Beta-2 microglobulin and amyloid osteoarthropathy in patients undergoing chronic hemodialysis

The incidence of beta-2 microglobulin amyloidosis was assessed in two populations of chronic hemodialysis patients. Out of 34 patients who underwent biopsy during orthopedic surgery (33 cases) or autopsy (1 case), 26 had amyloid deposits which fixed anti-beta microglobulin serum. Out of 55 unselected patients treated for over months at the dialysis centre, 14 (25%) had clinical symptoms suggesting amyloidosis and out of 43 patients who had a systematic radiological skeletal survey, 23 (53%) had bone deposits. The plasma beta microglobulin concentrations (about 20 times the normal value) we not significantly different whether or not the patients had histological proven amyloidosis, clinically or radiologically probable amyloidosis, no detectable amyloidosis. However, the duration of hemodialysis was longer in those with proven or highly probable amyloidosis. The finding illustrate the indirect role of elevation of beta-2 microglobulin in the genesis of this pathology and also the necessity of lowering its concentration in order to avoid the long term complications of osteoarticular deposits, the functional consequences of which may be very serious.     

Antibodies to the ADP/ATP carrier, an autoantigen in myocarditis and dilated cardiomyopathy, penetrate into myocardial cells and disturb energy metabolism in vivo

We identified the ADP/ATP carrier, located within the inner mitochondrial membrane, to be an organ- and conformation-specific autoantigen in myocarditis and dilated cardiomyopathy. We also showed that autoantibodies to the ADP/ATP carrier inhibit the nucleotide transport in vitro. Specific binding of the autoantibodies to the carrier was demonstrated by radioimmunoassay and the immunoblot technique; the inhibition of the nucleotide transport was determined by the inhibitor stop method. To establish if these autoantibodies might also affect cardiac energy metabolism in vivo, we measured whether they are capable of penetrating into myocytes and whether subcellular ATP/ADP ratios and phosphorylation potentials of ATP change in hearts of guinea pigs that have been immunized with the isolated ADP/ATP carrier. An intracellular deposition of autoantibodies was observed by direct immunofluorescence and by immunoperoxidase staining on cryosections of the myocardial tissue of animals immunized with the ADP/ATP carrier. Furthermore, binding of autoantibodies to mitochondrial membrane structures was shown by immunoelectron-microscopic methods. The cytosolic and intramitochondrial distribution of adenine nucleotides in stimulated, isolated perfused hearts of guinea pigs immunized with the ADP/ATP carrier was measured by nonaqueous fractionation. Compared with controls performing equal external heart work, the cytosolic ATP decreased in the immunized animals, whereas the mitochondrial ATP increased strongly; ADP concentrations showed an opposite change. Thus, a resultant cytosolic decrease and a marked mitochondrial increase of the ATP/ADP ratio was established. As a consequence, the cytosolic-mitochondrial phosphorylation potential of ATP was diminished. These findings demonstrate that antibodies against intracellular antigens are able to penetrate into living cells, and that autoimmunity to the ADP/ATP carrier may contribute to the pathophysiology of myocarditis and dilated cardiomyopathy by causing an autoantibody-mediated imbalance between intracellular energy delivery and demand.     

Lyme arthritis

Evanescent arthralgias and myalgias are common early symptoms of Lyme disease. Transient, intermittent episodes of monoarticular, oligoarticular, or sometimes migratory polyarticular arthritis, lasting weeks to months, with disease-free intervals, are frequently observed in untreated patients with erythema chronicum migrans. A minority of patients develop chronic joint involvement, most commonly affecting the knee. Antibiotic therapy given during erythema chronicum migrans is often protective with regard to late joint manifestations. In chronic Lyme arthritis, however, the response to antibiotics is variable.     

Enhanced progesterone and testosterone secretion and depressed estradiol secretion in vitro from small white follicle cells of incubating turkey hens

This study was conducted to determine if lower steroid secretion by the small white follicles in incubating turkey hens contributes to lower circulating steroid concentrations during this time. Turkey hens were grouped as either laying or incubating. Serum samples and the ovarian small white follicles (SWF; 2-7 mm diameter) were collected from each hen. The SWF were pooled for each group and their cells were dispersed by trypsin digestion. Serum-luteinizing hormone (LH), progesterone (P), testosterone (T), and estradiol (E) concentrations were lower and serum prolactin concentration was higher during incubation than during egg laying. SWF cells from incubating hens secreted more P and T and less E in response to ovine luteinizing hormone (oLH) than did similar cell suspensions from laying hens. The incubating hens' SWF cells' capacity to secrete E but not their capacity to secrete P or T in vitro is consistent with the observed circulating levels. It is hypothesized that lower levels of circulating LH and/or higher levels of prolactin found in incubating hens may have a depressing effect on aromatase activity and/or an up-regulating effect on LH-induced P and T secretion by the SWF cells.     

Prospective randomized comparison of mezlocillin therapy alone with combined ampicillin and gentamicin therapy for patients with cholangitis

Forty-six patients with cholangitis were randomized to receive therapy with mezlocillin sodium (24 patients) or a combination of ampicillin sodium--gentamicin sulfate (22 patients). The biliary concentration of mezlocillin was 112 times higher than that of ampicillin and 778 times higher than that of gentamicin. The ratio of the concentration in serum or bile over the minimum inhibitory concentration against aerobic gram-negative bacilli (therapeutic index) was higher for mezlocillin than for either ampicillin or gentamicin. Twenty (83%) of 24 patients were cured following mezlocillin therapy compared with 9 (41%) of 22 patients after ampicillin-gentamicin therapy. The 3 patients with superinfection were in the ampicillin-gentamicin arm of the study. Fewer toxic or adverse effects occurred in association with mezlocillin treatment than with ampicillin-gentamicin treatment. Mezlocillin therapy was more effective, less toxic, and less expensive than treatment with ampicillin and gentamicin for patients with cholangitis.     

Preparation of leukocyte-poor platelets by filtration

There is evidence that leukocyte contaminating red blood cells and platelet concentrates are responsible for refractoriness to platelet transfusions. The efficacy of a cotton-wool filter to remove leukocytes from red blood cells has been documented previously. The present study was designed to evaluate whether the cotton-wool filters can effectively remove leukocytes from platelet concentrates. Sixty pools of random-donor platelets and single-donor plateletpheresis products were filtered through a cotton-wool filter. The efficacy of filtration was determined by measuring the absolute numbers of leukocytes and platelets and subpopulations of mononuclear cells. The average platelet loss was 8% per pool of random platelets and 10% per plateletpheresis product. The average leukocyte removal was 99% from a pool of random platelets and plateletpheresis concentrates collected by CS-3000 and 90% from plateletpheresis concentrates harvested by single-stage COBE/IBM-2997. The filtration removed 100% of granulocytes, 95% of monocytes, 90% of B-lymphocytes, and 85% of T-lymphocytes. We conclude that filtration through a cotton-wool filter is an efficient and cost-effective method for preparation of leukocyte-poor platelets.