Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease.

In patients with uremia, increased blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) have been linked to the severity of atherosclerosis and to excess cardiovascular mortality. The ADMA levels and several traditional cardiovascular risk factors were assessed in 44 untreated nonsmoking patients with confirmed primary chronic renal disease at different stages of renal disease. True GFR was assessed by means of the inulin-clearance technique. For comparison, nonsmoking subjects matched with respect to age, gender, and body-mass index were examined. Mean plasma ADMA concentration was markedly higher (P < 0.0001) in all patients combined (4.2 +/- 0.9 micromol/L) than in control subjects (n = 16; age 45 +/- 10 yr; serum creatinine 1.0 +/- 0.1 mg/dl; ADMA 1.4 +/- 0.7 micromol/L). However, mean ADMA levels were similar in patients with normal renal function (n = 16; age 41 +/- 9 yr; serum creatinine 1.1 +/- 0.1 mg/dl; GFR 120 +/- 14 ml x min(-1) x 1.73 m2; ADMA 4.0 +/- 0.7 micromol/L), in patients with moderate renal failure (n = 15; 47 +/- 7 yr; 1.8 +/- 0.3 mg/dl; 65 +/- 10 ml x min(-1) x 1.73 m2; 3.8 +/- 0.6 micromol/L) and in patients with advanced renal failure (n = 13; 46 +/- 9 yr; 4.2 +/- 0.9 mg/dl; 25 +/- 4 ml x min(-1) x 1.73 m2; 4.7 +/- 1.2 micromol/L). Furthermore, ADMA levels were increased to the same extent in normotensive (n = 17; 4.0 +/- 0.8 micromol/L) and in hypertensive (n = 27; 4.2 +/- 0.9 micromol/L) patients. In contrast to ADMA, mean total plasma homocysteine concentration were similar in control subjects (10.6 +/- 2.9 micromol/L) and in patients with normal GFR (11.0 +/- 2.9 micromol/L), but were significantly higher in patients with moderate renal failure (17.7 +/- 4.1 micromol/L) and particularly in patients with advanced renal failure (28.2 +/- 10.6 micromol/L). Finally, mean total serum cholesterol concentrations were comparable in the control group and in the three groups of patients with renal disease. In contrast to several traditional cardiovascular risk factors, markedly increased blood concentrations of ADMA, a putative biochemical marker of atherosclerosis, are present even in nonsmoking patients without diabetes with incipient primary renal disease. Thus, the early increase of ADMA levels may be of relevance for the excess cardiovascular morbidity and mortality due to arterio- and atherosclerotic complications in patients with renal disease.     

Intrascrotal adenomatoid tumors

Adenomatoid tumors are regarded as uncommon neoplasms of the paratesticular tissues, probably of mesothelial origin. The majority of cases reported have involved the epididymis. We report our experience with 8 cases of testicular tumors and 11 of epididymal adenomatoid tumors during a 13-year period, and review the relevant literature. The incidence of adenomatoid tumors relative to all tumors in the testis was 6.9% (8 of 116), exceeding that of Leydig cell tumors, which were previously believed to be the most common benign testicular neoplasms. The adenomatoid tumors included 38% epididymal tumors (11 of 29). The clinical course of the tumors was benign, without recurrences. Local excision is regarded as the treatment of choice for epididymal and testicular adenomatoid tumors.     

Image analysis of DNA cytometry for assessing prognosis after resection of esophageal cancer]

Esophagus cancer is a heterogeneous disease with considerable differences in malignant behaviour. Some relevant factors for prognosis are known. In this study we analyzed DNA-ploidy as a potential prognostic parameter in esophagus carcinoma. Paraffin embedded histological material from 50 patients with an esophagus cancer, obtained by resection, were selected for analysis. Tumor areas within the paraffin material were identified by HE-stained reference sections. One 50 microns section was dewaxed, rehydrated and mechanically and enzymatically treated to a suspension of 10,000 cells/ml. 1 ml of the suspension, containing bare nuclei with small rests of cytoplasma was centrifuged on glass slides. The fixed nuclei were air-dried and stained by Feulgen-SITS technique, which allows quantitative measurement of DNA. The DNA analysis was carried out with a computer-controlled single cell cytophotometry (Leytas 2, Leitz, Wetzlar). In contrast to the flow cytometry with image cytometry only tumors cells were measured. Overlapping nuclei, dirt and other artefacts as well as inflammatory cells were efficiently eliminated. With the DNA image cytometry we could differentiate between diploid and hypotriploid, hypertriploid aneuploid tumors. Best prognosis had diploid and hypotriploid tumors, the worst hypertriploid carcinomas. In the multivariate analysis the DNA-content of the tumor cells in esophagus cancer was the only prognostic parameter. DNA-content of tumor cells may become considerably clinical relevant in esophagus cancer for the decision to perform a resection or palliative treatment. In patients with hypertriploid tumors an adjuvant oncological therapy may increase the prognosis.     

Use of electric stimulation for activating the process of bone consolidation

A method of electrostimulation aimed at activation of bone adhesion processes was developed and introduced into practice at the Latvian Research Institute of Traumatology and Orthopedics on the basis of data on bone bioelectric activity. The method was used in complex with external fixation of the fracture by Kalnbers' apparatus. The phase pattern of callus formation necessitated the employment of the appropriate potential of direct current. Cyclic potentials similar to piezopotentials of a normal bone in cyclic physiological load were used in the phase of functional reorganization. Positive results were achieved in 88.4% of 79 patients.     

Biochemical effects and monitoring of exposure of rats to 4-methylcyclohexyl-1,6-dicarboxylic acid anhydride vapour

Male Wistar rats exposed to 5, 10 or 20 p.p.m. 4-methylcyclohexyl-1,6-dicarboxylic acid anhydride vapour for 2-11 weeks showed dose-dependent blood anhydride concentrations. The maximum concentrations were found after two weeks. At five exposure weeks, they were smaller but they did not decrease further thereafter. The change was coincident with increased epoxide hydrase activity in liver. The excretion of 4-methylcyclohexyl-1,6-dicarboxylic acid was detected in the urine. The excretion was linearly related to the exposure in specimens collected during the 10th and 11th week. Brain acetylcholinesterase activity was transiently inhibited by the exposure at the two higher doses while decreased enzyme activity in the isolated spinal cord axons was only found after 11 weeks. This change was simultaneous with increased creatine kinase activity in the cerebellar homogenate. In the occupational setting, acetylcholinesterase activity might only be significantly inhibited in lungs because of the low exposure levels.     

Misuse of zopiclone and convulsions during withdrawal.

It has been documented that benzodiazepines have the potential to cause dependence and withdrawal reactions, including convulsions. However, the available data concerning zopiclone, a nonbenzodiazepine hypnotic, are insufficient. The present study describes the case of a 36-year-old man who repeatedly misused zopiclone, in daily doses of 60-90 mg. Furthermore, the patient suffered from convulsion on two occasions following abrupt withdrawal of zopiclone. The concomitant use of alcohol, trimipramine, and promazine may have contributed to the development of convulsions. It is concluded that zopiclone may cause problems associated with misuse and withdrawal reactions similar to those of benzodiazepines.