Guidelines for international collaborative research

OBJECTIVE: As the global village becomes a reality, there is an increasing need to conduct international collaborative studies in family practice. A workshop at the WONCA meeting in Hong Kong used international attendees to produce a set of guidelines for international research. METHODS: At the workshop four completed international projects, each using a different strategy, were presented so that common themes might become apparent. The themes were then discussed and guidelines emerged from the process. RESULTS: Seven guidelines emerged for consideration before embarking on an international collaborative research project in family medicine. The guidelines deal with the characteristics of the research question and the importance of communication. The need for simple, brief methods of data collection, funding and pilot testing were identified. CONCLUSION: The question must be relevant to all participants to maintain interest and measurement tools must be validated to understand the impact of cultural differences in understanding.      

Angioimmunoblastic lymphadenopathy and transient Fanconi syndrome

A case of angioimmunoblastic lymphadenopathy (AIL) is presented in which the transient presence of a Fanconi syndrome was detected. Both the AIL and the Fanconi syndrome were ameliorated after steroid therapy.     

Influence of lisuride, a dopaminergic agonist, on the sexual function of male patients with chronic renal failure

The effects of Lisuride, a dopaminergic agonist, on the levels of plasma prolactin (PRL), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and on the variations of libido and coital frequency of patients with chronic renal failure (CRF) have been investigated in a group of 20 male patients (ten normoprolactinemic and ten hyperprolactinemic). Ten patients were included in a hemodialysis program and another ten received conservation therapy (all had creatinine clearance rates below 15 mL/min). The response of PRL to TRH administration and that of LH and FSH to LH-RH administration have also been studied. Low levels of plasma testosterone found initially in all the patients, increased in both normoprolactinemic (P less than 0.05) and hyperprolactinemic patients (P less than 0.01) during Lisuride administration. PRL decreased (P less than 0.01) in both groups during therapy. The increase of plasma testosterone was greater in hyperprolactinemic patients (86% v 15% in normoprolactinemic) and was accompanied by a clear improvement in the studied parameters of sexual behaviors. The response of PRL to TRH was modified in hyperprolactinemic patients while that of LH and FSH to LH-RH was not modified, although Lisuride induced an increase of the basal value of LH (P less than 0.01) in the hyperprolactinemic group. The drug was fairly well tolerated, did not induce hypotension, and the overall incidence of side effects decreased along the study. These results stress the need for further studies with this agent in patients with chronic renal failure and sexual dysfunction.     

Anomalous origin of the left coronary artery from the pulmonary artery in adults

A 24 year old male with anomalous origin of the left coronary artery from the pulmonary artery was surgically treated with aortocoronary bypass with saphenous vein graft. The clinical signs and pathophysiology of this cardiopathy are reviewed, with emphasis on the great importance of collateral circulation in its prognosis.     

Pharmacokinetic profile of ganciclovir after its oral administration and from its prodrug, valganciclovir, in solid organ transplant recipients

BACKGROUND: Valganciclovir (Valcyte) has recently been approved for the prevention of cytomegalovirus (CMV) disease in high-risk (CMV donor positive [D+]/recipient negative [R-]) solid organ transplant (SOT) recipients. Large-scale studies describing the pharmacokinetics of valganciclovir in SOT recipients are lacking. A recent randomised, double-blind study of valganciclovir in 364 D+/R- (intent-to-treat population) SOT recipients provided valuable data on which a population pharmacokinetic analysis was performed. METHODS: The pharmacokinetics of ganciclovir from oral ganciclovir (Cymevene, 1000 mg three times daily) and from valganciclovir (900 mg once daily) were described with plasma levels from 240 patients (1181 datapoints describing 449 pharmacokinetic profiles) using nonlinear mixed-effects modelling (NONMEM) software. A two-compartment pharmacokinetic model with separate absorption/metabolism and absorption parameters for valganciclovir and ganciclovir, respectively, was developed. RESULTS: Exposure to ganciclovir from valganciclovir averaged 1.65-fold greater than that from oral ganciclovir (95% CI 1.58, 1.81); respective daily area under the plasma concentration-time curve values were 46.3 +/- 15.2 microg . h/mL and 28.0 +/- 10.9 microg . h/mL. The relative systemic exposure of ganciclovir was approximately 8-fold higher from valganciclovir than oral ganciclovir. Exposure to ganciclovir from valganciclovir was similar among liver, heart and kidney transplant recipients (46.0 +/- 16.1, 40.2 +/- 11.8 and 48.2 +/- 14.6 microg . h/ mL, respectively). Adherence to the prescribed dosing regimens, which were reduced for renal impairment, gave consistent exposure to ganciclovir. CONCLUSION: Oral valganciclovir produces exposures of ganciclovir exceeding those attained with oral ganciclovir, but in line with those reported after standard intravenous administration of ganciclovir. This indicates that oral valganciclovir is suitable in circumstances requiring prophylactic use of ganciclovir and allows for more convenient management of patients at risk of CMV disease.     

A Study of the Effect of Proinflammatory Cytokines on the Epithelial Cells of Smokers,With or Without COPD

IntroductionCigarette smoke is the main cause of inflammation in COPD. The mechanisms that differentiate smokers who develop COPD are diverse. In this study, we analyzed the presence of cytokines in the respiratory secretions of smokers with or without COPD and the secretory properties of the differentiated bronchial epithelium obtained from the individuals themselves after exposure to tobacco smoke.Material and methodsTwenty-seven smokers were studied, 12 of whom had COPD that had not been previously treated with steroids. In 11, samples were obtained by means of induced sputum, and the remaining samples were collected from bronchial aspiration after bronchoscopy. Concentrations of IL8, IL13, and TNFα in the supernatant were determined. The results obtained were compared between individuals with and without COPD, and we studied their relationship with the severity of COPD as expressed by the degree of obstruction, dyspnea, presence of hypersecretion and intensity of smoking. Bronchial epithelial cell cultures were obtained by air–liquid interface in 4 smokers. The samples were exposed to increasing concentrations of cigarette smoke (5%–20%) and the epithelial mRNA expressions of Muc5AC, IL8, and TNFα were determined.ResultsCOPD patients had significantly higher values of IL8 than healthy smokers (41 [22] pM vs 21 [12] pM). The values of IL8 correlated significantly with the severity of the obstruction (r=0.6; P<.05), dyspnea (r=0.45; P<.05) and the presence of hypersecretion. There was no relationship between cytokines and the intensity or duration of the tobacco habit. Cigarette smoke produced a dose-dependent increase in the expression of RNAm for Muc5AC, IL8, and TNFα.ConclusionsThere are differences in cytokine production (fundamentally IL8) between smokers and smokers with COPD which could be explained by the direct action of cigarette smoke on epithelial cells.