IgG-anticardiolipin-antibodies are markers for cerebral and peripheral artery disease.

Anticardiolipin-antibodies are antibodies to phospholipids which were first detected in patients with arterial thrombosis and lupus erythematosus. In this prospective study, IgG- and IgM-anticardiolipin-antibodies were determined in patients with cerebral and/or peripheral artery disease but without autoimmune disorders. 123 randomly selected patients (88 males, 35 females; mean: 65 +/- 10, range: 41-85 years) were included and divided into four groups: 18 patients with isolated cerebrovascular disease (group A), 35 patients with peripheral artery disease only (group B), 35 patients suffering from cerebral and peripheral artery disease (group C) and 35 patients as controls (group D). In family history, cholesterol, blood sugar and prothrombin time the four patient groups did not differ significantly, whereas patients of group B and C were more often smokers than those in groups A and D. However, IgG-anticardiolipin-antibody-levels were significantly elevated in patients with cerebral and peripheral artery disease compared to controls (p less than 0.01). The highest values were seen in group C where patients suffered from cerebral and peripheral artery disease (n.s.). On the other hand, IgM-anticardiolipin-antibody-levels did not show any differences in the four groups. Furthermore, there was no correlation between vascular risk factors and/or laboratory findings with IgG- and IgM-antibody-levels. Thus, elevated IgG-anticardiolipin-antibodies appear to be independent markers for severe cerebral and peripheral artery disease and should be determined in patients at increased risk.     

Myoblast transfer in duchenne muscular dystrophy

One biceps muscle of 8 patients with Duchenne muscular dystrophy was injected at 55 sites with a total of 55 million viable, purified, and contamination-free normal myoblasts (myoblast transfer). The other biceps of each patient was injected with a placebo to serve as a control. The procedure was blinded to the patients, parents, and investigators. Myoblasts derived from a biopsy specimen of the fathers were cultured and purified under strict conditions and carefully screened for microbial contamination. All patients received cyclophosphamide for immunosuppression for 6 or 12 months. No serious complications were observed after myoblast transfer, indicating that the procedure is safe. The overall therapeutic efficiency of myoblast transfer was poor as judged by the results in maximal voluntary force generation, dystrophin content of the muscle, magnetic resonance imaging of the muscle, and the lack of donor-derived DNA and dystrophin messenger RNA in the injected muscle. An improved efficiency of the take of myoblasts might be achieved by using younger cells and injecting the myoblasts with a myonecrotic agent (to increase the prevalence of regeneration) and a basal laminal fenestrating agent.     

Continuous arteriovenous hemofiltration: in vivo functional characteristics and its dependence on vascular access and filter design

The in vivo functional characteristics of continuous arteriovenous hemofiltration (CAVH) were studied in 21 intensive-care patients with acute renal failure. FH-66 hemofilters were applied. The relationships between prefilter blood pressure (BP), blood flow (QB) and filtration rate (QF) were evaluated by stepwise clamping of the arterial access and simultaneous measurements of these parameters. The correlations between BP and QB, and between QB and QF, were linear (p less than 0.001). The total pressure drop across the extracorporeal circuit was 90 +/- 12 mmHg with Scribner shunt and 70 +/- 13 mmHg with femoral catheters as vascular access. The relative pressure drops across arterial access, hemofilter and venous access for Scribner shunt and for femoral catheter were 30%, 43% and 27% and 12%, 74% and 14%, respectively. At a given BP, QB was lower and transmembrane filtration pressure (TMP) higher in CAVH with Scribner shunt. QB was 102 +/- 38 ml/min; QF was 20 +/- 7 ml/min. The effects of hemofilter geometry and membrane material on functional parameters of CAVH were evaluated by applying four hemofilters (Amicon D-20 HP, D-30 HP, Gambro FH-66, Fresenius AV-400) consecutively in the same patient. The filters were different with respect to hollow fiber length, its internal diameter, number of fibers and membrane material. BP, hematocrit (Hct) and plasma protein remained constant during measurements. QB increased with decreasing filter resistance. QF did not increase with increasing QB. QF was also not closely related to membrane surface area. The hydraulic permeability (Lp) had a major impact on QF.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term effects of treatment with recombinant human erythropoietin on haemodynamics and tissue oxygenation in patients with renal anaemia

Regional peripheral vascular resistance, transcutaneous oxygen pressure and blood pressure were studied in seven normotensive, chronically haemodialysed patients with renal anaemia before and after 3 and 12 months of rHuEpo therapy. Haematocrit increased from 21% to 33% within 3 months of commencing therapy, and remained stable throughout the following observation time. Though regional blood flow of the calf was markedly reduced after 3 and 12 months of rHuEpo compared to pretreatment values, transcutaneous oxygen pressure was significantly increased after 3 months and remained constantly elevated after 12 months. Mean arterial blood pressure increased significantly by 7.3 mmHg after 3 months of rHuEpo treatment but did not reach hypertensive values and was no longer different from pretreatment values 12 months after the start of rHuEpo. Results of peripheral haemodynamic studies were compared to those obtained by measurement of central haemodynamics in four further normotensive anaemic patients. In these patients cardiac output decreased, total peripheral vascular resistance increased and blood pressure increased slightly (by 5.5 mmHg) when a haematocrit of 37% was reached after 8 weeks of rHuEpo therapy. These effects were partly reversed when the maintenance haematocrit decreased to 32% (after 16 weeks of rHuEpo). In summary rHuEpo treatment induced a long-term increase of the total and regional peripheral resistance, an increase of blood pressure within the normal range, and a decrease in cardiac output. Despite these changes tissue oxygenation improved.     

Microalbuminuria in children and adolescents with and without Type-I diabetes mellitus (IDDM)

In 73 healthy (group I) and 32 children and juveniles with insulin dependent diabetes mellitus (IDDM, group II) urinary albumin excretion is determined by radioimmunoassay (RIA). In both groups albumin excretion is observed in every urine sample when measured by RIA (mean +/- SD: group I: 7-19 h: 5.17 +/- 5.28 mg, 19-7 h: 3.86 +/- 4.00 mg, 24 h: 9.03 +/- 8.60 mg; group II: 7-19 h: 6.68 +/- 6.86 mg, 19-7 h: 3.46 +/- 2.82 mg, 24 h: 10.13 +/- 9.25 mg). No significant difference is detected between the values of the two groups. However in diabetic patients a significant difference is observed between diurnal and nocturnal urinary albumin excretion. Microalbuminuria is defined as an albumin excretion above 30 mg/d and is present in 6.9% of the values in group I and in 3.1% in group II. The physiological limits of microalbuminuria in children and juveniles compared to adults and several methods of urine sampling are discussed.     

Importance of thiols in the reductive binding of 2-nitroimidazoles to macromolecules

Reductive activation of 2-nitroimidazoles in the presence of bovine serum albumin (BSA) led to binding of the nitroheterocycles to the protein. The binding was most efficient to BSA in which protein disulfides had been reduced to thiol groups. Protein thiols were at least twenty times more efficient than other protein, RNA or DNA nucleophiles in binding the reductively-activated nitroheterocycles. This result is of practical importance in the development of immunoassays for 2-nitroimidazoles as hypoxia markers in normal and tumor tissue.     

Candida albicans infection of a prosthetic knee replacement: a report and review of the literature

A woman with rheumatoid arthritis who underwent total knee arthroplasty is described. The implant became infected with Staphylococcus epidermidis and she received a prolonged course of postoperative antistaphylococcal antibiotics. Four months postoperatively she developed a calf ulcer that grew Pseudomonas aeruginosa and required further antibiotic therapy. One year later she presented with a painful, swollen knee with radiographic findings suggesting loosening of the prosthetic knee implant. Arthrocentesis cultures grew Candida albicans. She was treated with arthrodesis, amphotericin B, 5-fluorocytosine, and ketoconazole and remains free of infection 21 months after removal of the prosthesis. The clinical course of 6 other cases of Candida prosthetic joint infections is reviewed.     

Identification of N2 as a metabolite of acetylhydrazine in the rat

 In the pathogenesis of isoniazid-induced hepatic injury, cytochrome P450-dependent metabolic activation of the metabolite, acetylhydrazine (AcHz), is the crucial step. Exhalation of [¹⁴C]-carbon dioxide has previously been used to quantify indirectly this pathway. In contrast, according to the current concept of AcHz bioactivation, molecular nitrogen is produced directly, but has not yet been identified. Here, we measured [¹⁵N]-nitrogen and ¹⁴CO₂ exhalation, after the administration of [¹⁵N₂]-[¹⁴C]-AcHz, in rats. Laser magnetic resonance (LMR) spectroscopy, a new sensitive and specific technique for the measurement of ¹⁵N and ¹⁴N in gas samples, was used. To demonstrate the involvement of cytochrome P450, rats were treated with phenobarbital (PB) or PB + cobalt(II) chloride (CoCl₂) (n=3 in each group). Time-dependent ¹⁵N₂ exhalation differed significantly between treatment groups (p<0.001). At 240 min, cumulative exhalation of ¹⁵N was 1.92±0.43% (mean±SE) of the dose in the control group, 2.53±0.23% in the PB group, and 1.00±0.15% in the PB+CoCl₂ group (p<0.05 compared to controls, p<0.01 compared to PB). Cumulative exhalation of ¹⁴CO₂ in 24 h ranged from 15.1 to 21.9%, with no significant difference between treatment groups. In conclusion, N₂ is a metabolite of AcHz. N₂ formation reflects the cytochrome P450-mediated activation of AcHz and can be used as an index of this pathway. Generally, LMR spectroscopy is valuable for monitoring any N₂-liberating process in vivo. Received: 14 March 1995/Accepted: 15 August 1995