Nitric oxide synthase in acute alteration of nitric oxide levels after subarachnoid hemorrhage

OBJECTIVE: Subarachnoid hemorrhage (SAH) is associated with acute decreases and subsequent recovery of cerebral nitric oxide (NO) levels, but the mechanisms of these alterations are not known. In this study, we measured NO synthase (NOS) protein and kinetics to determine its involvement in the alterations of cerebral NO levels after SAH. METHODS: The endovascular rat model of SAH was used. The number of NOS-1 (neuronal) and NOS-2 (inducible)-positive cells (0-96 h) was determined by counting immunoreactive cells in 8-microm cryostat sections. The tissue content of active NOS and its kinetic parameters were studied with an enzymatic l-citrulline assay. RESULTS: The number of NOS-1-positive cells increased between 1 and 3 hours after SAH, decreased to and below control values at 6 and 72 hours after SAH, and increased to control values 96 hours after SAH. The number of NOS-2-positive cells increased 1 hour after SAH, decreased to control values at 24 hours, and increased above control values 96 hours after SAH. The Michaelis-Menten kinetic parameters (V(max), K(m), slope) of NOS remained unchanged at 10 and 90 minutes after SAH. CONCLUSION: NOS-1 and -2 proteins undergo a triphasic alteration after SAH, whereas the amount of active NOS and its kinetic parameters remain unchanged during the first 90 minutes after SAH. Depletion of NOS is not involved in the acute alterations of cerebral NO levels after SAH.     

Body Dysmorphic Disorder: Suggestions for Detection and Treatment in a Surgical Dermatology Practice

BACKGROUND: Body dysmorphic disorder is a relatively common condition in patients seeking elective surgery. Little has been written, however, in the dermatologic surgery literature about body dysmorphic disorder, where proper recognition and management of this disorder is needed during this time of increased demand for aesthetic dermatologic surgery. OBJECTIVE: The objective was to review the prevalence, demographics, clinical features, treatment approaches, and referral suggestions for patients with body dysmorphic disorder in an attempt to facilitate care of such patients in a general dermatologic surgical practice. METHODS: We reviewed the dermatologic, cosmetic surgical, and psychiatric literature regarding body dysmorphic disorder and related disorders. RESULTS: Body dysmorphic disorder is observed in 6% to 15% of dermatologic and cosmetic surgery patients and in 2% of the general population. Surgical treatment of patients with body dysmorphic disorder typically leads to no change or worsening of symptoms in the majority of patients. The use of screening questionnaires and observation for hallmark features are helpful for clinicians in managing patients with body dysmorphic disorder. Psychiatric referral is desirable, because cognitive behavioral therapy and pharmacologic intervention with selective serotonin reuptake inhibitors are often efficacious. CONCLUSIONS: Body dysmorphic disorder is often underdiagnosed and suboptimal management is common. Effective treatment consists of behavioral and pharmacologic intervention. Use of the Dufresne Body Dysmorphic Disorder Questionnaire appears to be useful as a screening tool in an outpatient setting, and awareness of clinical features of body dysmorphic disorder in the dermatologic surgical setting may spare patients significant morbidity while allowing surgical dermatologists to manage their patients and practices more effectively.     

Outcomes of interlaminar and transforminal spinal injections

Epidural spinal injections can be administered via a translaminar or transforaminal route, depending on the clinical scenario. When it is more desirable to target a specific nerve root, a transforaminal approach is typically used, and when the target is more diffuse, a translaminar method is chosen. Both are commonly used and can be utilized similarly in the lumbar or cervical spine. However, it is essential that the clinician understand the risks and benefits of these injections. In the lumbar spine, both translaminar epidural steroid injections (TLESI) and transforaminal epidural steroid injections (TFESI) have been shown to provide up to 6 months of pain relief, though long-term benefits are less reliable. In the cervical spine, translaminar injections may provide longer relief and have a lower complication rate than cervical transforaminal injections. Proper technique is essential to minimize the rate of these rare but occasionally severe complications.     

Prognostic value of diffusion tensor imaging parameters in severe traumatic brain injury

Diffusion tensor imaging (DTI) has recently emerged as a useful tool for assessing traumatic brain injury (TBI). In this study, the prognostic value of the relationship between DTI measures and the clinical status of severe TBI patients, both at the time of magnetic resonance imaging (MRI), and their discharge to acute TBI rehabilitation, was assessed. Patients (n=59) admitted to the trauma center with severe closed head injuries were retrospectively evaluated after approval from the institution's institutional review board, to determine the prognostic value of DTI measures. The relationship of DTI measures, including apparent diffusion coefficient (ADC), fractional anisotropy (FA), axial (λ‖) and radial diffusivity (λ⊥) from the whole brain white matter, internal capsule, genu, splenium, and body of the corpus callosum, were compared with neurological status at MRI and at discharge to acute TBI rehabilitation. Whole brain white matter averages of ADC, λ‖, and λ⊥, and their coefficient of variation (CV) were significantly correlated with the Glasgow Coma Scale (GCS) score on the day of MRI. The average λ‖ was significantly correlated with GCS scores on the day of MRI in all measured brain regions. Outcomes were associated with whole brain white matter averages of ADC and λ‖, and the CVs of FA, ADC, λ‖, and λ⊥; and the averages and CVs of FA and λ‖ in all corpus callosum regions. The inclusion of regional and global DTI measures improved the accuracy of prognostic models, when adjusted for admission GCS score and age (p<0.05). Whole brain white matter and regional DTI measures are sensitive markers of TBI, and correlate with neurological status both at MRI and discharge to rehabilitation. The addition of DTI measures adjusted for age, gender, and admission GCS score significantly improved prognostic models.     

Dimethylamino Parthenolide Enhances the Inhibitory Effects of Gemcitabine in Human Pancreatic Cancer Cells

Introduction

Gemcitabine is standard treatment for pancreatic cancer but has limited clinical benefit due to chemoresistance. Nuclear factor-kappaB (NF-??B) can promote chemoresistance and is therefore an attractive therapeutic target. We hypothesize that NF-??B suppression with the novel, orally bioavailable inhibitor dimethylamino parthenolide (DMAPT) will sensitize pancreatic cancer cells to gemcitabine.

Methods

BxPC-3, PANC-1, and MIA PaCa-2 human pancreatic cancer cell lines were treated with gemcitabine and/or DMAPT. Effects on the NF-??B pathway were determined by electrophoretic mobility shift assay, ELISA, or Western blot. Proliferation and apoptosis were measured by cell counts and ELISA, respectively. The effect of gemcitabine in vivo was determined using a MIA PaCa-2 heterotopic xenograft model.

Results

Gemcitabine induced NF-??B activity in BxPC-3, PANC-1, and MIA PaCa-2 cells and decreased the level of the NF-??B inhibitor I??B?? in BxPC-3 and PANC-1 cells. DMAPT prevented the gemcitabine-induced activation of NF-??B. The combination of DMAPT/gemcitabine inhibited pancreatic cancer cell growth more than either agent alone. Gemcitabine also induced intratumoral NF-??B activity in vivo.

Conclusions

DMAPT enhanced the anti-proliferative effects of gemcitabine in association with NF-??B suppression in pancreatic cancer cells in vitro. Furthermore, gemcitabine induced NF-??B activity in vivo, thus supporting the evaluation of NF-??B-targeted agents to complement gemcitabine-based therapies.     

Intracranial hypotension producing reversible coma: a systematic review, including three new cases

Intracranial hypotension is a disorder of CSF hypovolemia due to iatrogenic or spontaneous spinal CSF leakage. Rarely, positional headaches may progress to coma, with frequent misdiagnosis. The authors review reported cases of verified intracranial hypotension-associated coma, including 3 previously unpublished cases, totaling 29. Most patients presented with headache prior to neurological deterioration, with positional symptoms elicited in almost half. Eight patients had recently undergone a spinal procedure such as lumbar drainage. Diagnostic workup almost always began with a head CT scan. Subdural collections were present in 86%; however, intracranial hypotension was frequently unrecognized as the underlying cause. Twelve patients underwent one or more procedures to evacuate the collections, sometimes with transiently improved mental status. However, no patient experienced lasting neurological improvement after subdural fluid evacuation alone, and some deteriorated further. Intracranial hypotension was diagnosed in most patients via MRI studies, which were often obtained due to failure to improve after subdural hematoma (SDH) evacuation. Once the diagnosis of intracranial hypotension was made, placement of epidural blood patches was curative in 85% of patients. Twenty-seven patients (93%) experienced favorable outcomes after diagnosis and treatment; 1 patient died, and 1 patient had a morbid outcome secondary to duret hemorrhages. The literature review revealed that numerous additional patients with clinical histories consistent with intracranial hypotension but no radiological confirmation developed SDH following a spinal procedure. Several such patients experienced poor outcomes, and there were multiple deaths. To facilitate recognition of this treatable but potentially life-threatening condition, the authors propose criteria that should prompt intracranial hypotension workup in the comatose patient and present a stepwise management algorithm to guide the appropriate diagnosis and treatment of these patients.