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.     

BOP reagent for the coupling of pGlu and Boc-His(Tos) in solid phase peptide synthesis

The model peptide TRH was successfully synthesized using benzotriazol-l-yl-oxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent). The coupling reactions were carried out in N,N-dimethylformamide or N-methylpyrrolidone. These solvents allowed the incorporation of the N-terminal pyroglutamic acid residue into the peptide chain, without using the derivative bearing the N-benzyloxycarbonyl group, which acts as a solubility promoter. A comparative racemization study showed that Boc-His(Tos) can be coupled by means of BOP reagent with less racemization than with DCC when the amount of diisopropylethylamine (DIEA) is kept minimal (same ratio of equivalents as for Boc-His(Tos), i.e. 3 equiv.). However, with the use of a larger amount of DIEA in the coupling mixture (9 equiv.), approximately 3% of epimer was found in the crude product. Our study showed that even under low DIEA conditions, the rate of coupling of the residues with BOP remained comparable to that observed with DCC.     

Trainee impact on advanced diagnostic bronchoscopy: An analysis of 607 consecutive procedures in an interventional pulmonary practice

Background and objective: Complications during advanced diagnostic bronchoscopy are rare and include: pneumothorax, bleeding, mediastinitis and lymphadenitis. Increased complications have been demonstrated in patients undergoing routine bronchoscopy procedures performed by trainees. This study aimed to determine the impact of trainees during advanced diagnostic bronchoscopy on procedure time, sedation use and complications. Methods: A retrospective review of a quality improvement database including consecutive pulmonary procedures performed by an interventional pulmonologist (D.R.S.) at the University of Calgary, from 1 July 2007 to 1 April 2011. Results: Six hundred seven (55.2%) of the 1100 procedures involved an advanced diagnostic procedure defined as: endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA), electromagnetic navigation bronchoscopy (ENB) and/or peripheral EBUS. A trainee participated in 512 (84.3%) procedures. A complication occurred in 25 patients (4.1%), with a trend towards increased complication rates in the trainee group (4.7% vs 1.1%, difference 3.6%, P = 0.076). Significant differences were seen when a trainee participated versus when no trainee participated for procedure length (58.32 min vs 37.69 min, difference 20.63 min (95% confidence interval: 19.07–22.19), P = 0.001) and for the dose of propofol (178.3 mg vs 137.1 mg, difference 41.2 mg (95% confidence interval: 19.81–63.38), P = 0.002). Conclusions: In an academic interventional pulmonology practice utilizing the apprenticeship model, trainee participation in advanced diagnostic bronchoscopy increased procedure time, increased the amount of sedation used and resulted in a trend to increased complications. Attempts to modify trainee procedural training to reduce the burden of procedural learning for patients are warranted.