Platelet alpha-adrenergic receptors in obesity: alteration with weight loss.

We studied platelet alpha-adrenergic receptor concentration and function in 19 subjects with simple obesity participating in a double-blind, controlled clinical trial of diet and anorexiants (phentermine, fenfluramine, or a combination of the two) or placebo. From wk 1 to wk 8, weight loss for the group as a whole was 4.9 +/- 0.7 kg (mean +/- SE). Concomitant with this weight loss, the platelet alpha-adrenergic receptor concentration rose from 85.7 +/- 5.8 to 113 +/- 5.8 fmol/mg protein. This increase moved the values for the obese subjects toward or beyond values in lean controls (100 +/- 10.5 fmol/mg protein). The response in the different treatment groups was similar. The receptor concentration increase was accompanied by a corresponding increase in alpha-adrenergic receptor-mediated platelet aggregation. For individual subjects the extent of weight loss over time generally correlated with percent receptor change. Altered adrenergic sensitivity occurring in obese subjects who are losing weight may have important implications in relation to external (therapeutic or inadvertent) administration of catecholamines.

Tremor at onset. Predictor of cognitive and motor outcome in Parkinson's disease?

We examined 46 male patients with idiopathic Parkinson's disease to see whether tremor at onset was as useful a predictor of benign clinical outcome as tremor predominance after several years. When we compared patients with tremor at onset (n = 27) with those whose disease began with brady-kinesia/rigidity (n = 9), or gait disorder (n = 10), we found no significant differences after a mean of 7 years in motor, cognitive, or affective status. Sixteen of the tremor-onset patients continued to have tremor predominance with minimal gait disorder after about 7 years. These tremor-predominant patients had significantly better motor outcome and somewhat better cognitive outcome than either tremor-onset patients who subsequently developed gait disorder (n = 11) or patients without tremor at onset (n = 19). Tremor predominance after several years appears to be a better predictor of a benign clinical course of Parkinson's disease than tremor at onset.

Saccadic latency measurements in dementia.

We measured saccadic latencies in patients with Alzheimer's dementia (AD) and other types of dementia. The saccadic latencies for both groups were considerably longer than those for age-matched controls. The prolongation was as extensive in patients with other types of dementia as it was in those with AD. There was no correlation between latency and the severity of the dementia.

CSF silicon in dementia: a prospective study.

We designed a prospective study to determine whether CSF silicon elevation is specific for Alzheimer-type dementia (ATD) and whether it is related to the severity of cognitive or functional impairment. We found elevated CSF silicon in 30% of 23 ATD patients but in only 1 of the 23 age-matched nondemented controls. In all ATD patients with elevated CSF silicon, symptoms began after age 65. Thirty-four percent of 29 patients with other types of dementia also had elevated CSF silicon. Therefore, elevated CSF silicon concentrations are not specific for ATD, but they correlate with age and severity of functional impairment in late-onset ATD.

Magnetic resonance imaging in vascular dementia.

Patients with vascular dementia show distinctive white matter lesions on MRI. We performed MRI on 34 patients with documented ischemic cerebrovascular disease to see whether demented and nondemented patients differ with respect to enlarged CSF spaces or white matter lesions. All eight demented patients had white matter lesions on MRI, just as did many borderline and nondemented patients. Enlargement of central CSF spaces was the only radiographic feature that was seen more commonly in demented than in nondemented patients with ischemic cerebrovascular disease.

Cerebrospinal fluid trace element content in dementia: clinical, radiologic, and pathologic correlations.

Using inductively coupled argon plasma emission spectroscopy, we measured 19 trace elements in cerebrospinal fluid of 265 patients who were undergoing diagnostic lumbar puncture. Thirty-three patients had Alzheimer-type dementia (ATD); 16 patients had other dementing illnesses; and 20 had no neurologic disease. There were seven cases of autopsy-proven Alzheimer's disease (AD) and eight autopsy controls. We found elevated CSF silicon in 24% of ATD and 71% of AD patients. We found no relationship between CSF aluminum, arsenic, lead, or manganese and ATD, AD, or other dementing illnesses.

Silicon as a potential uremic neurotoxin: trace element analysis in patients with renal failure.

We analyzed multiple trace elements in tap water, dialysis fluids, and CSF of patients on dialysis and with chronic renal insufficiency. Before placement of a deionizer in the dialysis unit, we found elevated levels of aluminum, barium, copper, silicon, and zinc in tap water and dialysis fluids. These were corrected by the deionizer. CSF silicon content was increased in patients with chronic renal insufficiency and on dialysis; CSF aluminum, barium, copper, and zinc were normal.

Stroke prevention in women: role of aspirin versus ticlopidine.

Stroke is the third leading cause of death in North America. Most studies indicate that women are just as likely as men to have an initial stroke but less likely to have a recurrent stroke. Aspirin and ticlopidine are two antiplatelet drugs that reduce the risk of recurrent stroke by 25% to 30%. In some stroke prevention trials, aspirin has been shown to be more effective for men than for women. In contrast, major stroke prevention trials using ticlopidine have demonstrated equal benefit in women and in men. The overall incidence of adverse effects seen with ticlopidine is not significantly different from that observed with aspirin. There are now two effective agents useful in stroke prevention in both men and women.

Effect of a drug holiday on plasma chlorpromazine levels in chronic schizophrenic patients.

Low chloropromazine (CPZ) levels have been measured in chronically treated schizophrenics. We tested six such patients to determine whether a 2-week CPZ-free period (drug holiday) would improve plasma CPZ levels. We also monitored psychiatric symptoms, autonomic function, and extrapyramidal signs. We found these patients to have low predose CPZ levels that did not change appreciably after the drug holiday. Peak levels following the holiday averaged 28 +/- 7 ng/ml higher than those measured prior to the holiday. Drug holidays are safe and should be examined more thoroughly as a means of improving plasma neuroleptic levels in chronically treated schizophrenics.

Parkinsonism associated with fluoxetine and cimetidine: a case report.

Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) are effective for the treatment of depression in the elderly and offer a safer side-effect profile as compared to tricyclics and monoamine oxidase inhibitors. We report a case in which a patient treated with fluoxetine developed parkinsonism following the introduction of cimetidine. Inhibition of hepatic P450 cytochrome enzymes by cimetidine with an increase in serum levels of norfluoxetine may have precipitated this extrapyramidal syndrome, which has been related to agonism of the serotonergic input to nigrostriatal tracts and basal ganglia. Parkinsonism as a side effect of SSRIs occurs infrequently, suggesting an idiosyncratic response resulting from a functional imbalance of serotonergic and dopaminergic activity in susceptible individuals. Careful monitoring of geriatric patients treated with fluoxetine is indicated, particularly for those on high doses, those with impaired hepatic functioning, or those treated with concurrent medications that slow the metabolism of fluoxetine.

Natural history of the vascular dementias: a prospective study of seven cases.

The clinical course of vascular dementia has been described as a stepwise deterioration over time. We studied the chronologic course of cognitive performance over 1-4 years in seven patients with known ischemic cerebrovascular disease whose dementia subtype was assigned according to the clinical history and the pattern of white matter lesions seen on magnetic resonance imaging (MRI). One patient had the lacunar state, three had subcortical arteriosclerotic encephalopathy and three had multiple cortical and subcortical strokes. All were being treated with an antiplatelet agent and six received antihypertensive therapy. Four of the seven vascular dementia patients improved cognitively over the first year. A fluctuating course was eventually seen in all patients. None showed stepwise deterioration of cognitive function over time. The MRI was useful in subclassifying vascular dementia patients, but the clinical course did not appear to vary as a function of the dementia subtype.

Comparing Differences in ADL Outcomes for the STOMP Intervention for Dementia in the Natural Home Environment Versus a Clinic Environment.

BACKGROUND: Few studies have examined structured rehabilitation techniques for improving activities of daily living in people with mild-moderate dementia. We sought to examine the advantages to delivering the Skill-building through Task-Oriented Motor Practice (STOMP) intervention in the home environment (versus the clinic), hypothesizing that ADL improvement would be significantly better, time to meeting goals would be faster and fewer displays of behavior would be noted. METHODS: Compared results of two quasi-experimental studies of STOMP, one completed in the home, one completed previously in a clinic. Participants were English-speaking; community dwelling adults aged 50-90 diagnosed with mild-moderate dementia who could participate in an intensive rehabilitation program (5 days/week, 3 hours/day, for 2 weeks). Outcome measurements include examiner-observation of performance and proxy-report of performance and satisfaction with performance in patient-selected goals. RESULTS: No differences existed in the sociodemographic characteristics between the home and clinic groups where the groups were primarily white, married, had > high school education and had mild-moderate dementia. Results from the home group indicate that participants made significant improvement in ADL which was generally retained at the 90 day follow-up. These results were not significantly different than the clinic group. No significant advantages were noted for the home group in terms of time to meeting goals or exhibition of fewer behaviors. DISCUSSION: The STOMP intervention appeared to work equally as well in the home and in the clinic. Future studies should continue to examine the benefits of massed practice using high-dose regimens.

Time to hospital arrival, use of thrombolytics, and in-hospital outcomes in ischemic stroke.

OBJECTIVE: To determine the interval between symptom onset and hospital arrival and its relationship to baseline clinical characteristics, use of thrombolysis, and in-hospital outcomes in patients with acute ischemic stroke admitted to the 11 hospitals in the Buffalo metropolitan area and Erie County. METHODS: The medical records of 1,590 patients were reviewed to determine the severity of the neurologic deficits (NIH Stroke Scale [NIHSS]), in-hospital mortality, favorable outcome (modified Rankin Scale score of < or = 2 at discharge), and strata of time interval between symptom onset and hospital arrival. RESULTS: The time interval between symptom onset and hospital arrival was 0 to 3 hours in 337 (21%) patients, 3 to 6 hours in 177 (11%) patients, 6 to 24 hours in 301 (19%) patients, > 24 hours in 420 (26%) patients, and undetermined in 355 (22%) patients. IV (n = 23) and intra-arterial (n = 4) thrombolysis was used in 27 (8%) of the 337 patients that presented within 3 hours of symptom onset. In 1,235 patients with known time interval between symptom onset and hospital arrival, an association (p = 0.008) was observed between strata of increasing time interval and higher proportion of favorable outcomes at discharge. The initial NIHSS score was higher with decreasing interval between symptom onset and hospital arrival (p < 0.0001). CONCLUSIONS: A small proportion of patients who present within 3 hours of symptom onset receive thrombolytic therapy. The observation that patients with more severe neurologic deficits and subsequently worse in-hospital outcomes appear to present early after symptom onset to the hospital may have implications for clinical studies.

Diagnosis and treatment of depression in the elderly.

Depression and suicide are significant problems in the elderly, both in terms of their severity and their prevalence. It is particularly difficult to distinguish depression from early dementia, since elderly depressed patients often deny mood disorder and focus on their memory problems. This differential diagnostic dilemma is further complicated by the fact that 20 percent of Alzheimer-type dementia patients have moderate to severe depression. An even higher prevalence of depression can be seen in elderly patients with stroke or Parkinson's disease. Most all of the depressive disorders of the elderly are amenable to one form or combination of therapies: pharmacologic, electro-convulsive, or psychotherapy. Tricyclic antidepressants are often associated with adverse drug reactions in the elderly, so alternatives such as MAO inhibitors, alprazolam, bupropion and psychostimulants are currently being explored in this patient population.

The use and abuse of the cerebrospinal fluid IgG profile in the adult: a practical evaluation.

Cerebrospinal fluid (CSF) samples from 150 patients with multiple sclerosis (MS) and 190 patients with other neurological disorders were examined with a battery of tests (the IgG profile) to detect quantitative and qualitative abnormalities in CSF IgG. The CSF IgG profile consisted of an IgG/albumin (IgG/alb) ratio, an IgG index, and examination by agarose gel electrophoresis (AGE) and isoelectric focusing (IF) to detect oligoclonal bands. The tests were compared for diagnostic accuracy, including false-positive results. The IgG/alb ratio was less reliable in confirming the diagnosis of MS, but no significant difference in accuracy was found among the other three methods. IF tended to identify more possible and probable MS cases than did AGE but gave a higher rate of false-positives. The IgG index and IgG synthesis rates showed no significant difference in their ability to identify MS patients. Steroid administration decreased the incidence of abnormal IgG/alb ratios and IgG indices, but not abnormal oligoclonal bands. Central nervous system (CNS) infections or immunological diseases involving the CNS produced a 28 to 40% incidence of abnormalities in the CSF. Neither the patient's age, sex, duration of illness, activity of disease, nor longitudinal course correlated with the CSF findings. A few (1%) control neurological patients had all components in the CSF IgG profile abnormal. For most routine clinical purposes the IgG index and AGE are sufficient for confirmation of diagnosis, and the IgG index was the best single test in our series.

Computerized tomography in the diagnostic evaluation of multiple sclerosis.

Sixty-six patients with a tentative or certain diagnosis of multiple sclerosis (MS) were examined with cranial computerized tomography (CT). Abnormalities found in 19 (29%) included discrete areas of decreased white matter density, enlarged ventricles, cortical atrophy, and focal areas of contrast enhancement. The presence of white matter lucencies and ventricular dilatation correlated with an increased incidence of diffuse hyperreflexia and mental impairment. Since half the patients with contrast-enhancing lesions were clinically stable, their lesions may represent acute asymptomatic plaques. Abnormalities on CT scan were observed more often in older patients whose disease had lasted longer and was clinically more definite. Since findings were sparse in early, less definite disease, the use of CT as a purely diagnostic tool is limited.