L-arginine reverses the antinatriuretic effect of cyclosporin in renal transplant patients

BACKGROUND: Cyclosporin has been shown to facilitate renal vasoconstriction and to have an antinatriuretic effect. The existence of an interference of cyclosporin with the vasodilating properties of endothelium mediated by nitric oxide production could mediate these effects. On the other hand, the infusion of the nitric oxide precursor L-arginine has been shown to induce renal vasodilatation and to facilitate natriuresis in normal volunteers. We have investigated the renal effects of the administration of an infusion of L-arginine in renal transplant patients chronically treated with cyclosporin. To facilitate the analysis of the data the effects of the administration of a similar dose of cyclosporin on renal function during the infusion of a vehicle were also investigated during the administration of a vehicle of L-arginine. DESIGN: Ten male renal transplant patients, chronically treated with cyclosporin and with a stable renal function were studied during 2 consecutive days after the administration of the usual morning dose of cyclosporin. The first day they received an intravenous infusion of vehicle and the second the infusion of graded doses of L-arginine (50, 100, 150 mg/kg/h) during 3 consecutive h. RESULTS: The first day, after cyclosporin administration a significant fall (P < 0.01) was observed in natriuresis and kaliuresis in the absence of changes in renal plasma flow and glomerular filtration rate. After the administration of L-arginine significant (P < 0.01) increases of renal plasma flow, glomerular filtration rate, and natriuresis were seen. The increase in blood levels of cyclosporin after its administration did not differ between days 1 and 2. CONCLUSION: These results indicate that L-arginine facilitates renal vasodilatation and natriuresis in renal transplant patients. Furthermore, the observed increase in sodium excretion could indicate that L-arginine counteracts the antinatriuretic effect of cyclosporin.      

RnaGel(R), a novel calcium- and aluminium-free phosphate binder, inhibits phosphate absorption in normal volunteers

Background: Available phosphate binders contain aluminium or calcium which can be associated with undesirable effects. RenaGel®, cross-linked poly(allyl-amine hydrochloride) is a non-absorbed phosphate binding polymer, free of calcium and aluminium. We conducted this study to examine the safety and phosphate binding efficacy of RenaGel in volunteers. Method: During 18 days (days 0-17) at the clinical study unit, 24 subjects consumed a phosphate-controlled diet designed to provide 37.5 mmol (1200 mg) elemental phosphorus per day. From the morning of day 5 to the morning of day 9, urine and faeces were collected. Average base line urine and faecal phosphorus contents were determined. On days 9-16, the subjects received either RenaGel 1 g, 2.5 g, or 5 g or placebo three times per day immediately prior to the meals. From the morning of day 13 to the morning of day 17, urine and faeces were again collected and phosphorus contents on treatment were determined. Results: RenaGel inhibited dietary phosphate absorption as measured by a decline in average daily urinary phosphorus excretion and an increase in average daily fecal phosphorus excretion. Average urine phosphorus contents on treatment were 2.7.2 mmol (870 mg) per day in the placebo group vs 23.8 mmol (762 mg), 19.5 mmol (625 mg), and 16.6 mmol (530 mg) per day in the renaGel 1-g, 2.5-g, and 5-g groups. Average daily faecal phosphorus content on treatment was markedly higher in the RenaGel 5-g group, 19.1 mmol (611 mg) per day vs 10.7 mmol (342 mg) per day for the placebo group. RenaGel also decreased total serum cholesterol by 0.71 mmol/L (27.5 mg/dl), 0.55mmol/l (21.3 mg/dl), and 1.08 mmol/l (41.8 mg/dl for the RenaGel 1-g,and 5-g groups. RenaGel was well tolerated with adverse events similar to placebo. Conclusion: RenaGel is a safe, effective, and well tolerated phosphate binder in normal volunteers. The degree of phosphate binding is consistent with its potential use as a phosphate binder in renal failure patients.     

Preoperative imaging of abnormal parathyroid glands in patients with hyperparathyroid disease using combination Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scans.

OBJECTIVE: To evaluate the efficacy of combined Tc-99m-pertechnetate and Tc-99m-sestamibi radionuclide scanning for imaging abnormal parathyroid glands in hyperparathyroid disease in a prospective study. SUMMARY BACKGROUND DATA: Established methods to localize abnormal parathyroid glands lack accuracy for routine use. Tc-99m-sestamibi used in conjunction with iodine-123 has excellent potential for preoperative imaging in patients with hyperparathyroid disease. An alternative method for parathyroid imaging was studied using Tc-99m-pertechnetate and Tc-99m-sestamibi. METHODS: Thirty patients with hyperparathyroid disease had Tc-99m-pertechnetate and Tc-99m-sestamibi subtraction radionuclide scanning to visualize abnormal parathyroid glands before surgery. The patients had surgery and pathologic confirmation of all parathyroid glands. RESULTS: In 23 patients with primary hyperparathyroidism, 12 of 13 solitary adenomas were visualized. Six of nine patients with diffuse hyperplasia had bilateral uptake consistent with diffuse hyperplasia. Three of nine patients had negative scans. One patient previously operated on for diffuse hyperplasia had only one gland scanned. Seven patients with renal failure-associated hyperparathyroid disease were scanned: five had bilateral uptake of Tc-99m-sestamibi consistent with hyperplasia, and two who had been previously operated on had localization of remaining abnormal parathyroid glands. CONCLUSIONS: Tc-99m-pertechnetate combined with Tc-99m-sestamibi subtraction radionuclide scanning is less cumbersome to implement than iodine-123 combined with Tc-99m-sestamibi scanning. It has a high sensitivity for imaging solitary parathyroid adenomas or persistent solitary hyperplastic glands. However it does not have the resolution necessary to delineate all parathyroid glands in diffuse hyperplasia.     

Kinaesthetic signals and muscle contraction.

Signals generated both peripherally and centrally contribute to the group of sensations termed kinaesthesia. Many experiments report sensations of position and movement under passive relaxed conditions without muscle contraction. However, kinaesthetic acuity is probably of greater functional value when subjects are active rather than passive and, accordingly, movement detection is markedly improved by muscular contraction. One mechanism contributing to this enhancement is likely to involve muscle spindle volleys. When identical microstimulation techniques are applied to skin, joint and muscle spindle endings innervating the hand, some cutaneous afferents and some joint afferents elicit a sensation, but activation of certain other cutaneous afferents and muscle spindle afferents rarely does. Activity in more than one muscle spindle afferent may be required for kinaesthetic sensations, whereas some single cutaneous and joint afferents may have a more 'secure' central projection.     

New reference allelic ladders to improve allelic designation in a multiplex STR system

This paper reports the composition of a new reference allelic ladder mixture for use with a multiplex DNA profiling system consisting of six short tandem repeat loci. The loci included in this mixture are HUMTH01, D21S11, D18S51, D8S1179, HUMVWAF31/A, HUMFIBRA/FGA and an amelogenin sex test. Sequence analysis of individual ladder alleles was carried out and allelic designations made in accordance with the recommendations of the International Society of Forensic Haemogenetics (1992; 1994). A series of rare alleles which increase the range of alleles previously reported were identified. By including some of the rare alleles into the ladder marker system, we have significantly improved the ability to identify new alleles in unknown samples. Received: 12 August 1997 / Received in revised form: 7 November 1997