Perceptions of analgesic use and side effects: what the public values in pain management

In this population-based telephone survey, we evaluated the attitudes of 302 adults toward analgesic use and related side effects. Over half (68%) reported prior experience with 2 or more side effects. Vomiting (34%), confusion (32%), and nausea (17%) were ranked as the worst side effects. Exploratory cluster analysis grouped responses to 6 questions about willingness to use analgesics into two categories. Participants in Cluster I (n=106), "Conservatives," were less willing to take analgesics for pain as compared to those in Cluster II (n=153), "Liberals." Univariate analysis found Hispanics, women, those less affluent or educated, and those with prior side-effect experience were more likely to be Conservative. Experience with side effects (OR=1.3) and being female (OR=2.1) were the strongest predictors of conservative cluster membership. To achieve better pain outcomes, clinicians and patients must identify factors that contribute to conservative decision-making about analgesic use and side effect management.     

Activated protein C preserves functional islet mass after intraportal transplantation: a novel link between endothelial cell activation, thrombosis, inflammation, and islet cell death

Clinical studies indicate that significant loss of functional islet mass occurs in the peritransplant period. Islets are injured as a result of detrimental effects of brain death, pancreas preservation, islet isolation, hypoxia, hyperglycemia, and immune-mediated events. In addition, recent studies demonstrated that islets are injured as a result of their exposure to blood and of activation of intrahepatic endothelial and Kupffer cells, resulting in inflammation and thrombosis. Activated protein C (APC) is an anticoagulant enzyme that also exerts anti-inflammatory and antiapoptotic activities by acting directly on cells. Here, we report that exogenous administration of recombinant murine APC (mAPC) significantly reduced loss of functional islet mass after intraportal transplantation in diabetic mice. Animals given mAPC exhibited better glucose control, higher glucose disposal rates, and higher arginine-stimulated acute insulin release. These effects were associated with reduced plasma proinsulin, intrahepatic fibrin deposition, and islet apoptosis early after the transplant. In vitro and in vivo data demonstrated that mAPC treatment was associated with a significant reduction of proinflammatory cytokine release after exposure of hepatic endothelial cells to islets. mAPC treatment also prevented endothelial cell activation and dysfunction elicited by intrahepatic embolization of isolated islets inherent to pancreatic islet transplantation (PIT). This study demonstrates multiple remarkable beneficial effects of mAPC for PIT and suggests that APC therapy may enhance the therapeutic efficacy of PIT in diabetic patients.     

Pharmacokinetic study of carbamazepine and its carbamazepine 10,11-epoxide metabolite in a group of female epileptic patients under chronic treatment

BACKGROUND: Although epileptic crises are equally frequent in women and men, several factors cause female epileptics to present a series of gender-specific problems. To date, few studies have been published on the kinetics of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZ-E) active metabolite in a Mexican population, and no information for epileptic women of reproductive age is available. The aim of the present work was to study the pharmacokinetic behavior of this group of women during steady state. METHODS: Fourteen epileptic women under chronic treatment receiving only the anticonvulsant CBZ to control their crises were studied. A blood sample was taken before breakfast, before the morning dose of 200 mg, and after the dose at 1, 2, 3, 4, 5, and 8 h. Serum was separated by centrifugation at 1,350 x g. Serum concentrations of carbamazepine (CBZ) and of the metabolite carbamazepine 10,11-epoxide (CBZ-E) were measured by HPLC. Pharmacokinetic parameters were calculated by statistical moment method after obtaining serum concentrations. RESULTS: Maximum time (T(max)) for CBZ was reached at 2.72+/-0.71 h and for CBZ-E, it was 3.60+/-0.79 h. C(max) for CBZ was 7.30+/-2.30 microg/mL, while C(min) for CBZ was 6.30+/-2.49. Maximum serum values for CBZ-E were 1.01+/-0.57, equivalent to 13.80% of CBZ; t(12) value for CBZ and CBZ-E was 18.20 and 16.10 h, respectively. AUC values for CBZ and metabolite were 70.33+/-17.10 microg/L/h and 9.20+/-2.50 microg/L/h, respectively. CBZ and CBZ-E clearance did not show differences and were 0.37 mL/kg/min and 0.40 mL/kg/min, respectively. Extraction index for serum concentrations of CBZ and CBZ-E AUC(CBZ)/AUC(CBZ-E) was 0.13; positive correlation was observed between serum concentrations of CBZ and E-CBZ, with r=0.94. CONCLUSIONS: The schedule we suggest for therapeutic monitoring of serum concentrations of CBZ in chronic treatments is 3 h for maximum peak concentration of C(max) after dose administration and for minimum peak concentration, C(min) prior to subsequent administration of the dose.     

Impact of participatory education on body mass index and blood glucose in obese type-2 diabetics

Exogenous obesity increases morbidity and mortality risk and has been associated with nutritional habits, which in turn can be affected by health education. Health education aims to promote patient participation in achieving behavior change and healthy lifestyles. The objective of this study is to show the advantages of participatory education in the modification of body mass index (BMI) in obese type-2 diabetics. A quasi-experimental study was performed with random allocation of two patient groups. The educational intervention was organized through a reflection-action process. BMI was measured at baseline and then monthly for 9 months during the intervention. The groups were analyzed by age and sex. Statistical analysis used the Student t test, with the mean difference for related groups. The control group showed a mean BMI of 33.89 + 1.96 and a final BMI of 33.2 +/- 2.15 (t:22.4; p:0.16). The experimental group had an initial value of 33.63 +/- 2.12 and a final BMI of 31.54 +/- 1.71; statistical difference: (t:11.55; p:0.003). The participatory educational intervention thus helped improve the BMI in obese type-2 diabetics.     

Risperidone in the treatment of patients with delirium

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of risperidone in the treatment of patients with delirium. METHOD: We conducted a prospective, multicenter, observational 7-day study in 5 university general hospitals. Sixty-four patients (62.5% male [N = 40]; mean age: 67.3 +/- 11.4 years) hospitalized due to a medical condition who met criteria for delirium according to DSM-IV were enrolled in the study. Fifty-six patients received 7 days of treatment or less, while 8 patients continued treatment for more than 7 days. Effectiveness was assessed using the Trzepacz Delirium Rating Scale (DRS), the positive subscale of the PANSS (PANSS-P), the Mini-Mental State Examination (MMSE), and the Clinical Global Impressions scale (CGI). Safety assessment included the UKU Side Effect Rating Scale. Risperidone was administered at the time of diagnosis, and treatment was maintained according to clinical response. Response to treatment was defined as a reduction in DRS score to below 13 within the first 72 hours. Data were gathered from April to December 2000. RESULTS: Risperidone (mean dose = 2.6 +/- 1.7 mg/day at day 3) was effective in 90.6% (58/64) of the patients and significantly improved all symptoms measured by the scales from baseline to day 7 (mean scores: DRS, 22.5 +/- 4.6 at baseline to 6.8 +/- 7.0 at day 7; PANSS-P, 21.5 +/- 8.8 to 10.1 +/- 7.3; MMSE, 13.1 +/- 10.9 to 26.4 +/- 8.9; and CGI, 4.5 +/- 0.9 to 1.9 +/- 1.2) (Friedman test, p <.001 in all cases). Two patients (3.1%) experienced adverse events, but none showed extrapyramidal symptoms. CONCLUSIONS: Low-dose risperidone proved to be a safe and effective drug in the treatment of symptoms of delirium in medically hospitalized patients. These data provide the rationale for a prospective randomized controlled trial.     

5-ht5B receptor mRNA in the raphe nuclei: coexpression with serotonin transporter

We used double-label in situ hybridization to examine the cellular localization of 5-ht(5B) receptor mRNA in relation to serotonin transporter mRNA in the rat dorsal raphe (DR) and central superior nucleus (CS, median raphe nucleus). 5-ht(5B) receptor mRNA hybridization signal was often found on serotonin transporter mRNA-positive neuron profiles. The degree of cellular colocalization of these mRNAs notably varied among the different regions of the raphe nuclei. In the DR, cell bodies showing 5-ht(5B) receptor mRNA expression were abundant in the medial portions of the nucleus, all of them being also labeled for serotonin transporter mRNA. In contrast, in the ventrolateral regions (lateral wings) of the DR, we observed serotonin transporter mRNA-positive cells, but they were devoid of 5-ht(5B) receptor mRNA signal. In the CS, the level of coexpression of 5-ht(5B) receptor mRNA with serotonin transporter mRNA was high in the intermediate portions of the nucleus; however, we were unable to detect specific 5-ht(5B) receptor mRNA hybridization signal in its caudal extent. Our results support the presence of 5-ht(5B) receptor in serotonergic neurons in the DR and CS, suggesting an autoreceptor role for this receptor subtype.     

Adenosine A2A receptors are involved in physical dependence and place conditioning induced by THC

A2A adenosine and CB1 cannabinoid receptors are highly expressed in the central nervous system, where they modulate numerous physiological processes including adaptive responses to drugs of abuse. Both purinergic and cannabinoid systems interact with dopamine neurotransmission (through A2A and CB1 receptors, respectively). Changes in dopamine neurotransmission play an important role in addictive-related behaviours. In this study, we investigated the contribution of A2A adenosine receptors in several behavioural responses of Delta9-tetrahydrocannabinol (THC) related to its addictive properties, including tolerance, physical dependence and motivational effects. For this purpose, we first investigated acute THC responses in mice lacking A2A adenosine receptors. Antinociception, hypolocomotion and hypothermia induced by acute THC administration remained unaffected in mutant mice. Chronic THC treatment developed similar tolerance to these acute effects in wild-type and A2A-knockout mice. However, differences in the body weight pattern were found between genotypes during such chronic treatment. Interestingly, the somatic manifestations of SR141716A-precipitated THC withdrawal were significantly attenuated in mutant mice. The motivational responses of THC were also evaluated by using the place-conditioning paradigm. A significant reduction of THC-induced rewarding and aversive effects was found in mice lacking A2A adenosine receptors in comparison with wild-type littermates. Binding studies revealed that these behavioural changes were not associated with any modification in the distribution and/or functional activity of CB1 receptors in knockout mice. Therefore, this study shows, for the first time, a specific involvement of A2A receptors in the addictive-related properties of cannabinoids.     

Efficacy and safety of memantine treatment for reduction of changes associated with experimental glaucoma in monkey, II: Structural measures

PURPOSE: To determine, using anatomic measurements, whether daily oral dosing with memantine is both safe and effective to reduce the injury associated with experimental glaucoma in primates. METHODS: Argon laser treatment of the anterior chamber angle was used to induce chronic ocular hypertension (COHT) in the right eyes of 18 macaque monkeys. Nine animals were daily orally dosed with 4 mg/kg memantine while the other nine animals received vehicle only. Measurements of intraocular pressure (IOP) from both eyes of all animals were made at regular intervals. Appearance of the optic nerve head, retinal vessels, and surrounding retina was documented with stereo fundus photographs obtained at multiple time points throughout the study. Measurements of optic nerve head topography were obtained from confocal laser scans made from animals with the highest IOPs at approximately 3, 5, and 10 months after elevation of IOP. At approximately 16 months after IOP elevation, animals were killed and histologic counts of cells in the retinal ganglion cell (RGC) layer were made. RESULTS: Histologic measurements showed that, for animals with moderate elevation of IOP, memantine treatment was associated with an enhanced survival of RGCs in the inferior retina. Measurements of optic nerve head topography showed less IOP-induced change in memantine-treated animals. This effect was seen in measurements of both the cup and the neuroretinal rim. A comparison of these same histologic and morphologic measurements in normotensive eyes from the two treatment groups showed that memantine treatment was not associated with any significant effects on these eyes. CONCLUSIONS: Histologic measurements of RGC survival as well as tomographic measurements of nerve head topography show that systemic treatment with memantine, a compound which does not lower intraocular pressure, is both safe and effective to reduce changes associated with experimental glaucoma.