Effects of nicotine on hippocampal and cingulate activity during smooth pursuit eye movement in schizophrenia.

BACKGROUND: Abnormal smooth pursuit eye movement (SPEM) in schizophrenic patients is a well known phenomenon, but the neurophysiological mechanisms underlying the deficit are unknown. Nicotine temporarily improves SPEM and has been associated with reduced hippocampal hemodynamic activity in schizophrenics. Nicotine's effect on brain activity in control subjects performing SPEM has not been studied. The purpose of this work was to determine if nicotine differentially affects brain activity in schizophrenic and control subjects during pursuit eye tracking. METHODS: 16 subjects with schizophrenia and 16 control subjects underwent functional MR imaging during SPEM after receiving placebo or nicotine gum. Four brain regions were analyzed for main effects of group, drug, and interactions: hippocampus, cingulate gyrus, frontal eye fields, and area MT. RESULTS: Nicotine reduced hippocampal activity in both groups, but the effect was greater in control subjects. A group by drug interaction was observed in the anterior cingulate gyrus, where nicotine decreased activity in control subjects and increased activity in schizophrenic subjects. There were no significant effects of group, drug, or interactions in frontal eye fields or area MT. CONCLUSIONS: Nicotine may improve SPEM performance in people with schizophrenia through cholinergic stimulation of the hippocampus and cingulate gyrus. Potential mechanisms include improved inhibitory function and attention.     

Decrement of the skin conductance response to repeated volitional inspiration.

OBJECTIVE: To examine response decrement of the recently reported inspiratory skin conductance response (SCR) [Lim CL, Seto-Poon M, Clouston PD, Morris JG. Sudomotor nerve conduction velocity and central processing time of the skin conductance response. Clin Neurophysiol 2003;114:2172-80]. METHODS: Twelve healthy adult volunteers performed 3 tasks (A) a control task of maintaining tidal breathing and then two randomized tasks, (B) a deep inspiration to a target oral pressure and (C) tapping with a finger. Each task was performed 30 times on cue every 20s in 3 runs with 5 min of rest between runs. The SCR, oral pressure, airflow, inspired volume and cue signal were recorded continuously and analysed offline. SCR amplitude was logarithmically transformed and then statistically analysed, using a linear mixed effects model, as a function of run number, trial number and absolute error between target and actual oral pressures. RESULTS: Inspiratory efforts elicited exponentially decreasing SCR amplitude with increasing trial number during each run (P < 0.0001). After adjusting for trial number, the mean SCR amplitude of the second and the third run were, respectively, 24.2 (95% CI (0.175, 0.336), P < 0.001) and 14.4% (95% CI (0.104, 0.200), P < 0.001) of the first run amplitude. CONCLUSIONS: Volitional deep inspiration reliably activates an SCR that exhibits response decrement with repetition, which may be habituation. SIGNIFICANCE: The volitional inspiratory SCR may assist in the assessment of sympathetic autonomic status in patients with peripheral afferent neuropathy.     

Laparoscopic nephron-sparing surgery for the small exophytic renal mass.

OBJECTIVES: Nephron-sparing surgery has emerged as the treatment of choice for the incidentally detected small renal mass, especially those less than 4 cm in size. We describe our technique and experience with the laparoscopic excision of these lesions. METHODS: Between June 2001 and October 2003, 20 patients underwent nephron-sparing surgery at our institution. Twenty-one laparoscopic partial nephrectomy procedures were performed. All tumors were detected incidentally by cross-sectional imaging. All patients had a solid renal mass or a complex cystic renal mass of Bosniak category III or greater. All solid tumors were exophytic and less than 4cm in diameter. Both transperitoneal and retroperitoneal approaches were used. Hemostasis was achieved without hilar control in 20 of the 21 cases. RESULTS: Twenty renal units were approached transperitoneally, and 1 retroperitoneally. Mean tumor size was 2.6 cm (range, 1.2 to 4). Mean estimated blood loss was 211 mL (range, 50 to 500), and mean operative time was 165 minutes. Pathology revealed renal cell carcinoma in 14 (70%). No intraoperative complications occurred. Two patients required blood transfusions postoperatively. CONCLUSION: Carefully selected patients with small, exophytic renal masses can safely undergo laparoscopic excision. When achievable, this procedure can be a more logical alternative to ablative techniques for the minimally invasive management of such lesions.     

Impact of major co-morbidities on mortality and complications after gastric bypass

BACKGROUND: We hypothesized that major co-morbidities affect survival and complications after gastric bypass. METHODS: A total of 1465 patients undergoing laparoscopic and open gastric bypass between 1995 and 2002 were studied. Patients with a body mass index >or= 35 kg/m(2) and major co-morbidities (group 1, n = 1045) were compared with patients with a body mass index >or= 40 kg/m(2) with minor/no co-morbidities (group 2, n = 420). RESULTS: Group 1 patients were older (43 versus 36 years, P < 0.001) and had a greater BMI (53 versus 50 kg/m(2), P < 0.001). Early postoperative complications were greater in group 1 than in group 2 and included leaks (4.1% versus 1.2%, P < 0.0032) and wound infections (3.9% versus 1.4%, P < 0.0133). Procedure-related mortality in the series was 1.7%. Mortality was 10-fold greater in group 1 (2.3% versus 0.2%, P < 0.0032). The incidence of small bowel obstruction, incisional hernia, and pulmonary embolism was similar in the two groups. Excess weight loss was significantly greater in group 2 (68% versus 62%, P < 0.001) at 1 year. Resolution of group 1 co-morbidities was great, including hypertension in 62%, diabetes in 75%, venous stasis disease in 96%, and pseudotumor cerebri in 98%. CONCLUSION: Outcomes analysis of obesity surgery requires risk stratification. The very low mortality rates in published studies are likely explained by surgical treatment of low-risk patients with minor co-morbidities, such as those seen in group 2. However, despite the increased perioperative risk, the group 1 patients (with major co-morbidities) demonstrated dramatic resolution of their co-morbid conditions, justifying the decision to go forward with surgery. The data support a radical change in treatment philosophy in which morbidly obese individuals should be offered bariatric surgery before major co-morbid conditions develop as a strategy to decrease the operative risk.     

Effects of gastric bypass procedures on bone mineral density,calcium, parathyroid hormone,and vitamin d

Weight loss after gastric bypass procedures has been well studied, but the long-term metabolic sequelae are not known. Data on bone mineral density (BMD), calcium, parathyroid hormone, and vitamin D were collected preoperatively and at yearly intervals after gastric bypass procedures. A total of 230 patients underwent preoperative BMD scans. Fifteen patients were osteopenic preoperatively, and three patients subsequently developed osteopenia postoperatively within the first year. No patient had or developed osteoporosis. At 1 year, total forearm BMD decreased by 0.55% (n = 91; P = .03) and radius BMD had increased overall by 1.85% (n = 23; P = .008); both total hip and lumbar spine BMD decreased by 9.27% (n = 22; P < .001) and 4.53% (n = 31; P < .001), respectively. By the second postoperative year, BMD in the total forearm had decreased an additional 3.62% (n = 14; P<.001), whereas radius BMD remained unchanged. Although total hip and lumbar spine BMD significantly decreased at 1 year, by year 2 both total hip and lumbar spine BMD only slightly decreased and were not significantly different from before the operation. Serum calcium decreased from 9.8 mg/dL to 9.2 during the first year (not significant [NS]) and then to 8.8 (NS) by the second year. Parathyroid hormone increased from 59.7 pg/mL (nl 10-65 pg/mL) preoperatively to 63.1 during year 1 (NS) and continued to increase to 64.7 by year 2 (NS). No difference was noted among levels of 25-hydroxy vitamin D preoperatively (25.2 ng/mL; nl 10-65 ng/mL), at 1 year (34.4), and at 2 years (35.4). Our data indicate that bone loss is highest in the first year after gastric bypass with stabilization, and that, in some cases, there is an increase in bone density after the first year. Presented at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–18, 2005 (oral presentation).     

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.     

Assessing the capacity to make everyday decisions: a guide for clinicians and an agenda for future research.

Assessing the capacity of patients to make decisions about their functional problems has substantial ethical, clinical, and financial implications. The growing population of older adults with cognitive impairment either in the community or in long-term care and medical facilities increase the importance of adequately assessing this capacity. This review examines the current approaches to making this assessment, demonstrates how they are incomplete, and considers potential approaches for improving these evaluations. Future research should develop and validate methods to identify patients with impaired capacity to make everyday decisions. These data will supplement functional, cognitive, and medical assessments.     

Cerebral lipid deposition in aged apolipoprotein-E-deficient mice.

To assess the influence of age and diet on cerebral pathology in mice lacking apolipoprotein E (apoE), four male apoE knockout mice (epsilon -/-), and five male wild-type (epsilon +/+) littermate controls were placed on a high-fat/high-cholesterol diet for 7 weeks beginning at 17 months of age. All four aged knockout mice developed xanthomatous lesions in the brain consisting mostly of crystalline cholesterol clefts, lipid globules, and foam cells. Smaller xanthomas were confined mainly to the choroid plexus and ventral fornix in the roof of the third ventricle, occasionally extending subpially along the choroidal fissure and into the adjacent parenchyma. More advanced xanthomas disrupted adjoining neural tissue in the fornix, hippocampus, and dorsal diencephalon; in one case, over 60% of one telencephalic hemisphere, including nearly the entire neocortex, was obliterated by the lesion. No xanthomas were observed in aged wild-type controls fed the high-fat/high-cholesterol diet. Brains from 42 additional animals, fed only conventional chow, were examined; 3 of 15 aged (15- to 23-month-old) apoE knockout mice developed small choroidal xanthomas. In contrast, no lesions were observed in five young (2- to 4-month-old) apoE knockout mice or in any wild-type controls between the ages of 2 and 23 months. Our findings indicate that disorders of lipid metabolism can induce significant pathological changes in the central nervous system of aged apoE knockout mice, particularly those on a high-fat/high-cholesterol diet. It may be fruitful to seek potential interactions between genetic factors and diet in modulating the risk of Alzheimer's disease and other neurodegenerative disorders in aged humans.