Relationships among the results of coagulase, staphylococcal toxin, and thermonuclease tests on staphylococci from cow milk.

Production of staphylococcal alpha- or alpha-beta-toxins correlated well with production of coagulase or thermonuclease (or both) in 203 Staphylococcus aureus isolates from milk and should be reliable indicators of S. aureus in the absence of Staphylococcus intermedius. Failures to produce toxin, tube coagulase, or thermonuclease occurred in only 1 to 2% of S. aureus. Evidence of beta- or alpha-beta-toxins was not found among 321 other staphylococci isolated from milk. A few coagulase- or thermonuclease-positive isolates not producing beta- or alpha-beta-toxins were found among the Staphylococcus hyicus isolates.     

The use of therapeutic apheresis in cardiovascular disease

In the last few years, therapeutic apheresis (TA) has emerged as a valuable treatment option for certain life‐threatening cardiovascular diseases (CVDs) and for all the cardiac dysfunctions caused by autoimmune or metabolic disorders. Besides the well‐established indications for apheresis treatment, such as familial hypercholesterolaemia, hyperviscosity syndrome and thrombotic thrombocytopenic purpura (TTP), we discuss the novel approaches in the therapy of dilated cardiomyopathy, cardiac failure and some specific syndromes of severe dysfunction occurring after heart transplantation. The rationale for using apheresis in such patients is the contribution in immune modulation that this procedure can undoubtedly provide. The clinical course of TTP has dramatically changed, thanks to the introduction of therapeutic plasma exchange. Low‐density lipoprotein apheresis has been extremely efficacious, safe and suitable for lowering cholesterol levels and can be used even for long‐term treatment. In Waldenström macroglobulinaemia and other hyperviscosity syndromes, plasma exchange has demonstrated to be an efficient tool for reducing blood viscosity and the risk of a consequent cardiac dysfunction. However, TA may induce oxidative injury to erythrocytes, making these cells more prone to haemolysis and causing a significant reduction in their half‐life. Ascorbate administration can be useful to lower the levels of hydrogen peroxide and proinflammatory mediators in patients undergoing apheresis. Further data are needed to support this benefit and to test other potential antioxidant therapies. Many of these therapeutic indications need further studies to be definitively approved, but preliminary data are encouraging.     

Update on medical therapy for obscure gastrointestinal hemorrhage]

The development of capsule endoscopy and double-balloon enteroscopy has increased diagnostic and therapeutic rates in obscure gastrointestinal hemorrhage, where angiodysplasia of the small bowel is the most frequent cause. Nevertheless, almost 25-40% of patients who are not candidates or do not respond to endoscopic, angiographic, or surgical management may be at high risk of rebleeding, and therefore lack a clearly effective medical therapy. The utility of hormonal therapy remains unclear and is burdened by adverse effects. Subcutaneous octreotide usually controls bleeding but does not seem adequate for maintenance therapy. Non-selective beta-blockers alone or in combination with other treatments, as in the prophylaxis of portal hypertension variceal bleeding, may be helpful. Recently, octreotide LAR, a depot formulation administered once a month intramuscularly, and oral thalidomide, a powerful inhibitor of angiogenesis, have demonstrated their effectiveness and safety for long-term therapy in anecdotal case reports and deserve further investigation.     

NPC2 facilitates bidirectional transfer of cholesterol between NPC1 and lipid bilayers, a step in cholesterol egress from lysosomes

Egress of lipoprotein-derived cholesterol from lysosomes requires two lysosomal proteins, polytopic membrane-bound Niemann-Pick C1 (NPC1) and soluble Niemann-Pick C2 (NPC2). The reason for this dual requirement is unknown. Previously, we showed that the soluble luminal N-terminal domain (NTD) of NPC1 (amino acids 25-264) binds cholesterol. This NTD is designated NPC1(NTD). We and others showed that soluble NPC2 also binds cholesterol. Here, we establish an in vitro assay to measure transfer of [(3)H]cholesterol between these two proteins and phosphatidylcholine liposomes. Whereas NPC2 rapidly donates or accepts cholesterol from liposomes, NPC1(NTD) acts much more slowly. Bidirectional transfer of cholesterol between NPC1(NTD) and liposomes is accelerated >100-fold by NPC2. A naturally occurring human mutant of NPC2 (Pro120Ser) fails to bind cholesterol and fails to stimulate cholesterol transfer from NPC1(NTD) to liposomes. NPC2 may be essential to deliver or remove cholesterol from NPC1, an interaction that links both proteins to the cholesterol egress process from lysosomes. These findings may explain how mutations in either protein can produce a similar clinical phenotype.     

Gastrobronchial fistula repair followed by esophageal leak--rescue by transesophageal drainage of the pleural cavity

A gastrobronchial fistula (GBF) associated with bilateral aspiration pneumonia was diagnosed six years after an esophagectomy with gastric pull-up. After failed surgical repair, an uncontained esophagopleural leak developed. Fistula closure was attempted by implanting a Wilson-Cook endoprosthesis, which quickly became dislodged. Transesophageal drainage was positioned endoscopically through the suture-line defect and led to closure of the leak after 10 days.     

The effectiveness and safety of d,l-sotalol in the ambulatory treatment of atrial fibrillation and flutter]

Data on short and long term efficacy and safety of d,l sotalol in patients with atrial fibrillation or atrial flutter is limited. The aims of this study were to (1) assess the antiarrhythmic efficacy of d,l sotalol maintaining normal sinus rhythm in patients with refractory atrial fibrillation or flutter, (2) evaluate the efficacy of d,l sotalol in preventing recurrences of paroxysmal atrial fibrillation or flutter, (3) evaluate the control of ventricular rate in patients with paroxysmal or refractory atrial fibrillation or flutter unsuccessfully treated with other antiarrhythmic agents, (4) determine predictors of efficacy (5) assess the safety of d,l sotalol in this setting. Two hundred patients with chronic or paroxysmal atrial fibrillation or atrial flutter or both, who had failed one to six previous antiarrhythmic drug trials were treated with d,l sotalol 80 to 440 mg/day orally. Fifty four percent was female, age 47 +/- 16 years (range 7-79), follow up period 7 +/- 7 months (range 1 to 14 months), 79% of patients had the arrhythmia for more than one year. The atrial fibrillation in 37.5% of patients was chronic and paroxysmal in 23.5. The atrial flutter was chronic in 31% of patients and paroxysmal in 8%. Eighty two percent of patients was in functional class I (NYHA) and 82% had cardiac heart disease: left atrial (LA) size 44 +/- 10 mm, right atrial (RA) size 37 +/- 7 mm and left ventricular ejection fraction (LVEF) 58 +/- 8%. Total success was achieved in 58% of patients (atrial fibrillation 40% and 18% in atrial flutter), partial success in 38% (atrial fibrillation in 18% and 20% in atrial flutter) and 4% of patients failure. It was p < 0.07 when compared total success vs partial success among atrial fibrillation and atrial flutter groups. Patients with cardiac heart disease responded worst (p = 0.10) to the drug than those without it, specially if the heart was dilated. We concluded that d,l sotalol has moderate efficacy to convert and maintain normal sinus rhythm, as well as it acts controlling paroxysmal relapses and ventricular heart rate.     

Longitudinal study on mitochondrial effects of didanosine-tenofovir combination

Tenofovir disoproxil fumarate (TDF) has been reported to be free of adverse effects on mitochondria. We evaluate the effects of the introduction of TDF in a didanosine (ddI)-based highly active antiretroviral therapy (HAART) on mitochondrial DNA (mtDNA) content, mitochondrial mass (MM), and cytochrome c oxidase (COX) activity of the oxidative phosphorylation (OXPHOS) system over a 12-month period. Forty-four asymptomatic HIV patients with undetectable viral load receiving a ddI-based HAART were recruited and switched to ddI plus TDF (ddI + TDF) and nevirapine (n = 22) or maintained with the same baseline ddIbased HAART scheme (n = 22). Peripheral blood mononuclear cells were obtained at 0, 6, and 12 months. COX activity and MM were determined by spectrophotometry and the mtDNA content by quantitative realtime PCR. The mtDNA content showed a progressive decrease over the 12-month period of the study for the two groups with respect to baseline, with such a decrease statistically significant only in the ddI + TDF group (55% decrease, p < 0.001). In addition, the decrease of mtDNA content over time was statistically different between both groups (p < 0.001). Consistently, MM and COX activity decreased significantly at 12 months with respect to baseline only in the ddI < TDF group (28% decrease for MM, p < 0.05; 47% decrease for COX activity, p < 0.001). We conclude that switching to a HAART regimen containing ddI + TDF is associated with evolutive mitochondrial damage expressed as mtDNA depletion, loss of MM, and decrease in COX efficiency. The particular relevance of either ddI, TDF, or any interaction between them in such a mitochondrial dysfunction remains to be established.