A kinetic study of leucine metabolism in severely burned patients. Comparison between a conventional and branched-chain amino acid-enriched nutritional therapy.

A cross-over design study was used to examine the metabolic consequences of enteral feeding for 48 to 96 hours with either a branched-chain amino acid (BCAA)-enriched (44% BCAA) or a conventional egg protein formulation in 12 severely burned adult patients. A stable isotope labeled leucine (L-1-13C-leucine) tracer approach was used to measure leucine flux and oxidation and to estimate rates of whole body protein synthesis and breakdown. Additionally, 15N2-urea and 6,6-2H-glucose were administered to assess the status of urea and glucose kinetics with these two nutritional treatments. Average patient age was 54 years, and average burn surface area was 36%. Studies were conducted at an average of 25 days postburn. Leucine flux and oxidation were significantly (p less than 0.01, by paired t-test) elevated with BCAA feeding as compared to the egg protein formulation. However, there were no significant differences in the rates of leucine incorporation into, or release from, proteins (p greater than 0.05) between the two dietary periods. Mean rates of body protein synthesis and breakdown for each diet were about twice the rates reported for healthy young adults. Apparent nitrogen balance measurements were not statistically different (p greater than 0.1) between the two diet periods. Furthermore, urea and glucose kinetics failed to show significant differences between the two diet periods. It appears from these results that the major consequences of increased intake of leucine from the BCAA formula is an enhanced rate of leucine oxidation. In conclusion, (1) the availability of BCAAs is not rate-limiting for enhanced protein synthesis in burn patients, and (2) the use of enriched BCAA formulas in burn therapy does not appear to offer advantages over a routinely used enteral egg protein formula, at least based on the present determinations.     

Osteitis Unterschenkel

Osteomyelitis patients feel their social and professional existence is threatened. Health insurances are faced with total treatment costs for each patient with osteomyelitis, which can reach 500.000,00 EUR. We must therefore make every effort, from the first onset of infection, to prevent the condition from becoming chronic and thus keep the potential problems to patients and insurance companies to a minimum: once the condition has become chronic there is absolutely no guarantee that treatment will be successful. Treatment must start with the removal of absolutely all necrotic tissue – soft tissue and bone – and of all implants. As in tumor surgery, en bloc resection is best. Up to now there is still no means of determining the exact limits of the infection. The surgeons's personal experience with osteomyelitis is the most important factor both in the treatment of these cases and therefore in the containment of treatment costs. Bone reconstruction is attempted after the soft tissue defects have been treated, either by bone grafting (defect < 3 cm) or by segment transfer. Modern techniques of reconstruction surgery can yield quite good results even in chronic oxteomyelitis, providing management has been optimum throughout. Patients with osteomyelitis should therefore be treated in specialist hospitals.     

Analgesic nephropathy in Hungary: the HANS study.

BACKGROUND: The diagnosis of analgesic nephropathy has improved significantly with modern imaging techniques. We reviewed a large portion of the Hungarian dialysis population to obtain additional insight into the problem. METHODS: Twenty-two participating dialysis units enrolled 1400 patients on renal replacement therapy between 1 January 1995 and 1 January 1998. Patients with no known aetiology (n = 284) were interviewed and studied with renal imaging. We assessed the presence of decreased renal mass combined with either bumpy contours, papillary calcification, or both. The subjects studied were interrogated extensively. RESULTS: Our survey suggested analgesic nephropathy in 47 of 1400 patients (3.3%), 3-fold higher than the EDTA database estimate for Hungary. The analgesics most commonly abused were phenacetin-containing mixtures. The driving symptoms were mainly headache and joint pain. Cardiovascular complications were more common than in the rest of the dialysis population, independent of smoking and lipid values (P<0.01). CONCLUSIONS: Phenacetin should be banned. Our study results support the need for longitudinal cohort and case-control studies in Hungary.     

Kidney Transplantation Substantially Improves Endothelial Progenitor Cell Dysfunction in Patients with End-Stage Renal Disease

Endothelial progenitor cells (EPC) are involved in endothelial repair and maintenance. Dysfunction of EPC may contribute to accelerated arteriosclerosis in chronic kidney disease. Kidney transplantation (KTx) improves both survival and endothelial function of dialysis patients. In a prospective study, we tested to which extent KTx changes EPC biology. We studied number and function (migratory activity, adhesion to extracellular matrix proteins and to mature endothelial cells [EC]) of EPC in 20 patients during dialysis and 3, 6, 9 and 12 months after KTx. Twenty-two healthy volunteers served as matched controls. Circulating precursor populations were measured by flow cytometric analysis. Cytokines relevant for EPC mobilization were monitored. Compared to the dialysis state, KTx increased the migration of EPC to approximately 2-fold. Adhesion to fibronectin and to collagen type IV was significantly increased after KTx. An improved adhesion rate of EPC to mature EC was observed. The number of EPC decreased. The amount of precursor populations showed no difference compared to the pretransplant state. Our study shows an improved function of EPC after KTx. This finding indicates an improved potential for endothelial repair which in turn may contribute to enhanced endothelial function and reduced cardiovascular morbidity after KTx.     

Anulus fibrosus in bulging intervertebral disks

In this investigation the association of radial tears of the anulus fibrosus and bulging of the intervertebral disk was studied. An index of disk bulging was measured in sagittal anatomic sections in 149 lumbar disks from 31 cadavers. The indexes of disk bulging were correlated with stages of disk development and the presence of an annular tear. The largest disk-bulging indexes were always associated with radial tears of the anulus. Eighty-four percent of the disks with radial tears had disk-bulging indexes greater than 2.5 mm. Most normal adult disks had an index of less than 2.5 mm. The results challenge the concept that the anulus fibrosus is intact in bulging disks, although ruptured in herniated disks.     

A pathway for the biosynthesis of straight and branched, odd- and even-length, medium-chain fatty acids in plants.

Pathways and enzymes of fatty acid synthase-mediated, long-even-chain (generally C16-C20) fatty acid synthesis are well studied, and general metabolism involved in short-chain (C4-C7) fatty acid biosynthesis is also understood. In contrast, mechanisms of medium-chain (C8-C14) fatty acid synthesis are unclear. Recent work suggests involvement of chain-elongation-terminating thioesterases in medium-chain fatty acid formation in oilseeds and animals. We have shown that iso- and anteiso-branched and straight, odd- and even-length, short-chain fatty acids esterified in plant-trichome-gland-produced sucrose esters are synthesized by using carbon skeletons provided by modified branched-chain amino acid metabolism/catabolism. The principal enzymes involved are those catalyzing leucine biosynthesis in all organisms and those leading to short-chain alcohols in mutant yeasts and alkyl acids in Clostridium species (products often serving as mammalian pheromones). Here we provide evidence that C10-C12 straight medium-chain and C10-C12 branched medium-chain acyl acids of tomato, C6-C8 straight-chain acyl acids of Petunia, and C6 and C8 branched acyl acids of Nicotiana glutinosa are formed by alpha-ketoacid elongation without participation of fatty acid synthase-mediated reactions or -independent thioesterases. This different metabolism suggests greater integration of amino acid and fatty acid metabolism than previously considered and provides other avenues to study and manipulate not only straight even-length but also odd- and even-length straight and branched medium-chain fatty acid biosynthesis.     

Cardioselectivity of alpha-tocopherol analogues, with free radical scavenger activity, in the rat.

MDL74270 (6-acetyloxy-3,4-dihydro-N,N,N,2,5,7, 8-heptamethyl-2H-1-benzopyran-2-ethanaminium, 4-methylbenzenesulfonate) is a quaternary amine analogue of alpha-tocopherol with free radical scavenger properties. Rats were injected iv with [14C]MDL74270 (0.91 mg/kg), and whole blood and heart tissue were sampled. Five min after drug, the heart tissue/blood ratio (T/B) of radioactivity was 3.5, whereas at 1 hr it was 20.1 and remained at this value up to at least 6 hr. After iv administration the t 1/2 of radioactivity in blood was 6.3 hr, but po blood levels could not be quantified. The 0- to 96-hr urinary elimination of radioactivity was 39.9 +/- 5.7% of the dose after iv and only 1.2 +/- 0.4% after po administration, conversely, 44.7 +/- 5.2% was excreted in feces after iv and 79.1 +/- 17.4% after po administration. These results confirmed poor oral absorption of the compound. Tissue distribution of [14C]MDL74270 was compared with that of its tertiary amine analogue [14C]MDL74366 in rat heart, skeletal muscle, brain, and whole blood, after iv administration (1 mg/kg). The heart T/B was above 20, 1-6 hr after [14C]MDL74270, whereas it was less than 2 after [14C]MDL74366. Over the 1- to 6-hr time interval, skeletal muscle T/B varied from 1.8 to 5 compared with 1.5 to 0.6 for [14C] MDL74366. Brain T/B was higher after the tertiary amine compound. Results showed marked cardioselectivity of radioactivity after [14C] MDL74270. Differential centrifugation of heart homogenates showed that radioactivity was equally distributed between the major subcellular fractions studied.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extrapulmonary location of sarcoidosis.

Two cases of sarcoidosis located outside the lungs are reported. In both cases the symptoms of the sicca syndrome were in the foreground. In the first case other clinical manifestations included mediastinal and retroperitoneal lymphadenopathy, and lacrimal gland impairment. In the other case the symptoms of the sicca syndrome were associated with polyneuropathy and maculopapular skin rash. The diagnosis of sarcoidosis was confirmed by histological examination of a biopsy specimen of lower lip mucosa in the first case, and biopsy of skin lesion in the second case. Abnormal results of laboratory tests included only raised erythrocyte sedimentation rate, in both cases and presence of circulating immune complexes in one case. Serological tests failed to demonstrate the presence of rheumatoid factor, antinuclear and anti-ds DNA antibodies. No decrease was observed also in the haemolytic activity of the complement, and cryoglobulins were absent. Regression of clinical signs was obtained in both cases after treatment with glucocorticosteroids.