Verbal working memory storage and processing deficits in HIV-1 asymptomatic and symptomatic individuals.

BACKGROUND: Verbal working memory (WM), which relies on intact functioning of frontostriatal circuits, has been suggested as a cognitive domain that is preferentially affected in HIV-1 infection. Although several studies have found WM impairments in HIV-1 infected patients, Baddeley's classic WM model has not been studied extensively in this population. METHODS: We used two cognitive neuropsychological approaches to examine verbal WM deficits in 18 HIV-1 seronegative, 16 HIV-1 asymptomatic, and 20 HIV-1 symptomatic patients. First, based on Baddeley's WM model of the Phonological Loop, we used the phonological similarity effect and the irrelevant speech effect to evaluate each individual's phonological store, and the word-length effect and the articulatory suppression effect to evaluate the articulatory control process. Secondly, an individual differences approach, which focuses on the capacity limitation of the WM system and potentially integrates the functions of Baddeley's Central Executive component with the Phonological Loop, was adopted. We evaluated each patient's simultaneous storage and processing of auditory material using the Verbal Memory Span test. RESULTS: The HIV-1 symptomatic individuals, but not the HIV-1 asymptomatic subjects, demonstrated impaired short-term storage of verbal material in the phonological store on Baddeley's measures. Although the HIV-1 asymptomatic and symptomatic subjects demonstrated intact rehearsal of speech-based material in the articulatory control process, both groups demonstrated impairment on the Verbal Memory Span test. CONCLUSIONS: These findings suggest that deficits in simultaneous short-term storage and processing occur during both early and later stages of HIV-1 infection.

Comparison of thalamotomy and pallidotomy for the treatment of dystonia.

OBJECTIVE: Thalamotomy and, more recently, pallidotomy have been used to treat selected patients with intractable dystonia, although few studies have compared the effectiveness of these two surgical procedures. In this study, we compare our results using thalamotomy and pallidotomy to treat patients with different forms of dystonia, and we discuss our results in the context of other published series. METHODS: Thirty-two patients with intractable dystonia underwent thalamotomy (n = 18) or pallidotomy (n = 14). Dystonia was classified according to cause and distribution, and each patient was evaluated postoperatively at two or more time points, using a global outcome scale. RESULTS: Although comparisons are limited by differences between the two surgical groups, including longer follow-up periods for the thalamotomy group, differences in symptom distribution, and more bilateral procedures for the pallidotomy group, patients with primary dystonia who underwent pallidotomies demonstrated significantly better long-term outcomes than did patients who underwent thalamotomies (P = 0.0467). Patients with secondary dystonia experienced more modest improvements after either procedure, with little or no difference in outcomes between the two procedures. CONCLUSION: For patients with primary dystonia, pallidotomy seems to result in better outcomes than does thalamotomy.

Corpora amylacea and heat shock protein 27 in Ammon's horn sclerosis.

Increased numbers of corpora amylacea have been observed in the resected mesial temporal lobe of many patients with complex partial seizures (CPS) and Ammon's horn sclerosis (AHS). Several heat shock proteins (HSPs) are induced by seizures and have been suggested as an etiologic factor in the formation corpora amylacea. We quantified corpora amylacea and HSP27-immunoreactive astrocytes in temporal lobe specimens from patients with CPS (28 AHS; 10 non-AHS) and in 5 autopsy controls. Corpora amylacea were increased in each sector of Ammon's horn in the AHS group, significantly so in CA1 and CA3 (p < 0.0001 and p = 0.0097, respectively), compared with the non-AHS group, although there was considerable variability among the specimens. We found HSP27 to be significantly but nonspecifically increased in the resected temporal lobe specimens from all patients with CPS, regardless of the underlying pathology. HSP27 was not, however, expressed within the corpora amylacea, and did not correlate with the number of corpora amylacea in any of the 9 mesial and lateral temporal lobe areas examined.

Phase I study of adenoviral delivery of the HSV-tk gene and ganciclovir administration in patients with current malignant brain tumors.

Between December 1996 and September 1998, 13 patients with advanced recurrent malignant brain tumors (9 with glioblastoma multiforme, 1 with gliosarcoma, and 3 with anaplastic astrocytoma) were treated with a single intratumoral injection of 2 x 10(9), 2 x 10(10), 2 x 10(11), or 2 x 10(12) vector particles (VP) of a replication-defective adenoviral vector bearing the herpes simplex virus thymidine kinase gene driven by the Rous sarcoma virus promoter (Adv.RSVtk), followed by ganciclovir (GCV) treatment. The VP to infectious unit ratio was 20:1. Our primary objective was to determine the safety of this treatment. Injection of Adv.RSVtk in doses <==2 x 10(11) VP, followed by GCV, was safely tolerated. Patients treated with the highest dose, 2 x 10(12) VP, exhibited central nervous system toxicity with confusion, hyponatremia, and seizures. One patient is living and stable 29.2 months after treatment. Two patients survived >25 months before succumbing to tumor progression. Ten patients died within 10 months of treatment, 9 from tumor progression and 1 with sepsis and endocarditis. Neuropathologic examination of postmortem tissue demonstrated cavitation at the injection site, intratumoral foci of coagulative necrosis, and variable infiltration of the residual tumor with macrophages and lymphocytes.

Up-regulation of base excision repair activity for 8-hydroxy-2'-deoxyguanosine in the mouse brain after forebrain ischemia-reperfusion.

The repair enzyme 8-oxoguanine glycosylase/ apyrimidinic/apurinic lyase (OGG) removes 8-hydroxy-2'deoxyguanosine (oh8dG) in human cells. Our goal was to examine oh8dG-removing activity in the cell nuclei of male C57BL/6 mouse brains treated with either forebrain ischemia-reperfusion (FblR) or sham operations. We found that the OGG activity in nuclear extracts, under the condition in which other nucleases did not destroy the oligodeoxynucleotide duplex, excised oh8dG with the greatest efficiency on the oligodeoxynucleotide duplex containing oh8dG/dC and with less efficiency on the heteroduplex containing oh8dG/dT, oh8dG/dG, or oh8dG/dA. This specificity was the same as for the recombinant type 1 OGG (OGG1) of humans. We observed that the OGG1 peptide and its activity in the mouse brain were significantly increased after 90 min of ischemia and 20-30 min of reperfusion. The increase in the protein level and in the activity of brain OGG1 correlated positively with the elevation of FblR-induced DNA lesions in an indicator gene (the c-fos gene) of the brain. The data suggest a possibility that the OGG1 protein may excise oh8dG in the mouse brain and that the activity of OGG1 may have a functional role in reducing oxidative gene damage in the brain after FblR.

Neuropsychological outcome following unilateral pallidotomy.

Despite the findings of significantly improved motor functioning following pallidotomy for the treatment of Parkinson's disease, the cognitive sequelae following surgery have yet to be clearly defined. With increasing knowledge of the surgery's effect on frontostriatal circuits, the cognitive processes potentially affected by the procedure require further exploration to evaluate fully the efficacy of the treatment. We reviewed 10 studies on the neuropsychological outcome after pallidotomy that were published in peer-reviewed journals. A general agreement exists that pallidotomy is a relatively safe and effective treatment for ameliorating the motor symptoms of Parkinson's disease, with relatively few cognitive changes reported following surgery. However, a number of conceptual and methodological concerns, including diverse selection criteria, small sample sizes and short follow-up periods, limit the interpretation and generalizability of these findings. These concerns are discussed in detail, along with a summary of the current neuropsychological literature, suggested guidelines for the conduct of research and future research directions. The neuropsychological findings are critically reviewed and tabulated by study, cognitive domain and follow-up period, with particular emphasis on hemisphere-specific cognitive changes.

Migrainous stroke causing thalamic infarction and amnesia during treatment with propranolol.

We report a case of migraine-associated ischemic stroke causing amnesia, wherein treatment with propranolol may have been contributory. The possible mechanisms involved in migrainous stroke occurring in association with use of propranolol are discussed.

Disproportionate loss of CA4 parvalbumin-immunoreactive interneurons in patients with Ammon's horn sclerosis.

We studied differences in the number and morphology of parvalbumin-immunoreactive (PV-IR) interneurons in 43 hippocampal specimens from patients with classical Ammon's horn sclerosis (AHS) who underwent anterior temporal lobectomy, as compared with 14 autopsy and non-AHS surgical control specimens. PV-IR neuronal loss in the AHS specimens varied significantly from that expected based on overall AHS-associated pyramidal and granule neuron loss. Most striking was the loss of PV-IR interneurons in CA4 of the AHS specimens, which was 12 times greater than AHS-associated pyramidal neuron loss, and significantly exceeded the PV-IR interneuron loss observed in the other sectors of the hippocampus. In addition, the PV-IR interneurons in the AHS specimens had markedly smaller and less defined cell bodies and shortened and simplified dendritic arbors compared with the PV-IR interneurons in the control specimens. Other differences noted in the AHS specimens included prominent dendritic varicosities; the loss or interruption of a band formed by PV-IR terminals in the dentate gyrus; and the virtual absence of a small, intensely staining PV-IR interneuron with a short, exuberant dendritic arbor that was readily identified in the autopsy specimens. We discuss these findings in relationship to the development of classical AHS and complex partial seizures (CPS).

The clinical significance of extracellular matrix in gangliogliomas.

Based on in vitro studies which demonstrate that collagen IV and laminin inhibit the proliferation and invasiveness of glioma cells, we investigated the clinical significance of these extracellular matrix proteins (ECM) in patients with gangliogliomas, tumors in which ECM is often a prominent feature. Our study compared the relative presence and deposition pattern of collagen IV and laminin in 19 gangliogliomas and in 18 gliomas without ganglion cell differentiation (8 low-grade astrocytomas, 7 anaplastic astrocytomas, and 3 anaplastic mixed gliomas). We also examined whether the presence of collagen IV and laminin correlated with other features often observed in gangliogliomas, including perivascular lymphocytic inflammation, granular bodies, microcalcification, and subarachnoid extension, and whether any of these features were associated with the patient's clinical course. Significant deposition of collagen IV and laminin was found in 9 gangliogliomas (47%), but in none of the other gliomas. The presence of these extracellular proteins in gangliogliomas correlated with both perivascular inflammation (P = 0.003), and involvement of the leptomeninges by tumor (P = 0.008). The duration of symptoms prior to surgical resection was significantly longer for patients whose tumors showed extracellular deposition of collagen IV and laminin than for patients whose tumors lacked deposition of these proteins (mean 13.7 vs 5.1 years; P = 0.02). In addition, the duration of symptoms was significantly longer for patients whose tumors exhibited perivascular inflammation than for patients whose tumors displayed little or no perivascular inflammation (mean 14.8 vs 4.8 years; P = 0.01). These findings suggests that collagen IV and laminin and perivascular inflammation are related to the indolent behavior of gangliogliomas.

Outcome after stereotactic thalamotomy for parkinsonian, essential, and other types of tremor.

A better understanding of the mechanisms underlying movement disorders, coupled with refinements in surgical technique, has led to a resurgence of interest in the surgical treatment of patients with tremor. We retrospectively analyzed the outcomes of 60 patients (62 patient sides) with medically intractable tremor who underwent stereotactic thalamotomy. Of these 60 patients, 42 had Parkinson's disease (of whom 2 patients underwent bilateral surgery for a total of 44 patient sides), 6 had essential tremor, 6 had cerebellar tremor, and 6 had post-traumatic tremor. The patients received follow-up for as long as 13 years (mean, 53.4 mo) after their operations. At the most recent follow-up visit, 86% of the patients with Parkinson's disease, 83% of the patients with essential tremor, 67% of the patients with cerebellar tremor, and 50% of the patients with post-traumatic tremor had cessation of or moderate-to-marked improvement in their contralateral tremor, with a concomitant improvement in function. The mean daily dose of levodopa for those patients preoperatively taking levodopa (n = 35) was reduced by approximately 156 mg at a mean of 53.4 months after thalamotomy. Immediate postoperative complications were common, occurring in 58% of patients. The most common complications were contralateral weakness (34%), dysarthria (29%), and confusion (23%). These complications generally resolved rapidly during the postoperative period.

Outcome after stereotactic thalamotomy for dystonia and hemiballismus.

The outcome after single or staged stereotactic thalamotomies in 17 patients with dystonia and 2 patients with hemiballismus is reviewed. All patients were severely disabled by their movement disorders despite optimal pharmacological therapies. Eight of the patients with dystonia (47%) showed moderate improvement immediately after the procedures. Six of these eight patients maintained their improvement, and two other patients with dystonia improved significantly, during the follow-up period (mean, 37.6 mo). The long-term outcome was better in patients with secondary dystonia (50% moderately or markedly improved at a mean of 41.0 mo) than in patients with primary dystonia (43% moderately or markedly improved at a mean of 32.9 mo). Excellent control was achieved in both of the patients who underwent thalamotomies for hemiballismus.

Disbudding of red deer stag calves to prevent antler growth.

Red deer stag calves aged five to seven months were disbudded with a standard cattle disbudding iron as a means of preventing antler growth and development. Two sizes of iron, one 2.2 cm in diameter and one 1.5 cm in diameter, were compared at disbudding in November or January. Disbudding in November and January with the 2.2 cm iron had success rates of 97 per cent and 92 per cent, respectively. Treatment with the 1.5 cm iron was less effective at both times. There was no significant difference between the liveweights of the treated groups and a non-disbudded control group at turnout in the spring or at slaughter in November when the stags were 16 months of age.

Tyrosine hydroxylase-immunoreactive neurons in the temporal lobe in complex partial seizures.

The anterior mesial portion of the temporal lobe removed from 16 patients who underwent surgery for the treatment of complex partial seizures was found to contain tyrosine hydroxylase-immunoreactive neurons. The distribution of these neurons was correlated with the underlying neuropathological features. Ammon's horn sclerosis was present in 8 patients; a ganglioglioma, in 7 patients; and an infarction in the distribution of the middle cerebral artery, in 1 patient. Tyrosine hydroxylase-immunoreactive neurons were found in Ammon's horn of 6 of the 8 patients with Ammon's horn sclerosis, and in the subiculum and entorhinal cortex of all 8 patients with the same pathology. None of these neurons were found in Ammon's horn of the 7 patients with a ganglioglioma, but were found in the subiculum of 5 of the 7 patients and in entorhinal cortex of all 7 patients. Tyrosine hydroxylase immunoreactivity was also studied in 13 control autopsy specimens. No tyrosine hydroxylase-immunoreactive neurons were found in Ammon's horn or the subiculum of any of the control specimens, but were found in the entorhinal cortex of 6 of the 13 specimens. The tyrosine hydroxylase-immunoreactive neurons in the mesial portion of the temporal lobe of patients with complex partial seizures may contribute to the increased levels of tyrosine hydroxylase found in neurochemical studies of specimens taken at temporal lobectomy.

Diagnosis of pregnancy and prediction of fetal age in red deer by real-time ultrasonic scanning.

Sixteen pregnant red deer hinds were scanned using real-time ultra sound at regular intervals during the first 150 days of pregnancy. In the early stages of pregnancy, an intra-rectal linear array transducer was used but later in pregnancy the hinds were scanned externally with a sector scanner. Pregnancy was determined from 30 days of gestation by intra-rectal scanning, and from 50 days by external scanning. With advancing age the size of the fetus increased, and linear regressions of size on age gave residual standard deviations of 0.508 days for head diameter and 0.506 days for trunk diameter. It is concluded that this technique can be used to determine pregnancy with a high degree of accuracy from 30 days of gestation and to predict calving date from fetal measurements within the range 1.5 cm to 7 cm for head diameter or 0.5 cm to 8 cm for trunk diameter, corresponding to a fetal age range of 35 to 150 days.

Fishing baboons at desert waterholes.

Live fish capture by wild chacma baboons is described. Fish were captured from drying desert pools and then covered with sand to immobilize active fish or to facilitate handling. Possible reasons omnivorous primates elsewhere do not capture live fish are considered.