PARATHYROID SUPPRESSIBILITY IN HYPERPARATHYROIDISM DUE TO CHRONIC RENAL FAILURE: STUDIES WITH AUTOTRANSPLANTED PARATHYROID TISSUE

Suppressibility of parathyroid hormone (PTH) secretion by calcium was evaluated in six patients with chronic renal failure and parathyroid tissue autotransplanted into the forearm. One patient was reinvestigated after renal transplantation. Plasma PTH levels were measured in the venous effluent of transplanted parathyroid tissue (VE) and in peripheral blood (PB) with two radioimmunoassays (RIA). One of these detected predominantly the intact human parathyroid hormone-(1–84) [PTH-(1–84)] (N-assay) and another in addition carboxyl (COOH)-terminal fragments (C-assay). At 5 min after the start of 12-min calcium infusions, resulting in a mean increase of plasma calcium levels of 0±6 mmol/l (P < 0±01), PTH was lowered to 44±10% (mean ± SE) (P < 0±01) of preinfusion levels in the VE and to 88±4% (P < 0±05) in PB, when measured in the N-assay; subsequently the plasma calcium level remained raised and PTH level lowered. When estimated in the C-assay, PTH was significantly lowered to 82± 6% (P < 0–05) in the VE at 120 min, and to between 91 ± 2% and 96 ± 2% (P < 0±01- < 0±05) in the PB at 20 to 120 min after the start of the calcium infusions. The results were extended with gel permeation chromatography of representative plasma samples. After renal transplantation and restoration of renal function gel filtration analysis indicated that the levels of intact PTH-(1–84) were 49±6 and of its COOH-terminal fragments 3±5 higher in the VE than in PB. In response to i.v. calcium administration intact PTH and its COOH-terminal fragments were lowered to 25% and 62% in the VE, and to 29% and 86% in PB, respectively. These findings demonstrate that the secretion of intact PTH-(1–84) is suppressed within minutes in response to i.v. calcium administration; a slower fall of the secretion of COOH-terminal PTH fragments was demonstrated only after restoration of near-normal renal function.     

Reduction of Energy Required for Defibrillation by Delivering Shocks in Orthogonal Directions in the Dog

Reduction of energy required to defibrillate (ERD) seems to represent a necessary condition for intensive development of implantable defibrillator, so as for minimization of cardiac and pulmonary damages provoked by high energy transthoracic defibrillation electric shocks. The present work describes a defibrillation method using shocks delivered in orthogonal directions and separated by a 100 ms delay. Defibrillation threshold measured with classical unidirectional shocks on 30 dogs has been found to be 286.8 ± 22.2 joules. In the same animals, defibrillation threshold measured by use of orthogonal shocks has been found to be 101.4 ± 14.9 joules. We conclude that this crossed shocks method leads to a substantial reduction of ERD (64%).     

ARTIFICIAL URETERAL REPLACEMENT FOR URETERAL NECROSIS AFTER RENAL TRANSPLANTATION: REPORT OF 3 CASES

Purpose

We applied a new minimally invasive technique of artificial ureteral replacement for renal transplant ureteral necrosis.

Materials and Methods

Artificial ureteral replacement was performed in 3 renal transplant recipients with ureteral necrosis (complete in 1 and distal in 2) after failure of primary endoscopic treatment. Under fluoroscopic guidance a percutaneous tract is created and progressively dilated. The ureteral silicone polytetrafluoroethylene bonded tube is introduced into the pyelocaliceal renal graft cavities, tracked subcutaneously down to the suprapubic area and introduced into the bladder via a short incision.

Results

There were no immediate postoperative complications except for transient postoperative acute prostatitis in 1 patient. No secondary complications were observed with a mean followup of 2.5 years. All grafts have good late function and all tubes are patent with no evidence of encrustation or obstruction. The tubes are well tolerated underneath the skin. Reflux was present in all 3 cases with no clinical manifestation. An asymptomatic episode of lower urinary tract infection was observed in the female patient.

Conclusions

In select cases of ureteral necrosis after renal transplantation artificial ureteral replacement by subcutaneous pyelovesical bypass offers a possible alternative to open ureteral reconstruction.     

Discovery of a pituitary adenoma following treatment with a gonadotropin-releasing hormone agonist in a patient with prostate cancer

We report the case of a T3 prostate cancer in a 70-year-old white man. Hormone therapy represents a prominent branch in the treatment of locally advanced and metastatic prostate cancer. Gonadotropin-releasing hormone agonists have been proven to have a double effect on androgen metabolism: an initially stimulating, followed by an inhibitory, effect on the pituitary gland. This phenomenon may be noxious in the case of gonadotroph adenoma, with subsequent symptoms of intracranial hypertension. Gonadotropin-releasing hormone antagonists (abarelix), by avoiding the flare-up reaction, might be used in such instances.     

Applications of BOP reagent in solid phase synthesis Advantages of BOP reagent for difficult couplings exemplified by a synthesis of [Ala 15]-GRF(1–29)-NH2

The BOP reagent [benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate] introduced by Castro et al. [Tetrahedron Lett. (1975) 14, 1219–1222] is ideally suited for solid phase peptide synthesis. The rate of coupling using BOP compared favorably to DCC and other methods of activation including the symmetrical anhydride and DCC/HOBt procedures. BOP couplings using the solid phase procedure proceeded more rapidly and to a greater degree of completion for peptide bond formations that were previously determined to be very slow using the conventional DCC method. Stepwise solid phase peptide synthesis using BOP was successfully utilized for the preparation of the (22–29) and (13–29) fragments of [Ala¹⁵]-GRF(1–29)-NH₂. Single couplings with 3 equiv. BOP and Boc-amino acids and 5.3 equiv. of diisopropylethylamine in DMF were used for each cycle. The yields of the fragments were superior and the purities comparable using the BOP procedure (single couplings) to those observed using multiple couplings via the DCC coupling method. A total synthesis of [Ala¹⁵]-GRF(1–29)-NH₂ was also carried out using the BOP procedure (single couplings and 3 equiv. BOP and Boc-amino acids and 5.3 equiv. diisopropylethylamine in DMF for each cycle). Multiple couplings were only required for Boc-Asn-OH due to the proposed formation of Boc-aminosuccinimide during activation. The resultant GRF(1–29) analog was comparable to a control prepared with multiple DCC couplings under optimized conditions. In a parallel study, unprotected Boc-(hydroxy)-amino acids were successfully coupled with the BOP reagent. However, the number of coupling cycles after the introduction of unprotected hydroxy-amino acid must be minimal (<10). The use of the BOP reagent with unprotected Tyr in solid phase peptide synthesis was also clearly established.     

Effect of Fat Substitutes,Sucrose Polyester and Tricarballylate Triester,on Digitoxin Absorption in the Rat

Abstract— The effect of non-absorbable fat substitutes (sucrose polyester (SPE) and tricarballylate triester (TCTE)) on [³H]digitoxin intestinal absorption was studied in the rat using a small intestine in-situ perfusion technique. The effect of SPE and TCTE was compared with that of sunflower oil, oleic acid, and saline. After 120 min perfusion, 5% SPE emulsion significantly reduced (P < 0·001) digitoxin absorption compared with all other treated groups. Five per cent TCTE emulsion had a less marked effect than SPE (P = 0·0002) and did not differ from sunflower oil. No difference was found between saline and 5% oleate emulsion, which did not reduce digitoxin absorption compared with other treated groups (P < 0·02). When taurocholic acid and lipase were added, results for the saline-, TCTE-, and SPE-treated groups were similar to those above, but the sunflower oil-treated group showed significantly enhanced (P < 0·01) digitoxin absorption. Thin-layer chromatography of the lipid phases showed hydrolysis of sunflower oil in the presence of taurocholic acid and lipase, but not of TCTE or SPE. The inhibitory effect of the nonabsorbable fat substitutes on digitoxin absorption could be related to drug sequestration by the persistent oil phase constituted by the undigested and then unabsorbed fat substitutes. That part of digitoxin dissolved in the undigested oil phase is consequently unavailable for intestinal absorption.     

Resin immobilized synthetic peptides used to characterize phosphorylation and antigenic properties of insulin receptor autophosphorylation domains

To develop a common strategy in peptide design for kinase assay, antibody production and affinity purification, we investigated phosphorylation and antigenic properties of peptides immobilized on an aminated polyacrylic resin (Expansin ?) corresponding to autophosphorylation domains of the insulin receptor tyrosine kinase. Immobilized peptides (1143–1155) and peptide (1314–1330), designated pl 151 and p1322, respectively, were good substrates for the insulin receptor with K_m, of 0.74 and 0.78 mM. By contrast, peptide (952–963), designated p960, was poorly phosphorylated. p1151 showed distinctive behaviour as a substrate, displaying a higher basal phosphorylation, a leftward shift of the insulin dose-response curve (ED₅₀= 0.7 ng mL- ¹ insulin compared to 20 ng mL ¹ for other substrates) and an inhibition by 90% of receptor autophosphorylation (ID₅₀So = 0.5 mM). Similar substrate behaviour was observed with another tyrosine kinase, the pp60^c-src. Antibodies against P1151 and p1322 have comparable reactivity in ELISA, but the antibody against p960 was poor. While purified immunoglobulins (IgG) against both p1151 and p1322 were inhibitors of receptor autophosphorylation and kinase, in immunoprecipitation the IgG against p1151 mainly interacted with the phosphorylated receptor and that against p1322 with non-phosphorylated forms. Functional mapping of the receptor with oligoclonal 1322-antibody revealed inhibition of phosphate transfer to exogenous substrate poly(Glu,Tyr) (4:l) but not towards immobilized p1151. These data provide further support for the distinctive features of endogenous phosphorylation domain 1151. We conclude that immobilized peptides on polyacrylic resin offer a major new potential for use in kinase assays, immunization, immunoabsorbent techniques and purification of well defined oligoclonal antibodies.     

Idiopathic hypersomnia

Abstract Identification of idiopathic hypersomnia dates back 20 years only. It typically consists of prolonged nocturnal sleep, great difficulty waking up in the morning or at the end of a nap, and constant or recurrent excessive daytime sleepiness. Complete and incomplete forms are encountered. Twenty-three subjects fulfilling ICSD criteria are reported with clinical, polysomnographic and immunogenetic data. Considering differential diagnosis is an important step in the diagnosis of idiopathic hypersomnia. Idiopathic hypersomnia is much less frequent than narcolepsy. A strong genetic component is suggested by the high proportion of familial cases. No association with HLA has been evidenced to date.