Axonal neuropathy in a patient with monoclonal IgM kappa reactive with Schmidt-Lantermann incisures

We report a patient with a progressive, predominantly sensory neuropathy and a IgM kappa M-protein that binds to Schmidt-Lantermann incisures. A sural nerve biopsy showed primary axonal damage and IgM deposits at Schmidt-Lantermann incisures were seen by direct immunoperoxidase. Serum from the patient injected into rat sciatic nerve reacts with the incisures as with those in the patient's nerve. The IgM kappa M-protein reacts with chondroitin sulfate C and binds to a broad nerve protein band with a mobility of between 170 and 118 kDa. Peripheral neuropathy may be related to the M-protein, which had immunocytochemical reactivity not previously described for patients with polyneuropathy and IgM monoclonal gammopathy.     

Diltiazem impairs maturation and functions of human dendritic cells

The aim of this study was to define the effects of diltiazem, a calcium antagonist drug used in cardiology and in clinical transplantation, on the differentiation and maturation of human dendritic cells (DC). Herein, we demonstrate that diltiazem, in association with granulocyte macrophage-colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), induces monocytes to differentiate into cells with many of the characteristic of DC. However, diltiazem-induced DC express high levels of mannose receptor and Fc gamma RII and, consequently, manifest a higher endocytic activity compared with GM-CSF+IL-4-induced DC. Importantly, diltiazem-induced DCs have an impaired responsiveness to lipopolysaccharide and CD40 ligand because they produce decreased levels of IL-12 and reveal a reduced ability to stimulate alloreactive T-cell responses as well as in inducing interferon-gamma producing Th1 cells. These effects may contribute to a decreased DC-dependent T-cell activation and may help to explain the immunoregulatory function of diltiazem and its effectiveness in preventing transplant rejection.     

Production and Characterization of a Human Recombinant Monoclonal Fab Fragment Specific for Influenza A Viruses

A human recombinant monoclonal Fab fragment that specifically recognizes all the influenza A virus strains tested was produced in transformed Escherichia coli using the phage display technique. No strain of influenza B virus reacted with it. It was purified after four cycles of panning and by a single passage through an immunoaffinity column. About 1 mg of pure monoclonal antibody was obtained from 1 liter of culture medium in 3 working days. The Fab fragment reacted with a viral 27-kDa protein, which could reasonably be a matrix protein. Indirect immunofluorescence tests performed on virus-infected MDCK cells showed that this Fab fragment was at least equally efficient as other commercial monoclonal antibody-based systems in detecting influenza A viral infections. The potential advantages of human recombinant Fabs on murine monoclonal antibodies are discussed.     

Hemodynamic changes during continuous infusion with dobutamine in candidates for lung transplantation. Lung Transplantation Group

BACKGROUND: The aim of this study is to analyze the effects of dobutamine (DBT) on pulmonary and systemic hemodynamics and oxygenation in lung transplant candidates. METHODS: Forty-five patients (21M, 24F) to be introduced in waiting list for lung transplantation were studied (14 pulmonary fibrosis, 15 COPD, and 16 cystic fibrosis). They were studied awake, while spontaneously breathing in two different phases: baseline--O2 100%; DBT phase--O2 100% after 10 minutes of DBT continuous infusion (10 mcg/Kg/min). Blood gas samples and hemodynamic data were collected during right heart catheterization. Data were statistically analyzed with Student's "t" test and values for p < 0.05 were considered as significant. RESULTS: During DBT phase, a significant increase of cardiac output with a decreasing in systemic and pulmonary vascular resistance was observed. Since the fall in pulmonary vascular resistance (PVRI) was not proportional to the increase of cardiac output, mean pulmonary artery pressure and transpulmonary gradient increased. The prevalent role of vascular recruitment as mechanism in PVRI reduction during DBT is supported by the concomitant fall in PaO2/FiO2. This strongly suggests a worsening of regional Va/Qc due to an increased perfusion of poorly ventilated areas. CONCLUSIONS: DBT reduces PVRI through a recruitment of vessels due to an increase of pulmonary flow. Dobutamine has a favorable hemodynamic effect in mild-to-moderate pulmonary hypertension in lung transplant candidates.