Chronic exposure of rats to cognition enhancing drugs produces a neuroplastic response identical to that obtained by complex environment rearing.

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.     

Peripheral pulmonary artery aneurysm in a patient with limited respiratory reserve: controlled resection using cardiopulmonary bypass

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.     

Zoladex (ICI 118,630): clinical trial of new luteinizing hormone-releasing hormone analog in metastatic prostatic carcinoma

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.     

Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls. A dose-response study

We compared the cognitive and behavioral responses to three intravenous doses of scopolamine (0.1, 0.25, and 0.5 mg) and placebo of ten patients with dementia of the Alzheimer type (DAT) and ten age- and sex-matched elderly control subjects. The patients with DAT showed significant behavioral and cognitive but not physiologic changes at a lower scopolamine dose (0.25 mg) than did the normal elderly controls. Cognitive tests of new learning and semantic knowledge revealed significant impairments at the 0.25-mg scopolamine dose in the patients with DAT, while the responses of the control population were essentially unchanged. Behaviorally, mild euphoria, motor incoordination, and hostility occurred in the patients with DAT but not the controls at the 0.25-mg dose. These differences were unrelated to peripheral physiologic changes produced by the different scopolamine doses. These results indicate that central nervous system functions such as cognition and certain elements of behavior are more sensitive to temporary cholinergic blockade in patients with DAT than in normal age-matched controls. We review implications concerning the status of central cholinergic function in patients with DAT in light of neuropathologically demonstrated cholinergic system lesions in DAT.     

Adding Bupivacaine to High-potassium Cardioplegia Improves Function and Reduces Cellular Damage of Rat Isolated Hearts after Prolonged, Cold Storage

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.     

Lymphoma associated bone marrow necrosis with raised anticardiolipin antibody.

A case of high grade B cell lymphoma presented with bone marrow necrosis, followed by development of extensive marrow fibrosis, the evolution of which was documented by serial magnetic resonance imaging and bone marrow trephine histology. A markedly raised anticardiolipin antibody titre at diagnosis suggests that lymphoma associated antiphospholipid syndrome may have contributed to the aetiology of the bone marrow necrosis.     

Puncture wound related pseudomonas infections of the foot in children

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.     

Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder

In the present study, we address the role of the gene for catechol-O-methyltransferase (COMT), a key modulator of dopaminergic and noradrenergic neurotransmission, in the genetic predisposition to obsessive-compulsive disorder (OCD). We show that a common functional allele of this gene, which results in a 3- to 4-fold reduction in enzyme activity, is significantly associated in a recessive manner with susceptibility to OCD, particularly in males. This association is further supported by psychiatric evaluation of patients who carry microdeletions encompassing the comt gene. The mechanism underlying this sex-selective association remains to be defined and may include a sexual dimorphism in COMT activity, although close linkage with a nearby disease susceptibility locus cannot be excluded at this point.     

Endometrial pipelle biopsy compared to conventional dilatation and curettage

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.