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Biomedical subjects

C J Earley

Publications and source records attributed to C J Earley.

At least 37 records · Page 2Linked to original sources
PubMed1999

Homocyst(e)ine and risk of cerebral infarction in a biracial population : the stroke prevention in young women study.

BACKGROUND AND PURPOSE: Genetic enzyme variation and vitamin intake are important determinants of blood homocyst(e)ine levels. The prevalence of common genetic polymorphisms influencing homocyst(e)ine levels varies by race, and vitamin intake varies by socioeconomic status. Therefore, we examined the effect of vitamin intake, race, and socioeconomic status on the association of homocyst(e)ine with stroke risk. METHODS: All 59 hospitals in the greater Baltimore-Washington area participated in a population-based case-control study of stroke in young women. One hundred sixty-seven cases of first ischemic stroke among women aged 15 to 44 years were compared with 328 controls identified by random-digit dialing from the same region. Risk factor data were collected by standardized interview and nonfasting phlebotomy. Plasma homocyst(e)ine was measured by high-performance liquid chromatography and electrochemical detection. RESULTS: Blacks and whites did not differ in median homocyst(e)ine levels, nor did race modify the association between homocyst(e)ine and stroke. After adjustment for cigarettes per day, poverty status, and regular vitamin use, a plasma homocyst(e)ine level of >/=7.3 micromol/L was associated with an odds ratio for stroke of 1.6 (95% CI, 1.1 to 2.5). CONCLUSIONS: The association between elevated homocyst(e)ine and stroke was independent not only of traditional vascular risk factors but also of vitamin use and poverty status. The degree of homocyst(e)ine elevation associated with an increased stroke risk in young women is lower than that previously reported for middle-aged men and the elderly and was highly prevalent, being present in one third of the control group.

Adolescent↗
PubMed1998

Increased carotid artery intimal-medial thickness in asymptomatic older subjects with exercise-induced myocardial ischemia.

BACKGROUND: Previous studies have shown an association between symptomatic coronary artery disease (CAD) and increased intimal-medial thickness of the common carotid artery (CCA IMT), a purported index of atherosclerosis. This study determines whether CCA IMT is increased in asymptomatic older subjects with an ischemic ST-segment response to treadmill exercise. METHODS AND RESULTS: CCA IMT was measured by B-mode ultrasound in community-dwelling volunteers from the Baltimore Longitudinal Study of Aging, including 397 healthy subjects (age, 58.5+/-15.8 years) with normal ECG responses to maximum treadmill exercise, 72 asymptomatic subjects (age, 66.1+/-13.4 years) with exercise-induced horizontal or downsloping ST-segment depression >/=1 mm, and 38 subjects (age, 77. 4+/-7.8 years) with clinically manifest CAD as diagnosed by medical history and resting ECG. Forty-three subjects with abnormal exercise ECGs also underwent exercise thallium scintigraphy. Exercise-induced ST-segment depression was associated with increased IMT (P<0.0001) independent of age and manifest CAD. After adjustment for age, IMT values progressively increased from healthy subjects to asymptomatic subjects with positive exercise ECG alone to those with concordant positive ECG and thallium scintigraphic findings who had virtually identical IMT to subjects with manifest CAD. Each 0.1-mm increase in IMT was associated with a 1.91-fold (95% CI, 1.46 to 2.50; P<0.0001) increased risk for concordant positive exercise tests or manifest CAD, independent of other significant predictors of CAD. CONCLUSIONS: CCA IMT is increased in older subjects with asymptomatic myocardial ischemia as evidenced by exercise ECG alone or in combination with thallium scan. Carotid ultrasound may help to identify asymptomatic individuals with CAD.

Adult↗
PubMed1998

Iron and the restless legs syndrome.

STUDY OBJECTIVES: Using blinded procedures, determine the relation between serum ferritin levels and severity of subjective and objective symptoms of the restless legs syndrome (RLS) for a representative patient sample covering the entire adult age range. DESIGN: All patient records from the past 4 years were retrospectively reviewed to obtain data from all cases with RLS. All patients were included who had ferritin levels obtained at about the same time as a polysomnogram (PSG), met diagnostic criteria for RLS, and were not on iron or medications that would reduce the RLS symptoms at the time of the PSG. SETTING: Sleep Disorders Center. PATIENTS: 27 (18 females, 9 males), aged 29-81 years. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Measurements included clinical ratings of RLS severity and PSG measures of sleep efficiency and periodic limb movements (PLMS) in sleep with and without arousal. Lower ferritin correlated significantly to greater RLS severity and decreased sleep efficiency. All but one patient with severe RLS had ferritin levels < or = 50 mcg/l. Patients with lower ferritin (< or = 50 mcg/l) also showed significantly more PLMS with arousal than did those with higher ferritin, but the PLMS/hour was not significantly related to ferritin. This last finding may be due to inclusion of two 'outliers' or because of severely disturbed sleep of the more severe RLS patients. CONCLUSIONS: These data are consistent with those from a prior unblinded study and suggest that RLS patients will have fewer symptoms if they have ferritin levels greater than 50 mcg/l.

Adult↗
PubMed1998

Blood-flow velocities and their relationships in carotid and middle cerebral arteries.

This study defines normative flow velocity (FV) ranges for the common carotid (CCA), internal carotid (ICA) and middle cerebral arteries (MCA), compares them to subjects with nonfocal vascular disease (mild to moderate hypertension, diabetes, hyperlipidemia or coronary artery disease), and clarifies the association between carotid and MCA FVs. FVs were measured by carotid and transcranial Doppler ultrasonography in 278 healthy and 190 vascular-disease subjects. Normative FV ranges for CCA, ICA and MCA were large in healthy subjects, with modest gender and age differences. Vascular-disease subjects had similar FVs to healthy controls. MCA FVs were significantly correlated with carotid FVs (r ranged 0.26-0.50), but were only weakly or not significantly associated with them (beta ranged 0.08-0.18) when controlling for age and gender. These findings suggest that normative FVs are not affected by the presence of nonfocal vascular disease, but carotid FVs do not aid in assessing MCA FVs.

Adult↗
PubMed1998

Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study.

BACKGROUND AND PURPOSE: Platelet glycoprotein IIb/IIa (GpIIb-IIIa), a membrane receptor for fibrinogen and von Willebrand factor, has been implicated in the pathogenesis of acute coronary syndromes but has not been previously investigated in relation to stroke in young adults. METHODS: We used a population-based case-control design to examine the association of the GpIIIa polymorphism P1A2 with stroke in young women. Subjects were 65 cerebral infarction cases (18 patients with and 47 without an identified probable etiology) 15 to 44 years of age from the Baltimore-Washington region and 122 controls frequency matched by age from the same geographic area. A face-to-face interview for vascular disease risk factors and a blood sample for the P1A2 allele and serum cholesterol were obtained from each participant. Logistic regression was used to estimate the odds ratio for one or more P1A2 alleles after adjustment for other risk factors. RESULTS: Among cases and controls, the prevalence rates of one or more P1A2 alleles were 21% and 22% among blacks and 36% and 28% among whites, respectively. This genotype was significantly associated with hypertension only in black control subjects but otherwise not with any of the established vascular risk factors. The adjusted odds ratio for cerebral infarction of one or more P1A2 alleles was 1.1 (confidence interval [CI], 0.6 to 2.3) overall, 0.5 (CI, 0.1 to 7.1) among blacks, and 1.4 (CI, 0.5 to 3.7) among whites. For the cases with an identified probable etiology, the corresponding odds ratios were 3.0 (CI, 0.9 to 10.4) overall, 0.7 (CI, 0.1 to 7.1) among blacks, and 12.8 (CI, 1.2 to 135.0) among whites. CONCLUSIONS: No association was found between the P1A2 polymorphism of GpIIIa and young women with stroke. However, subgroup analyses showed that the P1A2 polymorphism of GpIIIa appeared to be associated with stroke risk among white women, particularly those with a clinically identified probable etiology for their stroke. Further work with an emphasis on stroke subtypes and with multiracial populations is warranted.

Adolescent↗
PubMed1998

Cerebral infarction in young adults: the Baltimore-Washington Cooperative Young Stroke Study.

BACKGROUND: Few reports on stroke in young adults have included cases from all community and referral hospitals in a defined geographic region. METHODS: At 46 hospitals in Baltimore City, 5 central Maryland counties, and Washington, DC, the chart of every patient 15 to 44 years of age with a primary or secondary diagnosis of possible cerebral arterial infarction during 1988 and 1991 was abstracted. Probable and possible etiologies were assigned following written guidelines. RESULTS: Of 428 first strokes, 212 (49.5%) were assigned at least one probable cause, 80 (18.7%) had no probable cause but at least one possible cause, and 136 (31.8%) had no identified probable or possible cause. Of the 212 with at least one probable cause, the distribution of etiologies was cardiac embolism (31.1%), hematologic and other (19.8%), small vessel (lacunar) disease (19.8%), nonatherosclerotic vasculopathy (11.3%), illicit drug use (9.4%), oral contraceptive use (5.2%), large artery atherosclerotic disease (3.8%), and migraine (1.4%). There were an additional 69 recurrent stroke patients. CONCLUSIONS: In this hospital-based registry within a region characterized by racial/ethnic diversity, cardiac embolism, hematologic and other causes, and lacunar stroke were the most common etiologies of cerebral infarction in young adults. Nearly a third of both first and recurrent strokes had no identified cause.

Adolescent↗
PubMed1998

Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke Study.

BACKGROUND: Limited information exists on the frequency, trends in occurrence, risk factors, mechanisms, and outcome of ischemic stroke associated with illicit drug use among young adults in a geographically defined population. METHODS: We reviewed ischemic stroke in young adults (aged 15 to 44 years) in 46 regional hospitals for 1988 and 1991. We examined stroke mechanisms and outcome in patients with recent drug use. RESULTS: Recent illicit drug use was noted in 51/422 (12.1%) stroke patients. Patients with drug use were more likely than other stroke patients to be black (p=0.01), aged 25 to 39 years (p=0.004), and smokers (p=0.006), and were less likely to have hypertension (p=0.004) or diabetes mellitus (p=0.004). Drug use was the probable cause of stroke in 20 (4.7%) patients. Among 31 (7.3%) patients with drug use as a possible stroke mechanism, more likely diagnoses included cardioembolic stroke in 18, hematologic/collagen vascular in 6, nonatherosclerotic vasculopathy in 5, and atherosclerosis in 3. There was no difference in outcome between drug-associated and non-drug associated stroke. CONCLUSIONS: Recent illicit drug use occurs in 12.1% of young adult stroke patients. Drug-associated young adult stroke seems to relate to vascular mechanisms other than those related to hypertension or diabetes. Case-control studies are needed.

Adolescent↗
PubMed1998

Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study.

BACKGROUND/PURPOSE: The Baltimore-Washington Cooperative Young Stroke Study is the largest biracial urban-suburban population-based study to examine the etiology of strokes in children. METHODS: We identified all children aged 1 to 14 years discharged from all 46 hospitals in central Maryland and Washington, DC with a diagnosis of ischemic stroke and intracerebral hemorrhage in the years 1988 and 1991. Each medical record was reviewed by two neurologists for appropriateness of the diagnosis of stroke and for information on the patient's history, clinical presentation, pertinent investigations, hospital stay, and outcome at time of discharge. RESULTS: Eighteen children with ischemic infarction and 17 with intracerebral hemorrhage were identified. The most common cause of ischemic stroke was sickle-cell disease (39%), followed by vasculopathic (33%) and indeterminate (28%) causes. Causes of intracerebral hemorrhages were arteriovenous malformation (29%), hematologic (23%), vasculopathy (18%), surgical complication (12%), coagulopathy (6%), and indeterminate (12%). The overall incidence for childhood stroke was 1.29 per 100,000 per year, with ischemic stroke occurring at a rate of 0.58 per 100,000 and intracerebral hemorrhage occurring at a rate of 0.71 per 100,000. The incidence of stroke among children with sickle-cell disease was estimated to be 0.28% or 285 per 100,000 per year. CONCLUSION: Sickle-cell disease plays a disproportionately high role in childhood stroke when a biracial population is surveyed.

Adolescent↗
PubMed1998

Randomized, double-blind, placebo-controlled trial of pergolide in restless legs syndrome.

OBJECTIVE: To assess the efficacy of pergolide in the treatment of restless legs syndrome (RLS). METHODS: A randomized, double-blind, parallel-treatment evaluation of pergolide versus placebo in patients with RLS was performed. Sixteen patients seen in the Sleep Disorders Center who met the clinical criteria for RLS were enrolled in the study. Treatment was either placebo (n=8) or pergolide (n=8), which was on a self-adjusted schedule that ranged from 0.05 to 0.65 mg/day. Outcome variables included the patient's rating of symptom improvement, duration of RLS symptoms throughout the day, and objective sleep assessments from an all-night polysomnogram (percent sleep efficiency and periodic leg movements). Baseline was assessed for 2 days before starting treatment. Dose adjustments were made over the first 14 days and were then held constant for 5 days, with repeat assessment for treatment effects on the last 2 days of treatment (days 17 and 18). RESULTS: As a group, pergolide recipients showed significant improvement clinically and statistically in all outcome measures when compared with baseline or with placebo treatment. On the other hand, placebo treatment led to no significant improvements in any outcome measures. CONCLUSIONS: Pergolide treatment significantly improved clinical symptoms and sleep efficiency, and reduced periodic limb movements of sleep in patients with RLS.

Adult↗
PubMed1998

Thermolabile methylenetetrahydrofolate reductase polymorphism (C677T) and total homocysteine concentration among African-American and white women.

A polymorphism associated with a thermolabile variant (C677T) of the enzyme methylenetetrahydrofolate reductase has been associated with both elevated total homocysteine (tHcy) levels and risk for cardiovascular disease. Data from the Stroke Prevention in Young Women Study were used to determine the prevalence of the C677T genotype and to assess whether environmental factors modified the association between genotype and tHcy concentration. The C677T genotype prevalence was 80% -/-, 20% +/-, and 0% +/+ among 46 African-American women; and 39% -/-, 53% +/-, and 8% +/+ among 77 white women (P < 0.01). There was a trend toward higher tHcy levels in African-American women with the +/- genotype when compared with the -/- genotype (6.9 mumol/L vs 5.3 mumol/L respectively, p = 0.10); no association was found among the white women (6.0 mumol/L, -/-; 4.5 mumol/L, +/-; and 6.2 mumol/L, +/+; p = 0.67). Among African American women, those who smoked and were +/- genotype had the highest tHcy levels (8.0 mumol/L); while among white women, those who smoked and were -/- had the highest tHcy levels (8.1 mumol/L). Despite being hampered by a limited sample size, the thermolabile allele is significantly less common among African-American than white women. The association between genotype and tHcy concentration is influenced by smoking and multivitamin use.

Adolescent↗
PubMed1996

Pregnancy and the risk of stroke.

BACKGROUND: It is widely believed that pregnancy increases the risk of stroke, but there are few data available to quantify that risk. METHODS: We identified all female patients 15 through 44 years of age in central Maryland and Washington, D.C., who were discharged from any of 46 hospitals in the study area in 1988 or 1991. Two neurologists reviewed each case, using data from the women's medical records. We determined whether the women had been pregnant at the time of the stroke or up to six weeks before it occurred. For purposes of this analysis, the six-week period after pregnancy could begin with an induced or spontaneous abortion or with the delivery of a live or stillborn child. RESULTS: Seventeen cerebral infarctions and 14 intracerebral hemorrhages occurred in women who were or had recently been pregnant (pregnancy-related strokes), and there were 175 cerebral infarctions and 48 intracerebral hemorrhages that were not related to pregnancy. For cerebral infarction, the relative risk during pregnancy, adjusted age and race, was 0.7 (95 percent confidence interval, 0.3 to 1.6), but it increased to 8.7 for the postpartum period (after a live birth or stillbirth) (95 percent confidence interval, 4.6 to 16.7). For intracerebral hemorrhage, the adjusted relative risk was 2.5 during pregnancy (95 percent confidence interval, 1.0 to 6.4) but 28.3 for the postpartum period (95 percent confidence interval, 13.0 to 61.4). Overall, for either type of stroke during or within six weeks after pregnancy, the adjusted relative risk was 2.4 (95 percent confidence interval, 1.6 to 3.6), and the attributable, or excess, risk was 8.1 strokes per 100,000 pregnancies (95 percent confidence interval, 6.4 to 9.7). CONCLUSIONS: The risks of both cerebral infarction and intracerebral hemorrhage are increased in the six weeks after delivery but not during pregnancy itself.

Cerebral Hemorrhage↗
PubMed1996

Pergolide and carbidopa/levodopa treatment of the restless legs syndrome and periodic leg movements in sleep in a consecutive series of patients.

Carbidopa/levodopa has become accepted as a primary treatment for both the restless legs (RL) syndrome and periodic leg movements in sleep (PLMS). It, however, usually significantly augments the RL symptoms in the day as well as night, requiring medication change for about 70% of the patients. The dopaminergic agonist pergolide provides a potentially useful treatment; doses given at dinner and before bed could suffice to treat the symptoms for most of the 24-hour day. A series of consecutive patients with RL syndrome or PLMS was studied using a standard medication protocol starting with carbidopa/levodopa, switching if needed to pergolide and, finally, to an opiate or other treatment. For 51 patients entered into the study, 21 (39%) continued on carbidopa/levodopa and 26 (50%) switched to pergolide. For those tried on pergolide, 19 (73%) responded well. Restless legs augmentation occurred for only four (15%) and was severe enough to require medication change for only one (4%) of these patients. The patients with PLMS responded best to carbidopa/levodopa, whereas severe RL patients responded best to pergolide. Pergolide provided a good treatment for the RL syndrome, particularly for the more severe RL cases without significant problems with RL augmentation.

Antiparkinson Agents↗
PubMed1996

Augmentation of the restless legs syndrome with carbidopa/levodopa.

Dopaminergic agents and carbidopa/levodopa have become the preferred treatment for both the restless legs (RL) syndrome and for periodic limb movements in sleep (PLMS). For once-nightly treatments with carbidopa/ levodopa, a problem with morning end-of-dose rebound increases in leg movements has been reported to occur in the about one-fourth of the patients. In our clinical studies a previously unreported but far more significant problem of markedly augmented RL symptoms occurred in the afternoon and the evening prior to taking the next nightly dose. A systematic prospective evaluation of this augmentation in 46 consecutive patients treated with carbidopa/ levodopa for RL syndrome or PLMS disorder found this augmentation to be the major adverse effect of treatment. Augmentation occurred for 31% of PLMS patients and 82% of all RL patients. It was greater for subjects with more severe RL symptoms and for patients on higher doses (> or = 50/200 mg carbidopa/levodopa) but was unrelated to gender, age or baseline severity of PLMS. This augmentation was severe enough to require medication change for 50% of the RL patients and 13% of PLMS patients. Augmentation resolved with cessation of the medication and could be minimized by keeping the dose low.

Carbidopa↗
PubMed1984

Hormonal regulation of adult sympathetic neurons: the effects of castration on tyrosine hydroxylase activity.

The effects of the hormone testosterone on neurotransmitter synthesis in peripheral sympathetic ganglia were examined in adult male Sprague-Dawley rats. Tyrosine hydroxylase (T-OH), the rate limiting enzyme in catecholamine biosynthesis was examined in the hypogastric (HG), coeliac (CG), and superior cervical ganglion (SCG) subsequent to castration. Initial studies indicated that 2 weeks after surgery, HG T-OH activity fell to approximately 30% of control. In order to more clearly define the pattern of testosterone effects, HG was examined 1, 2 and 4 weeks after surgery. T-OH activity was 67%, 50% and 11% of control at these 3 respective time points, and the observed alteration in T-OH activity appeared to parallel changes in the size of pelvic target organs. Similar hormonal effects did not occur in other peripheral sympathetic ganglia; T-OH activity was unchanged in SCG and CG when examined 1 month after castration. Enzyme activity was restored following replacement therapy with testosterone, whereas the neural metabolite 17-beta estradiol was without effect. The recovery in T-OH activity was associated with partial recovery of target organ size. These studies suggest that hormonal factors regulate neurotransmitter synthesizing enzymes in adult sympathetic neurons and may do so via consequences of alterations in target organs. These observations parallel similar events in the developing nervous system.

Animals↗
PubMed1981

Isolation of tryptophan, 5-HT, and 5HIAA from single brain areas using disposable columns packed with sephadex G-10 resin.

Using disposable Bio-Rad Columns packed with Sephadex G-10 resin (7 x 40 mm resin column), tryptophan, 5HT, and 5HIAA can be isolated from single discrete brain areas. The preparation of Sephadex G-10 columns requires a minimum amount of time, and once prepared, the columns require very little maintenance. Since the procedures involve gel filtration and not affinity chromatography, equilibration of the resin to its appropriate ionic strength or pH is not required. Brain tissue weighing 25-200 mg is homogenized in 1 ml of 0.4 M HClO4. After centrifugation at 4800 g, the supernatant is decanted onto the columns. Washing and eluting involve twelve 1 ml applications of either a phosphate buffer or a carbonate-NH4OH solution. Tryptophan and 5HIAA are eluted with the third, fourth, and fifth washings while 5HT is eluted with the last five washings. Tryptophan, 5HT and 5HIAA are all assayed by fluorometric techniques. These methods provide recovery values, reproducibility, and sensitivity comparable with cation exchange and some solvent extract methods.

Animals↗
PubMed1979

The effect of amitriptyline and mianserine (Org. GB94) on food motivated behaviour of rats trained in a runway: possible correlation with biogenic amine concentration in the limbic system.

Rats on a 23 h food deprivation schedule were trained to run down a straight runway for a food reward. Neither amitriptyline nor mianserine had an effect on the running time for the food reward during the period of continuous reinforcement. However both antidepressants delayed the extinction of this response. It seems unlikely that this effect on extinction was due to an altered motivation for the food reward as amitriptyline significantly decreased the food intake of the experimental animals while mianserine increased the food intake throughout the period of the experiment. The observation that both these antidepressants reduce the speed of extinction of rewarded behaviour may be explicable in terms of observed changes in the concentration of biogenic amines in the limbic system.

Amitriptyline↗