Use of polyethylene glycol-modified uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma

Modification by covalent attachment of monomethoxypolyethylene glycol (PEG) can reduce the immunogenicity and prolong the circulating life of injected enzymes, making their use as therapeutic agents feasible. We report the first clinical use of PEG-modified Arthrobacter protoformiae uricase (PEG-uricase) to treat hyperuricemia in a patient with non-Hodgkin lymphoma and renal insufficiency who was allergic to allopurinol. Two intramuscular injections totaling 3 U/kg body weight during the first 30 hours of treatment lowered the plasma urate level from 910 to 190 mumol/L (15.3 to 3.2 mg/dL), after which a dose of 2 U/kg every 5 to 6 days maintained the plasma urate level at 540 mumol/L (9 mg/dL) or lower. After the injection of PEG-uricase, uricase activity appeared in plasma rapidly, peaking within 24 hours and persisting for approximately 5 days; an inverse relation between plasma uricase activity and plasma urate concentration was noted. The agent was nontoxic and well tolerated. No antibody to either PEG-uricase or unmodified uricase developed over a 3-week period, during which four doses of PEG-uricase were administered. Because of its long circulating life, PEG-uricase is probably a more effective hypouricemic agent than unmodified uricase, which has previously had limited use. As an adjunct to cytolytic therapy for hematologic malignancies when protection from hyperuricemia is needed rapidly, PEG-uricase deserves further study.     

Brazilian guidelines for the management of candidiasis – a joint meeting report of three medical societies: Sociedade Brasileira de Infectologia,Sociedade Paulista de Infectologia and Sociedade Brasileira de Medicina Tropical

Candida infections account for 80% of all fungal infections in the hospital environment, including bloodstream, urinary tract and surgical site infections. Bloodstream infections are now a major challenge for tertiary hospitals worldwide due to their high prevalence and mortality rates. The incidence of candidemia in tertiary public hospitals in Brazil is approximately 2.5 cases per 1000 hospital admissions. Due to the importance of this infection, the authors provide a review of the diversity of the genus Candida and its clinical relevance, the therapeutic options and discuss the treatment of major infections caused by Candida. Each topography is discussed with regard to epidemiological, clinical and laboratory diagnostic and therapeutic recommendations based on levels of evidence.     

Massive hemoptysis: control by embolization of the thyrocervical trunk

A case of recurrent hemoptysis following bronchial artery embolization is presented. The bleeding was successfully controlled by embolization of the thyrocervical trunk.     

Endomorphin-1 and endomorphin-2 activate µ-opioid receptors in myenteric neurons of the guinea-pig small intestine

The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central μ-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM–1 μM) inhibited (–log EC₅₀ values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective μ-opioid receptor antagonist, d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH₂ (CTOP), caused a concentration-dependent (30 nM–1 μM), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA ₂ values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective δ-receptor antagonist) or 30 nM nor-binaltorphimine (a selective κ-receptor antagonist). These results demonstrate that endomorphins selectively activate μ-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists. Received: 6 August 1998 / Accepted: 5 October 1998     

Long-term stability of skeletal Class III patients treated with splints, Class III elastics, and chincup.

Long-term results from orthopedic management of skeletal Class III malocclusions are sparse. The purpose of this study was to evaluate the stability of results after facial growth and treatment with splints, Class III elastics, and chincup (SEC III) and to investigate the main determinants of relapse. Data from pretreatment, posttreatment, and long-term (at least 3 years after retention) serial cephalograms of 52 patients who received SEC III treatment were studied: only those with long-term data when growth had ceased (women over 18 and men over 21 years of age) were selected. At the end of the follow-up period (an average of 9 years), only 6 of the 52 patients had clinical relapse (overjet 相似文献   

A re-appraisal of the nature of the atropine-resistant contraction to electrical field stimulation in the human isolated detrusor muscle

We investigated whether in human isolated detrusor strips the atropine-resistant contractile response to electrical field stimulation was mediated by ATP (or a related purine), as previously shown in the urinary bladder of other mammalian species. Electrical stimulation (1–50Hz for 5s at 1min intervals, 0.1ms pulse width, 60V) elicited reproducible, frequency-dependent twitch contractions, which were markedly reduced by atropine (10μM). Tetrodotoxin (TTX: 1μM) inhibited contractile responses to a similar degree. When applied together, atropine and TTX caused an inhibition which was superimposable to that caused by either drug alone. The TTX-resistant contractions were totally unaffected by omega-conotoxin GVIA (ω-CTX: 0.1μM). The atropine-resistant contractions were unaffected by the P₂-purinoceptor antagonists suramin (300μM) and PPADS (30μM), at concentrations which virtually suppressed the contractile response induced by applied ATP (10μM–1mM). As previously described, antagonism of the ATP-induced contractions by suramin (30, 100, 300μM) and PPADS (3, 10, 30μM) was insurmountable, with apparent ‘pA₂’ values (calculated at the lowest antagonist concentrations) of 4.9 and 5.2, respectively. It is concluded that, under our experimental conditions, the non-cholinergic (atropine-resistant) component of the excitatory transmission in the human detrusor is not mediated by neural release of ATP, in spite of the presence of excitatory P₂-purinoceptors on the effector cells. The TTX- and ω-CTX-resistant, non-cholinergic component might be related to the release of unknown transmitter(s) through a mechanism independent of both Na⁺- and N-type Ca²⁺-channels. More likely, the atropine-resistant component may reflect direct smooth muscle excitation since the human detrusor has a very short chronaxie (Sibley 1984). Received: 26 June 1997 / Accepted: 26 August 1997