Serotonergic agents in the treatment of fibromyalgia syndrome

OBJECTIVE: To evaluate literature that discusses the treatment of fibromyalgia syndrome (FMS) with agents that involve the neurotransmitter serotonin. DATA SOURCES: Biomedical literature accessed through MEDLINE (1966-August 2001) and International Pharmaceutical Abstracts. DATA SYNTHESIS: The cause and pathophysiology of FMS remain elusive, although abnormalities in the serotonin pathway have been implicated. Several serotonergic agents have been studied for use in FMS. Trials and case reports focusing on the use of newer agents: the selective serotonin reuptake inhibitors, venlafaxine and tramadol, were reviewed. CONCLUSIONS: Current research suggests that the serotonergic agents may reduce at least some of the symptoms of FMS. However, medications that act on multiple neurotransmitters may prove to be more effective in symptom management. Additional long-term studies are required in order to validate these results.     

Suboptimal restraint affects the pattern of abdominal injuries in children involved in motor vehicle crashes

Background

Both solid and hollow visceral abdominal injuries have been associated with the use of seat belts in children involved in motor vehicle crashes. The relationship between the types of restraint used and the pattern of abdominal injury is unknown.

Methods

A probability sample of restrained children involved in crashes was enrolled in an ongoing crash surveillance system (1998 through 2002) linking insurance claims data to telephone survey and crash investigation data. Significant abdominal injuries were considered when the Abbreviated Injury Scale (AIS) score was ≥2 and were defined as hollow visceral (HV; intestine, bladder), or solid visceral (liver, spleen, pancreas, kidney). Restraint type was categorized as optimal restraint (OR) or suboptimal restraint (S-OR) based on the child’s age and size.

Results

For the 33 months of review, interviews were obtained for 13,558 restrained children aged 0 to 15 years, of which, 56% were OR (n = 7,591) and 44% were S-OR (n = 5,967). A significant abdominal injury was recorded in 78 children. A hollow visceral injury was recorded in 38 (9 OR and 29 S-OR), and a solid visceral injury in 32 (18 OR and 14 S-OR). Both hollow and solid visceral injuries were present in 8 children (2 OR and 6 S-OR). Suboptimally restrained children had a higher risk for hollow visceral injury when compared with optimally restrained children (Odds Ratio, 4.14 [95% Confidence Interval 1.33 to 13.22, P < .01]).

Conclusions

Among restrained children with intraabdominal injuries, those who were suboptimally restrained were 4 times more likely to have a hollow visceral than a solid visceral injury when compared with those who were optimally restrained. This suggests that the mechanism of injury for hollow viscus may be directly related to the improper positioning of the restraint.     

Antimicrobial activity of N-acylphenothiazines and their influence on lipid model membranes and erythrocyte membranes

The antibacterial activity and influence on lipid model membranes and erythrocyte membranes of 24 N-acylphenothiazines and trifluoperazine were studied. (1) Among 24 phenothiazines, the antimicrobial activity of amino maleates was the highest. (2) The influence of phenothiazines on model liposome and erythrocyte membranes was studied using N-phenyl-1-naphthylamine (NPN) as fluorescence probe. From the three types of phenothiazine substitution (H, Cl, CF3) at position 2, CF3-phenothiazines were the most effective in the interaction with liposomal membranes. (3) As measured by the polarization degree of 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence, the alteration of membrane fluidity induced by CF3-phenothiazines was the biggest. Surprisingly, phenothiazines induced stomatocytic shape alterations (invaginations) in erythrocytes and at higher concentrations, also hemolysis of erythrocytes was observed. (4) The microcalorimetic measurements of influence of phenothiazines on thermal behaviour of synthetic lipid systems confirmed the previously obtained results. The main transition temperature and enthalpy of transition of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) were significantly modified by CF3-phenothiazines, suggesting their penetration of the lipid bilayer. Above results show that phenothiazine maleates were generally more effective than other phenothiazines used in this study.     

Transgenic and knockout mice to study the renin-angiotensin system and other interacting vasoactive pathways

Essential hypertension is an insidious disease in which the afflicted person risks disability and death from myocardial infarction and stroke. Many factors contribute to the development of essential hypertension, including environment, diet, daily stress, and genetics. Although several single gene disorders causing high blood pressure have been identified, the genetics of essential hypertension are much more complicated. The current hypothesis is that a combination of genetic variations in multiple genes may predispose a person to hypertension. Both overexpression and gene inactivation ("knockout") have proven useful tools to evaluate the genetics of essential hypertension and to identify pathways regulating blood pressure. Molecular and physiologic evaluations of transgenic and knockout mice carried out over the past 5 years have provided a plethora of information about the mechanisms of blood pressure regulation and the development and maintenance of hypertension. This review focuses on the newer mouse models that have been developed to investigate hypertension with an emphasis on vascular and renal mechanisms, contributed by the renin-angiotensin system, and other pathways intersecting with the renin-angiotensin system.     

Expert clinical assessment of thorax stiffness of infants and children during chest compressions

BackgroundHigh-fidelity manikins have been shown to be useful in teaching appropriate cardiopulmonary resuscitation (CPR) techniques. Similarity of manikin chest compression characteristics to real children is desirable. Little data exists on thorax stiffness in infants and children to guide manikin construction.ObjectiveTo determine a ‘consensus clinical-expert assessment’ of the pediatric chest stiffness for two specific age groups—infants and 5-year-olds.MethodsFour manikins in each of two sizes (5-year child, 6-month infant) were identically constructed, except for thorax downstroke spring stiffness. Health care providers with pediatric CPR experience provided chest compressions to each manikin in random order, masked to thoracic stiffness. Each health care provider was instructed to identify the manikin with downstroke thoracic stiffness most similar to children on whom they have performed chest compressions. Duplicate assessment of a randomly selected, previously assessed manikin was performed to assess health care provider consistency using the kappa statistic. Subject inter-rater agreement on which manikin best approximated a child of that age was assessed by calculating the percentage of subjects who identified that manikin as the best approximation of an actual child.ResultsA convenience sample of 63 international experts was obtained: 52 from Critical Care, 3 from Emergency Medicine, 4 from Pediatrics, and 4 from other specialties. There were 6 and 8 experts whose assessments were inconsistent for the infant manikins and child manikins, respectively. Approximately half of the subjects agreed on a single manikin as the best approximation of the human for both the infant (46%) and child manikins (43%). Excluding assessments of stiffness “out of range”, the percentage of experts who agreed on a single manikin as the best approximation for the human increased to approximately 90% for each manikin size.ConclusionExperienced health care providers consistently identified and agreed on the manikin thorax stiffness which they felt best approximated downstroke chest compression stiffness of children and infants. Expert opinion can be used to create manikins with realistic spring stiffness for CPR training. Further study is needed to evaluate whether enhanced manikin biofidelity will improve CPR performance.     

Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation photosensitizer

Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; ¶2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.     

Scaling up community-based obesity prevention in Australia: Background and evaluation design of the Health Promoting Communities: Being Active Eating Well initiative

Background  

There is only limited evidence available on how best to prevent childhood obesity and community-based interventions hold promise, as several successful interventions have now been published. The Victorian Government has recently funded six disadvantaged communities across Victoria, Australia for three years to promote healthy eating and physical activity for children, families, and adults in a community-based participatory manner. Five of these intervention communities are situated in Primary Care Partnerships and are the subject of this paper. The interventions will comprise a mixture of capacity-building, environmental, and whole-of-community approaches with targeted and population-level interventions. The specific intervention activities will be determined locally within each community through stakeholder and community consultation. Implementation of the interventions will occur through funded positions in primary care and local government. This paper describes the design of the evaluation of the five primary care partnership-based initiatives in the 'Go for your life' Health Promoting Communities: Being Active Eating Well (HPC:BAEW) initiative.     

Enzymes of glutathione metabolism as biochemical markers during hepatocarcinogenesis

Enzymes of glutathione metabolism, particularly gamma-glutamyltransferase (GGT) and glutathione S-transferase (GST), play a role in multistage hepatocarcinogenesis. The enhanced expression of these enzymes in preneoplastic altered hepatic foci, nodules, and hepatocellular carcinomas has been demonstrated after treatment with a variety of initiating and promoting agents. Glutathione is necessary for the detoxification of xenobiotics and carcinogens and for cell replication. Induction of GGT in altered hepatocytes may permit these cells to utilize extracellular glutathione to preserve their internal glutathione levels. GST induction allows glutathione utilization for the protection of the altered hepatocyte in an environment of exposure to xenobiotics, such as promoting agents. Thus, the combined effects of GGT and GST, in a toxic environment, may provide for the enhanced proliferation observed in preneoplastic hepatocytes.New clinical and research opportunities may involve the use of GGT and the placental isozyme of GST (PGST) as markers of preneoplasia and neoplasia in humans. Many factors, such as hormones, diet, and exposure to initiating and promoting agents, influence GGT and GST expression. The recent cloning of cDNAs to GGT and PGST offers opportunities for the study of factors involved in the genetic expression of these two enzymes. Coupled with the use of hepatocyte culture and transplantation, the factors involved at the molecular level in the creation of hepatocellular neoplasia may be discovered.     

Survival and cell mediated immunity after burn injury in aged mice

The elderly are less able to survive burn injury than young healthy individuals. Regardless of age, burn victims often succumb to secondary infections rather than the primary injury. Since immune responses diminish with age, it is likely that aged individuals are predisposed to a poor outcome by virtue of their weak immune system. Elevated production of macrophage-derived mediators, including interleukin-6 (IL-6), may lead to post-injury immunosuppression in young adults. Healthy aged individuals produce high circulating levels of these mediators; therefore, the combination of the age and burn trauma could further suppress immune responses and contribute to the rapid demise of aged burn patients. Herein, the effects of age and burn trauma using a murine scald injury model were examined. After injury, aged mice are less likely to survive, are unable to mount immune responses, and produce more IL-6 when compared to young adult mice given the same size injuries. Enhancing our understanding of the mechanisms responsible for regulating cell-mediated immune responses after injury could lead to the development of therapies designed to treat aged burn patients.