Recent data suggest that Alzheimer's patients who discontinue treatment with cholinesterase inhibitors have a significantly delayed cognitive decline as compared to patients receiving placebo. Such observations suggest cholinesterase inhibitors to provide a disease-modifying effect as well as symptomatic relief and, moreover, that this benefit remains after drug withdrawal. Consistent with this suggestion, we now demonstrate that chronic administration of tacrine, nefiracetam, and deprenyl, drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability. As a combination of both interventions failed to further increase basal polysialylated cell frequency, complex environment rearing and chronic drug regimens most likely enhanced cognitive performance by the same mechanism(s). These findings suggest that improved memory-associated synaptic plasticity may be the fundamental mechanism underlying the disease modifying action of drugs such as cholinesterase inhibitors. Moreover, the molecular and cellular events underpinning neuroplastic responses are identified as novel targets in the search for interventive drug strategies for the treatment of neurodegenerative and neuropsychiatric disorders. 相似文献
Pulmonary artery aneurysms are rare lesions for which operative management is not frequently undertaken. When operation is indicated, central lesions involving the pulmonary trunk, right main pulmonary artery, or left main pulmonary artery are repaired using cardiopulmonary bypass. Peripheral aneurysms in segmental intrapulmonary arteries have been managed most frequently by lobectomy, but occasionally by aneurysmectomy and pulmonary arterial repair. We used cardiopulmonary bypass for peripheral pulmonary aneurysmectomy in a patient with limited respiratory reserve because he had undergone prior contralateral bilobectomy; this allowed controlled resection while preserving a maximal amount of pulmonary parenchyma. 相似文献
Background: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone.
Methods: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 [mu]m bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4[degrees]C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured.
Results: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. 相似文献
Eleven children with Pseudomonas aeruginosa infection complicating foot puncture wounds were reviewed. Delay in presentation
(mean 2 days) and diagnosis (mean 9 days) due to a paucity of clinical signs of deep infection was characteristic of this
condition. Septic arthritis (5 patients) and osteomyelitis (3 patients) were frequent complications. Treatment involved multiple
surgical debridements and prolonged intravenous antibiotic therapy. The clinical outcome was good although long-term radiographic
changes were common. 相似文献
Dilatation and curettage (D+C) is the most common operation performed in Britain. The liberal use of D+C has been criticised.
The objective of this study was to evaluate the use of outpatient endometrial pipelle biopsy and determine its safety in terms
of detecting abnormalities. Complications and financial costs were also evaluated. Data were reviewed from an active gynaecological
unit from February 1993 to January 1995. A total of 303 D+Cs and 104 endometrial pipelle biopsies were performed in this period.
Nine malignancies were detected by D+C and 1 by pipelle biopsy. A total of 24 and 3 benign abnormalities were detected by
each method respectively. There was a higher complication rate in the D+C group but the failure rate was higher in the endometrial
pipelle biopsy group. The monetary savings over this period is estimated at £20,307. There were no missed malignancies to
our knowledge over the 8 yr period since endometrial pipelle biopsy was introduced to the hospital. 相似文献
The known effects of drugs from a variety of pharmacologic/therapeutic classes on the respiratory system and worldwide regulatory requirements support the need for conducting respiratory evaluations in safety pharmacology. The objective of these studies is to evaluate the potential for drugs to cause secondary pharmacologic or toxicologic effects that influence respiratory function. Changes in respiratory function can result either from alterations in the pumping apparatus that controls the pattern of pulmonary ventilation or from changes in the mechanical properties of the lung that determine the transpulmonary pressures (work) required for lung inflation and deflation. Defects in the pumping apparatus are classified as hypo- or hyperventilation syndromes and are evaluated by examining ventilatory parameters in a conscious animal model. The ventilatory parameters include respiratory rate, tidal volume, minute volume, peak (or mean) inspiratory flow, peak (or mean) expiratory flow, and fractional inspiratory time. Defects in mechanical properties of the lung are classified as obstructive or restrictive disorders and can be evaluated in animal models by performing flow-volume and pressure-volume maneuvers, respectively. The parameters used to detect airway obstruction include peak expiratory flow, forced expiratory flow at 25 and 75% of forced vital capacity, and a timed forced expiratory volume, while the parameters used to detect lung restriction include total lung capacity, inspiratory capacity, functional residual capacity, and compliance. Measurement of dynamic lung resistance and compliance, obtained continuously during tidal breathing, is an alternative method for evaluating obstructive and restrictive disorders, respectively, and is used when the response to drug treatment is expected to be immediate (within minutes post-dose). The species used in the safety pharmacology studies conducted in our laboratory are the same as those used in toxicology studies since pharmacokinetic and toxicologic/pathologic data are available in these species. These data can be used to help select test measurement intervals and doses and to aid in the interpretation of functional change. The techniques and procedures for measuring respiratory function parameters are well established in guinea pigs, rats, and dogs. 相似文献
Of 258 cases of dacryocystorhinostomy performed on children in the period September 1981 to September 1991, 130 were for simple, unresolved congenital nasolacrimal duct obstruction. Other indications for surgery included punctal agenesis, lacrimal fistula, post-traumatic and post-inflammatory canalicular obstruction. Of 177 children without canalicular pathology, 171 (96%) were relieved of symptoms with one operation, without canalicular intubation. Of 81 cases with canalicular disease, 55 of 70 (79%) who underwent DCR plus canalicular intubation, and 10 of 11 who underwent DCR plus Lester-Jones tube, were substantially improved with one operation. No child required peroperative or postoperative blood transfusion. Dacryocystorhinostomy in childhood, in experienced surgical hands, is a safe procedure, achieving relief of symptoms in most cases, particularly in the absence of canalicular disease. 相似文献
Published reports of the effectiveness of preterm birth prevention programs have produced mixed results. Many larger observational studies suggest benefit. The randomized trials, however, suggest no effect on reducing rates of preterm birth in high-risk populations. This article reviews and critiques these reports and suggests areas for further research. 相似文献