Diagnosis of hyperlipidemia and treatment with a statin in the outpatient stroke clinic.

The aim of this study was to assess a stroke clinic's performance in the diagnosis of hyperlipidemia and more specifically to evaluate the effectiveness of statins in patients with cerebrovascular disease not enrolled in a research study. The records of 370 consecutive patients seen at a stroke clinic over a 4-year period were reviewed, and information regarding neurologic diagnosis, lipid profile, and use and type of cholesterol-lowering medication was abstracted. Hyperlipidemia was defined as a total cholesterol level equal to or more than 200 mg/dL. Forty-eight patients meeting specific criteria were further analyzed to monitor the effects of statins. Cholesterol testing was obtained in 324 patients (88%) and 178 (55%) were hyperlipidemic, but only 86 (48%) patients received treatment. The mean cholesterol level of the 48 patients dropped from 246.2 mg/dL to 197.1 mg/dL (P < .0001) after the initiation of statin therapy, and significant reductions were present in subgroups with pretreatment levels of 200 to 249 mg/dL and 250 to 299 mg/dL. Of the 21 patients with repeated cholesterol testing more than 6 months after the first posttreatment test, only 11 (52%) maintained a level below 200 mg/dL. Effective control of hyperlipidemia can be achieved in patients with cerebrovascular disease, but not all are adequately tested or treated. Improved physician awareness and more effective health care delivery systems are needed.

Risk factor modification in stroke prevention: the experience of a stroke clinic.

BACKGROUND AND PURPOSE: [corrected] We reviewed Stroke Clinic data to determine the extent of risk factor modification achieved in patients with cerebrovascular disease over 2 years. METHODS: Visits to the Stroke Clinic of a tertiary medical center from July 1, 1994, through June 30, 1996, were reviewed. Obesity, smoking, hypertension, hyperlipidemia, hyperglycemia, and lifestyle changes were noted in patients with >/=2 visits (n=61) and measures (number varied) of these parameters. RESULTS: Fifty-six patients (92%) had primary care physicians. In the 49 patients with >/=2 weight measurements, 33 (67%) were moderately or severely overweight by weight-height correlation. Forty-four patients (90%) remained in the same weight category. Of the 60 patients with available blood pressure data, 50 (83%) were hypertensive. At their last visits, 43 of the 50 (86%) were receiving medications, and 22 of the 43 treated (51%) were controlled. Serum glucose remained elevated in 14 of 47 patients (30%) and in 11 of 16 diabetic patients (69%). Thirty-six of 47 patients (55%) had elevated lipid measurements. None of the 21 smokers quit during the study period. Few patients modified dietary and exercise practices. Of 61 patients, 29 (48%) sustained vascular events during the study, with 17 of these 29 patients (59%) having strokes or transient ischemic attacks. CONCLUSIONS: Although most patients were asked to quit smoking, received advice regarding diet and exercise, and were medicated for hypertension, elevated glucose, and cholesterol levels, their risk factor profiles showed little improvement during the 2-year period. More effective methods of controlling stroke risk factors are needed.

Methsuximide for complex partial seizures: efficacy, toxicity, clinical pharmacology, and drug interactions.

Methsuximide (MSM; Celontin) was administered for 8 weeks to 26 patients with complex partial seizures (CPS) refractory to phenytoin and carbamazepine and phenobarbital or primidone. A 50% or greater reduction in CPS frequency was obtained in eight patients. MSM therapy was continued chronically in these eight patients, and five continued to have a 50% or greater reduction in CPS frequency after 3 to 34 months of follow-up. Drowsiness, gastrointestinal disturbance, hiccups, irritability, and headache were the common side effects of MSM. No serious toxicity occurred. N-desmethylmethsuximide was the principal substance detected in plasma and had the following pharmacokinetic values: accumulation half-life, 49.7 hours; time to steady state, 10.4 days; elimination half-life, 72.2 hours; therapeutic range of plasma concentration, 10 to 30 mg per liter. Plasma concentrations of phenytoin and phenobarbital derived from primidone rose significantly (p less than 0.05) after addition of MSM.

Cobalamin analogues are present in human plasma and can mask cobalamin deficiency because current radioisotope dilution assays are not specific for true cobalamin.

Since R protein binds cobalamin (vitamin B12) and cobalamin analogues, whereas intrinsic factor is highly specific for true cobalamin, we compared the serum cobalamin values obtained with these proteins in radioisotope dilution assays. With R protein, eight of 21 patients with cobalamin deficiency had serum cobalamin levels (mean, 204, range, 85 to 355 pg per milliliter) that overlapped with values for 74 normal subjects (mean, 576, range, 220 to 1230). With intrinsic factor, no patient values (mean, 36, range, less than 10 to 78 pg per milliliter) overlapped with the normal values (mean, 322, range, 130 to 785). Paper chromatography showed that these differences were due to the presence of cobalamin analogues. R protein constituted 51 to 85 per cent of the cobalamin-binding protein in 10 commercial serum cobalamin assay kits, which were said to contain "intrinsic factor". Human plasma contains cobalamin analogues that can mask cobalamin deficiency with current radioisotope dilution assays.

Correction of cobalamin malabsorption in pancreatic insufficiency with a cobalamin analogue that binds with high affinity to R protein but not to intrinsic factor. In vivo evidence that a failure to partially degrade R protein is responsible for cobalamin malabsorption in pancreatic insufficiency.

In vitro studies indicate that [(57)Co]cobalamin (Cbl) is preferentially bound to salivary R protein as opposed to intrinsic factor (IF) and that [(57)Co]Cbl bound to R protein is not transferred to IF at either pH 2 or pH 8. Incubation of R protein-[(57)Co]Cbl with pancreatic proteases causes a partial degradation of the R protein moiety and a rapid transfer of [(57)Co]Cbl to IF. We have postulated that the etiology of Cbl malabsorption in pancreatic insufficiency is an inability to partially degrade R protein because of a lack of pancreatic proteases. We have tested this hypothesis by determining the ability of a nonradioactive Cbl analogue, bound with high affinity by R protein but not by IF, to correct the malabsorption of [(57)Co]Cbl in patients with pancreatic insufficiency.R protein bound the Cbl analogue known as cobinamide with affinities that were the same and only 14-fold lower than those for Cbl at pH 8 and pH 2, respectively. Cobinamide was bound by IF with affinities that were 600,000- and 10,000-fold lower than those for Cbl at pH 8 and 2, respectively. The addition of 125 pmol of nonradioactive cobinamide to 0.5 pmol of [(57)Co]Cbl before being added to 1 pmol of R protein and 1 pmol of IF, markedly inhibited the ability of R protein to compete with IF for binding the [(57)Co]Cbl. Similar results were obtained with freshly aspirated gastric juice. This change was essentially indistinguishable from that observed previously when R protein or R protein-[(57)Co]Cbl was incubated in vitro with trypsin. The oral administration of 100 nmol of nonradioactive cobinamide in Schilling tests was equivalent to trypsin in its ability to completely correct the malabsorption of 0.4 nmol of [(57)Co]Cbl in three patients with pancreatic insufficiency. The fact that both trypsin and nonradioactive cobinamide inhibit the ability of R protein to compete with IF for [(57)Co]Cbl binding in vitro, and correct the mal-absorption of [(57)Co]Cbl in patients with pancreatic insufficiency in vivo, supports our hypothesis that the primary defect in Cbl absorption in this disease is an inability to partially degrade R protein because of a lack of pancreatic proteases.