Manganese and arteriosclerosis

The relations between manganese and atherosclerosis were examined on rabbits with experimental atherosclerosis, on patients with atherosclerosis and on workers exposed to manganese. Here a favourable influence of manganese was shown which effected a decrease of the cholesterol content of serum, liver and aorta and inhibited the entry of lipids into the aorta. The influence of the manganese on various enzymes as well as a manganese-copper interaction are discussed as possible causes.     

Cutaneous leishmaniasis: Clinical report of two cases and review of the recent literature

With 1–1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self‐healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the host's immunological and genetic status. Species‐specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.     

H2-receptor antagonists and the incidence of gastroduodenal ulcer perforation and hemorrhage. An epidemiological study

The only curative treatment to proximal bile duct cancers with involvement of both hepatic ducts is liver transplantation. A curative resection with wide lateral clearance is limited due to the neighbourhood of vital anatomic structures in the liver hilum. The majority of patients with bile duct cancers is over 60 years of age and due to concomitant disease, they do not fulfill the requirements for liver transplantation. Our treatment strategy in adequate cases is palliative tumor resection and reconstruction of bile passage by sutureless biliodigestive anastomosis as proposed by Rodney Smith. We treated 11 patients with this method, in 5 patients an additive combined radiotherapy by percutaneous radiation and intraluminal after-loading therapy was performed. Our results indicate that this strategy leads to effective palliation in cases provided that only microscopic residual tumor is left in situ (R1-resection). Our observed survival times compare favorably to survival times after liver transplantation (average survival time 11.5 months median survival time 10 months).     

Experimental studies on the action of extracts of herba recens Echinaceae purpureae on skin flaps

In animal experiments the effects of Echinacin, a sap made from Herba recens Echinaceae purpureae, on the rate of necrosis of skin flaps were studied in comparison with NaCl and pentoxifylline. The fluoresceine test was used as an indicator of peripheral circulation. The noncirculated area of the skin flap was significantly smaller in Herba Echinaceae treated animals than in control animals (p less than 0.01). On the day of the operation the size of the noncirculated flap area was only 56.0%, whereas it was 77.8% in the NaCl group and 67.4% in the pentoxifylline group. Until the 5th postoperative day the ratios changed to 47.4% (Herba Echinaceae), 76.6% (NaCl) and 50.4% (pentoxifylline). While more than two thirds of the skin flap area were to become necrotic in the NaCl group, less than half of the skin flap was so in the Herba Echinaceae group. Thus Herba Echinaceae significantly decreased the rate of necrosis of skin flaps in animal experiments.     

Odd-numbered long-chain fatty acids in erythrocyte phospholipids as long-term follow-up parameter in propionic acidemia.

Odd-numbered long-chain fatty acids (OLCFAs) increase in total erythrocyte lipids or plasma in patients with propionic acidemia and have been proposed as a useful parameter of metabolic control. However, up to now no parameter for long-term metabolic control has been available for this disorder. In contrast to previous investigations, we investigated OLCFAs with particular reference to differences for two phospholipid fractions of erythrocyte lipids. The phosphatidylethanolamine (PE) fraction of erythrocyte lipids has a slow turnover rate and might reflect the metabolic propionyl-CoA burden over a period of some weeks. Distinct increases in OLCFA of up to 200% in the phosphatidylcholine fraction were observed after episodes of metabolic decompensation and maximum OLCFA levels were found 3 weeks after the onset of a crisis. As a sign of poor metabolic control, OLCFA levels in PE steadily increased after recurrent episodes of decompensation, but not in clinically stable patients. However, in one patient with clinically good metabolic control, OLCFAs continually increased after the second year of life for an as yet unknown reason. In conclusion, data from this study indicate the usefulness of OLCFA analysis in the PE fraction of erythrocyte lipids, in particular with regard to the need for such a parameter for evidence-based improvement of management strategies in propionic acidemia.     

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Deep venous thrombosis: rate of spontaneous lysis and thrombus extension.

AIM: Although recanalization occurs after an episode of venous thrombosis, the exact timing for this process, the rate of clearing at the different venous segments and the nature of the mechanisms involved and their progression are not well known. Recognition of these competing events is important in understanding the natural history and the mechanisms responsible for lysis of the thrombus and for the development of the post-thrombotic syndrome METHODS: During the course of 5 consecutive years, 110 patients (126 legs) with deep vein thrombosis (DVT) were prospectively followed using ultrasonic duplex. Follow-up studies were performed at intervals of 1 and 7 days, 1 month, every 3 months for the 1(st) year, and yearly thereafter. Mean duration of follow-up was 329 days. RESULTS: When only legs with initial complete occlusion are considered, the prevalence of occlusion progressively decreases to 33% after 6 months, 17% after the 1(st) year, and 0% after 3 years. Recanalization of individual segments occurred even more rapidly. After 3 months, recanalization of completely occluded segments was present in 93% of common femoral veins, 79% of superficial femoral veins (proximal segment), 84% of popliteal veins, and 72% of posterior tibial veins. The rate of recanalization was highest for multisegmental disease. Propagation of thrombi to adjacent venous segments occurred in 15% of the limbs. Propagation was usually limited to 1 or 2 adjacent segments. CONCLUSION: Lysis occurred early and was progressive. After 1 year most legs have recanalized. After 3 years recanalization occurred in all legs although residual thrombosis (partial obstruction) was still present in 50% of the limbs. Propagation of the thrombus was a limited process.     

Mammalian nuclear transfer.

During development, the genetic content of each cell remains, with a few exceptions, identical to that of the zygote. Differentiated cells, therefore, retain all the genetic information necessary to generate an entire organism (nuclear totipotency). Nuclear transfer (NT) was initially developed to test experimentally this concept by cloning animals from differentiated cells. It has, since then, been used to study the role of genetic and epigenetic alterations during development and disease. In this review, we highlight some of the milestones in mammalian NT reached in the 50 years after the first nuclear transplantations in frogs. We also address problems associated with mammalian nuclear transfer and provide a survey on current NT and stem cell technology. In the long term, nuclear transfer or alternative strategies aim to generate customized pluripotent cells, which would be invaluable to medical research and therapy.