Blockade of epinephrine priming of the cerebral auditory evoked response by cortical cholinergic deafferentation

The present study tested hypotheses derived from a neurobehavioral model of anxiety that posits an important role of the basal forebrain cholinergic system in the cortical processing of anxiety-associated stimuli and contexts. We hypothesized that visceral afferent activity induced by systemic administration of epinephrine would enhance the processing of auditory stimuli as evidenced by the cerebral auditory evoked response. We further predicted that selective lesions of the basal forebrain cortical cholinergic projection system would disrupt this processing, and would further block the effects of epinephrine. Results confirmed these hypotheses. Epinephrine was found to enhance the amplitude of the P70 component of the auditory evoked response in rats. Selective lesions of the basal forebrain corticopetal cholinergic projection, by intrabasalis infusions of 192 IgG saporin, delayed and reduced the amplitude of the P70 component, and blocked the potentiating effects of epinephrine on the auditory evoked response. The present results are consistent with the view that visceral afferent input may modulate cortical processing of sensory signals via the basal forebrain cholinergic system. These considerations emphasize the potential importance of ascending, bottom-up modulation of processing by telencephalic circuits that may impact on a wide range of behavioral functions.     

Disruption of kinesin II function using a dominant negative-acting transgene in Xenopus laevis rods results in photoreceptor degeneration

PURPOSE: Kinesin II is a motor protein that moves on microtubules and whose importance in ciliary and flagellar transport has been well documented. In the current study, the role of kinesin II in rod photoreceptors was examined by expressing a dominant negative-acting transgene that disrupts kinesin II function in Xenopus laevis rods of transgenic tadpoles. METHODS: A previously characterized dominant negative-acting kinesin II transgene tagged with enhanced green fluorescent protein (EGFP) driven by the Xenopus rod opsin promoter was used to make Xenopus transgenic tadpoles to disrupt kinesin II function specifically in rod photoreceptors. Transgenic tadpole retinas were examined to ascertain transgene expression pattern and morphologic phenotype. Rod-to-cone ratios were determined in experimental and control retinas. RESULTS: Visualized by its EGFP tag, the kinesin II transgene was expressed in rods in a mosaic pattern in the retina. Subcellular localization of transgenic kinesin II was similar to that of endogenous kinesin II subunit photoreceptor expression-that is, it was localized to the connecting cilium, inner segment, and synapse. However, in kinesin II transgene-expressing animals, fluorescence was transient. Ocular fluorescence was lost 6 days after its first detection. The disappearance of fluorescence was due to degeneration of rods expressing the transgene. Retinas of 7- to 9-day old kinesin II transgenic tadpoles had significantly fewer rods than did control retinas. CONCLUSIONS: The observation that rod degeneration is produced by expression of a dominant negative-acting kinesin II transgene in Xenopus rods is consistent with previous studies in mice, suggesting that kinesin II function is required for photoreceptor survival.     

Transitions in American hospitals: the necessary reshaping is taking place. "Turnaround" processes in organizations

American hospitals are reshaping and redefining the way they are managed and the way they provide care. More American healthcare organizations are stating that they are in a turnaround situation. Although there are no definite guidelines or criteria that place an organization in a turnaround situation, there are certain circumstances that are frequently present. These circumstances most often include a somewhat sudden change from a financially favorable situation. This may include revenue lost and/or increases in cost from operations, decreases in volumes that are most positive and favorable to the organization, sudden changes in key management or board representation, and sudden loss of key managers and staff needed for the successful operation of the organization. Any one of these factors or several can place an organization in such jeopardy that quick and decisive actions must be taken to ensure survival and future success. The specific conditions of a turnaround and the effectiveness of quick and decisive actions are critical for the survival of an organization or a system.     

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

PURPOSE: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy. This study tests the tolerance and antineoplastic activity of sequential infusions of partially HLA-matched allogeneic blood mononuclear cells (obtained from relatives) when administered outside of the context of a hematopoietic stem-cell transplantation. The cells are irradiated to prevent graft-versus-host disease. PATIENTS AND METHODS: Fifteen patients with relapsed or refractory malignancies for which no standard therapy was available were enrolled onto a clinical trial designed to assess the tolerability and antineoplastic effects of irradiated partially HLA-matched blood mononuclear cells obtained from relatives. RESULTS: There was disease regression in three patients with metastatic renal cell carcinoma during treatment. There was disease progression in six patients with metastatic renal cell carcinoma and two patients with metastatic melanoma during treatment. There was no change in disease state in several other patients. CONCLUSION: Irradiated allogeneic blood mononuclear cells administered outside the context of hematopoietic stem-cell transplantation may induce disease responses in patients with relapsed or refractory malignancies. Transfusion of irradiated allogeneic blood mononuclear cells should be developed further as a novel therapeutic antineoplastic approach.     

Clinical and Biochemical Evaluation of Patients with Hirsutism

Summary: Patients with moderate to severe hirsutism presenting over an 18-month period to an endocrine clinic were assessed by clinical evaluation and hormone measurements. Hair growth rate was estimated by a photographic technique and the severity of hirsutism graded using an objective scale. Of 43 patients, 9 had polycystic ovaries and the remainder were considered to have idiopathic hirsutism. The most severely affected group had significantly increased hair growth rates compared with less clinically affected subjects, and 47% of this group showed objective features of virilization. However, apart from a significantly higher 24-hr urine 17-ketosteroid excretion all other hormonal patterns were not significantly different between severely and mildly affected patients. Serum levels of testosterone (T), sex hormone-binding globulin (SHBG), free T (calculated from T and SHBG values), and androstenedione (A) were abnormal in 44%, 51%, 60% and 60% of patients respectively, whereas plasma levels of the specific adrenal androgen DHAS were increased in 40% of patients. There was an overlap between patients with elevated hormone levels, although isolated elevation of T, A or DHAS were seen in 9%, 19% and 3% of patients respectively. In 19% of patients all serum androgen measurements were normal. Gonadotrophin levels were significantly lower in the more severely affected group. Thus androgen levels in patients with idiopathic hirsutism or polycystic ovaries, show considerable overlap with measurements in normal subjects, and elevated plasma androgens may be of adrenal (DHAS) or combined adrenal/ovarian (T, A) origin.     

Absorbance of amniotic fluid at 650 nm as a fetal lung maturity test: A comparison with the lecithin/sphingomyelin ratio and tests for disaturated phosphatidylcholine and phosphatidylglycerol

We compared absorbance of amniotic fluid at 650 nm (A₆₅₀) against the lecithin/sphingomyelin ratio, the quantity of disaturated phosphatidylcholine, and the presence or absence of phosphatidylglycerol in 374 uncontaminated amniotic fluid samples. In addition, we studied these measures of fetal lung maturity in 80 pregnancies where neonatal outcomes were known. Statistical analysis revealed a significant association between increasing absorbance and biochemical indices of lung maturation. Our results indicate that A₆₅₀ of amniotic fluid is useful as a measure of lung maturity but that the greatest utility may be for samples with either low absorbance (<0.10) or high absorbance (>0.20). Because of large false positive and false negative values between these two absorbances, other lung maturity estimates should be used when absorbances fall within this range. Therefore, A₆₅₀ may be most useful as a screen or as part of a battery of lung maturity estimates. We are exploring these possibilities as a means of providing better fetal lung maturity estimates.