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Biomedical subjects

R Spiegel

Publications and source records attributed to R Spiegel.

At least 19 recordsLinked to original sources
PubMed2005

Cognitive performance in Alzheimer's disease patients receiving rivastigmine for up to 5 years.

This analysis aimed to assess mini-mental state examination (MMSE) scores in patients with Alzheimer's disease who received rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine data came from two pooled open-label extensions of four 6-month, randomised, placebo-controlled trials. Projections of decline, had the same patients not been treated, were made using a baseline-dependent mathematical model. MMSE data were available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients declined below 10 points on the MMSE at about 3 years, while the mean MMSE score of patients who remained on rivastigmine stayed above 10 points for 5 years.

Aged↗
PubMed2004

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease.

BACKGROUND: Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. OBJECTIVE: To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. METHODS: We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. RESULTS: This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. CONCLUSION: Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.

Aged↗
PubMed2004

Preserved cognitive function after 12 months of treatment with rivastigmine in mild Alzheimer's disease in comparison with untreated AD and MCI patients.

Cholinesterase inhibitors (ChEIs) have shown positive symptomatic effects on cognition, activities of daily living, and behavior in patients with Alzheimer's disease (AD). Rivastigmine is a slowly reversible ChEI that inhibits acetylcholinesterase and butyrylcholinesterase. We evaluated the effects of long-term rivastigmine treatment on cognitive function and plasma levels of ChE activity, and the relationship between ChE activity and cognition. Patients with mild AD (n = 11) treated with rivastigmine for 12 months were compared with matched groups of untreated patients with AD (n = 21) or mild cognitive impairment (MCI; n = 22) representing the natural course of the pre-clinical and very early stage of disease. For untreated AD patients, neuropsychological assessment was made at baseline and 12 months. Determination of ChE activity in plasma and assessment of global cognition, episodic memory, visuospatial ability, and attention were performed at 0 (baseline), 3, 6, and 12 months for treated AD patients and untreated MCI patients. At 12 months, cognitive function was slightly improved or maintained in mild AD patients treated with rivastigmine. In contrast, cognition was markedly worsened in untreated AD patients and unchanged or slightly worsened in untreated MCI patients. In the group of treated AD patients, there was a significant correlation between plasma ChE inhibition and cognition, particularly in relation to attention. This effect was most apparent at 3 months of treatment. In conclusion, a clear beneficial effect of rivastigmine was shown on cognitive function for patients with mild AD and plasma values of ChE inhibition were associated with attention.

Aged↗
PubMed2002

Inhibition of acetyl- and butyryl-cholinesterase in the cerebrospinal fluid of patients with Alzheimer's disease by rivastigmine: correlation with cognitive benefit.

Cholinesterase (ChE) inhibition represents the most efficacious treatment approach for Alzheimer's disease (AD) to date. This multiple-dose study has examined the relationship between inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in the cerebrospinal fluid (CSF) and cognitive change (measured by the Computerised Neuropsychological Test Battery [CNTB]) following administration of the ChE inhibitor, rivastigmine (Exelon). In 18 patients with mild to moderate AD, CNTB scores, activities of AChE and BuChE in the CSF, and plasma BuChE activity were determined prior to treatment with rivastigmine. Doses of rivastigmine were then titrated (1 mg b.i.d./week) to final doses of 1, 2, 3, 4, 5 or 6 mg b.i.d. (n = 3 per dose). Following treatment with the target dose of rivastigmine for at least 3 days, CNTB scores were re-determined. CSF samples were continuously collected together with plasma samples prior to and for 12 hours after the final dose of rivastigmine, and AChE and BuChE activities determined.AChE in CSF and BuChE in plasma were dose-dependently inhibited by rivastigmine treatment. The inhibition of BuChE in CSF was not clearly dose-dependent. A statistically significant correlation was observed between the change in CNTB summary score and inhibition of AChE activity (r = -0.56, p < 0.05) and BuChE activity (r = -0.65, p < 0.01) in CSF. Improvement in speed-, attention- and memory-related subtests of the CNTB correlated significantly with inhibition of BuChE but not AChE activity in CSF. Weak or absent correlation with change in cognitive performance was noted for inhibition of plasma BuChE. These results indicate that cognitive improvement with rivastigmine in AD is associated with central inhibition of ChEs and support a role for central BuChE in addition to AChE inhibition in modulating cholinergic function in AD.

Acetylcholinesterase↗
PubMed2002

West Nile virus meningoencephalitis complicated by motor aphasia in Hodgkin's lymphoma.

A 4 year old boy with Hodgkin's lymphoma was admitted to the paediatric ward with meningoencephalitis dominated by generalised seizures and motor aphasia. Serum IgM specific antibodies to West Nile virus were positive. In view of ongoing neurological deterioration and immunocompromised state he was treated with oral ribavirin for 14 days. A gradual improvement was noted within two weeks of therapy initiation, and with intensive supportive care he recovered completely after four months.

Antiviral Agents↗
PubMed2002

Effects of rivastigmine on cognitive function in dementia with lewy bodies: a randomised placebo-controlled international study using the cognitive drug research computerised assessment system.

This study was designed to assess the effects of rivastigmine (Exelon) on the cognitive functioning of patients suffering from dementia with Lewy bodies. This was a prospective, multi-centre, randomised, double-blind, placebo-controlled exploratory study conducted at sites in the UK, Spain and Italy. The treatment period was 20 weeks with a 3-week posttreatment follow-up. The primary outcome measures were the Cognitive Drug Research (CDR) computerised assessment system and the Neuropsychiatric Inventory. Testing was conducted prior to dosing and then again at weeks 12, 20 and 23. Analysis of the data from the 92 patients who completed the study identified a significant pattern of benefits of rivastigmine over placebo on the CDR system. These benefits were seen on tests of attention, working memory and episodic secondary memory. Taking attention for example, patients given placebo showed a significant deterioration from predosing scores at 12 and 20 weeks, whereas patients on rivastigmine performed significantly above their predosing levels. These effects were also large in magnitude, the decline under placebo at week 12 being 19%, while the improvement under rivastigmine was 23%. The clinical relevance of this 23% improvement was that it took the patients 33% towards being normal for their age on this assessment of attention. These benefits to cognitive function were accompanied by a significant improvement of the other primary outcome measure, the Neuropsychiatric Inventory. Three weeks after discontinuation of rivastigmine, most parameters of cognitive performance returned to predrug levels.

Aged↗
PubMed2001

A retrospective study of diagnosis and management of mesenteric vein thrombosis.

BACKGROUND: Mesenteric vein thrombosis (MVT) is an uncommon type of intestinal ischemia associated with significant mortality and morbidity because of its delay in diagnosis. METHODS: A retrospective analysis of 9 patients treated surgically for MVT during 1982 to 1997 was performed. RESULTS: Nine patients underwent surgical therapy for intestinal ischemia due to MVT. The most common presenting symptom was abdominal pain with bloody diarrhea in 3 patients; preoperative diagnosis of MVT was suspected in 2. Radiologic tests included plain roentgenograms, computed axial tomography, and ultrasound. Time to surgery ranged from 3 hours to 7 days after admission. All patients underwent resection of infarcted bowel with primary anastomosis and immediate postoperative anticoagulation. No patient underwent a second-look operation. The postoperative morbidity and mortality rates were 55% and 11%, respectively. CONCLUSION: Diagnosis of intestinal ischemia from MVT is often delayed, and strong clinical suspicion and aggressive treatment are necessary in its management.

Adult↗
PubMed2001

A double-blind comparative study of clozapine and risperidone in the management of severe chronic schizophrenia.

OBJECTIVE: This prospective, double-blind, multicenter, parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response. METHOD: Male or female patients aged 18-65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response (N=273) were randomly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments. The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) scores. Adverse events were recorded throughout the study. RESULTS: The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group. Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures (Positive and Negative Syndrome Scale, Calgary Depression Scale, Psychotic Depression Scale, and Psychotic Anxiety Scale). The adverse event profile was similar for both treatment groups, with a lower risk of extrapyramidal symptoms in the clozapine group. CONCLUSIONS: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.

Adolescent↗
PubMed2000

Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study.

BACKGROUND: Dementia with Lewy bodies is a common form of dementia in the elderly, characterised clinically by fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism, and other neuropsychiatric features. Neuroleptic medication can provoke severe sensitivity reactions in patients with dementia of this type. Many deficits in cholinergic neurotransmission are seen in the brain of patients with Lewy-body dementia; therefore, drugs enhancing central cholinergic function represent a rationally-based therapeutic approach to this disorder. Rivastigmine, a cholinesterase inhibitor, was tested in a group of clinically characterised patients with Lewy-body dementia. METHODS: A placebo-controlled, double-blind, multicentre study was done in 120 patients with Lewy-body dementia from the UK, Spain, and Italy. Individuals were given up to 12 mg rivastigmine daily or placebo for 20 weeks, followed by 3 weeks rest. Assessment by means of the neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23. A computerised cognitive assessment system and neuropsychological tests were also used, and patients underwent close medical and laboratory safety analysis. FINDINGS: Patients taking rivastigmine were significantly less apathetic and anxious, and had fewer delusions and hallucinations while on treatment than controls. Almost twice as many patients on rivastigmine (37, 63%), than on placebo (18, 30%), showed at least a 30% improvement from baseline. In the computerised cognitive assessment system and the neuropsychological tests, patients were significantly faster and better than those on placebo, particularly on tasks with a substantial attentional component. Both predefined primary efficacy measures differed significantly between rivastigmine and placebo. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse events of cholinesterase inhibitors (nausea, vomiting, anorexia) were seen more frequently with rivastigmine than with placebo, but safety and tolerability of the drug in these mostly multimorbid patients were judged acceptable. INTERPRETATION: Rivastigmine 6-12 mg daily produces statistically and clinically significant behavioural effects in patients with Lewy-body dementia, and seems safe and well tolerated if titrated individually.

Aged↗
PubMed2000

KRIT1 is mutated in hyperkeratotic cutaneous capillary-venous malformation associated with cerebral capillary malformation.

Hyperkeratotic capillary-venous malformations (HCCVMs) are rare cutaneous lesions that occur in a small subgroup of patients with cerebral capillary malformation (CCM). CCMs cause neurological problems that range from headaches to life-threatening intracranial bleeding. CCMs and HCCVMs have a similar histopathological appearance of dilated capillary-venous channels. Genetic linkage of inherited CCMs has been established to three chromosomal loci, 3q25. 2-27, 7p13-15 and 7q21-22. The first mutations were identified in the CCM1 gene (located on 7q21-22), which encodes KRIT1 protein (KREV1 interaction trapped 1), presumably a membrane-bound protein with signalling activity. Although KRIT1 is known to interact with KREV1/RAP1A, a Ras-family GTPase, the exact function of KRIT1 in the formation of cerebral capillaries and veins is poorly understood. In this study, we screened five families with CCM for mutations in the KRIT1 gene. In one of the families, CCMs co-segregated with HCCVMs. We identified a KRIT1Delta(G103)mutation in this family, suggesting that this rare form of the condition is also caused by mutations in the CCM1 gene and that KRIT1 is probably important for cutaneous vasculature. Interestingly, this deletion introduces the earliest stop codon among identified mutations, suggesting a possible correlation between the molecular alteration and the cutaneous phenotype. Another novel mutation, KRIT1(IVS2+2(T-->C)), was found in a family with only cerebral capillary-venous malformations.

Brain↗
PubMed2000

Dementia with lewy bodies: findings from an international multicentre study.

OBJECTIVES: To describe the baseline demographic, neuropsychiatric and neurological data of a large selected clinical sample of patients with dementia with Lewy Bodies (DLB) from an international multicentre trial with rivastigmine. To examine the usefulness of the Consensus Criteria for the diagnosis of DLB in different countries. METHODS: Seventeen centres from Spain, the UK and Italy recruited patients diagnosed clinically as probable DLB according to recent Consensus Criteria (McKeith et al., 1996). A standard clinical protocol including inclusion/exclusion criteria, collection of demographic and medical data, cognitive (Mini Mental State Examination: MMSE), motor (Unified Parkinson's Disease Rating Scale: UPDRS) and neuropsychiatric (Neuropsychiatric Inventory: NPI) examinations, was applied after obtaining informed consent. Data were summarised and compared across countries with uni- and multivariate analyses. RESULTS: One hundred and twenty patients were recruited: 56.7% males, mean (SD) age 73.9 (6.4) years, range 57 - 87 years. Sixty percent fulfilled all three core diagnostic features of DLB, and 40% only two ('parkinsonism' 92.4%, 'cognitive fluctuations' 89.1%, 'visual hallucinations' 77.3%). 'Systematised delusions' (46%) and 'repeated falls' (42%) were the most frequent supportive diagnostic features. There were no differences across countries in demographic, diagnostic or clinical features. Patients showed a wide range of psychopathology which was weakly correlated with cognitive impairment. Some mild extrapyramidal signs (EPS) were observed in most patients. CONCLUSIONS: The Consensus Criteria for DLB can be consistently applied across many different sites for multicentre studies. 'Parkinsonism' and 'cognitive fluctuations' as core features and 'systematised delusions' and 'repeated falls' as supportive features are the most frequent diagnostic clues. Neuropsychiatric disturbances, in particular apathy, delusions, hallucinations and anxiety, and mild symmetric EPS are frequent in DLB and are only related weakly to cognitive impairment.

Aged↗
PubMed1999

[Conviction as a basis for compliance and strategies for improving compliance].

The aim of the present study was to correlate statements made by 100 patients of an internal medicine ward regarding their compliance before hospitalization, with their personal knowledge of an convictions about their own pharmacotherapy. Data were collected in structured interviews of 9 questions carried out by a medical person not involved in current treatment. The patient sample (mean age +/- SE: 6.8 +/- 1.3 years) included 42 women and 58 men whose mean number of prescribed medications before hospitalization was 4.7 +/- o.22. Good treatment compliance was reported by 78% of the patients, while 13% admitted non- compliance. Knowledge about the drugs they had been prescribed ranged from perfect (30%) to none (34%) and was significantly different between compliers and non-compliers, with patients who know their medications at least by name being fairly compliant (p = 0.048). Independently of the statement about compliance, the patients used three main strategies to ensure regular intake of daily medication: visual aids (69%), coupling to a ritual (26%) or supervision by a third person (6%). Criteria such as gender, the number of prescribed medications, personal perseverance, or personal definition of the sense of the prescribed pharmacotherapy, or the arguments expected to be used by a physician when recommending a pharmacotherapy did not differ between compliers and non-compliers. Thus, compliance appears to have its roots mainly in the conviction level of each patient : intention will be transformed into action when deemed correct according to the individual's personal criteria. This may lead to both compliance and to non-compliance with medical recommendations. This study, which is based on patient reports, supports the conclusion that drug compliance may be enhanced by increasing patient's knowledge about their own pharmacotherapy and by having patients use specific strategies to guarantee regular daily intake of drugs. Prospective studies should therefore address the question of whether providing specific information according to a patient's convictions will untimately translate into improved compliance.

Aged↗
PubMed1999

Polygraphic sleep criteria as predictors of successful aging: an exploratory longitudinal study.

BACKGROUND: A cohort of 57 elderly healthy volunteers (34 male, 23 female) was studied in a sleep laboratory on four consecutive nights when their average age was 63.5 +/- 3.7 years. Thirty subjects (20 male, 10 female) were assessed 14 years later; 21 had either died in the meantime or were very ill, and 6 did not participate for other reasons. METHODS: Two operationalizations of successful aging were applied: survival in relatively good health (30 survivors vs. 21 nonsurvivors), and cognitive competence as assessed in the survivors by means of tests of cognitive function. RESULTS: Whereas none of the sleep characteristics determined at baseline distinguished the survivors from the nonsurvivors, several parameters [REM (rapid eye movement) sleep latency, REM density, and NREM (non-REM) shifts] were significantly correlated with one or more measures of cognitive functioning at follow-up. These polygraphic sleep parameters also distinguished a subgroup of cognitively fully competent subjects from those who, according to their performance in tests of cognitive function, could be considered as mildly demented. CONCLUSIONS: While the REM latency and density findings support the theory of a functional link between brain cholinergic activity, timing, and density of REM sleep and cognitive functioning, the positive association between the number of NREM shifts at baseline and cognitive performance 14 years later is difficult to explain. It is suggested that the findings of the present study, in particular the potential predictive value of REM latency and REM density for cognitive functioning in the old, need replication in other subject samples followed for similar time periods.

Aged↗
PubMed1998

[X-chromosomal bulbospinal muscular atrophy (Kennedy syndrome)].

Two brothers with slowly progressive weakness and congenital nystagmus are presented. DNA analysis confirmed X-linked recessive bulbospinal muscular atrophy (XBSMA, Kennedy's disease) by demonstration of increased size of a CAG-triplet repeat on the androgen receptor gene on the X-chromosome. XBSMA is characterized by almost symmetrical muscular atrophy, weakness and fasciculations predominantly of bulbar, facial and proximal muscles of the extremities, with onset in the third to fifth decade. Tendon reflexes are depressed and pyramidal signs are absent. Sensory symptoms are clinically rare, but sensory nerve action potentials are frequently abnormal. Additional symptoms are important for differential diagnosis, and include postural tremor, gynecomastia, diabetes mellitus, testicular atrophy and impotence. Differentiation of this hereditary disorder from treatable conditions such as multifocal motor neuropathy or amyotrophic lateral sclerosis is essential. Though life expectancy is normal, patients become disabled in the course of the disease and need supportive care. Periodic testing for diabetes is recommended, and genetic counseling should be provided for patients and their relatives.

Adult↗
PubMed1998

[Familial giant hemangiomas of the liver. Study of a family and review of the literature].

In this report we present for the first time strong evidence for autosomal-dominant inheritance of grant liver hemangiomas. Furthermore, we review the current literature about incidence, pathogenesis, clinics, as well as diagnostic and therapeutic aspects of LH. A large family of Italian origin is described where three female patients in three successive generations suffered from large symptomatic LH. In addition, two other female relatives exhibited asymptomatic LH on sonographic scans. The restriction of the disease to the female gender could be explained by a sex-dependent difference in penetrance or expressivity of a presumable "liver-hemangioma" gene, or by known proliferative factors such as female sex hormones. We also observed an increased incidence of adenomas of the thyroidea among members with or without LH of the presented family. This uncommon familial association has also not yet been described and its genetic aspects are discussed.

Adenoma↗
PubMed1997

[Pyogenic liver abscess in children].

2 children with pyogenic liver abscesses were hospitalized during the past 2 years. A 6-year-old boy had high fever and hepatomegaly, and a large liver abscess was found in the right hepatic lobe. Streptococcus milleri was isolated from the pus. Treatment with a combination of prolonged drainage of the abscess and antibiotic therapy was successful. A 4-month-old girl who had prolonged fever was found to have osteomyelitis of 3 thoracic vertebrae and 2 liver abscesses in the right lobe. She was treated successfully with broad spectrum antibiotics. Additional workup revealed that she had chronic granulomatous disease.

Anti-Bacterial Agents↗