Test facility management: Responsibilities and paradigms of a new era.

GLP test facility management refers to the proper management and organization of a facility that conducts studies according to GLP regulations. Compliance with GLP regulations is necessary for data generated in such facilities to be accepted by regulatory authorities. According to GLP Principles, Test facility management (TFM) is responsible for a wide range of tasks and responsibilities to ensure the smooth and efficient operation of the facility. The framework in which the TFM operates within the Test Facility is certainly much more complex than in the early days of the GLP, and moreover it is unlikely that anything will change from a scientific and technological point of view in the years to come. Several aspects have changed from a scientific and technological point of view, and we know that innovation is very rapid. From the above considerations emerges the need for a major change in the performance of the TFM's role.

Comparison of effectiveness of two commonly used two-handed mask ventilation techniques on unconscious apnoeic obese adults.

BACKGROUND.: Mask ventilation and tracheal intubation are basic techniques for airway management and mutually inclusive rescue measures to restore ventilation. The aim of this study was to compare the effectiveness of mask ventilation between two commonly used techniques of two-handed mask ventilation in obese unconscious apnoeic adults. METHODS.: Eighty-one obese adults received mask ventilation after induction using C-E clamp and modified V-E clamp techniques in a randomized crossover manner. Mechanical ventilation was provided using a pressure-control mode, at a rate of 10 bpm, with an inspiratory-to-expiratory time ratio of 1:2 and a pre-set plateau airway pressure of 20 cm H 2 O. The primary outcome was expired tidal volume. RESULTS.: The BMI for the subjects was 37 ( sd 4.9) kg m -2 . The failure rates for mask ventilation (tidal volume≤anatomical dead space) were 44% for the C-E technique and 0% for the V-E technique ( P <0.001). Tidal volume was significantly lower for the C-E than the V-E technique [371 ( sd 345) vs 720 (244) ml, P <0.001]. The peak airway pressures were 21 ( sd 1.5) cm H 2 O for the C-E technique and 21 (1.3) cm H 2 O for the V-E technique. CONCLUSIONS.: Mask ventilation using the modified V-E technique is more effective than with the C-E technique in unconscious obese apnoeic adults. Subjects who fail ventilation with the C-E technique can be ventilated effectively with the V-E technique. CLINICAL TRIAL REGISTRATION.: NCT02580526.

The relation between dietary habits and urinary levels of 3-phenoxybenzoic acid, a pyrethroid metabolite.

Concerns about pesticide exposure through food consumption have increased during the past several years. Pyrethroids are applied as insecticides throughout the world. Human metabolism of pyrethroids results in urinary metabolites that are suitable for biological monitoring. The objective of our study was to investigate the relation between food consumption and urinary levels of 3-phenoxybenzoic acid (3-PBA), a general metabolite of pyrethroids, in a non-occupational exposed adult population from the IDI-IRCCS, Rome, Italy. Information on socio-demographic characteristics, smoking, diet and self-reported household pesticide exposure was collected. Urinary 3-PBA level of each subject was measured and adjusted by urinary creatinine. We found that people consuming both raw and cooked vegetables five times weekly or more had higher mean levels of 3-PBA in urine (1.03 µg/g creatinine versus 0.52 µg/g creatinine; p=0.009 and 0.99 µg/g creatinine versus 0.58 µg/g creatinine; p=0.01, respectively) than subjects consuming less than five times weekly. In a multivariate model, after adjusting for age, sex, BMI, smoking and household insecticide exposure, high intake of raw vegetables (OR: 5.31; 95%CI: 1.32-21.3) and high intake of cooked vegetables, in particular cruciferous (OR: 4.67; 95%CI: 1.07-20.5) and leafy vegetables (OR: 6.88; 95%CI: 1.50-31.7), were associated with high urine 3-PBA levels (≥0.70 µg/g creatinine). The results of this study suggest that part of the variation in pyrethrois intake is explained by vegetable intake.

A protective effect of the Mediterranean diet for cutaneous melanoma.

BACKGROUND: Many studies have investigated the Mediterranean diet as a risk factor for cancer, none of which has included cutaneous melanoma. The latter is usually fatal, rendering knowledge about prevention extremely important. We assessed the role of some food components of the Mediterranean diet and cutaneous melanoma. METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy including 304 incident cases of cutaneous melanoma and 305 controls, frequency matched to cases. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected. Logistic regression was the method used to estimated odds ratio and 95% CIs. RESULTS: After careful control for several sun exposure and pigmentary characteristics, we found a protective effect for weekly consumption of fish (OR, 0.65, 95%CI = 0.43-0.97), shellfish (OR, 0.53, 95%CI = 0.31-0.89), fish rich in n-3 fatty acids (OR, 0.52, 95%CI = 0.34-0.78), daily tea drinking (OR, 0.42, 95%CI, 0.18-0.95; P(trend) = 0.025) and high consumption of vegetables (OR, 0.50, 95%CI = 0.31-0.80, P(trend) = 0.005) in particular carrots, cruciferous and leafy vegetables and fruits (OR, 0.54, 95%CI =0.33-0.86, P(trend) = 0.013), in particular citrus fruits. No association was found for alcohol consumption and any other food items. CONCLUSION: Overall, our findings suggest that some dietary factors present in the Mediterranean diet might protect from cutaneous melanoma.

Selective down-regulation of [(125)I]Y0-alpha-conotoxin MII binding in rat mesostriatal dopamine pathway following continuous infusion of nicotine.

Prolonged exposure to nicotine, as occurs in smokers, results in up-regulation of all the neuronal nicotinic acetylcholine receptor subtypes studied so far, the only differences residing in the extent and time course of the up-regulation. alpha6beta2*-Nicotinic acetylcholine receptors are selectively enriched in the mesostriatal dopaminergic system and may play a crucial role in nicotine dependence. Here we show that chronic nicotine treatment (3mg/kg/day for two weeks, via s.c. osmotic minipumps) caused a significant decrease (36% on average) in the binding of [(125)I]Y(0)-alpha-conotoxin MII (a selective ligand for alpha6beta2*-nicotinic acetylcholine receptors in this system) to all the five regions of the rat dopaminergic pathway analyzed in this study. After one week of withdrawal, binding was still lower than control in striatal terminal regions (namely the caudate putamen and the accumbens shell and core). In somatodendritic regions (the ventral tegmental area and the substantia nigra) the decrease was significant at the end of the treatment and recovered within one day of withdrawal. This effect was not due to displacement of [(125)I]Y(0)-alpha-conotoxin MII binding by residual nicotine. In fact the binding was not changed by 565 ng/g nicotine (obtained with a single injection of nicotine), a concentration much higher than that found in the brain of rats chronically treated with nicotine (240 ng/g). In addition, consistent with previous studies reporting an up-regulation of other subtypes of nicotinic acetylcholine receptors, we found that nicotine exposure significantly increased (40% on average) the binding of [(125)I]epibatidine (a non-selective agonist at most neuronal heteromeric nicotinic acetylcholine receptors) in three up to five regions containing only alpha-conotoxin MII-insensitive [(125)I]epibatidine binding sites, namely the primary motor, somatosensory and auditory cortices. In conclusion, this work is the first to demonstrate that alpha6beta2*-nicotinic acetylcholine receptors, unique within the nicotinic acetylcholine receptor family, are down-regulated following chronic nicotine treatment in rat dopaminergic mesostriatal pathway, a finding that may shed new light in the complex mechanisms of nicotine dependence.

Therapeutic approach to patients complaining of high blood pressure in a cardiological emergency room.

OBJECTIVE: To evaluate the management of patients complaining of high blood pressure (BP) in a cardiological emergency room. METHODS: Patients referred to the cardiological emergency room with the main complaint of high blood pressure were consecutively selected. The prescriptions and the choice of antihypertensive drugs were assessed. The classification of these patients as hypertensive emergencies or pseudoemergencies, according to the physician who provided initial care, was recorded. RESULTS: From a total of 858 patients presenting to the emergency room, 80 (9.3%) complained of high BP, and 61 (76.3%) received antihypertensive drugs. Sublingual nifedipine was the most commonly used drug (59%). One patient received intravenous medication, one patient was hospitalized and 6 patients (7.5%) were classified as hypertensive emergencies or pseudoemergencies. CONCLUSION: High BP could seldom be classified as a hypertensive emergency or pseudoemergency, even though it was a frequent complaint (9.3% of visits). Currently, the therapeutic approach is not recommended, even in specialized clinics.

Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist.

Environmental stimuli that are reliably associated with the effects of many abused drugs, especially stimulants such as cocaine, can produce craving and relapse in abstinent human substance abusers. In animals, such cues can induce and maintain drug-seeking behaviour and also reinstate drug-seeking after extinction. Reducing the motivational effects of drug-related cues might therefore be useful in the treatment of addiction. Converging pharmacological, human post-mortem and genetic studies implicate the dopamine D3 receptor in drug addiction. Here we have designed BP 897, the first D3-receptor-selective agonist, as assessed in vitro with recombinant receptors and in vivo with mice bearing disrupted D3-receptor genes. BP 897 is a partial agonist in vitro and acts in vivo as either an agonist or an antagonist. We show that BP 897 inhibits cocaine-seeking behaviour that depends upon the presentation of drug-associated cues, without having any intrinsic, primary rewarding effects. Our data indicate that compounds like BP 897 could be used for reducing the drug craving and vulnerability to relapse that are elicited by drug-associated environmental stimuli.

Differential effects of serial hemodilution with hydroxyethyl starch, albumin, and 0.9% saline on whole blood coagulation.

STUDY OBJECTIVES: To determine by thrombelastography assessed coagulation, the effects of progressive hemodilution with three intravascular volume expanders. DESIGN: Prospective, controlled, whole blood, volumetric ex vivo hemodilution study. SETTING: University of Pennsylvania Medical Center Operating Rooms. PATIENTS: 60 ASA physical status I and II patients; phlebotomy prior to administration of IV fluids or medications. INTERVENTIONS: Analysis of whole blood clotting determined by six thrombelastographic channels for control and five volumetric hemodilutions (11%, 25%, 33%, 50%, and 75%) with 0.9% saline, 5% albumin, and 6% hydroxyethyl starch (n = 20 for each diluent group). MEASUREMENTS AND MAIN RESULTS: Thrombelastographic parameters R (minutes), angle alpha (degree), MA (mm), and lysis (%) were measured and compared to the sample control for each dilution of the same specimen. There was no significant difference between control groups in any thrombelastographic variable (R, angle alpha, MA, or lysis). No changes were seen in any variable from any diluent at 11% hemodilution. Seventy-five percent hemodilution caused significantly hypocoagulable changes from control for all thrombelastographic parameters for all three diluents. Thrombelastographic indices differed significantly from controls at intermediate hemodilutions. Both colloids caused decreases in measured angle alpha and MA at lower hemodilution than did 0.9% saline. Albumin 5% caused significant hypocoagulable changes from control values at lower hemodilution than did either 0.9% saline or 6% hydroxyethyl starch for all thrombelastographic parameters. Saline 0.9% increased angle alpha significantly at 50% hemodilution. Abnormal lysis did not occur at any dilution. Differing ex vivo effects of three different intravascular fluids thrombelastography assessed coagulation are found. CONCLUSION: No differences were found after 11% hemodilution with any volume expanders. Hemodilution with up to 50% saline maintained thrombelastographic indices. Albumin produced early and profound hypocoagulable effects. Significant hypocoagulability occurred for all three diluents at 75% hemodilution. The study supports the use of albumin in patients at risk for thrombosis, and saline in patients with a need for normal hemostasis.

[Clinico-diagnostic considerations on various cases of lymphogranuloma venereum]. / Considerazioni clinico-diagnostiche su alcuni casi di linfogranuloma venereo.

The authors report some recently observed cases of lymphogranuloma venereum and focus their attention on the complex approach to clinical and laboratory diagnosis. Furthermore they underline the importance and the spread of this disease in new geographical area, such as Europe.

Lidocaine inhibits blood coagulation: implications for epidural blood patch.

Lidocaine in the epidural space, through inhibitory effects upon coagulation, may contribute to inefficacy of epidural autologous blood patch (EBP). This study was undertaken to evaluate the effect of achievable epidural concentrations of lidocaine on blood coagulation as a step in testing this hypothesis. Ex vivo blood coagulation using whole blood (n = 20) was studied with computerized thrombelastography (TEG). Each blood specimen was exposed to serial dilutions of lidocaine hydrochloride or saline to form end-concentrations of 0.0 mM, 2.3 mM, 4.6 mM, 9.2 mM, 18.5 mM, and 36.9 mM lidocaine. Statistical analysis using analysis of variance for repeated measures revealed that the three highest lidocaine concentrations tested caused hypocoagulable and/or fibrinolytic changes as compared with controls. Achievable epidural admixtures of lidocaine and whole blood will impair coagulation. Therefore, residual lidocaine in the epidural space may contribute to failures of immediate or early EBP.

Predictors of outcome for uvulopalatopharyngoplasty.

The objective of this study was to assess the value of preoperative fiberoptic nasopharyngoscopy with the Müller maneuver (FNMM) and cephalometric radiography in predicting response to uvulopalatopharyngoplasty (UPPP) in patients with obstructive sleep apnea syndrome. Fifty-three such patients having significant obstruction at the soft palatal level and variable degrees of obstruction at the base-of-tongue level underwent both diagnostic procedures before UPPP. Outcome was assessed by the apnea-plus-hypopnea index (AHI) as determined by polysomnography, which was performed before and after surgery. As a group, patients exhibited a significant 10-point reduction in AHI (46.5 to 36.7). However, 17 (32.1%) were judged to be responders as defined by a reduction of the AHI by an increment of 50% or greater with respect to baseline. Of all the cephalometric variables assessed, soft palate length was the only one that differed between responders and nonresponders (45.5 mm versus 42.6 mm, respectively). However, this difference only approached significance (P = .067). Similarly, FNMM results did not discriminate between responders and nonresponders. These results indicate that preoperative cephalometric radiography and FNMM cannot be reliably used to enhance surgical success.

Community benefit: a first and second generation approach.

Seven years ago, leaders at Community Medical Center in Toms River, NJ, made a decision to forge a new direction in health care delivery--to look beyond just the physical health care needs of the community and also address nutrition, housing, social support, environment, and educational needs. Today, Community Medical Center serves as a national model for how a community benefit initiative can work. In this article, the authors talk about the rationale behind the hospital's community benefit initiative, the evolution of the process over first and second generations, and points of learning for hospitals wishing to take the lead in improving the health status of their communities.