Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions.

PURPOSE: The permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions is described. METHODS: Thirteen cytotoxic agents were prepared at the highest concentrations normally encountered by pharmacy personnel. Four glove types--neoprene, natural rubber latex, nitrile, and vinyl--were exposed to the cytotoxic agents for 15, 30, and 60 minutes. Tests were conducted using the middle finger of each glove. Linearity, reproducibility, and sensitivity were evaluated for each drug tested. Assays were run using liquid chromatographic tandem mass spectrometry (LC/MS/MS) and high-performance liquid chromatography with ultraviolet light (HPLC-UV). Permeability testing was conducted using an original system designed to evaluate dynamic constraints, such as rubbing, stretching, and tension. RESULTS: Linearity by LC/MS/MS and HPLC-UV was confirmed at concentrations up to 1000 ng/mL for all drugs. Most glove materials were permeable at rates below ASTM recommendations over the one-hour testing period. Vinyl was the most permeable material. Carmustine permeated the widest variety of materials. Due to the high sensitivity of the analytic methods, all materials displayed low but significant permeability for at least one drug after one hour. Higher resistance to permeation was recorded for all neoprene, some natural rubber latex, and one nitrile glove. CONCLUSION: Neoprene, natural rubber latex, and nitrile gloves displayed the highest resistance to permeation of the 13 cytotoxic agents studied. Additional factors, such as duration of exposure, glove thickness, and drug liposolubility and molecular weight, also affected permeability.     

Endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation

Objective: Whatever the surgical technique used, false aneurysm formation is one of the long-term complications of repair of aortic coarctation. Conservative management is associated with a 100% rate of rupture. The conventional surgical approach is complex and associated with high morbidity and mortality rates. We report our experience of endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation. Methods: Between October 2005 and 2006, stent-grafting of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation was performed in four patients. Median age was 31.5 years (range: 24–38). Two patients had undergone two previous interventions. The last previous surgery consisted of graft interposition (N = 2), subclavian flap aortoplasty (N = 1) and aorto-aortic bypass (N = 1). Median size of the pseudo-aneurysm was 31.5 mm (range: 20–58). Mean time between the last surgery and endovascular treatment was 24 years (range: 3–32). One patient was treated emergently because of hemoptysis in relation with an aorto-bronchial fistula, the three other patients were treated electively. A transfemoral approach was used in all patients. The Zenith TX2^® (Cook) thoracic stent-graft was used in all the patients, one patient underwent previous dilatation at the coarctation level. When present, the ostium of the left subclavian artery was always covered (N = 3). Results: No major complication occurred during the procedure and no patient died during the follow-up. One patient presented a type II endoleak which spontaneously healed during the first month. Another patient with his left subclavian artery covered presented claudication of the left arm requiring a carotid-subclavian bypass. After a median follow-up of 7.5 months (range: 1–12.9), the patients were asymptomatic and CT scans demonstrated complete exclusion of all treated postcoarctation aneurysms without recoarctation and without any stent-graft-related complication. Conclusions: The endovascular management of pseudo-aneurysms after previous surgical repair of congenital aortic coarctation is feasible. This approach was safe and effective. Long-term clinic and imaging follow-up is mandatory.     

A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy.

OBJECTIVE: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. SETTING AND PATIENTS: The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. RESULTS: In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. CONCLUSIONS: A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.     

Prevention of adoptive transfer in BB rats by prophylactic insulin treatment.

Prophylactic insulin can prevent diabetes in the BB rat. We evaluated its use to prevent adoptive transfer of diabetes by activated splenocytes. ConA-activated spleen cells from acutely diabetic BB rats were divided into two equal aliquots and injected intravenously in paired diabetes-prone BB rat littermates. At the time of cell injection, subcutaneous insulin injections (15 U.kg-1.day-1) were started in one of each pair (n = 21) of littermates, and the control littermates (n = 21) were injected with saline. The incidence of diabetes, observed 35 days after cell injection, was 95% in control rats compared with 29% in insulin-treated rats (P less than 0.05). To confirm the absence of diabetes, insulin was stopped in all nondiabetic insulin-treated rats at 63 days of age. An OGTT was performed at 65 days of age: 4 rats were glucose intolerant. All rats received comparable numbers of ConA-activated splenocytes. At the time the rats were killed, 3 insulin-treated rats had a completely normal morphology and a normal glucose tolerance. All control rats had insulitis whether they were diabetic or not. No significant difference in any mononuclear subset was observed in relation to insulin treatment. We conclude that prophylactic insulin can prevent adoptive transfer of diabetes in the BB rat without inducing changes in the mononuclear cell subsets.     

An A2-purinoceptor agonist, NECA, potentiates acetylcholine-induced glucagon secretion.

The effect of a stable structural analogue of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), was studied on glucagon secretion induced by acetylcholine (ACh) in the isolated perfused pancreas of the newborn dog. The perfusion solution contained a physiological concentration of glucose (4.2 mM). In the first set of experiments, ACh (0.5 microM) infused alone for 10 min induced a significant rise of glucagon secretion (370 +/- 98%, 4 min after the beginning of infusion). In the second set, NECA (2.2 nM) infused 10 min before ACh administration, had no effect per se, but considerably increased the response to ACh (929 +/- 262% of basal value within 3 min). So, the more specific A2 purinoceptor agonist, NECA, potentiated glucagon secretion induced by the cholinoceptor agonist, ACh.     

Dynamics of asexual transmission of a mitochondrial plasmid in Cryphonectria parasitica

In the chestnut blight fungus Cryphonectria parasitica, as in most fungi, little is known about the efficiency of the asexual transmission of optional mitochondrial plasmids, vertically through conidia, and horizontally through hyphal anastomoses. In this paper, we show that pCRY1, a circular mitochondrial plasmid, is transmitted vertically with 100%-efficiency through conidia. Moreover, the plasmid is transmitted horizontally through hyphal contact from donor strains to vegetatively compatible and most incompatible strains. An allelic difference between the donor and recipient strain, at only one of the five nuclear incompatibility genes that were tested strongly inhibited, but did not absolutely prevent, the transfer of pCRY1 through hyphal fusions. In contrast, allelic differences in any one or several of the other four heterokaryon-compatibility loci suppressed the transmission of the plasmid only partially or not at all. The plasmid was also transmitted among incompatible strains by protoplast fusion without the concomitant transfer of mitochondrial DNA (mtDNA). A comparison of plasmid-bearing with plasmid-free isogenic strains revealed that pCRY1 significantly diminishes the pathogenic potency of some strains of the fungus, but does not affect the virulence of others. Collectively, the observations indicate that the introduction of deleterious mitochondrial genetic elements into natural populations may be a means for managing fungal pathogens. Received: 22 August 1999 / 9 December 1999     

Magnocellular neurons of the rat supraoptic nucleus are endowed with functional nicotinic acetylcholine receptors

Acetylcholine can stimulate the release of vasopressin. In organ-cultured hypothalamo-neurohypophyseal systems, acetylcholine enhanced vasopressin release by acting in or near the supraoptic nucleus Extracellular recordings suggested that acetylcholine can increase supraoptic neuron excitability. These effects could be mimicked, in part, by nicotine or blocked by nicotinic antagonists, suggesting that they might be mediated by nicotinic acetylcholine receptors. Autoradiography indicated that alpha-bungarotoxin binding sites are present in the supraoptic nucleus; however, neither acetylcholine nor nicotine binding sites could be detected. Thus, the existence, let alone the nature, of nicotinic receptors in the supraoptic nucleus has so far remained elusive. The present work attempts to determine: (i) whether functional nicotinic receptors are present in this nucleus; (ii) whether they are located on neurosecretory magnocellular cells or at presynaptic sites; (iii) what their pharmacological and biophysical properties are; (iv) whether they influence the activity of all or only part of supraoptic neurons. Whole-cell recordings were performed in hypothalamic slices or in acutely dissociated supraoptic neurons and the effect of nicotinic agonists was tested under voltage-clamp conditions. Autoradiography was done in coronal hypothalamic sections, using [3H]epibatidine and [125I]alpha-bungarotoxin as ligands. Our results indicate that supraoptic neurons possess functional nicotinic receptors containing the alpha7 subunit.     

Escherichia coli strains from pregnant women and neonates: intraspecies genetic distribution and prevalence of virulence factors

To determine the extent to which the vagina, endocervix, and amniotic fluid screen the Escherichia coli strains responsible for neonatal infections, we studied the genetic relationships among 105 E. coli strains isolated from all of the ecosystems involved in this infectious process. Twenty-four strains were isolated from the intestinal flora, and 25 strains were isolated from the vaginas of pregnant women. Twenty-seven strains were isolated from the amniotic fluid, blood, and cerebrospinal fluid (CSF) of infected neonates. The intraspecies genetic characteristics of all of the isolates were determined by random amplified polymorphic DNA (RAPD) analysis, PCR ECOR (E. coli reference) grouping, and PCR virulence genotyping. A correlation was found between the intraspecies distributions of the strains in the A, B1, B2, and D ECOR groups and in the two major RAPD groups (I and II). Nevertheless, the distribution of the E. coli strains in the RAPD groups according to their anatomical origins was more significant than their distribution in the ECOR groups. This may be explained by the existence of an E. coli subpopulation, defined by the RAPD I group, within the ECOR B2 group. This RAPD I group presents a major risk for neonates: 75% of the strains isolated from patients with meningitis and 100% of the strains isolated from patients with bacteremia were in this group. The vagina and the amniotic fluid are two barriers that favor colonization by highly infectious strains. Indeed, only 17% of fecal strains belonged to the RAPD I group, whereas 52% of vaginal strains and 67% of amniotic fluid strains belonged to this subpopulation. The ibeA and iucC genes were significantly associated with CSF strains, whereas the hly and sfa/foc genes were more frequent in blood strains. These findings could serve as a basis for developing tools to recognize vaginal strains, which present a high risk for neonates, for use in prophylaxis programs.     

EMG power spectra of elbow extensors during ramp and step isometric contractions

Summary The goal of the present study was to compare electromyogram (EMG) power spectra obtained from step (constant force level) and ramp (progressive increase in the force level) isometric contractions. Data windows of different durations were also analysed for the step contractions, in order to evaluate the stability of EMG power spectrum statistics. Fourteen normal subjects performed (1) five ramp elbow extensions ranging from 0 to 100% of the maximum voluntary contraction (MVC) and (2) three stepwise elbow extensions maintained at five different levels of MVC. Spectral analysis of surface EMG signals obtained from triceps brachii and anconeus was performed. The mean power frequency (MPF) and the median frequency (MF) of each power spectrum were obtained from 256-ms windows taken at 10, 20, 40, 60 and 80% MVC for each type of contraction and in addition on 512-, 1024-and 2048-ms windows for the step contractions. No significant differences (P>0.05) were found in the values of both spectral statistics between the different window lengths. Even though no significant differences (P>0.05) were found between the ramp and the step contractions, significant interactions (P<0.05) between these two types of contraction and the force level were found for both the MPF and the MF data. These interactions point out the existence of different behaviours for both the MPF and the MF across force levels between the two types of contraction.