PubMed Health⌕ Search

Biomedical subjects

R S Black

Publications and source records attributed to R S Black.

At least 19 recordsLinked to original sources
PubMed2005

Clinical effects of Abeta immunization (AN1792) in patients with AD in an interrupted trial.

BACKGROUND: AN1792 (beta-amyloid [Abeta]1-42) immunization reduces Abeta plaque burden and preserves cognitive function in APP transgenic mice. The authors report the results of a phase IIa immunotherapy trial of AN1792(QS-21) in patients with mild to moderate Alzheimer disease (AD) that was interrupted because of meningoencephalitis in 6% of immunized patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of IM AN1792 225 microg plus the adjuvant QS-21 50 microg (300 patients) and saline (72 patients) included patients aged 50 to 85 years with probable AD, Mini-Mental State Examination (MMSE) 15 to 26. Injections were planned for months 0, 1, 3, 6, 9, and 12. Safety and tolerability were evaluated, and pilot efficacy (AD Assessment Scale-Cognitive Subscale [ADAS-Cog], MRI, neuropsychological test battery [NTB], CSF tau, and Abeta42) was assessed in anti-AN1792 antibody responder patients (immunoglobulin G titer > or = 1:2,200). RESULTS: Following reports of meningoencephalitis (overall 18/300 [6%]), immunization was stopped after one (2 patients), two (274 patients), or three (24 patients) injections. Of the 300 AN1792(QS-21)-treated patients, 59 (19.7%) developed the predetermined antibody response. Double-blind assessments were maintained for 12 months. No significant differences were found between antibody responder and placebo groups for ADAS-Cog, Disability Assessment for Dementia, Clinical Dementia Rating, MMSE, or Clinical Global Impression of Change, but analyses of the z-score composite across the NTB revealed differences favoring antibody responders (0.03 +/- 0.37 vs -0.20 +/- 0.45; p = 0.020). In the small subset of subjects who had CSF examinations, CSF tau was decreased in antibody responders (n = 11) vs placebo subjects (n = 10; p < 0.001). CONCLUSION: Although interrupted, this trial provides an indication that Abeta immunotherapy may be useful in Alzheimer disease.

Aged↗
PubMed2005

Effects of Abeta immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease.

BACKGROUND: Alzheimer disease (AD) is characterized by progressive cerebral atrophy that may be measured using MRI. Reported are MRI findings of a Phase IIa immunotherapy trial in AD prematurely terminated owing to meningoencephalitis in a subset of patients. OBJECTIVE: To assess cerebral volume changes in patients immunized with AN1792 (beta-amyloid [Abeta] 1 to 42) who were antibody responders (anti-AN1792 IgG titer of > or =1:2,200) compared with placebo patients. METHODS: This randomized, multicenter, placebo-controlled, double-blind trial of AN1792 225 mug plus QS-21 50 mug included 372 patients with probable AD. Patients received one to three injections of AN1792/QS-21 or saline and were assessed for 12 months. Volumetric MRI was performed pre dose and at month 12 or early termination. Brain, ventricular, and hippocampal volume changes were measured from registered scan pairs. RESULTS: Two hundred eighty-eight patients had paired scans (mean interval 10.9 months). Antibody responders (n = 45) had greater brain volume decrease (3.12 +/- 1.98 vs 2.04 +/- 1.74%; p = 0.007), greater ventricular enlargement as a percentage of baseline brain volume (1.10 +/- 0.75 vs 0.48 +/- 0.40%; p < 0.001), and a nonsignificant greater hippocampal volume decrease (3.78 +/- 2.63 vs 2.86 +/- 3.19%; p = 0.124) than placebo patients (n = 57). Increased losses in brain volume were not reflected in worsening cognitive performance; a composite z score across a Neuropsychological Test Battery showed differences favoring antibody responders over placebo (0.03 +/- 0.39 vs -0.24 +/- 0.45; p = 0.008). CONCLUSIONS: A dissociation between brain volume loss and cognitive function was observed in AN1792/QS-21 antibody responders. The reasons for this remain unclear but include the possibility that volume changes were due to amyloid removal and associated cerebral fluid shifts.

Aged↗
PubMed2000

Doppler ultrasound of the maternal uterine arteries: disappearance of abnormal waveforms and relation to birthweight and pregnancy outcome.

BACKGROUND: To assess whether the gestation at which abnormal uterine artery waveforms disappear is related to birthweight and complications of pregnancy. METHODS: A prospective study of outcome of pregnancy after a uterine artery Doppler screening program set in an inner city teaching hospital. One thousand five hundred and twenty-four consecutive women attending the Obstetric Department for a routine anomaly scan at between 19 and 21 weeks gestation had maternal uterine arteries assessed using color wave Doppler. Those women in whom the flow was deemed abnormal were recalled for a further scan at 24-26 weeks gestation. The main outcome measures were birthweight, gestation at delivery and incidence of pre eclampsia. RESULTS: The women in whom the uterine artery blood flow was normal at 20 weeks had babies with significantly higher mean birthweight than those who normalized between 20 and 24-26 weeks gestation ('late normalizers') after adjustment for confounding factors; gestational age, maternal height, parity, ethnic group and smoking (mean difference=173 g, 95% confidence intervals 42 to 303 g). CONCLUSIONS: The timing of trophoblast invasion, as reflected by abnormal uterine artery waveforms, may have an effect on birthweight.

Adult↗
PubMed1999

Glyceryl trinitrate and ritodrine in tocolysis: an international multicenter randomized study. GTN Preterm Labour Investigation Group.

OBJECTIVE: To compare the efficacy of transdermal glyceryl trinitrate and intravenous (IV) ritodrine as tocolytics. METHODS: Two hundred forty-five women with preterm labor and intact membranes between 24 and 36 weeks' gestation were randomized to transdermal glyceryl trinitrate or intravenous ritodrine. Treatment was continued until contractions stopped or a maximum of 7 days. Glyceryl trinitrate was administered as a 10- or 20-mg transdermal patch. Intravenous ritodrine was administered according to nationally available guidelines. The primary outcome was prolongation of gestation expressed as a percentage of the time from entry to 37 weeks. Secondary outcomes were proportion of women who delivered the same day, next day, or within 7 and 14 days of entry, and by 32, 34, and 37 weeks. Analysis was by intention to treat. RESULTS: Twelve women (5%) were lost to follow-up. Glyceryl trinitrate and ritodrine prolonged gestation by 74% of time to 37 weeks (difference glyceryl trinitrate-ritodrine 0%; 95% confidence interval (CI) -10%, +10%). There was no significant difference in the proportion of women receiving glyceryl trinitrate or ritodrine who delivered within the specified days from study entry or weeks of gestation; however, 42 women who received glyceryl trinitrate and 58 women who received ritodrine delivered by 37 weeks (difference -11%; 95% CI -24%, +2%). No serious maternal side effects were reported for ritodrine or glyceryl trinitrate. CONCLUSION: We found no overall difference between glyceryl trinitrate and ritodrine in the acute tocolysis of preterm labor but a suggested advantage of glyceryl trinitrate over ritodrine in reducing preterm delivery rate. The maternal side effect profile and treatment discontinuation rates were fewer for glyceryl trinitrate, suggesting it was a safer alternative to ritodrine.

Adolescent↗
PubMed1999

Maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate and intravenous ritodrine.

OBJECTIVE: To determine the maternal and fetal cardiovascular effects of transdermal glyceryl trinitrate compared with ritodrine for acute tocolysis. METHODS: Sixty women in preterm labor were enrolled in this study that was part of a multicenter study of glyceryl trinitrate. Once randomized, the women received transdermal glyceryl trinitrate or intravenous ritodrine for acute tocolysis. Measurements of maternal pulse, blood pressure (BP), and fetal heart rate (FHR) were recorded for up to 24 hours and compared over the treatment course. RESULTS: Changes from baseline in mean maternal heart rate, FHR, and maternal BP (mean arterial pressure [MAP]) were compared between the glyceryl trinitrate and ritodrine groups over the entire treatment course. The mean change from baseline in maternal heart rate was 21.1 beats per minute less (95% confidence interval [CI] 15.7, 26.5, P < .001), and the mean maternal heart rate was 21.8 beats per minute lower (95% CI 16.9, 26.7, P < .001) in the glyceryl trinitrate group. The mean change in FHR was 9.2 beats per minute less (95% CI 3.8, 14.6, P = .001) and the mean FHR significantly lower (6.9 beats per minute, 95% CI 1.9, 11.9, P = .008) during glyceryl trinitrate treatment. Ritodrine had a significantly hypotensive effect on MAP (95% CI -4.3, 0.0, P = .03). Mean arterial pressure was not significantly different over the treatment course. CONCLUSION: At doses required for acute tocolysis, transdermal glyceryl trinitrate had minimal effects on maternal pulse, BP, and FHR, and significantly fewer adverse cardiovascular effects than intravenous ritodrine. Thus, transdermal glyceryl trinitrate might be a safer treatment for women in preterm labor.

Administration, Cutaneous↗
PubMed1998

A novel approach to the management of pregnancies complicated by uteroplacental insufficiency and previous stillbirth.

To our knowledge, this is the first time that a combination of aspirin and glyceryl trinitrate (GTN) has been used in the prophylaxis of preeclampsia and fetal growth retardation, and their use associated with not only Doppler screening of the uterine arteries but also regular Doppler follow-up of the fetal arterial and venous circulation. Whilst future trials are needed to prove whether screening, prophylaxis and Doppler management are individually beneficial, we propose that this combination of management strategies contributed to a good outcome in the cases described. Furthermore, randomized trials are required to determine the safety and efficacy of prophylactic low-dose aspirin combined with GTN treatment in pregnancies affected by an impaired uteroplacental circulation.

Adult↗
PubMed1996

Preterm labour and delivery.

Preterm birth is a major cause of perinatal morbidity and mortality. It accounts for 5-10% of all births, and any treatment to prevent it could have a profound effect on neonatal outcome in both human and economic terms. The pathogenesis of both term and preterm birth remain poorly understood. Our ability to predict those at risk of preterm labour is also inaccurate, despite the creation of scoring systems, uterine activity monitoring, cervical ultrasound and several biochemical markers. Current drug therapies for preterm labour have not been shown in randomised controlled trials to significantly affect perinatal morbidity and mortality. Furthermore, most are associated with significant maternal or fetal side effects. Nitric oxide (NO) is a potent smooth muscle relaxant, produced when NO synthase acts on the amino acid L-arginine. Its presence has been demonstrated in human myometrium. We have conducted an observational study which has suggested that glyceryl trinitrate (GTN), and NO donor, may be effective in prolonging gestation. A randomised trial comparing GTN to intravenous ritodrine is currently recruiting patients; results will be available in the Spring of 1997. Few side effects have so far been encountered. Evidence suggests that GTN, an NO donor, should be a safe and effective tocolytic and early observations are encouraging; randomised trials currently underway should determine the significance of this breakthrough in the management of preterm labour.

Adrenergic beta-Agonists↗
PubMed1994

Expression of neuronal proteins in cells from normal adult rat brain propagated in serial culture.

Cells have been cultured from the brains of 60-day-old rats and propagated through 12 passages. The cells contain the high and middle, but not low, molecular weight neurofilament subunits and neuron-specific enolase, demonstrated by immunoblotting and immunocytochemistry with redundant antibodies. The cells did not have the morphology of neurons when cultured in medium containing fetal calf serum and growth factors. In low serum medium containing the same growth factors with the addition of dibutyryl cyclic AMP, the cells became smaller and developed long processes. Three clonal lines derived from these cultures had the same properties. These observations are in agreement with recent observations using mouse and human brain tissue and demonstrate that proteins normally associated with neurons can be found in dividing cells cultured from the brains of young adult rats.

Animals↗
PubMed1993

Relationship between cognitive status and behavioral symptoms in Alzheimer's disease and mixed dementia.

OBJECTIVE: To investigate the relationship between cognitive and behavioral impairments in Alzheimer's disease (AD) and to examine whether the addition of cerebrovascular disease modifies that relationship. DESIGN: Correlational analysis. SETTING: An outpatient dementia clinic. PATIENTS: An autopsy-confirmed series of 28 patients with AD and 16 patients with mixed Alzheimer and vascular dementia (MIX). MEASUREMENTS: Neuropsychological and behavioral tests during life: Mini-Mental State (MMS), Blessed Dementia Scale (BDS), Haycox Dementia Behavior Scale (HDBS), and two non-cognitive functional scales derived from the BDS and HDBS. RESULTS: In the AD group, MMS scores correlated significantly with scores on the BDS, HDBS, and two non-cognitive functional scales. In the MIX group, however, no significant relationship was observed between MMS scores and scores on any of the behavioral measures. CONCLUSIONS: These observations suggest that in AD, cognitive and behavioral impairments progress simultaneously. However, with the addition of a vascular component to the dementing process, cognitive and behavioral impairments may progress more independently.

Aged↗
PubMed1992

Presence of typical neuronal markers in serially cultured cells from adult human brain.

Typical markers for neurons but not for astroglia have been identified in cells cultured from a sample of normal adult human temporal lobe, which was removed to gain access to a glioma. Cells were grown in medium containing growth factors, including fibroblast growth factor and nerve growth factor. The cells grew slowly (doubling time, 18 days) and have been carried as far as passage 8 over 10 months. Both immunoblotting and immunocytochemistry with redundant antibodies demonstrated the presence of neurofilaments (NF-H, NF-M, NF-L), but not glial fibrillary acidic protein (GFAP). Neuron-specific enolase (NSE) was also found. Morphologically, the cultures consisted of a pleimorphic population of cells with frequent long processes. Cells demonstrating neuronal rather than astroglial markers can be cultured from normal adult human brain.

Biomarkers↗
PubMed1992

Pentoxifylline in cerebrovascular dementia.

OBJECTIVE: To test the effect of pentoxifylline, a hemorheologic agent used to treat intermittent claudication, on the course of vascular dementia. DESIGN: Randomized, double-blind, placebo-controlled, parallel group trial. SETTING: Outpatient tertiary care center. PATIENTS: 64 patients meeting DSM-III criteria for multi-infarct dementia with modified Hachinski ischemic scores greater than or equal to 6, 38 of whom completed the trial. INTERVENTION: Pentoxifylline (Trental) 400 milligram tablets three times daily vs placebo for 36 weeks. MAIN OUTCOME MEASURE: Alzheimer's Disease Assessment Scale (ADAS). RESULTS: Baseline demographic values and psychometric variables were similar in the placebo and control groups; endpoint statistical analysis was used to allow the use of data from all patients in this clinically high-risk group. For the total group, the slowing of deterioration did not reach statistical significance (by 2-tailed t test), as measured by scores on the total ADAS (P = 0.058) or on the cognitive (ADAS items 1-11; P = 0.064) or non-cognitive subscales (ADAS items 12-21; P = 0.234), although it was significant on the cognitive subscales excluding memory (ADAS items 2-6, 8-10; P = 0.036). For the subgroup of 40 patients who had CT and/or MRI evidence of stroke as well as meeting the other inclusion criteria, treatment with pentoxifylline was associated with significantly slower deterioration, as measured by the total ADAS (P = 0.023) and cognitive subscores (P = 0.020) but not non-cognitive subscores (P = 0.118). For the subgroup of 37 patients who had at least one discrete clinical stroke, treatment with pentoxifylline was associated with significantly less deterioration on the total ADAS (P = 0.002) and both the cognitive (P = 0.001) and non-cognitive (P = 0.017) subscores. CONCLUSION: Treatment with pentoxifylline may slow the progression of dementia in patients who meet DSM-III criteria for "multi-infarct dementia" and who also have clinical and neuroradiological evidence of cerebrovascular disease.

Academic Medical Centers↗
PubMed1991

A trial of thiamine in Alzheimer's disease.

Because a previous short-term study demonstrated a statistically significant, but not clinically important, improvement in cognitive test scores during thiamine treatment in patients with dementia of the Alzheimer's type, a 12-month, double-blind, parallel-group study was conducted to examine whether long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type. Fifteen subjects were enrolled and 10 completed the 1-year study. Data are available for two additional subjects through the first 9 months of study. No significant differences were found between the placebo and thiamine groups at any point during the study. In both groups, overall means for the Mini-Mental State Examination, verbal learning, and naming scores decreased significantly over the 12-month study period. These results do not support the hypothesis that long-term administration of thiamine at 3 g/d might slow the progression of dementia of the Alzheimer's type.

Aged↗
PubMed1991

Expression of 'Alzheimer antigens' in cultured skin fibroblasts.

When cultured skin fibroblasts were exposed to culture conditions designed to favor the expression of neuronal antigens, cells from each of 19 patients with Alzheimer's disease reacted immunocytochemically with antibodies to paired helical filaments, Alz-50, or both compared with only a small fraction of cells from 19 identically treated age-matched control cultures. Immunoblots confirmed the presence of soluble material reacting with Alz-50 antibody in the Alzheimer fibroblasts. Ultrastructurally, fascicles of 10-nm filaments were seen that occasionally twisted around each other, but no structures were seen that were identical to paired helical filaments. Thus, cultured skin fibroblasts from patients with Alzheimer's disease developed greater immunocytochemical reactivity with antibodies raised to paired helical filaments than did fibroblasts from control subjects, when cultured under the specified conditions.

Aged↗
PubMed1991

Delirium: phenomenology and diagnosis--a neurobiologic view.

"Delirium" is a reversible confusional state. It results from widespread but reversible interference with the function of cortical neurons, as documented by diffuse slowing on EEG and decreases in cerebral metabolic rate. Delirium can be due to impairments in neuronal metabolism, in neurotransmission (notably cholinergic), or in input from subcortical structures. Engel and Romano (1959) formulated delirium and dementia as the two poles of a spectrum of "cerebral insufficiency," with delirium resulting from reversible functional impairment and dementia from irreversible anatomic damage. So many disorders can precipitate delirium that the differential diagnosis tests every facet of one's knowledge of medicine. With aging, both normative changes in the brain and the increasing incidence of brain diseases predispose to the development of delirium. The brain damage responsible for a dementia can sensitize to the development of a superimposed delirium.

Aged↗
PubMed1990

Induction of Alzheimer antigens by an uncoupler of oxidative phosphorylation.

Since previous studies have suggested that the coupling of oxidation to phosphorylation is impaired in Alzheimer brain and fibroblasts, the effects of carbonyl cyanide m-chlorophenylhydrazone, a hydrazone known to uncouple mitochondrial oxidative phosphorylation, were tested on the development of immunoreactivity with antibodies to "Alzheimer antigens" in cultured fibroblasts from cognitively intact subjects. The fibroblasts were exposed for 10 to 14 days to a medium (DMd) modeled on media that favor neuronal differentiation in fetal brain cultures. The addition of a 10-microns concentration of carbonyl cyanide m-chlorophenylhydrazone to the DMd culture medium increased by more than 10-fold the proportion of cells reacting immunocytochemically with antibodies to paired helical filaments and by 157-fold the proportion of cells reacting with the Alz-50 monoclonal antibody. These observations suggest that the oxidative abnormalities previously described in tissues from patients with Alzheimer's disease may contribute to the accumulation of abnormal cytoskeletal materials in this disorder.

Aged↗
PubMed1985

Intracortical 5,7-dihydroxytryptamine depletes brain serotonin concentrations without affecting spontaneous activity.

Microinjections of either 2 or 4 micrograms of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) were made into either the right or left frontal cortex of male rats pretreated with desmethylimipramine. Although both the 2 and 4 micrograms doses produced significant depletions of serotonin concentrations in the cortex and median raphe, neither dose produced a significant increase in spontaneous activity. This is in contrast to our findings with the noradrenergic neurotoxins, 6-hydroxydopamine and DSP-4, which produced hyperactivity following right but not left hemisphere injections. These findings do not rule out the involvement of 5-HT in the asymmetrically elicited hyperactivity but they do suggest some transmitter and neural pathway specificity to the lateralized response to cortical injury.

5,7-Dihydroxytryptamine↗