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Biomedical subjects

P Sandor

Publications and source records attributed to P Sandor.

At least 37 records · Page 2Linked to original sources
PubMed1997

Gastrointestinal lymphomas in patients with AIDS.

Non-Hodgkin-lymphoma (NHL)-most frequently high grade B-cell lymphoma-occurs in 5-10% of individuals with HIV-infection. The gastrointestinal tract (GIT) is the most frequent extranodal site of the disease. The optimal therapy for HIV-related lymphoma remains a matter of controversy. In a retrospective analysis we found gastrointestinal lymphoma in ten of 306 HIV-infected patients (3.3%) with a median CD4-count of 92/microliter at time of diagnosis. Median survival for the chemotherapy treatment group was 15 months. The high incidence of gastrointestinal NHL prompted us to commence a prospective survey on diagnostic procedures, therapy and outcome of patients with HIV-infection and gastrointestinal symptoms. 93 of 341 HIV-infected patients with gastrointestinal symptoms were examined by endoscopy. In selected patients we used in addition endoscopic ultrasound (EUS) for visualization and staging before and after chemotherapy. NHL of the GIT was detected in seven of 93 endoscopically examined patients (7.5%). All patients were treated with CHOP initially. Mean survival time was ten months, mean CD4-count at diagnosis 193/microliter (range 0-417). Our results indicate that the diagnosis of gastrointestinal lymphoma should be considered in any HIV-infected patient presenting with unexplained gastrointestinal symptoms. In this group of patients NHL was detected in 7.5% of cases. The use of EUS improves the staging procedure before therapy. Treatment with CHOP resulted in relatively high remission rates and was associated with a low rate of treatment-induced myelosuppression.

Adult↗
PubMed1996

No evidence for a major gene effect of the dopamine D4 receptor gene in the susceptibility to Gilles de la Tourette syndrome in five Canadian families.

Gilles de la Tourette Syndrome (TS) is neuropsychiatric disorder characterized by both motor and vocal tics affecting approximately 1/10,000 females and 1/2000 males. Because of the success of neuroleptics and other agents interacting with the dopaminergic system in the suppression of tics, a defect in the dopamine system has been hypothesized in the etiology of TS. In this paper we test the hypothesis that the dopamine D4 receptor (DRD4) is linked to the genetic susceptibility to TS in five families. We tested three polymorphisms in the DRD4 gene and a polymorphism in the closely linked locus, tyrosine hydroxylase (TH). We found no evidence for linkage of DRD4 or TH to TS using an autosomal dominant model with reduced penetrance or using non-parametric methods. The presence of a mutation that results in a truncated non-functional D4 receptor protein was also tested for, but was not observed in these families.

Canada↗
PubMed1996

Remoxipride in the treatment of levodopa-induced psychosis.

Levodopa-induced psychotic symptoms frequently complicate the management of patients with Parkinson's disease (PD). We examined the efficacy and tolerability of a novel antipsychotic, remoxipride, in this population. This was a 7-week, open-label pilot evaluation of patients with moderate to severe PD and levodopa-induced psychotic symptoms of at least 2 months' duration. The patients were recruited at the Movement Disorders Clinic, The Toronto Hospital, a tertiary referral center. After 1 week of baseline observation, the patients received remoxipride, 25 mg, three times a day orally, with the dose increasing by 25 to 50 mg each week as tolerated. The outcome measures included the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impressions (CGI) scale, and the United Parkinson's Disease Rating Scale. Adverse symptoms were elicited by an open-ended questionnaire and a symptom checklist. Six men and three women aged 69.3 +/- 9 years received remoxipride 147 +/- 57 mg/day. Total BPRS score decreased modestly in eight of nine subjects, and there was a statistically significant improvement of mental status as indicated by the CGI scale score, which decreased from 3.8 +/- 0.4 at baseline to 2.4 +/- 1.3 at last rating (p < 0.05; Wilcoxon signed rank test). The motor performance deteriorated somewhat in two subjects, whereas the rest showed no appreciable change. The most common adverse effects included tremor, rigidity, akathisia, and hypersalivation. Remoxipride treatment reduced psychotic symptoms in eight of nine subjects while having no appreciable effect on the parkinsonian status of seven of nine subjects.

Aged↗
PubMed1996

Limited usefulness of electroconvulsive therapy in progressive supranuclear palsy.

OBJECTIVE: To perform a pilot study of the efficacy of electroconvulsive therapy (ECT) in improving motor function in progressive supranuclear palsy (PSP). BACKGROUND: Few effective treatments are available for PSP. Tricyclic antidepressants and idazoxan (which increases central norepinephrine) have shown benefits in small clinical trials, and dopaminergic therapy has been reported, anecdotally, to be beneficial. ECT exerts effects on all of these transmitter systems, possibly by inducing increased receptor sensitivity. We postulated that by sensitizing dopaminergic and noradrenergic systems, ECT might improve motor symptoms of PSP. METHODS: Five patients with clinically diagnosed PSP were evaluated before and after nine ECT treatments using the Unified Parkinson's Disease Rating Scale (UPDRS) and an apomorphine challenge to assess dopaminergic responsiveness. RESULTS: No permanent side effects were seen. Transient side effects included confusion in all patients, worsening of speech and swallowing in two, and dystonic posturing of the foot in one. One patient experienced a dramatic response (going from a completely wheelchair-bound state to independent ambulation), two were mildly improved, and two were unchanged. CONCLUSIONS: Although ECT may ameliorate motor symptoms in PSP, the long hospitalization and the significant treatment-induced confusion limit the usefulness of this technique.

Aged↗
PubMed1995

Relationship between dopamine release in nucleus accumbens and place preference induced by substance P injected into the nucleus basalis magnocellularis region.

The activity of the neurotransmitter dopamine in the nucleus accumbens is considered to be an important element in the central processing of reinforcement. Unilateral administration of the neurokinin substance P into the area of the nucleus basalis magnocellularis of rats was found to be reinforcing, as assessed by the conditioned place preference paradigm. Simultaneous in vivo microdialysis showed that administration of substance P into the area of the nucleus basalis magnocellularis could increase extracellular concentrations of dopamine in the contralateral nucleus accumbens. Only those animals in which the administration of substance P induced this increase in dopamine levels acquired place preference. Furthermore, the changes in extracellular dopamine levels after substance P administration had a bimodal time course with an acute increase (to about 160% of baseline) during the first hour after injection, with a low (to 120-130%) and enduring increase occurring thereafter. Interestingly, during this second increase there were indications for positive correlations with the degree of place preference induced by substance P. Further positive correlations with place preference were found in the levels of the serotonergic metabolite 5-hydroxyindoleacetic acid. In contrast to dopamine, these were observed ipsi- and contralateral to the side of substance P administration. By combining the methods of in vivo microdialysis and conditioned place preference it was shown that the reinforcing effect induced by unilateral substance P injection in the nucleus basalis magnocellularis is related to dopaminergic (and possibly serotonergic) mechanisms in the nucleus accumbens.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1995

Self-concept and self-consciousness in adults with Tourette syndrome.

The hypothesis that adults with Tourette Syndrome (TS) have a lower level of self-concept and a higher level of public self-consciousness and social anxiety than the general population was examined. Ninety-eight suitable adults responded to a letter distributed to the members of the Tourette Syndrome Foundation of Canada. The findings indicated that the group with TS and high obsessive-compulsive symptoms, but not TS alone, had significantly lower self-concepts than the general population. Both males and females with TS and high obsessive-compulsive symptoms scored higher on social anxiety than the general population, but no differences in public self-consciousness were found. The results of this study argue that people with TS alone do not have impaired self-concepts or social anxiety, but both of these disorders tend to be present among those who suffer from both TS and significant obsessive-compulsive symptoms.

Adaptation, Psychological↗
PubMed1995

Clinical management of Tourette's syndrome and associated disorders.

OBJECTIVE: To review the clinical management of Tourette's syndrome (TS) and the associated disorders, namely obsessive-compulsive disorder (OCD) and attention deficit hyperactivity disorder (ADHD) with an emphasis on the pharmacologic intervention strategies. METHOD: English language literature on the pharmacologic management of TS and the associated disorders published between 1985 and 1994 was critically reviewed. RESULTS: Pharmacologic management was placed in the context of the overall clinical management. Pharmacologic strategies for treatment of TS, OCD and ADHD were organized according to the therapeutic agent class. CONCLUSIONS: The treatment of TS and its associated disorders requires the application of the full range of psychiatric skills to achieve a favourable outcome.

Adolescent↗
PubMed1995

Linkage studies on Gilles de la Tourette syndrome: what is the strategy of choice?

For a linkage study it is important to ascertain family material that is sufficiently informative. The statistical power of a linkage sample can be determined via computer simulation. For complex traits uncertain parameters such as incomplete penetrance, frequency of phenocopies, gene frequency and variable expression have to be taken into account. One can either include only the most severe phenotype in the analysis or apply multiple linkage tests for a gradually broadened disease phenotype. Gilles de la Tourette syndrome (GTS) is a chronic neurological disorder characterized by multiple, intermittent motor and vocal tics. Segregation analyses suggest that GTS and milder phenotypes are caused by a single dominant gene. We report here the results of an extensive simulation study on a large set of families. We compared the effectiveness of linkage tests with only the GTS phenotype versus multiple tests that included various milder phenotypes and different gene frequencies. The scenario of multiple tests yielded superior power. Our results show that computer simulation can indicate the strategy of choice in linkage studies of multiple, complex phenotypes.

Chromosome Mapping↗
PubMed1995

REM changes in narcolepsy with selegiline.

The purpose of this study was to establish the effects of selegiline HCl on sleep parameters in narcolepsy and to contrast these effects with the effects of methylphenidate. Eleven subjects with narcolepsy were studied drug-free and while receiving selegiline (15-30 mg/day) by polysomnography. The methylphenidate-treated group consisted of 11 age-matched subjects with narcolepsy. On overnight polysomnography, compared to pretreatment values, selegiline treatment resulted in a significant increase in rapid eye movement (REM) latency (138.1 +/- 62.8 vs. 48.7 +/- 42.3 minutes, p < 0.05) and sleep stage changes per hour. The increase in REM latency in subjects treated with methylphenidate was marginally significant (116.9 +/- 78.3 vs. 54.3 +/- 23.7 minutes, p = 0.054). Maintenance of wakefulness testing during treatment revealed the methylphenidate-treated group to be significantly more alert than the selegiline-treated group (18.4 +/- 1.9 vs. 9.4 +/- 4.8 minutes, p < 0.001); a retrospective survey of subjects treated with selegiline found that a majority reported clinical improvement with selegiline treatment. These results suggest that selegiline should be considered for further investigation as a treatment for narcolepsy.

Adult↗
PubMed1995

Remoxipride in Parkinson's disease: differential response in patients with dyskinesias fluctuations versus psychosis.

Remoxipride is a novel substituted benzamide that more effectively blocks mesolimbic than striatal D2 dopamine receptors. We used remoxipride in the management of nine patients with Parkinson's disease (PD) who were experiencing visual hallucinations due to dopaminergic therapy. Remoxipride was begun in a dose of 25 mg three times daily and gradually increased to 75-225 mg/d (mean 161 mg). The psychiatric status improved in eight patients. Little or no change in the severity of parkinsonism was noted in five, a mild increase in two, and a moderate increase in two. Because one patient with moderately severe levodopa-induced dyskinesias experienced a reduction in the abnormal movements without a substantial increase in parkinsonism, we began a trial of remoxipride for disabling peak-dose dyskinesias. The trial was abandoned after every one of the first four patients entered experienced an immediate, severe, and prolonged increase in off periods with single 10- to 25-mg doses. This striking differential response to an atypical neuroleptic with weak striatal D2 antagonist properties indicates that different states of postsynaptic dopamine receptor sensitivity or synaptic dopamine levels may be associated with various disease- and treatment-related problems found in late-stage PD.

Aged↗
PubMed1994

Sleep patterns in depression and anxiety: theory and pharmacological effects.

Sleep is invariably disrupted in patients who have depression and in patients with anxiety disorders. Depression and anxiety frequently coexist and are associated with disturbances in various neurotransmitters. The authors explore the relationship between sleep and the two disorders as well as the effects of antidepressants and anxiolytics on sleep architecture. The effects on sleep of various neurotransmitter systems implicated in depression and anxiety are outlined. Lastly, various theoretical models are proposed to account for the above mentioned phenomena and further directions for research are suggested.

Anti-Anxiety Agents↗
PubMed1994

Major role of nitric oxide in the mediation of regional CO2 responsiveness of the cerebral and spinal cord vessels of the cat.

The role of nitric oxide (NO) in the mediation of cerebrovascular CO2 responsiveness was studied in 10 distinct brain and spinal cord regions of the anesthetized, ventilated, temperature-controlled, normoxic cat. Regional CBF was measured with 15-micron radiolabeled microspheres in hypocapnic, normocapnic, and hypercapnic conditions. CO2 responsiveness of each region was determined from the equation of the best-fit regression lines to the obtained flow values. The effect of altered endothelial and/or neuronal NO synthesis on CO2 responsiveness was studied following either selective blockade of the NO synthase enzyme by N omega-nitro-L-arginine methyl ester (L-NAME; 3 or 30 mg/kg i.v.) or simultaneous administration of L-NAME (3 mg/kg i.v.) and a large dose of the NO precursor L-arginine (30 mg/kg i.v.). Blockade of NO synthesis by 30 mg/kg L-NAME resulted in a significant reduction of the steady-state regional blood flow values and in an almost complete abolition of the CO2 sensitivity in each region studied. Changes of the basal flow values as well as the reduction of the regional CO2 sensitivity were dose dependent. Hypothalamic, sensorimotor cortical, and cerebellar regions were the areas most sensitive to the NO blockade. Impaired CO2 responsiveness following NO synthase inhibition, however, was reversed in these regions by simultaneous administration of a large dose of intravenously injected L-arginine. These findings suggest a major role of nitric oxide in the mediation of regional cerebrovascular CO2 responsiveness in cats.

Amino Acid Oxidoreductases↗
PubMed1993

"Signing tics"--insights into the pathophysiology of symptoms in Tourette's syndrome.

We describe the case of a young woman with Tourette's syndrome who incorporated sign language into her tic behavior. Sign language was used in complex "phonic tics" such as swearing, echoing what others said, or repeating what she said, read, or thought. We suggest the descriptive terms "coprolaliopraxia," "echolaliopraxia," and "palilaliopraxia" to denote these symptoms. The incorporation of such complex, learned movements into the repertoire of hyperkinesias further emphasizes the complicated association between purposeful and automatic execution of movements comprising tic behavior. This case also provides strong evidence against the suggestion that obscenities vocalized in Tourette's syndrome are due to a random generation of high-probability sequences of letters or phonemes.

Adult↗
PubMed1993

Gilles de la Tourette syndrome: a neuropsychiatric disorder.

Gilles de la Tourette Syndrome is a neuropsychiatric disorder which manifests with neurological psychological and psychiatric symptoms. Understanding of this complex disorder has grown rapidly in the past 25 years. This paper reviews the current knowledge of biological and psychological factors which interact to produce a variable yet clearly recognisable syndrome. New directions for research are explored. Current literature suggests that despite many gains, much remains to be learned about this disorder.

Adolescent↗
PubMed1993

Ultrasound as a tool to evaluate remission of cutaneous Kaposi's sarcoma.

OBJECTIVE: To evaluate ultrasound measurement of Kaposi's sarcoma (KS) tumour volume for follow-up during therapy. Two-dimensional evaluation of size and description of gross alteration (for example, colour, nodularity, resolution) was used to assess treatment of KS. Flattening of palpable cutaneous KS lesions during anti-KS therapy has not been quantified objectively by a reliable method. METHODS: In six patients with advanced AIDS and KS, a total of 17 cutaneous lesions were evaluated prospectively by ultrasound and surface measurements. KS lesions were examined histologically before and after 12 weeks of chemotherapy with liposomal doxorubicin. RESULTS: In comparison with size reduction, volume measurement showed a more pronounced reduction of tumour volume. The mean tumour volume was reduced by 94% from 451 mm3 +/- 655 mm3 to 66 mm3 +/- 165 mm3 at week 12 (P < 0.001). Histological evaluation of lesions no longer detectable by ultrasound after therapy showed abundant siderophages but no increase in spindle cells and no mitoses. CONCLUSIONS: Our findings suggest that ultrasound is a useful method with which to follow growth and remission of cutaneous KS. In contrast, pigmentation due to iron deposition is unaffected by chemotherapy because, despite histological remission, pigmentation can persist. Though ultrasound cannot replace histologic evaluation for complete response, we suggest the use of ultrasound assessment, thus introducing a more objective criterion than subjective rating of nodularity.

Adult↗
PubMed1991

Hypothalamic blood flow autoregulation remains unaltered following surgical and pharmacological blockade of central vasopressin.

Experiments were carried out in urethane anaesthetized, ventilated rats to determine if brain arginine-vasopressin (AVP) plays a physiological role in cerebral blood flow autoregulation. Autoregulation was tested by determining local hypothalamic blood flow in the mediobasal hypothalamic area (HBF; H2-gas clearance technique) during consecutive stepwise lowering of systemic mean arterial pressure to 80, 60 and 40 mm Hg, by hemorrhage. Endogenous AVP was blocked by transecting the rostral, lateral and dorsal neuronal connections of the hypothalamus (including the median eminence) from all major brain areas, by bilateral transection of the vasopressin-containing fibres in the hypothalamo-hypophyseal tract to the median eminence at the level of the lateral retrochiasmatic area (RCAL), and finally by intracerebroventricular (i.c.v.) administration of an AVP antagonist, d(CH2)5Tyr(Me)AVP (AAVP). Significant increases of daily water intake indicated impaired vasopressin release following both types of surgical transection. Resting HBF was significantly elevated both after surgical isolation of the hypothalamus and after 10 ng AAVP administration compared to controls. Blood flow autoregulation in the hypothalamic region was seriously impaired following surgical isolation of the hypothalamus. However, HBF autoregulation remained just as effective as that of the control rats following either selective bilateral transection of the vasopressin pathways or following AAVP treatment. The present data indicate that AVP may play a role in the control of resting hypothalamic blood flow, but does not support a role of AVP in HBF autoregulatory mechanisms.

Animals↗