The effect of multiple neuroimaging studies on classification, treatment, and outcome of acute ischemic stroke.

OBJECTIVE: To examine the effect of serial neuroimaging studies on the diagnosis, therapy, and outcome of patients with acute stroke. DESIGN: Retrospective case series. SETTING: Tertiary care teaching hospital. PATIENTS: 206 adult patients (mean age +/- SD, 66.0 +/- 10.8 years) hospitalized with a diagnosis of acute stroke between 1990 and 1993. MEASUREMENTS: Strokes were retrospectively assigned to five categories (large-vessel, small-vessel, cardioembolic, other, or unknown) using standardized criteria based on the history, physical examination, ancillary test results, and first computed tomographic (CT) or magnetic resonance imaging (MRI) study of the head. Strokes were reclassified after the results of further neuroimaging studies, if any, were reviewed. The type and timing of therapy and the patient outcome at hospital discharge were documented. RESULTS: The additional studies changed stroke classification in only 20.0% of the 140 patients who had two or more neuroimaging studies. All classification changes were from the unknown cause category to a category with a specific cause. In most patients receiving treatment (93.2%), therapy began before an additional CT or MRI study was obtained. In patients who had one neuroimaging study, 70.1% went home, 24.0% went to a skilled nursing facility, and 5.9% died; the corresponding percentages in persons who had multiple studies were 73.3%, 24.4%, and 2.2% (P > 0.1). CONCLUSIONS: Serial neuroimaging studies did not alter the classification of strokes for which an initial diagnosis had already been made. However, they were useful in determining the cause of strokes initially classified as having an unknown cause. Therapy was almost always begun immediately after the first CT or MRI study was obtained. Outcome at hospital discharge was not significantly related to the number of neuroimaging studies obtained.

Exercise-induced changes in blood minerals, associated proteins and hormones in women athletes.

The acute effects of prolonged exercise on the body's distribution of trace minerals in women athletes has not been examined. To this end, plasma concentrations of zinc, copper, and iron; erythrocyte zinc (EZn) and copper (ECu); and the associated proteins, ceruloplasmin and transferrin were measured in 38 highly trained women runners under resting conditions and again after running a competitive 26.2 mile marathon. The hormones, cortisol (C), estradiol (E2), prolactin (Prl), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were also measured because of reported effects of hormones on trace mineral distribution. Menstrual status was assessed by questionnaire: 8 women were in the follicular phase, 13 in mid-cycle, 8 in the luteal phase and 9 were amenorrheic (AM). Significant post-race increases were noted for all plasma minerals, associated proteins, and the hormones C and Prl, whereas EZn decreased. No significant changes in ECu, E2, FSH or LH were noted. Menstrual status in terms of cycle phase or amenorrhea did not appear to modify the response. Exercise-induced changes in minerals may reflect release from other tissues and/or changes in the concentration of associated proteins. Whether these changes serve adaptive and/or specific functions during exercise is unknown.

Amenorrhea in Olympic marathon runners.

Women who exercise heavily may develop secondary amenorrhea. Since the mechanism of so-called "runner's amenorrhea" has not been conclusively established, the authors examined the occurrence of amenorrhea in one of the most intensively exercising groups of female runners in the United States (average, 70 miles/week): those women participating in the marathon trials for the 1984 Olympics. Nineteen percent of these Olympic runners were amenorrheic. When compared with eumenorrheic marathon runners, these amenorrheic runners were significantly (P less than 0.05) younger (24.8 +/- 1.2 [standard error of the mean] versus 30.8 +/- 0.8 years), lighter (108.4 +/- 2.5 versus 114.6 +/- 1.7 lb), and leaner (11.2 +/- 0.5 versus 12.5 +/- 0.3% body fat). There were no differences between the two groups in weekly training mileage, proportion completing the marathon trial, finishing time, basal serum prolactin, or postmarathon serum prolactin. Although basal serum cortisol was slightly higher in the amenorrheic group (26.6 +/- 0.8 versus 22.3 +/- 0.7 micrograms/dl; P less than 0.05), postmarathon serum cortisol was similar in the two groups. This study supports the concept that training intensity above a certain threshold seems to have little effect on the development of runner's amenorrhea, and vigorously training national caliber marathon runners have a lower incidence of amenorrhea than previously predicted.

Emotional eccrine sweating. A heritable disorder.

A family with hereditary emotional hyperhidrosis is described. The inheritance pattern is autosomal dominant. A simple quantitative palmar sweat test was used to objectively confirm historical data. Of two family members tested, both had a marked decrease in palmar sweat secretion during administration of diltiazem, a calcium-channel blocker. Additional studies in a large group of patients are needed to extend this observation.

Effects of exercise and conditioning on clotting and fibrinolytic activity in men.

Sixty healthy men in three physical fitness categories (sedentary, on no organized fitness program; joggers, running 5-15 miles/wk; and marathoners, running greater than 50 miles/wk) were evaluated for changes in blood clotting and fibrinolytic activity before and after maximum exercise on a treadmill according to the Bruce protocol. The rate of blood clotting, as measured by prothrombin times, partial thromboplastin times and thrombin times, was accelerated by exercise (all P less than 0.005). The ability of euglobulin clots and plasma clots to lyse incorporated 125I-fibrin, termed 125I-euglobulin clot lysis (IEL) and 125I-plasma clot lysis (IPCL), were used as indexes of fibrinolytic activity. Marathoners had greater increases in fibrinolytic activity with exercise (76% compared with 63% for joggers and 55% for sedentary subjects by IEL; 427% compared with 418% for joggers and 309% for sedentary subjects by IPCL; all P less than 0.05). Fibrin degradation products increased with exercise (P less than 0.005 for the total group of 60 subjects). The absolute concentrations of alpha 2-plasmin inhibitor, alpha 2-macroglobulin, and antithrombin III increased with exercise (all P less than 0.005), but when concentrations were corrected for acute shifts of plasma water during exercise, the quantity of these inhibitors actually decreased (all P less than 0.005). The changes in clotting assays with exercise were not significantly correlated with changes in whole blood lactate, blood pyruvate, or rectal temperatures. Fibrinolytic assays before and after exercise correlated poorly to moderately with blood lactates (IEL: r = 0.441 and r = 0.425, respectively; IPCL: r = 0.294 and r = 0.544, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnesium homeostasis during high-intensity anaerobic exercise in men.

This study was conducted to determine whether short-term, high-intensity anaerobic exercise alters Mg homeostasis. Thirteen men performed intermittent bouts of treadmill running at 90% of their predetermined maximum O2 uptake until exhaustion on one occasion during a week in which all men were consuming a standard diet (115 mg Mg/1,000 kcal). Plasma and erythrocyte Mg concentrations and peripheral blood mononuclear cell Mg content were measured before and after the exercise. Complete 24-h urine collections were obtained on control days, on the day of exercise, and on the day after exercise. Exercise induced a transient but significant decrease in plasma Mg content (-6.8%; P less than 0.01); over 85% of the loss could be accounted for by a shift to the erythrocytes. Significant increases in urinary excretion of Mg were observed on the day of exercise (131.5 +/- 6.8 mg/day) compared with control days (108 +/- 6.6 mg/day), with the percent increase correlating with postexercise blood lactate concentration (r = 0.68; P less than 0.01) and oxygen consumption during recovery (r = 0.84; P less than 0.001). The data indicate that high-intensity anaerobic exercise induces intercompartmental Mg shifts in blood that return to preexercise values within 2 h and urinary losses on the day of exercise that return to base line the day after exercise. It is postulated that the exercise-induced increase in Mg excretion may depend on the intensity of the exercise, and the relative contribution of anaerobic metabolism to the total energy expended during exercise.

Nutritional survey of highly trained women runners.

Mean daily intakes from 3-day dietary records for calories, energy-providing nutrients, and selected minerals were calculated for 51 highly trained women runners. Selected blood constituents relating to mineral status were also measured. Intakes of calcium, magnesium, iron, and copper were above the amounts recommended by the National Research Council whereas zinc intake was below the recommended dietary allowances (RDA). Caloric intakes, although above the RDA for sedentary women, appeared low for women running 10 miles/day. Concentrations of serum ferritin and plasma zinc were indicative of marginal iron and zinc status in many of the women. Whether the nutrient content of the diets consumed by these women is adequate relative to energy output or whether training lowers nutrient requirements by enhancing metabolic efficiency will require further investigation.

Nutritional intakes and status of highly trained amenorrheic and eumenorrheic women runners.

This study was conducted to determine whether nutritional status contributes to the amenorrhea associated with long distance running. Dietary intakes and biochemical measures of nutritional status were compared in highly trained amenorrheic (AM) and eumenorrheic (EU) women runners matched for height, weight, percent fat (11% to 12%) and training distance (113 km/week). Serum estradiol (E2) (EU, 104.7 pg/ml, versus AM, 22.5 pg/ml) and cortisol (EU, 22.4 micrograms/dl, versus AM, 26.6 micrograms/dl) concentrations differed between the two groups. Three-day dietary records revealed that fat intake by AM runners was significantly lower than by EU runners (EU, 97 gm/day, versus AM, 66 gm/day). AM runners consumed large amounts of vitamin A activity, probably in the form of B-carotene, and fairly high quantities of crude fiber. Zinc intake by AM runners was well below the recommended dietary allowances (RDA), compared with EU runners (EU, 15.4 mg, versus AM, 10.9 mg). Further, plasma zinc tended to be lower for the AM runners (EU, 85.7 micrograms/dl, versus AM, 81.2 micrograms/dl). It was concluded that the potential contributions of dietary fat, B-carotene, and zinc to inducing changes in menstrual function and the metabolism of certain hormones should be investigated.

Plasma viscosity elevations with simulated weightlessness.

Bed rest studies which simulate weightlessness have demonstrated marked changes in the state of hydration of subjects as well as decrements in aerobic capacity. These two phenomena may be linked through increases in blood viscosity which is altered by a loss of free water and which, in turn, influences blood flow needed for aerobic muscular work. This study examines changes in the rheologic properties of blood which attend changes in plasma volume with bed rest in humans and correlates these changes with alterations in aerobic capacity. Eight healthy human subjects were studied on the 6th day of bed rest during two consecutive 10-d bed rest periods separated by a 14-d recovery interval designed to simulate the flight-layover schedule of shuttle astronauts. Plasma viscosity was measured with a Wells-Brookfield viscometer, plasma volume by dye dilution, and maximal aerobic capacity (VO2max) by recumbent cycle ergometry. Bed rest resulted in significant increases in hematocrit and in total plasma protein concentration and fibrinogen concentration, both of which contribute to an elevation in plasma viscosity. The greater than 20% increase in fibrinogen concentration was much greater than could be explained by hemoconcentration. VO2max decreased significantly in the first but not the second bed rest cycle. In many individuals, a decrease in plasma volume and aerobic capacity was coupled with elevated plasma viscosity and hematocrit; however, significant correlations between these variables were lacking. Although significant rheologic perturbations do occur with bed rest, in this study, blood viscosity elevation failed to directly correlate with the reduction in VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood viscosity responses to maximal exercise in endurance-trained and sedentary female subjects.

To assess whether the rheological properties of blood might be altered by exercise, we measured whole blood viscosity, plasma viscosity, and its components in healthy female subjects before, immediately after, and 1 h after maximal upright exercise using the Bruce graded exercise protocol. Forty-seven female subjects (15 sedentary, 14 who ran 5-15 miles/wk, and 18 who ran greater than 50 miles/wk), ages 18-43 yr, were evaluated. Whole blood viscosity, measured with a cone and plate viscometer, increased an average of 12.6% with exercise. The increase was greater than can be attributed to the observed 8.9% increase in hematocrit alone due to a coincident increase in plasma protein concentration. However, plasma viscosity did not rise to the degree expected, likely due to a disproportionate observed loss of fibrinogen from the protein pool. These changes were independent of conditioning level or aerobic capacity. In this cross-sectional study, there appears to be no adaptive adjustment in females to physical conditioning that results in changes in blood viscosity.

Hemoglobin Osler: report of a new family with exercise studies before and after phlebotomy.

Five members of a new family with hemoglobin Osler are described. Exercise studies were performed before and after phlebotomy in one patient. These studies demonstrated that anaerobic threshold was directly related to hematocrit. Our data suggest that the elevation of red cell mass seen with this high oxygen affinity hemoglobin is an appropriate physiologic response which improves tissue oxygen delivery. Despite the increase in whole blood viscosity associated with erythrocytosis, our data do not support the use of therapeutic phlebotomy to improve exercise performance in patients with hemoglobin Osler.

Increased heat sensitivity of red blood cells in hereditary elliptocytosis with acquired cobalamin (vitamin B12) deficiency.

Structural membrane proteins were studied from erythrocytes (RBC) of a patient with a nonhemolytic form of hereditary elliptocytosis (HE) who developed a microcytic anemia with fragmented RBC while cobalamin (B12) deficient. Evidence is presented for qualitative changes in the patient's RBC membranes not related to a loss of structural proteins. Sensitivity of RBC to heat treatment was studied as well as quantitative changes in proteins by densitometry of 1% SDS--10% PAGE gels. Fractions of RBC of various sizes from the patient while B12 deficient all possessed a marked degree of heat sensitivity when compared to RBC from the patient after B12 repletion, normal family members, HE controls, B12-deficient controls, anemic controls, and normal controls. Because loss of spectrin (bands 1 + 2) from heat-sensitive RBC membranes in hereditary pyropoikilocytosis has been reported, the amount of spectrin relative to band 3 was measured. No decrease in the ratio of bands (1 + 2)/3 was found. In addition, no chromatographically abnormal membrane proteins were found by SDS-PAGE of the patient's RBC while B12 deficient. Our findings indicate that B12 deficiency results in an abnormal membrane with enhanced instability in some forms of HE. Since protein loss was not found, we conclude that an alteration in membrane protein interaction may be involved.

Hypocupremia induced by zinc therapy in adults.

Hypocupremia occurred in an adult with sickle cell anemia who received zinc as an antisickling agent for two years. The hypocupremia was associated with microcytosis and relative neutropenia. Administration of copper resulted in an increase in RBC size and leukocyte counts. We have since observed hypoceruloplasminemia of varying degrees in several other sickle cell anemia patients who were receiving oral zinc therapy. This complication was easily corrected by copper supplementation.

Pharmacologic stimulation of erythrocyte 2,3-diphosphoglycerate production in vivo.

The ability of phosphate alone and in combination with sodium bicarbonate, vitamin C and pyruvate to elevate 2,3-diphosphoglycerate (DPG) levels was examined in normal human subjects in vivo. Statistically significant increases in DPG levels were noted (P less than .001) for all regimens pooled. Average rise in DPG levels reached 6% above pretreatment levels after 2 to 3 days of treatment. No changes in DPG levels were detectable in a group of control subjects over the same time period. Variation among pharmacologic trials and among subjects within trials in the actual magnitude of DPG build-up was marked. Significant differences could not be detected among the pharmacologic regimens in their ability to produce DPG increases. Previous reports suggested the use of these agents to stimulate red cell glycolysis but it seems that their effects and the mechanisms of glycolytic control in vivo are considerably more complex than has been previously suggested.

Clinical decision analysis. The hazard of using additional data.

Acquisition of laboratory data bearing on a clinical problem may make patient care worse rather than better. The hazards of obtaining new information, that go beyond the monetary costs and risks to physical well-being, are frequently not appreciated by physicians. In the complex and many-faceted practice of medicine, intuition, even when expressed by experienced clinicians, may lead to faulty judgments. Decision analysis gives a systematic exposition of clinical management, and lessens, if not eliminates, the influence of biased and unreliable intuition. With practice, most physicians could employ decision analysis to help solve moderately complicated problems at the bedside or in the office. Use of this tactic will make gaps in knowledge explicit, and may thereby stimulate investigations to ensure better clinical judgments in the future.

Trace elements in sickle cell disease.

Trace elements in 84 adult patients (38 men and 46 women) with sickle cell disease (SCD) were reflected in clinical and biochemical data. Height was retarded in six men and five women. Eighty percent of the SCD patients in this sample were below the 50th percentile from the normal mean for weight. Twenty-eight men showed a lack of facial and body hair, and five additional subjects showed only scanty facial hair. Whereas zinc in plasma, red blood cells, and hair was decreased, the excretion of zinc in urine was increased in SCD patients as compared to the controls. We believe that one of the mechanisms accounting for zinc deficiency in SCD may be hyperzincuria and that growth retardation and hypogonadism in men so commonly seen in SCD may be related to zinc deficiency.