Disrupted amygdala-prefrontal functional connectivity in civilian women with posttraumatic stress disorder

Many features of posttraumatic stress disorder (PTSD) can be linked to exaggerated and dysregulated emotional responses. Central to the neurocircuitry regulating emotion are functional interactions between the amygdala and the ventromedial prefrontal cortex (vmPFC). Findings from human and animal studies suggest that disruption of this circuit predicts individual differences in emotion regulation. However, only a few studies have examined amygdala-vmPFC connectivity in the context of emotional processing in PTSD. The aim of the present research was to investigate the hypothesis that PTSD is associated with disrupted functional connectivity of the amygdala and vmPFC in response to emotional stimuli, extending previous findings by demonstrating such links in an understudied, highly traumatized, civilian population. 40 African-American women with civilian trauma (20 with PTSD and 20 non-PTSD controls) were recruited from a large urban hospital. Participants viewed fearful and neutral face stimuli during functional magnetic resonance imaging (fMRI). Relative to controls, participants with PTSD showed an increased right amygdala response to fearful stimuli (p_corr < .05). Right amygdala activation correlated positively with the severity of hyperarousal symptoms in the PTSD group. Participants with PTSD showed decreased functional connectivity between the right amygdala and left vmPFC (p_corr < .05). The findings are consistent with previous findings showing PTSD is associated with an exaggerated response of amygdala-mediated emotional arousal systems. This is the first study to show that the amygdala response may be accompanied by disruption of an amygdala-vmPFC functional circuit that is hypothesized to be involved in prefrontal cortical regulation of amygdala responsivity.     

Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition

Human leukocyte antigen (HLA) gene polymorphism plays a critical role in protective immunity, disease susceptibility, autoimmunity, and drug hypersensitivity, yet the basis of how HLA polymorphism influences T cell receptor (TCR) recognition is unclear. We examined how a natural micropolymorphism in HLA-B44, an important and large HLA allelic family, affected antigen recognition. T cell–mediated immunity to an Epstein-Barr virus determinant (EENLLDFVRF) is enhanced when HLA-B*4405 was the presenting allotype compared with HLA-B*4402 or HLA-B*4403, each of which differ by just one amino acid. The micropolymorphism in these HLA-B44 allotypes altered the mode of binding and dynamics of the bound viral epitope. The structure of the TCR–HLA-B*4405^EENLLDFVRF complex revealed that peptide flexibility was a critical parameter in enabling preferential engagement with HLA-B*4405 in comparison to HLA-B*4402/03. Accordingly, major histocompatibility complex (MHC) polymorphism can alter the dynamics of the peptide-MHC landscape, resulting in fine-tuning of T cell responses between closely related allotypes.     

Diabetic mastopathy. A clinicopathologic review

Diabetic mastopathy, an uncommon form of lymphocytic mastitis and stromal fibrosis, typically occurs in longstanding type 1 diabetes. Nineteen cases meeting predetermined histopathologic criteria for diabetic mastopathy were correlated as to clinical history and disease recurrence. Physical examination revealed palpable discrete masses or diffuse nodularity, both predominantly in the subareolar region. One nonpalpable lesion was detected incidentally during reduction mammoplasty. All cases contained lymphocytic ductitis and lobulitis with varying degrees of keloidal fibrosis, vasculitis, epithelioid fibroblasts, and lymphoid nodule formation. Single mammary lesions were found in 11 patients with type 1 diabetes, 1 with type 2 diabetes, and 3 without diabetes. Four cases were bilateral (3 patients with type 1 and 1 patient with type 2 diabetes). Six of 19 cases recurred (3 ipsilateral, 2 contralateral, and 1 bilateral). We confirm the histopathologic constellation for diabetic mastopathy. However, we question the specificity of these features because of identical findings in patients with type 2 diabetes and nondiabetic patients. We found diabetic mastopathy in men and women, as a solitary mass or bilateral disease, and recurrence in either breast, sometimes multiple. Recognition of potential recurrence is important because it might spare patients with documented diabetic mastopathy from repeated breast biopsies.     

Education of physicians-in-training can decrease the risk for vascular catheter infection

BACKGROUND: Procedure instruction for physicians-in-training is usually nonstandardized. The authors observed that during insertion of central venous catheters (CVCs), few physicians used full-size sterile drapes (an intervention proven to reduce the risk for CVC-related infection). OBJECTIVE: To improve standardization of infection control practices and techniques during invasive procedures. DESIGN: Nonrandomized pre-post observational trial. SETTING: Six intensive care units and one step-down unit at Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina. PARTICIPANTS: Third-year medical students and physicians completing their first postgraduate year. INTERVENTION: A 1-day course on infection control practices and procedures given in June 1996 and June 1997. MEASUREMENTS: Surveys assessing physician attitudes toward use of sterile techniques during insertion of CVCs were administered during the baseline year and just before, immediately after, and 6 months after the first course. Preintervention and postintervention use of full-size sterile drapes was measured, and surveillance for vascular catheter-related infection was performed. RESULTS: The perceived need for full-size sterile drapes was 22% in the year before the course and 73% 6 months after the course (P < 0.001). The perceived need for small sterile towels at the insertion site decreased reciprocally (P < 0.001). Documented use of full-size sterile drapes increased from 44% to 65% (P < 0.001). The rate of catheter-related infection decreased from 4.51 infections per 1000 patient-days before the first course to 2.92 infections per 1000 patient-days 18 months after the first course (average decrease, 3.23 infections per 1000 patient-days; P < 0.01). The estimated cost savings of this 28% decrease was at least $63000 and may have exceeded $800000. CONCLUSIONS: Standardization of infection control practices through a course is a cost-effective way to decrease related adverse outcomes. If these findings can be reproduced, this approach may serve as a model for physicians-in-training.     

Effectiveness of medical resident education in mechanical ventilation

Specific methods of mechanical ventilation management reduce mortality and lower health care costs. However, in the face of a predicted deficit of intensivists, it is unclear whether residency programs are training internists to provide effective care for patients who require mechanical ventilation. To evaluate these educational outcomes, we administered a validated 19-item case-based test and survey to resident physicians at 31 diverse U.S. internal medicine residency programs nationwide. Of 347 senior residents, 259 (75%) responded. The mean test score was 74% correct (SD, 14%; range, 37 to 100%). Important items representing evidence-based standards of critical care answered incorrectly were as follows: use of appropriate tidal volume in the acute respiratory distress syndrome (48% incorrect), identifying a patient ready for a weaning trial (38% incorrect), and recognizing indication for noninvasive ventilation (27% incorrect). Most accurately identified pneumothorax (86% correct) and increased intrathoracic positive end-expiratory pressure (93% correct). Better scores were associated with "closed" versus "open" intensive care unit organization (76 versus 71% correct, p = 0.001), resident perception of greater versus lesser ventilator knowledge (79 versus 71% correct, p = 0.001), and graduation from a U.S. versus international medical school (75 versus 69% correct, p = 0.033). Although overall training satisfaction correlated strongly with program use of learning objectives (r = 0.89, p < 0.0001), only 46% reported being satisfied with their mechanical ventilation training. We conclude that senior residents may not be gaining essential evidence-based knowledge needed to provide effective care for patients who require mechanical ventilation. Residency programs should emphasize evidence-based learning objectives to guide mechanical ventilation instruction.     

Whiplash injury--a retrospective study on patients seeking compensation

The purpose of this cohort study is to evaluate the objective long-term findings and the final outcome of a population suffering from whiplash-associated disorders (WAD) after rear-end car collision and claiming legal compensation. Eight hundred and sixty-six patients after whiplash injury were followed up on average 32 months post-trauma. All patients had clinical examination and radiographs performed on the day of the accident and at follow up. MRI, CT scan, bone scan, electromyographic (EMG) tests were performed upon request of the treating physician and correlated by the authors with the clinical findings. Cervical pain was the most common complaint (96%). Radiating pain to one side of the upper limbs or the shoulder was also very common (36 and 24%, respectively). Chin to chest test was found to be a strong indicator in differentiating between the less severe (grades 1 and 2) to more severe (grades 3 and 4) WAD patients. In 10% of the patients with normal radiographic findings, degenerative changes were found at follow up. CT scan and MRI did not add to patient diagnosis, except for those patients suffering from degenerative changes and decreased range of motion (RoM). Based on our findings the initial radiograph taken in the emergency room was the best imaging modality and probably the only one needed routinely following whiplash injury. Although this is a special subgroup of patient seeking compensation, the overall prognosis is favorable in all grades of WAD injury and there is no need for further diagnostic expenditures.     

Alpha-2 agonists: can they modify the outcomes in the Postanesthesia Care Unit?

While most patients recover uneventfully from the effects of anesthesia and surgery, for a small percentage of patients the immediate postoperative period can be a period of significant physiological stress. Hence the goal for a Post Anesthesia Care Unit (PACU) is to provide a safe environment for a patient to recover, while avoiding the undesirable side effects of pain, nausea, vomiting and shivering, and to monitor for potentially life threatening hemodynamic and respiratory complications that may require admission into the intensive care unit (ICU). Anesthetic techniques in the operating room are extremely important as these may have significant bearing on the post-operative course. The type of surgery, the patients' co morbid conditions, anticipated extubation and recovery of the patient, as well as the sophistication of the PACU and the expertise of its staff, all influence the choice of anesthetic technique. These agents, however, may themselves contribute to some of the complications and unpleasant events encountered in the PACU. Therefore, evaluation of newer and safer agents, which promote a smoother PACU transition, are warranted. Alpha 2 agonists are increasingly being used as adjuvant therapeutic agents in the perioperative period because of their ability to block the sympathetic stress response, complete with their anesthetic and analgesic sparing properties, lack of respiratory depression and low and predictable side effect profile.