Effect of nickel chloride on body temperature and behavioral thermoregulation in the rat

This study was designed to assess the effects of acute nickel chloride administration on behavioral and autonomic thermoregulation in the rat. In one experiment, male rats of the Fischer 344 strain were injected with nickel chloride (IP) at dosages of 0 to 24.0 mg/kg and placed in an environmental chamber maintained at an ambient temperature (Ta) of 10 or 20 degrees C. Colonic temperature was measured 60 min postinjection. Nickel chloride caused a dose-related decrease in colonic temperature, and the hypothermia was accentuated at the cooler Ta. In a second study, rats injected with 0, 6.0, 12.0, or 24.0 mg/kg nickel chloride were placed in a temperature gradient which allowed the rats to select their preferred thermal environment. Nickel chloride at dosages of 12.0 and 24.0 mg/kg caused a significant reduction in the selected Ta. At these dosages the rats were also significantly hypothermic at 60 min postinjection. In a third experiment, whole-body oxygen consumption (i.e., metabolic rate) was measured at Ta's of 10, 20, and 30 degrees C following a 12.0 mg/kg injection of nickel chloride. Nickel chloride caused an initial depression in metabolic rate and hypothermia at Ta's of 10 and 20 degrees C but not at 30 degrees C. In conclusion, (a) nickel chloride affects both behavioral and autonomic control of thermoregulation in the rat and appears to induce a regulated decrease in body temperature and (b) the behavioral thermoregulatory response of the rat is less sensitive to nickel chloride when compared to the mouse.     

Utility of the dexamethasone suppression test in the diagnosis of poststroke depression.

The utility of the dexamethasone suppression test (DST) in the diagnosis of depression was examined in an outpatient sample of 29 stroke patients. Results indicated that the DST's sensitivity was 15%, its specificity was 67%, and its positive predictive value was 48%. These findings suggest that the DST yields no more information than would be gained from random assignment of the diagnosis of depression. Therefore, it is not a useful measure of mood in these patients.     

Role of immediate versus delayed nephrectomy for failed renal transplants

The role of timing of transplant nephrectomy after renal transplantation has not been well defined. This report compares the morbidity, mortality, and hospitalization costs of 37 patients undergoing transplant nephrectomy within 14 days after graft failure and return to dialysis, with 31 patients undergoing delayed transplant nephrectomy (less than 14 days after graft failure and return to dialysis). This analysis revealed that there were no significant (P greater than .05) differences in patient morbidity and mortality between these groups. There was, however, a substantial increase (P less than .05) in the cost of hospitalization in the delayed nephrectomy group. For this reason, we recommend early nephrectomy after renal transplant failure in order to minimize the cost of health care for these patients undergoing failed cadaver donor transplant nephrectomy.     

Molecular determinants of cetuximab efficacy.

PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment.     

Cerebral type 2 astroglia are heterogeneous with respect to their ability to respond to neuroligands linked to calcium mobilization.

Very little information is available concerning the pharmacology of type 2 astroglia. During the past decade it has become apparent that two distinct lineages of astroglial cells can be defined in vitro. These two lineages are commonly referred to as type 1 and type 2 and are distinguished from each other on the basis of their morphological features and antigenic phenotypes. In contrast to type 1 astroglia, very little is known about the pharmacology of type 2 astroglia. The lack of information concerning the responsiveness of these cells stems primarily from difficulties encountered in isolating large numbers of type 2 astroglia free of other cell types. In the present study video- and photometer-based imaging systems were used to monitor the influence of a series of neuroligands on the intracellular calcium levels of individual cerebral type 2 astroglia in order to assess their expression of calcium-mobilizing receptors. The responses of 85 immunocytochemically identified cerebral type 2 astroglia to bradykinin (BK), norepinephrine (NE), histamine (HIST), carbachol (CARB), 2-methyl-thio ATP (2MT-ATP), glutamate (GLUT), and serotonin (5-HT) were analyzed. Approximately 50% of cerebral type 2 astroglia responded to BK, NE, HIST, CARB, and 2MT-ATP whereas only 16% and 9% of the cells responded to GLUT and 5-HT, respectively. The number of neuroligands that increased calcium in individual cells ranged from 0 to 6. These responses are quite similar to those previously demonstrated in cultured cerebral type 1 astroglia. No pattern of receptor co-expression was observed for the different neuroligands tests.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of Major Effects on Mouse Brain Adenosine A1 Receptors of Oral Carbamazepine and Calcium Antagonists

Interaction with adenosine A1 receptors is a possible contributory mechanism to the anticonvulsant effects of carbamazepine (CBZ) and the dihydropyridine calcium antagonists. We measured the binding of [3H]cyclohexyladenosine to adenosine A1 receptors in mouse brain stem, cerebellum, and cortex after oral administration of nifedipine, nimodipine (NMD), and CBZ for 7 days and compared the results with binding in control mice. Equilibrium dissociation constant (Kd) and receptor numbers (Bmax) were calculated using Scatchard and saturation isotherm analyses. Mean Kds (SEM) in control brain stem, cerebellum, and cortex were 2.09 (0.31), 2.39 (0.2), and 3.12 (0.28) nM, respectively. Results of Bmax for the same areas were 188 (26), 280 (24), and 449 (54) fmol/mg protein. Nifedipine (p less than 0.005) and NMD (p less than 0.02) raised the Kd of A1 receptors only in the cerebellum, and CBZ increased cerebellar Bmax (p less than 0.05). These minor effects on A1 receptors in CF1 mice, when given in doses previously shown to have anticonvulsant properties in these animals, do not suggest that alteration in A1 receptor activity is an important mechanism for the anticonvulsant effects of these drugs.     

Intrapersonal, Interpersonal, and Contextual Factors in Engaging in and Responding to Extramarital Involvement

Extramarital involvement (EMI) occurs with high prevalence among couples in clinical and community settings, frequently resulting in considerable distress both to participants and their spouses. The field lacks a synthesized review of this literature. Without such a synthesis, it has been difficult for researchers and clinicians to have an understanding of what is and is not known about EMI. This article reviews the large and scattered EMI literature using a framework that encompasses multiple source domains across the temporal process of engaging in and responding to EMI. In addition, this review delineates conceptual and methodological limitations to previous work in this area and articulates directions for further research.     

Pitfalls in diagnosis of aortic dissection by angiography: Algorithmic approach utilizing CT and MRI

Dissection of the thoracic aorta is a life-threatening event requiring imaging studies to define the level of the tear and the intinmal flap. The “gold standard” has been angiography. This method may fail to demonstrate the dissection, however, due to overlap of the true and false lumens or a very thin flap that is imaged en face rather than tangentially. Computed tomography has a diagnostic accuracy of 95%, but can fail to image the dissection due to technical factors or a thrombosed false hunen. Magnetic resonance imaging requires a hemodynamically stable and cooperative patient. A diagnostic algorithm is proposed for diagnosis of aortic dissection based on renal function and the surgeon's imaging modality preference.