Pain continues to be a signi®cant management problem in people with spinal cord injuries. Despite this there is little consensus regarding the nature, terminology and de®nitions of the various types of pain that occur following spinal cord injury. This has led to large variations in the reported incidence and prevalence of pain following spinal cord injury. Treatment studies have been hampered by inconsistent and inaccurate identi®cation of pain types. We believe that both research and management would bene®t from an agreed upon classi®cation system which accurately and reliably identi®es the types of pain that occur following spinal cord injury. We have reviewed the literature on the classi®cation of pain following spinal cord injury and have developed a classi®cation system which adopts the strengths of previous systems and attempts to avoid the weaknesses inherent in others. Our proposed classi®cation system of pain following spinal cord injury includes four major divisions: musculoskeletal, visceral, neuropathic and other types of pain. We have divided neuropathic pain on the basis of region into two subdivisions: neuropathic at level and neuropathic below level pain. We have further divided neuropathic at level pain into two categories: radicular and central, to indicate the presumed site of the lesion responsible for pain generation. We believe that our proposed classi®cation system is comprehensive, simple and readily applicable in the clinical and research situation. It is our hope that this proposed classi®cation will contribute to the eventual development of a universal system for the classi®cation of pain following spinal cord injury.

In vitro studies suggest that collecting duct-derived (CD-derived) endothelin-1 (ET-1) can regulate renal Na reabsorption; however, the physiologic role of CD-derived ET-1 is unknown. Consequently, the physiologic effect of selective disruption of the ET-1 gene in the CD of mice was determined. Mice heterozygous for aquaporin2 promoter Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene (called CD-specific KO of ET-1 [CD ET-1 KO] mice) were generated. These animals had no CD ET-1 mRNA and had reduced urinary ET-1 excretion. CD ET-1 KO mice on a normal Na diet were hypertensive, while body weight, Na excretion, urinary aldosterone excretion, and plasma renin activity were unchanged. CD ET-1 KO mice on a high-Na diet had worsened hypertension, reduced urinary Na excretion, and excessive weight gain, but showed no differences between aldosterone excretion and plasma renin activity. Amiloride or furosemide reduced BP in CD ET-1 KO mice on a normal or high-Na diet and prevented excessive Na retention in salt-loaded CD ET-1 KO mice. These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP. IntroductionEndothelin-1 (ET-1) was initially described as a potent endothelial cell-derived vasoconstrictor (1); however, the peptide is now known to be produced by many cell types and to elicit multiple biologic effects (2). The kidney is likely an important target; ET-1 causes renal vasoconstriction, mesangial cell contraction, glomerular cell proliferation, ECM accumulation, and alterations in nephron fluid and electrolyte transport (2). While many renal cell types synthesize and bind ET-1, the collecting duct (CD) is of particular importance: The renal inner medulla contains the highest concentration of ET-1 in the body (3), and the inner medullary CD (IMCD) is the predominant renal site of ET-1 production (4-8) and receptor expression (9-11).In vitro studies suggest that ET-1 inhibits Na and water reabsorption in the cortical CD (CCD) and IMCD and that this occurs through activation of the ET B receptor (ETRB). ET-1 inhibits vasopressin-stimulated (AVP-stimulated) water flux in isolated CCD (9, 12) and reduces AVP-stimulated cyclic AMP accumulation (13-15) and osmotic water permeability (16, 17) in isolated IMCDs. ET-1 also inhibits mineralocorticoid and AVP-stimulated Na and Cl reabsorption in isolated CCDs (12,18,19) and decreases Na/K-ATPase activity in suspensions of IMCDs (20). Despite these data, demonstrating such an ET-1 effect in vivo and clarifying how CD-derived ET-1 physiologically regulates Na and water transport has been problematic. This difficulty stems, in part, from

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Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infections worldwide, yet no effective vaccine or antiviral treatment is available. Here we report the discovery and initial development of RSV604, a novel benzodiazepine with submicromolar anti-RSV activity. It proved to be equipotent against all clinical isolates tested of both the A and B subtypes of the virus. The compound has a low rate of in vitro resistance development. Sequencing revealed that the resistant virus had mutations within the nucleocapsid protein. This is a novel mechanism of action for anti-RSV compounds. In a three-dimensional human airway epithelial cell model, RSV604 was able to pass from the basolateral side of the epithelium effectively to inhibit virus replication after mucosal inoculation. RSV604, which is currently in phase II clinical trials, represents the first in a new class of RSV inhibitors and may have significant potential for the effective treatment of RSV disease.Human respiratory syncytial virus (RSV) is the most important respiratory pathogen that causes lower respiratory tract infections, such as bronchiolitis and pneumonia, in infants and young children, resulting in up to 125,000 hospitalizations annually in the United States (3). The infants most at risk of severe disease are those under 6 weeks of age, those with bronchopulmonary dysplasia, congenital heart disease, or immunodeficiency, and those born prematurely. Hospital admission rates for these groups range between 5% and 30% (20,25). The mortality rate among children admitted to hospital is approximately 3% for those with heart and lung problems and up to 1% for those without these risk factors (11,25). In adults and the elderly, RSV pneumonia is increasingly recognized as a significant cause of morbidity and mortality, being associated with more than 17,000 deaths annually between 1991 and 1998 (9, 22). Among the hospitalized elderly, mortality can be as high as 10 to 20%, and among severely immunocompromised patients with RSV pneumonia, it can be on the order of 50 to 70% (10). There is therefore an urgent and unmet medical need for novel therapies to deal with infections caused by this virus.The development of new therapeutics for RSV was recently reviewed (17,19). Although research into the prevention and treatment of RSV infection has been ongoing for almost 40 years, vaccine development is difficult (8, 13), and to date, there is no clinically approved vaccine. The development of RSV vaccines for use in young infants has been complicated by reduced immune responses in this age group due to immunologic immaturity and the immunosuppressive effects of maternal antibodies. Passive immunization with the monoclonal antibody palivizumab (Synagis) has provided about 50% protection to high-risk children (21). These include infants born prematurely and those with congenital conditions. Because the antibody has to be given prophylactically and treatment is very expensive, its use is limited mainly to developed countries. The effect...

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This study evaluated the prevalence and correlates of sexual abuse history among women seeking treatment for severe premenstrual syndrome (PMS). Of 77 women participating in a randomized clinical trial of non-pharmacological treatments for severe PMS, 42 were interviewed regarding their sexual abuse history. The interviewed women were a mean of 38 years old, and most were of European ancestry, heterosexual, married, employed and well-educated. At least one attempted or completed sexual abuse event was reported by 95% of the women, with 81% reporting completed penetration against their will and 85% of these sustaining physical threat or harm. Compared to prior studies of sexually abused women in general populations, these women were abused earlier in life, more frequently and by similar types of offenders. Most of the abused women (65%) were estimated to have post-traumatic stress disorder (PTSD). Most abused women (83%) had never disclosed the abuse to a health practitioner. The findings suggest that a history of sexual abuse, particularly in childhood or adolescence, may be extremely common among women seeking treatment for severe PMS, and that substantial undiagnosed PTSD may also be present in this population. Implications for patient screening and treatment are discussed.

Motor imagery performance is disrupted in patients with knee OA, but is also disrupted in patients with arm pain. Accuracy of left/right judgements is disrupted in a spatially defined manner, raising the important possibility that brain-grounded maps of peripersonal space contribute to the cortical proprioceptive representation.

In painful knee OA, tactile acuity at the knee is decreased, implying disrupted representation of the knee in primary sensory cortex. That TPD and MIP were unrelated in knee OA, but related in back pain, suggests that the relationship between them may vary between chronic pain conditions. That pain was not related to TPD threshold nor MIP suggests against the idea that disrupted cortical representations contribute to the pain of either condition.