Actin-free Gc globulin: a rapidly assessed biomarker of organ dysfunction in acute liver failure and cirrhosis.

Reductions in serum levels of Gc globulin, a hepatically synthesized component of the extracellular actin scavenger system responsible for complexing circulating actin and attenuating intravascular microthrombus formation, are associated with poor outcome in acute liver failure. Clinically applicable assays of the important actin-free fraction (Af-Gc) have not been available until now. We measured actin-free Gc globulin levels with a novel, rapid assay in 61 cases of acute liver failure (ALF) and in 91 patients with cirrhosis (40 of whom were clinically unstable with extrahepatic organ dysfunction), and studied associations with liver dysfunction, extrahepatic organ dysfunction, indices of disseminated coagulation, and outcome. Reductions in Af-Gc levels mirrored hepatic dysfunction and organ dysfunction in both groups, and discriminated patients with poor prognosis from those with good prognosis in the ALF cohort. Levels were lowest in patients with ALF (10% of control values), but levels were also markedly reduced in both unstable (28%) and stable (44%) patients with cirrhosis. Associations with markers of disseminated intravascular coagulation were seen in both groups, most notably in the cirrhosis cohort, supporting a pathophysiological role for reduced Af-Gc in the evolution of organ dysfunction. In acetaminophen-induced ALF, Af-Gc identified patients with poor prognosis as well as did the Acute Physiology and Chronic Health Evaluation (APACHE II) score (area under the receiver operating characteristic curve, 0.7), and in cirrhosis, Af-Gc was an independent predictor of mortality by multifactorial analysis. In conclusion, the importance of Af-Gc reductions in the development of multiple organ dysfunction in ALF and cirrhosis is highlighted, probably resulting from reduced hepatic production and peripheral exhaustion of this arm of the extracellular actin scavenger system.     

POL32, a subunit of the Saccharomyces cerevisiae DNA polymerase δ, defines a link between DNA replication and the mutagenic bypass repair pathway

Pol32 is a subunit of Saccharomyces cerevisiae DNA polymerase δ required in DNA replication and repair. To gain insight into the function of Pol32 and to determine in which repair pathway POL32 may be involved, we extended the analysis of the pol32Δ mutant with respect to UV and methylation sensitivity, UV-induced mutagenesis; and we performed an epistasis analysis of UV sensitivity by combining the pol32Δ with mutations in several genes for postreplication repair (RAD6 group), nucleotide excision repair (RAD3 group) and recombinational repair (RAD52 group). These studies showed that pol32Δ is deficient in UV-induced mutagenesis and place POL32 in the error-prone RAD6/REV3 pathway. We also found that the increase in the CAN1 spontaneous forward mutation of different rad mutators relies entirely or partially on a functional POL32 gene. Moreover, in a two-hybrid screen, we observed that Pol32 interacts with Srs2, a DNA helicase required for DNA replication and mutagenesis. Simultaneous deletion of POL32 and SRS2 dramatically decreases cellular viability at 15 °C and greatly increases cellular sensitivity to hydroxyurea at the permissive temperature. Based on these findings, we propose that POL32 defines a link between the DNA polymerase and helicase activities, and plays a role in the mutagenic bypass repair pathway. Received: 25 May 2000 / Accepted: 3 July 2000     

Some technical improvements for the voltage clamp with the double sucrose gap

Summary A new double sucrose gap chamber using electrodes of high stability and low resistance is described. The size of each sucrose gap and the central node can be modified independently so that this chamber is suitable for research on multicellular or unicellular excitable preparation under voltage clamp conditions. The shape of the central channel is made so as to reduce the series resistance between the preparation and the recording electrode to a minimum. A window made in the floor of the chamber allows to observe the preparation under a microscope.This work was performed under the I.N.S.E.R.M. grant no. 17.75.40.     

Transmetatarsal Amputation in the Setting of Antiphospholipid Antibody Syndrome

Antiphospholipid syndrome is a hypercoagulable disease that can present foot and ankle surgeons with a unique challenge in treating patients who present with thrombosis and ischemia despite having normal pedal pulses. Appropriate perioperative management is imperative in these patients, because limb- and life-threatening complications can occur postoperatively, despite aggressive anticoagulation. We present the case of a 46-year-old male who underwent a transmetatarsal amputation and, despite aggressive therapy, developed a myriad of complications postoperatively. At 10 months postoperatively, the patient was doing well in an accommodative orthotic with minimal pain while receiving continued aggressive therapy and follow-up examinations by a number of specialists to treat his antiphospholipid syndrome.     

Rifampicin reverses nicardipine effect inducing uncontrolled essential hypertension

Dihydropyridine calcium‐channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67‐year‐old hypertensive female treated with a four‐drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high‐performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.     

Hypnosis Before Diagnostic or Therapeutic Medical Procedures: A Systematic Review

The aim of this systematic review was to estimate the efficiency of hypnosis prior to medical procedures. Different databases were analyzed to identify randomized controlled trials (RCTs) comparing hypnosis to control interventions. All RCTs had to report pain or anxiety. Eighteen RCTs with a total of 968 patients were included; study size was from 20 to 200 patients (14 RCTs ≤ 60 patients). Fourteen RCTs included 830 adults and 4 RCTs included 138 children. Twelve of 18 RCTs had major quality limitations related to unclear allocation concealments, provider’s experience in hypnosis, patient’s adherence to hypnotic procedures, and intention-to-treat design. This systematic review observed major methodological limitations in RCTs on hypnosis prior to medical procedures.     

Hand‐foot‐skin reaction related to use of the multikinase inhibitor sorafenib and hard orthotics

Hand‐foot‐skin reaction is a distinct clinical condition arising in association with the use of multikinase inhibitors, including sorafenib. Because multikinase inhibitors are increasingly being used in children with cancer, recognition of this previously unfamiliar condition is of importance to pediatric dermatologists. We describe the diagnosis and successful treatment of a case of hand‐foot‐skin reaction in a child taking sorafenib for an unresectable desmoid tumor.