The Effects of Cyclophosphamide on the Pharmacokinetics of Triiodothyronine in the Male Rat

In the present study, the possibility that cyclophosphamide or a cyclophosphamide metabolite may be accelerating the clearance of triiodothyronine has been examined. Following administration of exogenous triiodothyronine to saline-and cyclophosphamide-treated rats, the area under the plasma-concentration time curve (AUC), apparent clearance (CL_app) and half-life of triiodothyronine were measured. AUC (34.43 ± 12.34 compared with 33.32 ± 9.92 nmol hL^?1), CL_app (36.30 ± 12.89 compared with 37.51 ± 11.16 mLh^?1) and half-life (7.50 ± 1.39 compared with 6.40 ± 0.96 h) were not significantly different in the control rats compared with the cyclophosphamide-treated rats. As cyclophosphamide does not appear to alter the elimination of triiodothyronine, it is likely that cyclophosphamide or a cyclophosphamide metabolite is acting at the hypothalamo-pituitary axis, reducing the synthesis or release of thyroid stimulating hormone and consequently decreasing the levels of triiodothyronine and thyroxine.     

Development of a panel of monochromosomal somatic cell hybrids for rapid gene mapping

We have assembled a panel of monochromosomal somatic cell hybrids for use in gene mapping. DNA from each individual hybrid was used as a probe on normal human metaphases to identify the human chromosome and any fragments by reverse painting. To test the efficiency of the panel PCR amplification of DNA from the monochromosomal somatic cell hybrid panel was used in combination with human specific oligonucleotide primers to assign α-catenin (CTNNA1) and p21/WAFl to chromosomes 5 and 6 respectively. These genes were localized further using hybrids containing specific translocations to 5qll-qter and 6p21 respectively. We also developed primers to enable us to assign 17 ESTs sequenced by the HGMP Resource Centre. The hybrid panel was developed with support of the UK HGMP and the DNA is available to all registered users.     

Mediation by B1 and B2 receptors of vasodepressor responses to intravenously administered kinins in anaesthetized dogs.

1. Vasodepressor responses to intravenous (i.v.) injection of bradykinin (BK) and des-Arg9-BK, a selective B1 kinin receptor agonist, were characterized following i.v. pretreatment with selective B1 ([Leu8]-des-Arg9-BK) and B2 (Hoe 140) kinin receptor antagonists in anaesthetized dogs. 2. Des-Arg9-BK (0.05-3.3 nmol kg-1) produced dose-dependent decreases in mean arterial blood pressure with a ED50 0.4 nmol kg-1. The vasodepressor effects evoked by des-Arg9-BK (0.6 nmol kg-1) and BK (0.2 nmol kg-1) were greater after i.v. and i.a. injections, respectively. 3. The vasodepressor response to BK (0.6 nmol kg-1) but not to des-Arg9-BK (0.6 nmol kg-1) was significantly (P < 0.001) blocked by pretreatment with the B2 receptor antagonist, Hoe 140. 4. The vasodepressor response to des-Arg9-BK (0.6 nmol kg-1) but not to BK (0.6 nmol kg-1) was significantly (P < 0.001) reduced by pretreatment with the selective B1 receptor antagonist, [Leu8]-des-Arg9-BK. Although both B1 and B2 receptor antagonists caused a transient fall in blood pressure, their inhibitory action was unlikely to be related to a desensitization mechanism. 5. Inhibition of prostaglandin synthesis with indomethacin prevented the vasodepressor response induced by arachidonic acid (1 mg kg-1, i.v.) but not that to BK or des-Arg9-BK (0.6 nmol kg-1). 6. These results suggest, firstly, that the vasodepressor responses to i.v. BK and des-Arg9-BK are mediated by the activation of B2 and B1 receptors, respectively; secondly, that prostaglandins are not involved in the vasodepressor responses to kinins.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intraoperative angiography in reconstructive surgery of aorto- iliac occlusions

In a group of 182 patients who underwent surgical treatment for aortoiliac occlusions 172 had to be subjected to intraoperative distal angiography. The operative tactics in this case was determined by the degree of affection of the peripheral vessels and the character of collateral circulation, which were appraised from the findings of the operative angiograms. According to this, all patients were divided into 4 groups. Two patients developed complications linked with faulty appraisal of the drainage paths.     

Use of immozymase in the treatment of suppurative wounds

The authors discuss the results of application of proteinase preparations immobilized on a water soluble carrier (Immozymase) and a water insoluble carrier (Profezyme) in the management of ++pyo-necrotic processes of various etiology and localization in 1,059 patients. The wounds were cleansed 1.5-2 times quicker than with the traditional methods of treatment. Immobilized proteinases possessing a prolonged therapeutic effect were found to stimulate the regeneration process. The authors believe the use of Immozymase to be promising in the treatment of purulent foci which are drained with difficulty and in intracavitary administration for treating purulent processes in the thoracic or abdominal cavity.     

Changes in plasma atrial natriuretic factor during sequential fluid removal and biochemical correction in end-stage chronic renal failure patients

Plasma immunoreactive atrial natriuretic factor (ANF) levels, their chromatographic profiles (high-performance liquid chromatography; HPLC) and changes during sequential ultrafiltration (UF; 1 litre/h) and biochemical correction without fluid removal (BC; 3 h) were studied in 8 end-stage chronic renal failure patients on intermittent haemodialysis (greater than 1 year). Patients entered randomly the UF-BC or BC-UF protocols that were reversed after 1 week. HPLC showed a single peak of ANF immunoreactivity in plasma of end-stage chronic renal failure patients before dialysis sessions. ANF at the end of fluid removal fell by 31 +/- 2% (p less than 0.01) during UF-BC and by 30 +/- 2% (p less than 0.01) at the end of BC during BC-UF. In both sequences a further slight reduction in plasma ANF was observed during the second phase: it was 8.5 +/- 5% (n.s.) during BC of the BC-UF and 12.5 +/- 2% (p less than 0.05) during fluid removal of BC-UF. Plasma ANF was not significantly removed by the machinery. BC did not modify the microhaematocrit in the BC-UF sequence while the microhaematocrit was significantly increased by UF (13 +/- 1 and 14 +/- 1%, p less than 0.005 vs. basal, respectively), and decreased by BC in the UF-BC sequence (-5 +/- 2% vs. end UF, p less than 0.05). Serum creatinine and urea decreased significantly during BC in both protocols while they were unmodified during UF. No significant changes were seen in PRC during either protocol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Management of fractures in patients with osteoporosis

The treatment of the most common osteoporotic fractures has been reviewed. In general, early functional treatment is used to allow early restoration of function and weight bearing. Fracture treatment should always be accompanied by an investigation of the bone mass in these patients. Nutritional support and calcium and vitamin supplementation should be provided during the healing phase.