ABSTRACT
Spinal p38 mitogen activated (MAP) kinase plays a key role in chronic pain behavior. However, clinical development of p38 inhibitors has been hindered by significant toxicity. To evaluate alternative strategies of p38 regulation, we determined if known upstream activators of p38 (mitogen activated kinase kinase [MKK] 3 and MKK6), are involved in development and maintenance of pain and spinal p38 phosphorylation. Acute pain behaviors were not altered in MKK3 or MKK6 deficient mice. The phase 2 formalin response was delayed in MKK3-/- mice, but unchanged in magnitude, while the response remained normal in MKK6-/- mice. More striking, late formalin allodynia (3-18 days post-injection) was prominent in wild type and MKK6-/- mice, but was delayed for several days in MKK3-/- mice. In wild type, but not MKK3-/- mice, intraplantar formalin elicited increases in ipsilateral spinal MKK3/6 phosphorylation acutely and again at 9 days postinjection. Phosphorylation of MKK3/6 correlated with phase 2 formalin behavior. Wild type (WT) and MKK3-/- mice both expressed increases in spinal phosphorylated p38, however in WT mice this response began several days earlier, and was of higher magnitude and duration than in MKK3-/- mice. This phosphorylation correlated with the late allodynia. Phosphorylated MKK3/6 was detected only in astrocytes, given that phosphorylated p38 (P-p38) is usually not seen in astrocytes this argues for astrocytic release of soluble mediators that affect p38 phosphorylation in microglia. Taking these data together, MKK3, but not MKK6, is necessary for normal development of chronic pain behavior and phosphorylation of spinal p38.
Subject(s)
MAP Kinase Kinase 3/physiology , Pain/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Acute Disease , Animals , Astrocytes/enzymology , Chronic Disease , Enzyme Activation , Formaldehyde , MAP Kinase Kinase 3/genetics , MAP Kinase Kinase 6/genetics , MAP Kinase Kinase 6/physiology , Mice , Mice, Knockout , Pain/physiopathology , Pain Measurement , Phosphorylation , Physical Stimulation , Spinal Cord/metabolismABSTRACT
Despite the increasing attention to caregivers of HIV patients, no previous study has systematically investigated the effects of the relationship quality between an HIV patient and their caregiver. The present study assessed 176 dyads consisting of an HIV-infected patient and their self-identified 'caregiver'. Relationship quality was measured by the Family Assessment Device (FAD). Dependent measures included the Beck Depression Inventory, SF-36 Physical Functioning Scale, Caregiver Strain Index and 4-day HIV treatment adherence. A substantial proportion of HIV patient-caregiver dyads reported difficulties in their relationships (17-66% depending upon FAD scale). The level of relationship difficulties was not strongly related to the type of patient-caregiver relationship. However, the quality of the HIV patient-caregiver relationship was significantly associated (p<0.05) with caregiver depression and burden as well as HIV patient depression, physical functioning and HIV medication adherence, even when the potential effects of length of HIV infection and social support were controlled. These results suggest that relationship quality is impaired in many patient-caregiver dyads and is uniquely associated with levels of depression, caregiver burden and treatment adherence.
Subject(s)
Caregivers/psychology , Depressive Disorder/etiology , HIV Infections/psychology , Interpersonal Relations , Adult , Antiretroviral Therapy, Highly Active/psychology , Cost of Illness , HIV Infections/therapy , Humans , Male , Patient Compliance , Stress, Psychological/therapyABSTRACT
Vietnam combat veterans with current posttraumatic stress disorder (PTSD), with other Axis-I disorders, or with no Axis-I disorders completed a series of tasks designed to elucidate the psychophysiological parameters of information-processing in PTSD. These tasks included a modified Stroop procedure (MSP), a standard Stroop procedure, a recognition memory task, and a threat rating task. Physiological responses were recorded throughout the study. Our data supported several predictions derived from information-processing models of PTSD. PTSD subjects exhibited greater MSP interference to high threat words than both comparison groups, and a liberal response bias toward recognizing military-related words. PTSD symptoms and threat reactions contributed to MSP interference effects for high-threat words after controlling for medications, depression, and baseline physiological activity.
Subject(s)
Arousal , Combat Disorders/psychology , Mental Recall , Veterans/psychology , Adult , Arousal/physiology , Color Perception , Combat Disorders/physiopathology , Combat Disorders/rehabilitation , Comorbidity , Discrimination Learning/physiology , Humans , Male , Mental Recall/physiology , Middle Aged , Perceptual Defense , Psychophysiology , Reaction Time , Semantics , Verbal Learning/physiology , VietnamABSTRACT
A scale for assessing war-zone-related posttraumatic stress disorder (WZ-PTSD scale) was derived from the Symptom Checklist-90-R by identifying items that best discriminated Vietnam theater veterans with and without PTSD (N = 202). The 25-item WZ-PTSD scale had excellent internal consistency, and signal detection analyses revealed that its diagnostic utility was comparable to or exceeded that of several established PTSD scales and measures of global distress. In a cross-validation sample (N = 99), the diagnostic utility of the WZ-PTSD scale was stable, whereas other PTSD scales performed more poorly. The WZ-PTSD scale appears to be a valuable new measure of PTSD that can be particularly useful in archival data sets or in any situation where other PTSD measures are not available.
Subject(s)
Psychological Tests , Stress Disorders, Post-Traumatic/diagnosis , Warfare , Adult , Humans , Male , Middle Aged , Psychometrics , Stress Disorders, Post-Traumatic/psychologyABSTRACT
Disorders of extreme stress (DES), previously referred to as disorders of extreme stress not otherwise specified and/or complex posttraumatic stress disorder, is a proposed diagnosis designed to describe the symptom presentation of those repeatedly exposed to traumatic stressors. Little is known, however, about the applicability of DES to combat veterans. We clinically assessed combat veterans for the presence or absence of DES in order to provide descriptive clinical information about the severity and patterns of endorsement of DES symptoms among combat veterans. Results indicate that DES is relevant to veterans and the implications of these results for both diagnoses and treatment are discussed.
Subject(s)
Combat Disorders/diagnosis , Veterans/psychology , Combat Disorders/classification , Combat Disorders/psychology , Factor Analysis, Statistical , Humans , Male , Middle Aged , Psychiatric Status Rating Scales/statistics & numerical data , Psychometrics , Severity of Illness Index , Terminology as TopicABSTRACT
Osteomyelitis, both acute and chronic, is difficult to treat and often does not respond to conventional methods of therapy. Hyperbaric oxygen can be used as an adjunctive treatment in chronic refractory osteomyelitis after all other types of therapy have proved unsuccessful or response is slow. Risk factors and cost must be considered when deciding whether to use hyperbaric oxygen in conjunction with other methods of therapy.
