Functional correlates of verbal memory deficits emerging during nicotine withdrawal in abstinent adolescent cannabis users.

BACKGROUND: Cannabis remains the most widely used illicit substance by adolescents and is typically consumed by this population in the context of ongoing tobacco use. Human studies have shown that both cannabis and tobacco exert effects on cognitive function; however, little is known about possible interacting effects of these drugs on brain function and cognition during adolescent development. METHODS: Verbal learning and memory were assessed in 20 adolescent users of tobacco and cannabis and 25 adolescent tobacco users with minimal history of cannabis use. Functional magnetic resonance imaging was used to examine brain function and functional connectivity while a subset of these subjects performed a verbal working memory task. RESULTS: Delayed recall of verbal stimuli deteriorated during nicotine withdrawal among cannabis users but not among comparison subjects. During high verbal working memory load, nicotine withdrawal selectively increased task-related activation of posterior cortical regions and was associated with disruption of frontoparietal connectivity in adolescent cannabis users relative to comparison subjects. CONCLUSIONS: These observations suggest that cannabis use during adolescent development may disrupt neurocircuitry supporting verbal memory formation and that deficits associated with disruption of these neurocircuits are unmasked during nicotine withdrawal.     

Transplantation for myocarditis: a controversy revisited.

Myocarditis is a major cause of end-stage heart failure and is responsible for up to 10% of cases of idiopathic dilated cardiomyopathy (IDC). Worldwide, approximately 45% of all heart transplants are performed for IDC and up to 8% for myocarditis. Early reports suggested that survival after transplantation for myocarditis was poor and patients had an increased risk of rejection. More recently, larger case series suggest that overall survival after transplantation for myocarditis is similar to survival after transplantation for other causes. However, certain disorders, including cardiac sarcoidosis and giant cell myocarditis (GCM), require heightened surveillance for post-transplantation disease recurrence. We present the case of a 42-year-old man with recurrence of GCM 8 years after transplantation and review the literature on the role of cardiac transplantation for patients with myocarditis.     

Anaesthesia for neurosurgery in the sitting position.

The sitting position offers many advantages in terms of surgical access for posterior fossa and posterior cervical spine surgery. However, these advantages must be balanced against the risks which include venous and paradoxical arterial air embolism, cerebral and myocardial ischaemia secondary to hypotension, and complications of the positioning itself. These are largely in the domain of the neuroanaesthetist. In this paper, therefore, we will review the advantages, disadvantages and management of complications of the sitting position, from the neuroanaesthetist's perspective.     

The versatile rhomboid (Limberg) flap

The rhomboid (Limberg) flap can be used to close defects almost anywhere on the body. It is versatile in that a random pattern flap can be raised from any one or all corners of the rhomboid. The defect is filled with tissue of the same thickness and colour, and with good vascularity. The present paper demonstrates the versatility of the rhomboid flap.     

Disposition of tacrolimus in isolated perfused rat liver: influence of troleandomycin, cyclosporine, and gg918.

The disposition of tacrolimus and the influence of cyclosporine, troleandomycin, and GF120918 (GG918, or N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)-ethyl]-phenyl]-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamine) on its hepatic disposition were examined in the isolated perfused rat liver. Livers from groups of rats were perfused in a recirculatory manner following a bolus dose of tacrolimus (100 microg), a substrate for P-glycoprotein (P-gp) and CYP3A, or with felodipine (200 microg), a substrate only for CYP3A. Perfusions of each substrate were also examined in groups of rats in the presence of the inhibitors: troleandomycin (20 microM, CYP3A inhibitor), GG918 (1 microM, P-gp inhibitor), or cyclosporine (10 microM, CYP3A and P-gp inhibitor). In all experiments, perfusate and bile were collected for 60 min. Tacrolimus, felodipine, and their primary metabolites were determined in perfusate and bile by liquid chromatography/tandem mass spectrometry. The area under the curve (AUC) from 0 to 30 min was determined. For the dual CYP3A and P-gp substrate, tacrolimus, AUC +/- S.D. was decreased from control (2,260 +/- 430 ng. min/ml) by GG918 (1,730 +/- 270 ng. min/ml, P < 0.05) and was increased by troleandomycin (5,200 +/- 2,470 ng. min/ml, P < 0.05) and cyclosporine (4,390 +/- 2,080 ng. min/ml, P < 0.05). For the exclusive CYP3A substrate, felodipine, AUC was unchanged from control by GG918 but increased by troleandomycin and cyclosporine. It is concluded that GG918 increased the hepatic exposure of tacrolimus by inhibiting the canalicular P-gp transport, whereas GG918 has no effect on hepatic disposition of felodipine. These results support our hypothesis that the hepatic metabolic clearance of a dual substrate will be increased by inhibiting the efflux transporter.     

Detection of chromosomal alterations affecting the 1cen-1q12 region in irradiated granulocytes and lymphocytes by multicolour FISH with tandem DNA probes

A multicolour tandem labelling fluorescence in situ hybridization(FISH) procedure was used to compare the frequencies of radiation-inducedchromosome breakage and hyperdiploidy of chromosome 1 occurringin non-cultured granulocytes and Go lymphocytes with those observedin cultured metaphase and interphase lymphocytes. Whole blood,obtained from healthy male donors, was exposed in vitro to 0,100, 200, 300 and 400 cGy of ionizing radiation from a ¹³⁷Cssource. Aliquots containing granulocytes and Go lymphocytesfrom each dose were treated immediately with hypotonic KCl onice and harvested. Cells were hybridized with     

Effects of the antimigraine compound zolmitriptan ('Zomig') on psychomotor performance alone and in combination with diazepam in healthy volunteers

Zolmitriptan (Zomig^TM) is a 5HT_1B/1D agonist which has the ability to cross the intact blood-brain barrier to access central as well as peripheral receptors. Because of the potential for central nervous system side effects, this randomized, double-blind, placebo-controlled, 6-period crossover study evaluated the effects of 2.5 and 5 mg doses of zolmitriptan on psychomotor performance and investigated any pharmacodynamic or pharmacokinetic interaction with diazepam. Twelve healthy volunteers received the following "treatments" as single doses: zolmitriptan 2.5 mg, zolmitriptan 5 mg, diazepam 10 mg, zolmitriptan 2.5 mg+diazepam 10 mg, zolmitriptan 5 mg+diazepam 10 mg and placebo. Pre-dose and at 1, 4, 8, and 24 h post-dose, the following validated battery of psychomotor tests was performed: Bond-Lader visual analogue scales (calmness, contentedness, and alertness factors), critical flicker fusion test, choice reaction time (recognition, motor, and total reaction times), finger-tapping test, number cancellation test and digit symbol substitution test. Plasma concentrations of zolmitriptan, its active metabolite, and diazepam and its active metabolites were measured at the same timepoints. Zolmitriptan 2.5 and 5 mg had no effect on psychomotor function when given alone. In contrast, diazepam 10 mg had profound effects, consistent with its sedative properties, but there was no synergism on concomitant administration of either dose of zolmitriptan. Plasma concentrations of zolmitriptan, diazepam, and their respective active metabolites were similar when the two drugs were given alone or in combination.     

Hodgkin disease: contributions of chest CT in the initial staging evaluation

Chest radiographs and chest computed tomography (CT) scans were compared in 203 patients with newly diagnosed Hodgkin disease. The incidence of positive findings was tabulated from six intrathoracic lymph node groups, lung parenchyma, pericardium, pleura, and chest wall. The discordant cases were assessed to determine impact on clinical management. The CT scans provided additional evidence of disease involvement, ranging from 0% to 15% at each of the designated anatomic sites. Treatment was altered in 9.4% of all patients (19 of 203), including 13.8% (nine of 65) of those undergoing radiation therapy alone and 8.2% (ten of 122) of those undergoing combined-modality treatment. We conclude that routine chest CT examinations are valuable in the clinical management of those patients for whom radiation therapy is planned.