The HK/MBD Questionnaire: Replication and Validation of Distinct Factors in a Nonclinical Sample

Although Tarter et al.'s (1977) HK/MBD questionnaire has been found useful in subtyping populations of clinical alcoholics, its potential utility in nonclinical populations has yet to be determined. The current study examined the family history, personality, and substance use/abuse correlates of Tarter et al.'s HK/MBD questionnaire and factor analytically derived subscales (Alterman and McLellan, 1986) in a nonclinical sample of 580 young, adult males. In addition, a factor analysis of the HK/MBD questionnaire was undertaken to assess the extent to which the factor structure determined on a clinical alcoholic sample replicates in a nonclinical sample. Results indicated that each of the HK/MBD subscales showed relatively unique patterns of correlations with the various personality measures employed suggesting that they are measuring separate constructs. Perhaps of greatest importance, the HK/MBD items that appear to be of greatest relevance for understanding substance use/abuse are those related to antisocial behavior. Finally, the factor structure of the HK/MBD questionnaire in the nonclinical sample was found to be quite similar to the structure obtained in a clinical sample. These results demonstrate the multidimensional structure of the HK/MBD questionnaire and the utility of using the more homogeneous subscales in research with both clinical and nonclinical samples.     

Role of 4-1BB in Allograft Rejection Mediated by CD8+ T Cells

Blockade of traditional costimulatory molecules fails to inhibit rejection in many models where CD8+ T cells are sufficient to mediate rejection. This observation demonstrates that in many settings CD8+ T cells are not dependent upon CD28 or CD154 signals to mediate rejection. 4-1BB (CD137) has been shown to be an important regulatory molecule for CD8+ T cells in a variety of nontransplant models. Here we show that blocking the 4-1BB pathway significantly inhibited rejection of intestinal allografts by CD8+ but not CD4+ T cells. This effect was associated with significantly decreased expression of the genes encoding TNFalpha and secondary lymphoid chemokine (SLC) within the spleens of recipient mice. Disruption of the 4-1BB pathway also impaired the priming of alloantigen-specific CD8+ T cells and the accumulation of recipient dendritic cells within the spleen. These data directly demonstrate an important role for 4-1BB in allograft rejection; particularly rejection mediated by CD8+ T cells. Our data suggest that in addition to providing a direct costimulatory signal to T cells, the 4-1BB pathway may regulate other important steps in the immune response such as the migration of T cells and dendritic cells.     

Neurotoxic effects of MDMA (“ecstasy”) administration to neonatal rats

3,4-Methylenedioxymethamphetamine damages fine serotonergic fibers and nerve terminals in adult organisms. Developing animals seem to be less susceptible to this effect, possibly due to a lack of drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 h after each of twice-daily MDMA (10 mg/kg s.c.) or saline injections administered from postnatal days 1–4. Other drug-treated and control litters were maintained at normothermic temperatures following injection. Changes in forebrain serotonergic innervation were assessed at postnatal day 25 (serotonin transporter binding and serotonin levels), postnatal day 60 (serotonin transporter binding), and 9 months of age (serotonin transporter immunohistochemistry). We also determined the influence of MDMA treatment on apoptotic activity by means of immunohistochemistry for cleaved caspase-3 at postnatal day 5. The hippocampus showed significant MDMA-related reductions in serotonergic markers at postnatal day 25 and postnatal day 60. At 9 months, there was no effect of prior MDMA exposure on serotonin transporter-immunoreactive fiber density in the hippocampus; however, significant reductions in fiber density were observed in two neocortical areas and a hyperinnervation was found in the caudate-putamen and nucleus accumbens shell. MDMA treatment also produced a two-fold increase in the number of cleaved caspase-3-immunoreactive cells in the rostral forebrain and hippocampus. All of these effects were completely independent of pup body temperature. These findings demonstrate that neonatal MDMA administration exposure stimulates apoptotic cell death in various forebrain areas and also leads to a long-term reorganization of the forebrain serotonergic innervation. Consequently, offspring of MDMA-using women may be at heightened risk for abnormal neural and behavioral development.     

Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis.

BACKGROUND: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) are medical emergencies associated with psychotropic administration. Differentiation and treatment can be complex, especially when features of both syndromes are present and the patient has taken both serotonergic and neuroleptic agents. METHOD: Case analysis of a poly-drug overdose (venlafaxine, topiramate, divalproex sodium, risperidone, and carbamazepine) presenting with mixed SS/NMS features and whose clinical management suggests a practical algorithm for treatment of undifferentiated SS/NMS in critical care settings. RESULTS: The suggested algorithm includes: 1) Supportive care and withdrawal of all potentially offending agents; 2) Laboratory evaluation with prompt initiation of treatment for both disorders--cyproheptadine for SS and dantrolene for NMS; 3) Do not use bromocriptine (contraindicated in SS) or chlorpromazine (contraindicated in NMS) initially; 4) Add bromocriptine when clinical presentation becomes consistent with NMS (SS can be prolonged if serotonergic agent has long half-life). CONCLUSIONS: Prompt and appropriate identification and intervention are essential for successful management of SS and NMS. The suggested treatment algorithm allows for specific treatment of both disorders and avoids potentially exacerbating either one. The algorithm derived from this case could serve as both a practical guideline and impetus for further investigation in light of increasing psychotropic co-administration.     

Comparison of Asymmetry in Cerebral Blood Flow Between Brain Hemispheres Using Digital Subtraction Angiography

BACKGROUND AND PURPOSE: Recently, endovascular techniques have gained significant therapeutic potential for both treatment and prevention of stroke. Cerebral angiography, which is an essential component of these procedures, has been used to provide morphological information regarding condition of blood vessels. In this study, we propose to determine the possibility of acquiring information regarding cerebral blood flow (CBF) in addition to morphologic information from data routinely available during angiography. METHODS: Digital subtraction angiography sequences were obtained for eight patients having occlusive disease in internal carotid artery (ICA) territories. Two regions-of-interest (ROIs) corresponding to the two brain hemispheres on AP view were delineated. For each image, the average pixel value within each ROI was calculated and used to generate time-density curves. Indices obtained from each curve were compared with each other and with the results obtained from the single photon emission computed tomography (SPECT) studies performed a pre- or postangiography procedure. RESULTS: Comparison between ICA stenosis and cerebral perfusion measurements revealed that cerebral perfusion deficit can be independent of arterial occlusive disease. The indices obtained from the time-density curves exhibit a correlating trend with the results from SPECT studies. However, lack of sufficient sample data prevented any meaningful statistical analysis to be conducted. CONCLUSIONS: We have developed a technique for utilizing the angiographic data for the important task of routinely and easily measuring CBF. Availability of CBF measurements during cerebral angiography may favorably impact upon the appropriate use of endovascular procedures and potentially contribute to the reduction of morbidity and mortality associated with stroke.     

Cognitive impairment of acute onset in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) study: occurrence, correlates, and outcomes.

OBJECTIVE: Having demonstrated that dementia of acute onset represents a distinct syndrome with distinct outcomes, the authors investigated whether similar attributes describe cognitive impairment of acute onset (CIAO). METHODS: The authors conducted a secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition study. RESULTS: Ninety patients met our criteria for CIAO. Compared with cognitive impairment of gradual onset, CIAO was associated with vascular features (odds ratio [OR]: 12.3, 95% confidence interval [CI]: 3.2-47.9), dementias other than Alzheimer disease (OR: 6.5, 95% CI: 2.1-20.8), and decreased survival (hazard ratio: 2.8, 95% CI: 1.6-4.6). CONCLUSIONS: Patients with CIAO are clinically identifiable and have distinct outcomes.     

Drug mixture which improves survival of ischemic rabbit epigastric skin flaps

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl₂ (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes. © 1994 Wiley-Liss, Inc.