Laparoscopy-assisted orchidopexy: an ideal treatment for children with intra-abdominal testes

BACKGROUND AND PURPOSE: The investigation of a child with a nonpalpable testis is probably the most frequent indication for laparoscopy in pediatric patients. The objective of this study was to evaluate the results and advantages of laparoscopy-assisted orchidopexy performed without dividing the spermatic vessels. PATIENTS AND METHODS: During a 3-year period, 85 boys with nonpalpable testes (NPT) (91 testes overall) underwent laparoscopic diagnostic exploration. Twenty-five patients (27.4%) showed an intra-abdominal testis (IAT): 24 underwent a laparoscopy-assisted orchidopexy (LAO) without sectioning of the spermatic vessels, and one, whose inner spermatic vessels were not adequately long for LAO without tension, underwent a two-step Fowler-Stephens (FS) procedure. The technique consists of dissection and mobilization of the inner spermatic vessels and the vas deferens from the posterior peritoneum, sectioning of the gubernaculum attachments, and bringing down of the testis into the scrotum through the internal inguinal ring, if open, or through a neo-inguinal ring created medial to the epigastric vessels. RESULTS: Surgery lasted between 40 and 80 minutes (median 60 minutes). All the testes were brought down into the scrotum. There was only 1 (4%) intraoperative complication, which occurred in the second patient operated on with this procedure. He experienced an iatrogenic rupture of the spermatic vessels secondary to excessive traction. CONCLUSION: Laparoscopic orchidopexy is the logical extension of diagnostic laparoscopy for the evaluation of NPT. Concerning the technique, we believe that LAO with intact spermatic vessels could be considered the treatment of choice in the patient with IAT, as it does not affect normal testicular vascularization. Alternatively, in the case of very high IAT (more than 3 cm from IIR), an FS procedure may be considered.     

Hemiretinal vein occlusion associated with membranous glomerulonephritis

PURPOSE: To report a patient in whom the finding of hemiretinal vein occlusion led to the diagnosis of membranous glomerulonephritis. DESIGN: Interventional case report. METHODS: A 44-year-old tennis instructor presented with a 1-week history of blurred vision in the left eye. Examination of the left eye demonstrated a best-corrected visual acuity of 20/40 and an inferior hemiretinal vein occlusion. RESULTS: Blood pressure was normal, and the patient was referred for a medical examination, which revealed membranous glomerulonephritis. The patient was treated with oral prednisone and cyclosporine. Four months after presentation, the left eye demonstrated resolution of the vascular abnormalities and had a best-corrected visual acuity of 20/20. CONCLUSION: Retinal vein occlusion may be associated with membranous glomerulonephritis. Treatment of the systemic disease may be associated with regression of the retinal vascular abnormalities.     

Scleral buckling technique without retinopexy for treatment of rhegmatogeneous: a pilot study

PURPOSE: To evaluate the role of retinopexy in the surgical management of primary rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy. The primary outcome was retinal attachment, and secondary outcomes were visual acuity results and complications. METHODS: A randomized controlled trial including 60 patients with RD caused by a break or a group of breaks no larger than one clock hour. Thirty eyes received no retinopexy (group 1), and 30 eyes received transscleral cryotherapy (group 2). An encircling buckle was placed in all eyes. In eyes with posterior breaks, segmental buckles were also added. In some eyes, subretinal fluid drainage or anterior chamber paracentesis and/or intravitreal air bubble injection was performed. RESULTS: No differences were found between the groups in terms of the preoperative clinical variables evaluated: age; sex; axial length; lens status; type, number, and location of breaks; extension of detachment; and macula status. There were no differences in the surgical procedures performed. The reattachment rate in group 1 was 90%, and in group 2, it was 87% (a difference that was not significant [P = 1.00]). Final visual acuity improved by two lines or more in 22 patients in group 1 and in 20 patients in group 2 (P = 0.317). CONCLUSIONS: Our results indicate that primary rhegmatogenous RD can be successfully treated with scleral buckling without retinopexy.     

Is the world full of circles?

The statistical arrangement of oriented segments in natural scenes was recently proposed to be indicative of a cocircularity rule. In particular, the probability density function of the relative position of two oriented segments was found to be maximal along fixed angles on the plane, consistent with the two segments being tangent to two points of a circle. Does this observation point to a prevalence of circles in natural scenes? Here we demonstrate that similar statistics can be obtained even when circles are not very common in visual scenes. The reason is that circles or near circular objects can heavily skew the distribution in favor of the cocircularity rule.     

The unbound percentage of saquinavir and indinavir remains constant throughout the dosing interval in HIV positive subjects

AIMS: To measure the unbound plasma concentrations of saquinavir (SQV) and indinavir (IDV) and to relate them to the total plasma concentrations in order to establish the unbound percentage of protease inhibitors in vivo during a full dosage interval profile. METHODS: HIV-infected subjects (n = 35; median CD4 cell count = 340 x 10(6) cells l-1, range: 120-825; viral load < 50 copies ml-1 in 22/35) treated with SQV or IDV containing regimens were studied. Plasma drug samples were collected at 0, 2, 4, 8 and 12 h postdose for the twice daily regimens and 0, 1, 2, 4 and 8 h for the three times daily regimens. Ultra-filtration was used to separate unbound IDV and SQV in plasma and their respective concentrations were measured by a fully validated method using high performance liquid chromatography-mass spectometry (h.p.l.c.-MS/MS). RESULTS: Based on the ratio AUCunbound/AUCtotal, the median unbound percentage (95% CI for differences) of SQV and IDV from all the samples studied was 1.19% (0.99, 1.58%) and 36.3% (35.1, 44.2%), respectively. No significant difference was seen in the percentage binding of SQV between patients receiving SQV alone (median = 1.49%) or with ritonavir (median = 1.09%; P = 0.141; 95% CI for difference between medians = -0.145, 0.937) over the pharmacokinetic profile. Similarly, no significant difference was seen in the percentage binding of IDV in patients receiving IDV alone (median 35.2%) or with ritonavir (median = 41.3%; P = 0.069; 95% CI for difference between medians = -0.09, 15.4). The unbound concentrations of SQV (P < 0.0001; 95% CI for r(2) = 0.634, 0.815) and IDV (P < 0.0001; 95% CI for r(2) = 0.830, 0.925) remained constant as a proportion of total concentration over the full dosing profile. CONCLUSIONS: These in vivo data confirm previously published in vitro measurements of SQV and IDV protein binding. The unbound percentage of both protease inhibitors remained constant over the dosing interval.     

Occupational risk factors for renal cell cancer: a case--control study in northern Italy

Relatively little is known about occupational and other risk factors for renal-cell carcinoma (RCC). Associations between RCC and occupations, exposures and other factors were investigated in a hospital-based case-control study in Bologna (central-northern Italy). Between 1986 and 1994, 324 histologically confirmed RCC cases were diagnosed at Policlinico S. Orsola-Malpighi in patients from the Province of Bologna. Corresponding control subjects admitted to the same hospital with any diagnosis except RCC were matched for sex, age, and residency. We studied the 249 cases and 238 controls for whom detailed information on occupational history, diet, smoking habits, alcohol and drug intake was obtained. At conditional logistic regression, among males (167 matched pairs), significant matched odds ratios (OR) were found, after adjusting for cigarette smoking and alcohol intake, for high body-mass index BMI (third quartile: OR, 4.91; confidence interval [95% CI], 1.56-15.5; last quartile: OR, 4.42; 95% CI, 1.48-13.18), railway workers (OR, 10.14; 95% CI, 1.46-70.17) and asbestos exposure (OR, 7.11; 95% CI, 1.46-34.51); nearly significant OR were found for managers (OR, 3.59; 95% CI, 0.82-15.59) and metal workers (OR, 2.21; 95% CI, 0.99-5.37). Among females (52 pairs), significant OR were found for BMI > 25.4 (OR, 8.46; 95% CI, 1.02-68.0). Railway workers (on or near to trains) may have increased risk of developing RCC, possibly due to asbestos exposure. Studies are required on possible risks encountered by railway (and metal) workers and by managers.     

Oral loading with propafenone for conversion of recent-onset atrial fibrillation: a review on in-hospital treatment

Atrial fibrillation (AF) is a very common arrhythmia. In order to treat acute AF rapidly, effective drug regimens are required. Propafenone is a class IC antiarrhythmic agent that is suitable for oral loading as it reaches peak plasma concentrations within 2 to 4 hours of administration. The use of propafenone loading in patients with AF must be based on appropriate patient selection in view of the negative inotropic effect and the potential proarrhythmic effects of the drug. A series of controlled trials in patients with recent-onset AF without heart failure who were hospitalised with enforced bed rest has shown that orally loaded propafenone (450 to 600 mg as single dose) exerts a relatively quick effect (within 3 to 4 hours) and a high rate of efficacy (72 to 78% within 8 hours). A potentially harmful effect of class IC agents is the risk of transforming AF into atrial flutter (3.5 to 5% of patients). However, atrial flutter with 1 : 1 atrioventricular response was observed in only two of 709 patients receiving propafenone (0.3% incidence). Nevertheless, the potential negative inotropic effect of propafenone demands careful patient selection, with systematic exclusion of patients with left ventricular dysfunction or congestive heart failure. Oral loading with propafenone can be considered as an episodic treatment in patients with AF recurrences, as has been proposed for other drugs in the past. However, the safety of oral loading with propafenone as an outpatient treatment in appropriately selected patients has to be assessed by appropriately designed prospective studies.     

Structure-activity relationships in 1,4-benzodioxan-related compounds. 7. Selectivity of 4-phenylchroman analogues for alpha(1)-adrenoreceptor subtypes

WB4101 (1)-related compounds 5-10 were synthesized, and their biological profile at alpha(1)-adrenoreceptor (AR) subtypes and 5-HT(1A) serotoninergic receptors was assessed by binding assays in Chinese hamster ovary and HeLa cell membranes expressing the human cloned receptors. Moreover, their receptor selectivity was further determined in functional experiments in isolated rat prostate (alpha(1A)), vas deferens (alpha(1A)), aorta (alpha(1D)), and spleen (alpha(1B)). In functional assays, compound 5 was the most potent at alpha(1D)-ARs with a reversed selectivity profile (alpha(1D) > alpha(1A) > alpha(1B)) relative to both prototype 1 and phendioxan (2) (alpha(1A) > alpha(1D) > alpha(1B)), whereas compound 8, bearing a carbonyl moiety at position 1, was the most potent at alpha(1A)-ARs with a selectivity profile similar to that of prototypes. The least potent of the series was the trans isomer 6, suggesting that optimum alpha(1)-AR blocking activity in this series is associated with a cis relationship between the 2-side chain and the 4-phenyl ring rather than a trans relationship as previously observed for the 2-side chain and the 3-phenyl ring in 2 and related compounds. Binding affinity results were not in complete agreement with the selectivity profiles deriving from functional experiments. Although a firm explanation was not available, neutral and negative antagonism and receptor dimerization were considered as two possibilities to account for the difference between binding and functional affinities. Finally, compound 5 was selected for a modeling study in comparison with 1, mephendioxan (3), and open phendioxan (4) to achieve information on the physicochemical interactions that account for its high affinity toward alpha(1d/D)-ARs.     

Oxygenated metabolites of anandamide and 2-arachidonoylglycerol: conformational analysis and interaction with cannabinoid receptors,membrane transporter,and fatty acid amide hydrolase

This study was aimed at finding structural requirements for the interaction of the acyl chain of endocannabinoids with cannabinoid receptors, membrane transporter protein, and fatty acid amide hydrolase (FAAH). To this end, the flexibility of the acyl chain was restricted by introduction of an 1-hydroxy-2Z,4E-pentadiene system in anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) at various positions using different lipoxygenases. This brought about selectivity and attenuated the binding potency of AEA and 2-AG. Although the displacement constants were modest, 15(S)-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoyl-N-(2-hydroxyethyl)amine was found to bind selectively to the CB(1) receptor, whereas its 1-arachidonoyl-sn-glycerol analogue and 13(S)-hydroxy-octadeca-9Z,11E-dienoyl-N-(2-hydroxyethyl)amine could selectively bind to the CB(2) receptor. 11(S)-Hydroxy-eicosa-5Z,8Z,12E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine did not bind to either receptor, whereas 12(S)-hydroxy-eicosa-5Z,8Z,10E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine did bind to both CB receptors with an affinity similar to that of AEA. All oxygenated anandamide derivatives were good inhibitors of FAAH (low micromolar K(i)) but were ineffective on the AEA transporter. 2-AG rapidly isomerizes into 1(3)-arachidonoyl-sn-glycerol. Both 1- and 3-arachidonoyl-sn-glycerol did not bind to either CB receptor and did not interfere with AEA transport. Thus, after it is isomerized, 2-AG is inactivated, thereby decreasing effective concentrations of 2-AG. Analysis of (1)H NMR spectra revealed that chloroform did not induce notably different conformations in the acyl chain of 15(S)-hydroxy-eicosa-5Z,8Z,11Z,13E-tetraenoic acid as compared with water. Molecular dynamics (MD) simulations of AEA and its analogues in the presence of explicit water molecules revealed that a tightly folded conformation of the acyl chain is not the only requirement for CB(1) binding. Structural details of the C(2)-C(15) loop, such as an sp(2) carbon at position 11, are necessary for receptor binding. The MD simulations may suggest that the average orientations of the pentyl tail of AEA and 12(S)-hydroxy-eicosa-5Z,8Z,10E,14Z-tetraenoyl-N-(2-hydroxyethyl)amine are different from that of the low-affinity, inactive ligands.     

Adenosine A(1) receptor: analysis of the potential therapeutic effects obtained by its activation in the central nervous system

Adenosine modulates several physiological functions in the CNS and in peripheral tissues via membrane receptors which have been classified into four adenosine subtypes. A(1) activation produces neuronal depression: this inhibition allows A(1) agonists to produce ischemic tolerance and protection in neuronal tissue. In order to selectively reproduce these effects, several A(1) selective ligands have been synthesised and evaluated to understand how they interact with the adenosine A(1) receptor. The investigation methods include SAR studies using native and chemically modified A(1) receptors, molecular cloning of native and mutant adenosine A(1) receptors, molecular modeling and thermodynamic analysis of drug-receptor interaction. Despite the great quantity of information available on the adenosine A(1) receptor, no A(1) agonist has so far entered in clinical use against brain diseases in view of the side effects; moreover selective A(1) agonists appear to be poorly adsorbed into the brain and can be quickly degraded in vivo or in the whole blood. In an attempt to overcome these problems studies have been undertaken dealing with the use of partial agonists to inhibit side-effects and the employment of prodrugs to increase stability and diffusion through lipid barriers of A(1) ligands. Other attempts involve either the use of A(1) receptor enhancers as modulators able to locally enhance the action of endogenously produced adenosine, or the encapsulation of A(1)agonists in drug delivery systems targeted to the brain. In this review, these approaches will be described together with the effects of adenosine A(1) receptor ligands and their binding mechanisms on the central nervous system.