Induction of mesothelioma after intrapleural inoculation of F344 rats with silicon carbide whiskers or continuous ceramic filaments.

OBJECTIVE: To find whether continuous ceramic filaments (CCFs) and silicon carbide whiskers (SiCWs), which are used in many industries as reinforcing materials in advanced ceramic composites, are carcinogenic in the intrapleural inoculation assay. METHODS: Samples of SiCWs, CCF, International Union Against Cancer crocidolite, or saline were injected into the pleural cavities of female F344/N rats to find whether the samples of SiCW and CCF had the potential to induce mesotheliomas after the direct application of the materials to the surface of the pleural mesothelium. RESULTS: Rats injected with two of the three individual samples of SiCW or the crocidolite had significantly reduced life spans compared with the rats treated with saline, CCFs, or the third SiCW sample. Rats treated with either of the two SiCW samples or crocidolite developed mesotheliomas. By contrast, rats treated with saline or CCF did not. The two SiCW samples that induced shortened life spans also induced a higher rate of mesothelioma (87%-90%), than the crocidolite (57%) and the third SiCW sample (23%). CONCLUSION: SiCWs but not CCFs could induce mesotheliomas after intrapleural injection in rats. The difference in biological activity between the SiCW samples could not be explained on the basis of their physical dimensions or biological activity toward cultured cells. Results from this study indicated that SiCWs should be handled with care as they might be carcinogenic if inhaled. However, there is controversy as to whether results of intrapleural injection assays are sufficient to determine a fibre's carcinogenic activity. The results also showed that a collection of fibrous materials such as SiCWs could have considerably different biological activities despite similar physical dimensions.     

Dyggve-Melchior-Clausen syndrome with increased pipecolic acid in plasma and urine

Summary A child with the Dyggve-Melchior-Clausen syndrome associated with elevated pipecolic acid levels in plasma and urine is described. Other studies of peroxisomal function, including phytanic acid, very long-chain fatty acids, and plasmalogen synthesis, were normal. This disorder may represent an incompletely characterized defect in peroxisomal metabolism.Dr Roesel died on 21 August, 1989.     

Pharmacokinetics of propentofylline and the quantitation of its metabolite hydroxypropentofylline in human volunteers

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be effective for the treatment of both vascular dementia and dementia of the Alzheimer type. The pharmacological effects of PPF may be exerted via the stimulation of nerve growth factor, increased cerebral blood flow, and inhibition of adenosine uptake. The objectives of this experiment are to determine the kinetic behavior of PPF, to identify, and to quantify its metabolite in human. Blood samples were obtained from human volunteers following oral administration of 200 mg of PPF tablets. For the identification and quantification of the metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine (PPFOH), PPFOH was synthesized and identified by gas chromatography/mass spectroscopy (GC/MS) and¹H-nuclear magnetic resonance spectroscopy. The molecular weight of synthesized metabolite is 308 dalton. The PPF and PPFOH in plasma were extracted with diethyl ether and identified by electron impact GC/MS. The plasma concentrations of PPF and PPFOH were determined by gas chromatography/nitrogen phosphorus detector in plasma and their pharmacokinetic parameters were determined. The mean half-life of PPF was 0.74 hr. The areas under the curve (AUCs) of PPF and PPFOH were 508 and 460 ng.hr/ml, respectively. C_max of PPF was about 828.4 ng/ml and the peak concentration was achieved at about 2.2 hr (T_max). These results indicate that PPF is rapidly disappeared from blood due to extensive metabolism into PPFOH.     

199. Thromboseprophylaxe mit niedermolekularem Heparin in der Unfallchirurgie

Zusammenfassung In einer kontrollierten, randomisierten Studie wurde die Wirksamkeit von niedermolekularem Heparin (Fragmin) im Vergleich zur Kombination Heparin + DHE an 98 Patienten mit Hilfe der Phlebographie geprüft. In der Fragmin-Gruppe traten keine, in der Heparin-DHE-Gruppe 3 Beinvenenthrombosen auf (2 oberflächliche, 1 tiefe). Der intraoperative Blutverlust war in der Fragmin-Gruppe deutlich höher, der postoperative geringer als in der Heparin-DHE-Gruppe. Die Anti-F-X_a-Aktivität lag signifikant höher bei Fragmin. Niedermolekulares Heparin ist in einmaliger täglicher Dosis von 5000 Anti-X_a-U ebenso effektiv wie die Prophylaxe mit 2 x 5000 E Heparin + 0,5 mg DHE.     

Reduced production of tumor necrosis factor by mononuclear cells in hairy cell leukemia patients and improvement following interferon therapy

In 16 patients with hairy cell leukemia (HCL) there was a marked reduction in the production of cytotoxins (CTXs) by peripheral blood mononuclear leukocytes in response to stimulation in vitro by phytohemagglutinin (PHA), 4 beta-phorbol-12-myristate-13-acetate (PMA), or Sendai virus. CTX yields of 23.5 +/- 21.5 U/ml, 15 +/- 18 U/ml, and 12.1 +/- 12.1 U/ml were obtained in response to PHA, PMA, and Sendai virus, respectively, as compared with corresponding yields of 207.3 +/- 93.1, 154 +/- 37.4, and 205.2 +/- 62.4 in healthy controls. The extent of reduced production of CTXs appeared to be correlated with the severity of the disease. Systemic interferon (IFN) administered to four patients caused CTX production to improve in response to PHA (147.5 +/- 55.1 U/ml compared with pretreatment values of 14.1 +/- 6 U/ml, P less than 0.05). However, CTX production in response to Sendai virus remained low. The extent to which CTX production by hairy cell leukemia mononuclear cells was reduced was proportionate to the observed decrease in monocyte counts. However, the degree to which CTX production improved after IFN treatment was significantly greater than the observed increase in monocyte counts. The major CTX induced by PHA in mononuclear cells of healthy donors and of IFN-treated HCL patients was identified as tumor necrosis factor-alpha.     

Ferrite particles for bowel contrast in MR imaging: design issues and feasibility studies

Diverse materials with varying physical and magnetic properties have been evaluated as gastrointestinal contrast agents for magnetic resonance (MR) imaging. Uniform marking of the small bowel remains the greatest challenge. Ferrites are magnetically active iron oxide particles that are miscible with water and cause loss of signal on MR images. The decrease in MR signal intensity produced by ferrites occurs with a wide range of iron concentrations (0.1-10 mM) and with both T1- and T2-weighted pulse sequences. These effects of ferrites are explained by predominant T2 shortening with negligible T1 effects. The ferrite preparation used in this study was stable in vitro, with little iron solubilized by acid. Intragastric administration of ferrite (5 mg of iron per kg in 6 ml) routinely marked the small bowel of rats. The authors conclude that ferrites represent a promising new class of contrast agents for gastrointestinal MR imaging.     

19-Hydroxylation and aromatization of androgens in the developing rat brain

Androgen aromatization in the human placenta proceeds through two successive hydroxylations at C-19, the products of which are then virtually completely converted to estrogens. In the neonatal rat brain, however, 19-hydroxylation has been shown to exceed significantly subsequent aromatization, suggesting that formation of 19-hydroxylated androgen metabolites might be important in brain differentiation in this species. Using [19-3H3]androstenedione, we found that the surplus activity of 19-hydroxylase relative to aromatase was independent of age, sex, and androgen substrate concentration, despite 100-fold differences in tissue aromatase activity during the course of development. In addition, the surplus 19-hydroxylation was not affected by several agents which otherwise decreased or increased the activity of the aromatase enzyme, including metyrapone, KCN, and cytochrome P-450 reductase, the latter indicating that the failure of the 19-hydroxylated products to proceed to aromatization was not due to a deficit of reducing equivalents. 19-Hydroxylation of androgens in the rat brain is a quantitatively significant metabolic pathway in this tissue, although present data do not confirm the existence of a steroid C-19 hydroxylase in the brain separate from that involved in aromatization.     

Leukocytosis after fluid loading and induction of epidural anesthesia

The present study shows that leukocytosis occurs from fluid loading and from the small amounts of adrenaline given epidurally. Five healthy volunteers received an intravenous infusion of 25 ml·kg⁻¹ b.w. of Ringer's acetate solution over 15, 30, 45, and 80 min, and epidural anesthesia (EDA) was induced in 25 urology patients using mepivacaine 2% with or without adrenaline 1∶200 000. In the volunteers, we found that the total leukocyte count increased by up to 33% within 1 h after rapid volume loading. This increase was accounted for by neutrophils and lymphocytes. In the patients, the leukocyte count increased by 32% during the onset of EDA when mepivacaine with adrenaline was used. This increase was accounted for by lymphocytes. Our results suggest that caution is needed when interpreting the importance of a raised leukocyte count in samples taken in association with fluid loading and also when EDA is induced by a local anesthestic solution that contains adrenaline.     

Die kombinierte „3-in-1“/Ischiadicus-Blockade Blockadeerfolg,Serumspiegel und Nebenwirkungen bei Einsatz von je 700 mg Mepivacain 1% ohne und mit Adrenalin sowie Prilocain 1%

A high dose of local anaesthetic is necessary for the combined “3-in-1”/sciatic nerve block. Prilocaine is recommended for its low toxicity. However, in some patients prilocaine results in pronounced methaemoglobin formation due to toludine. Little has been known hitherto about the use of high-dose mepivacaine for the combined 3-1/sciatic nerve block. This study was undertaken to compare the use of 700?mg mepivacaine 1% and of 700?mg prilocaine 1%. Methods. The study was approved by the ethics committee of our hospital. Once their informed consent had been obtained in writing 3×20 patients (ASA 1–2) undergoing planned surgery on the foot or ankle joint were enrolled in the study. The patients were randomized to the following three groups on a double-blind basis: group 1,700?mg mepivacaine without epinephrine; group 2,700?mg mepivacaine with 0.2?mg epinephrine (1:350000); group 3,700?mg prilocaine 1%. Arterial blood samples for determination of local anaesthetic serum levels were collected over a 120-min period. We determined methaemoglobin and oxygen saturation before and 120?min after the blockade and continued these measurements for 6?h in group 3. At 15-min intervals, all patients were questioned about early signs of toxicity. The perioperative monitoring including blood pressure, ECG and pulse oximetry. Data were analysed using ANOVA and Student's t-test, P<0.05 considered statistically significant. Results. The blocking efficacy did not differ among the groups (groups 1, 2, 3: 90%, 95%, 90%). The maximum mepivacaine serum level in group 1 was 3.91?μg/ml ±0.95 and 2.94?μg/,ml ±0.58 in group 2 (Fig. 2). Over the entire observation period the addition of epinephrine resulted in a significant reduction of the serum level (between 60.3% at t=15 min and 19.7% at t=120?min). In the prilocaine group the maximum serum level was 2.07?μg/ml ±0.56, significantly less than in either mepivacaine group. No patient showed signs or symptoms of local anaesthetic toxicity. In the prilocaine group there was wide variation in methaemoglobin formation among the patient, with a median of 10.1% (Fig. 3, Table 3). Three patients showed a maximum methaemoglobinemia between 16% and 17%. Five patients were still cyanotic after 6?h when they were transferred to the ward. The fractional SaO₂ values amounted to 88% (median) with a minimum of 80.3%. Conclusion. Both mepivacaine 1% and prilocaine 1% are appropriate local anaesthetics for the combined 3-in-1/sciatic nerve block at a dose of 700?mg. There was no difference in the blocking efficacy. No patient showed clinical signs or symptoms of a local anaesthetic toxicity. Following prilocaine we are sometimes faced with high methaemoglobinemia, which may necessitate prolonged monitoring.