechanical circulatory support. Two experienced physicians should work together to obtain vascular access and manage sedation, airway control, and cardiovascular support. Acute heart failure syndrome in children may be related to cardiomyopathy, myocarditis, congenital heart disease, and acute rejection post heart transplantation. Each of these causes requires a different approach. Fulminant myocarditis may lead to severe morbidity and requires intensive support, although its outcome is considered to be good. Acute heart failure related to newly diagnosed dilated cardiomyopathy may represent end-stage heart failure; therefore, long-term mechanical circulatory support and heart transplantation may be considered to avoid other end-organ dysfunction. Hypertrophic cardiomyopathy may lead to acute decompensation due to 1) left ventricular outflow obstruction, 2) restrictive physiology leading to pulmonary hypertension, or 3) myocardial is chemia associated with coronary artery bridging. Decompensated heart failure associated with congenital heart disease usually represents end-stage heart failure and requires thorough evaluation for heart transplantation. Children with single-ventricle physiology who develop decompensated heart failure after a Fontan procedure are not candidates for mechanical circulatory support and therefore may not survive to heart transplantation. Acute heart failure due to posttransplantation acute rejection requires aggressive antirejection treatment, which places these patients at significant risk for overwhelming opportunistic infections. In our opinion, mechanical circulatory support should be initiated early in children who present with end-stage heart failure associated with hemodynamic instability to avoid end-organ damage.     

Endobronchial echinococcosis presenting as non-resolving pneumonia

Hydatid disease of the lungs is caused by larval cysts of the Echinococcus tapeworm. Pulmonary cysts may occasionally invade bronchi or pleura as a result of coughing, trauma, or elevated intra-abdominal pressure. We present the case of a patient evaluated for non-resolving pneumonia whose radiographic and bronchoscopic findings were strikingly similar to those seen in pulmonary tuberculosis with endobronchial invasion; he was ultimately diagnosed with pulmonary echinococcosis. This case underscores the importance of considering unusual diagnoses even when typical features of more common conditions are present.     

Novel Indications for Fecal Microbial Transplantation: Update and Review of the Literature

Background and Aims

Fecal microbial transplantation (FMT) is an established successful treatment modality for recurrent Clostridium difficile infection (CDI). The safety profile and potential therapeutic advantages of FMT for diseases associated with dysbiosis and immune dysfunction have led to many publications, mainly case series, and while many studies and reviews have been published on the use of FMT for inflammatory bowel disease (IBD), its potential use for other disease conditions has not been thoroughly reviewed. The aim of this review was to investigate the evidence surrounding the use of FMT in conditions other than IBD and CDI.

Methods

A PubMed search was performed using the terms “Fecal microbiota transplantation” OR “FMT” OR “Bacteriotherapy.”

Results

A total of 26 articles describing the use of FMT in a variety of both intra-and extraintestinal disease conditions including gastrointestinal, hematologic, neurologic, metabolic, infectious, and autoimmune disorders have been included in this review and have demonstrated some positive results. The studies included were case reports, case series, controlled trials, and cohort studies.

Conclusions

The findings of these studies demonstrate that FMT, particularly in conditions associated with gastrointestinal dysbiosis, shows promise to provide another effective tool in the therapeutic armament of the practicing physician. FMT was found to be possibly effective in various diseases, mostly associated with enteric dysbiosis or with immune dysfunction. Randomized clinical studies on large populations should be performed to explore the effectiveness of this therapy, and basic research studies should be designed to gain understanding of the mechanisms through which impact these disorders.

     

Outcome of prenatally diagnosed trisomy 6 mosaicism

We report the prenatal diagnosis of trisomy 6 mosaicism via amniocentesis, in which trisomy 6 cells were identified in three of five culture vessels with 33% (5/15) of colonies showing trisomic cells. The pregnancy was electively terminated and examination revealed minor abnormalities (shortening of the femurs, micrognathia, posterior malrotation of the ears, and bilateral camptomelia of the second digit of the hands and fifth digits of the feet). Cytogenetic analysis of the placenta showed trisomy 6 in 100% of 20 cells studied. Karyotype was 46,XX in 100 cells examined from fetal skin. There are relatively few prenatally diagnosed cases of mosaic trisomy 6 at amniocentesis. Confined placental mosaicism (CPM) has been postulated in other cases where follow-up cytogenetic studies were not available. The present case differs from those previously reported, as it appears to represent CPM of chromosome 6 with phenotypic effects to the fetus.     

Living related liver transplant following bone marrow transplantation from same donor: Long‐term survival without immunosuppression

Granot E, Loewenthal R, Jakobovich E, Gazit E, Sokal E, Reding R. Living related liver transplant following bone marrow transplantation from same donor: Long‐term survival without immunosuppression.
Pediatr Transplantation 2012: 16: E1–E4. © 2010 John Wiley & Sons A/S. Abstract: We report long‐term (seven yr) immunological tolerance in a 16‐yr‐old boy, to a liver allograft donated by his father following a bone marrow transplant at age 2.5 yr from the same donor. The bone marrow transplant was complicated by severe GVHD leading to liver failure and the ensuing need for a liver transplant, performed under planned avoidance of immunosuppression. At one wk post‐transplant, although a liver biopsy was histologically compatible with acute rejection, favorable clinical and biochemical evolution precluded initiating immunosuppressive therapy, thus highlighting the need for caution when interpreting early histological changes so that administration of unnecessary immunosuppression can be avoided. Induction of tolerance in transplant recipients remains an elusive goal. In those patients who had received conventional bone marrow transplants and had endured the consequences of GVHD, development of macrochimerism may allow immunosuppression‐free solid organ transplantation from the same donor.