Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.     

Inhalation of chlorine gas

The clinical features of acute chlorine gas inhalation, and its management are reviewed. Current medical views on the chronic effects of an acute overwhelming exposure on lung function (reactive airways dysfunction syndrome), and the more controversial field of lung disease secondary to repeated inhalations of lower concentrations of chlorine gas are discussed.     

Arthritic temporomandibular joint: correlation of macromolecular contrast-enhanced MR imaging parameters and histopathologic findings

PURPOSE: To assess the utility of macromolecular contrast material-enhanced magnetic resonance (MR) imaging parameters for determining the histopathologic severity of temporomandibular joint (TMJ) arthritis. MATERIALS AND METHODS: Ovalbumin was used to induce arthritis in the TMJs of 10 previously sensitized adult white rabbits. Five rabbits composed the sham-treated control group. Dynamic spin-echo imaging was performed immediately before and for 30 minutes after injection of macromolecular contrast medium. Histologic specimens of TMJ were assessed quantitatively for arthritis. Changes in MR signal intensity were derived from the synovial and subsynovial tissues of the TMJ, and plasma volume (PV) and permeability surface area product (PS) were calculated. These MR parameters and the arthritic scores were compared between sham-treated and antigen-challenged TMJs. The relationships between MR parameters and histopathologic indexes were also determined. RESULTS: Arthritic TMJs showed marked enhancement of the synovial and subsynovial tissues over the imaging period. PS and all histopathologic indexes of arthritis were significantly greater (P < .005) in antigen-challenged than in sham-treated TMJs. PS demonstrated strong positive relationships with all histologic parameters of arthritis, indicating its utility for assessing the severity of joint inflammation. CONCLUSION: Macromolecular contrast-enhanced MR imaging enables quantification of PS and PV in inflamed joints. This technique may provide insights into the pathogenesis of joint inflammation and noninvasive monitoring of disease severity and treatment response in arthritis.     

Transmitter-induced calcium responses differ in astrocytes acutely isolated from rat brain and in culture

Glial fibrillary acid protein (GFAP)-positive astrocytes isolated from the cerebral cortices of 3-10-day-old rats frequently showed increased intracellular Ca2+ concentration responses to L-glutamate and glutamate analogues. However, few of the acutely isolated cells responded to ATP, and no such cells responded to serotonin [5-hydroxytryptamine (5-HT)]. The same cell that failed to respond to ATP or 5-HT often responded to glutamate. Culturing acutely isolated cells in media containing horse serum decreased Ca2+ responses to glutamate but increased the responses to ATP and induced responses to 5-HT. In primary cultures prepared from the cerebral cortices of 1-day-old rats and cultured in horse serum, fewer of the cells responded to glutamate, but almost all cells responded to ATP and 5-HT. The lack of or limited response to, 5-HT or ATP in the acutely isolated cells seems unlikely to be due to selective damage to the respective receptors because acutely isolated GFAP-negative cells showed responses to ATP, several different proteases and mechanical dissociation yielded cells that also responded to glutamate but not to ATP, and exposure of primary cultures to papain did not abolish Ca2+ responses to several transmitters. The responses of the acutely isolated cells to glutamate but limited or lack of responses to ATP and 5-HT also correspond to what has been seen so far for astrocytes in situ. Thus, the present studies provide direct evidence that some of the receptors seen in primary astrocyte cultures may reflect a response to culture conditions and that, in the context of the relevant information so far available, acutely isolated astrocytes seem to reflect better the in vivo state.     

Influenza vaccination in 22 developed countries: an update to 1995

This study expands and updates through 1995 our earlier report on influenza vaccine use in 18 developed countries. Five of the six countries with high levels of vaccine use in 1992 (> or = 130 doses/1000 population) showed little change or slight declines over the subsequent 3 years. The exception was the United States, where a new federal program for vaccination reimbursement for the elderly helped to increase vaccine distribution from 144 to 239 doses/1000 population. The six countries with medium levels of vaccine use in 1992 (76-96 doses/1000 population) increased to > or = 100 doses/1000 population by 1995. Among the six low-use countries in 1992 (< or = 65 doses/1000 population), only Finland showed substantial improvement (96 doses/1000 population) in 1995. Four new countries were added to the study. In Germany, vaccine use increased to 80 doses/1000 population in 1995, but in Ireland it remained at a low level (48 doses/1000 population). In Korea, vaccine use increased from 17 to 95 doses/ 1000 population during the period 1987-1995. In Japan, very high levels of vaccine use (approximately 280 doses/1000 population) in the early 1980s were associated with vaccination programs for school children. However, vaccine use fell precipitously when these programs were discontinued, and only 2 and 8 doses/1000 population were used in 1994 and 1995, respectively. In all 22 countries, higher levels of vaccine use were associated with vaccination reimbursement programs under national or social health insurance and were not correlated with different levels of economic development. Excluding Japan, in 1995 there was still a greater than fourfold difference between the highest and lowest levels of vaccine use among the other 21 countries in the study. Given its well established clinical effectiveness and cost-effectiveness, none of these countries has yet achieved the full benefits of its programs for influenza vaccination.     

Risk factors for emotional/behavioral problems in young adolescents: A prospective analysis of adolescent and parental stress and symptoms.

Stressful events in the lives of 309 10- to 15-year-olds and stressful events and psychological symptoms reported by their parents were examined in a 9-month study. Ss' self-reported emotional/behavioral problems were predicted by their reports of stressful events and their fathers' reports of psychological symptoms in cross-sectional analyses. Analyses at follow-up after controlling for initial reports of emotional/behavioral problems and prospective analyses predicting from first assessment to follow-up yielded significant effects for Ss' self-reported stressful events. Mothers' reports of children's problems were predicted by mothers' psychological symptoms in cross-sectional analyses and at follow-up after controlling for initial emotional/behavioral problems. Only prior levels of maternal reports of emotional/behavioral problems predicted mothers' reports of their children's problems 9 months later. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact fracture toughness tests on polymers

A series of impact tests are described in which the plane strain fracture toughness, K_c1, of five different polymers is measured using a three point bend specimen at striker speeds up to 5m/s. At low speeds K_c1 is determined using the maximum load and a static analysis, but at speeds greater than 1 m/s the dynamic effects render the load signal unusable. For the higher speeds the fracture is timed using contact and crack propagation gages and the analysis is performed using the striker displacement at fracture. A dynamic analysis is used to convert this measurement to the true specimen displacement and K_c1 is determined from this. The apparent downward trends in the K_c1 results obtained, especially at speeds above 3m/s, are discussed.     

Accurate molecular weight distribution of polymers using thermal field-flow fractionation with deconvolution to remove system dispersion

Thermal field-flow fractionation (ThFFF) is an elution process that separates polymeric materials by molecular weight. Elution profiles thus provide approximations to the molecular weight distributions of polymers. The accuracy of such approximate distributions is expected to be improved by accounting for the effect on the elution profile of band-broadening processes in the FFF system. Fortunately this intrinsic band broadening, referred to as system dispersion, is theoretically well-defined in ThFFF. In this article we present an algorithm that corrects ThFFF elution profiles by removing system dispersion. The program is applied to ThFFF fractograms of standard polymers having both narrow and broad molecular weight distributions. The increased accuracy obtained by accounting for system dispersion is demonstrated. For the narrow standard, deconvolution shows that the polydispersity (weight/number-average mol. wt.) is only 1.004. For the broad standard, NBS 706, the molecular weight distribution and parameters obtained agree well with previously published results. Application to a simulated fractogram resulting from mixing five narrow standards helps define the conditions under which accurate molecular weight information can be recovered.