Sparing of attentional relative to mnemonic function in a subgroup of patients with dementia of the Alzheimer type

Patients with dementia of the Alzheimer type (DAT) received two tests of visual selective attention, together with tests of spatial and visual recognition memory and visuospatial conditional learning previously used to show deficits early in the course of DAT. One set of attentional tests compared visual discrimination learning along intra- and extra-dimensional shifts, using a "total change" design. In the 12 DAT patients capable of attempting the extra-dimensional shift (subgroup 1), performance was equivalent to that of controls. This subgroup was also unimpaired at simple and compound discrimination learning and reversal and an intra-dimensional shift. They were as accurate as controls on a visual search task requiring matching of stimuli on two dimensions with variable numbers of alternatives, but were significantly impaired in the tests of recognition memory and learning. By contrast, the other 13 patients showed marked impairments in the attentional tasks. This subgroup was also significantly worse than subgroup 1 in performance on the visual recognition and conditional learning tasks, and showed greater severity on most of the clinical ratings of dementia. The sparing of attentional shifting in patients early in the course of DAT is contrasted with the impairments previously described in patients with Parkinson's disease with only mild or absent memory loss. The implications of this double dissociation of deficits for understanding the neural bases of the cognitive deficits in these two neurodegenerative diseases are discussed and their significance for the staging of DAT is considered.     

Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease

This report describes the anaesthetic management of a women with a term gestation, Von Hippel Lindau disease (VHLD), and a phaeochromocytoma, scheduled for a combined phaeochromocytoma resection and Caesarean section. Von Hippel Lindau disease is characterized by diffuse haemangioblastomas of the central nervous system (CNS) and viscera. It is also associated with phaeochromocytomas and renal cell carcinomas. Patients frequently have asymptomatic spinal cord and intracranial pathology. The patient and her fetus presented a challenge because of the anaesthetic restrictions imposed by VHLD, and her pregnancy. She was also at risk of developing malignant hypertension from the phaeochromocytoma. The patient was not a candidate for regional anaesthesia because of the possibility of spinal cord haemangioblastomas. She had received adrenergic blockade with phentolamine (total 30 mg a day) and propranolol (total 40 mg a day) since the 27th wk of gestation in order to control hypertension secondary to the phaeochromocytoma. General anaesthesia was administered with aggressive management of hypertension with adrenergic blockers (labetalol 1.0 mg · kg^?1 and esmolol 0.75 mg · kg^?1) and sodium nitroprusside 1.5 μg · kg^?1 (total). Before delivery of the baby, opioids, which could have resulted in a fetus with CNS depression, were avoided. After delivery, opioids (sufentanil 0.4 ng · kg^?1 hr^?1) were used to limit the use of inhalational anaesthesia which may contribute to uterine atony. Postoperative pain was managed with an intravenous narcotic infusion. Both patients had uneventful postoperative courses.     

Cisplatin-induced reductions in renal functional reserve uncovered by unilateral nephrectomy: an experimental study in the pig

Summary Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to90, 120 and 150 mg/m²) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [^{99 m}Tc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically,and GRF and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with 2mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S₁ portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GRF and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was <50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically silent until exposure to an additional nephrotoxic insult.This study was supported by the Cancer Research Campaign     

Mesoaccumbens dopamine-opiate interactions in the control over behaviour by a conditioned reinforcer

These experiments examined the role of dopamine-opiate interactions in the ventral tegmental area (VTA) and nucleus accumbens in the mediation of reinforcement-related behaviour. It has been shown previously that opiates induce a dopamine-dependent increase in locomotor activity in rats when infused into the VTA, and a dopamine-independent hyperactivity when infused into the nucleus accumbens. The present study investigated the generality and significance of these two findings, by examining dopamine-opiate interactions in the control over behaviour exerted by a conditioned reinforcer (CR), an arbitrary stimulus which gains control by association with primary reinforcement. Rats were trained to associate a light/noise stimulus with sucrose reinforcement, and the efficacy of the CR in controlling behaviour was assessed by measuring its ability to support a new lever pressing response. Responding on one lever (CR lever) produced the CR, responding on the other lever had no programmed consequences. In experiment 1, intra-accumbens infusions ofd-amphetamine (10 µg), the D₁ dopamine receptor agonist SKF-38393 (0.1 µg), the D₂ dopamine receptor agonist LY-171555 (quinpirole; 0.1 µg) or the opiate receptor agonist [d-Ala²]-methionine enkephalinamide (DALA; 1 µg) selectively increased responding on the CR lever. Infusion with DALA intra-VTA had no effect. However, pretreatment with DALA intra-VTA (10 × 1 µg/day) subsequently reduced the selectivity of the response to infusions intra-accumbens withd-amphetamine or SKF-38393, and blocked the response to LY-171555 or DALA. Pretreatment also shifted to the right the dose-response function for DALA intra-accumbens. In experiment 2, intra-accumbens infusions ofd-amphetamine, SKF-38393, LY-171555 or DALA again increased responding on the CR lever only. Pretreatment with intra-accumbensd-amphetamine (5 × 1 µg/day) reduced the selectivity of the response subsequently tod-amphetamine, and blocked the response to SKF-38393, LY-171555 or DALA. In experiment 3, intra-accumbens infusions of the -opiate receptor agonist [d-Ala²,N-Me-Phe⁴,Gly⁵-ol]-enkephalin (0.003–0.1 µg), or the -opiate receptor agonist [d-Pen^2, 5]-enkephalin (0.03–1 µg) enhanced selectively responding on the CR lever. Thus, the dopamine-dependent locomotor-stimulant properties of intra-VTA infusions of opiates are associated with impaired conditioned reinforcer efficacy. Finally, repeated stimulation of the mesoaccumbens dopamine pathway may compromise the dopamine-independence of the opiate system within the nucleus accumbens.