Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial.

Corticosteroid-induced osteoporosis is the most common secondary cause of osteoporosis. We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy x-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SE) changes in BMD of the lumbar spine by QCT and DXA in the PTH group were 35+/-5.5% and 11+/-1.4%, respectively, compared with a relatively small change of 1.7+/-1.8% and 0+/-0.9% in the estrogen-only group. The differences in mean percentage between the groups at 1 yr were 33.5% for the lumbar spine by QCT (P < 0.001) and 9.8% for the lumbar spine by DXA (P < 0.001). The changes in the hip and forearm were not significantly different between or within the groups. During the first 3 mo of PTH treatment, markers of bone formation increased to nearly 150%, whereas markers of bone resorption increased only 100%, suggesting an early uncoupling of bone turnover in favor of formation. These results suggest that parathyroid hormone dramatically increases bone mass in the central skeleton of postmenopausal women with corticosteroid- induced osteoporosis who are taking hormone replacement.

Electrophysiologic effects of adenosine in patients with supraventricular tachycardia.

BACKGROUND: We correlated the electrophysiologic (EP) effects of adenosine with tachycardia mechanisms in patients with supraventricular tachycardias (SVT). METHODS AND RESULTS: Adenosine was administered to 229 patients with SVTs during EP study: atrioventricular (AV) reentry (AVRT; n=59), typical atrioventricular node reentry (AVNRT; n=82), atypical AVNRT (n=13), permanent junctional reciprocating tachycardia (PJRT; n=12), atrial tachycardia (AT; n=53), and inappropriate sinus tachycardia (IST; n=10). There was no difference in incidence of tachycardia termination at the AV node in AVRT (85%) versus AVNRT (86%) after adenosine, but patients with AVRT showed increases in the ventriculoatrial (VA) intervals (13%) compared with typical AVNRT (0%), P<0.005. Changes in atrial, AV, or VA intervals after adenosine did not predict the mode of termination of long R-P tachycardias. For patients with AT, there was no correlation with location of the atrial focus and adenosine response. AV block after adenosine was only observed in AT patients (27%) or IST (30%). Patients with IST showed atrial cycle length increases after adenosine (P<0.05) with little change in activation sequence. The incidence of atrial fibrillation after adenosine was higher for those with AVRT (15%) compared with typical AVNRT (0%) P<0.001, or atypical AVNRT (0%) but similar to those with AT (11%) and PJRT (17%). CONCLUSIONS: The EP response to adenosine proved of limited value to identify the location of AT or SVT mechanisms. Features favoring AT were the presence of AV block or marked shortening of atrial cycle length before tachycardia suppression. Atrial fibrillation was more common after adenosine in patients with AVRT, PJRT, or AT. Patients with IST showed increases in cycle length with little change in atrial activation sequence after adenosine.

Electrophysiological effects of ibutilide in patients with accessory pathways.

BACKGROUND: Atrial fibrillation (AF) may cause life-threatening ventricular arrhythmias in patients with Wolff-Parkinson-White syndrome. We prospectively evaluated the effects of ibutilide on the conduction system in patients with accessory pathways (AP). METHODS AND RESULTS: In part I, we gave ibutilide to 22 patients (18 men, 31+/-13 years of age) who had AF during electrophysiology study, including 6 pediatric patients

Atypical right atrial flutter patterns.

BACKGROUND: The purpose of our study was to define the incidence and mechanisms of atypical right atrial flutter. METHODS AND RESULTS: A total of 28 (8%) of 372 consecutive patients with atrial flutter (AFL) had 36 episodes of sustained atypical right AFL. Among 24 (67%) of 36 episodes of lower loop reentry (LLR), 13 (54%) of 24 episodes had early breakthrough at the lower lateral tricuspid annulus, whereas 11 (46%) of 24 episodes had early breakthrough at the high lateral tricuspid annulus, and 9 (38%) of 24 episodes showed multiple annular breaks. Bidirectional isthmus block resulted in elimination of LLR. A pattern of posterior breakthrough from the eustachian ridge to the septum was observed in 4 (14%) of 28 patients. Upper loop reentry was observed in 8 (22%) of 36 episodes and was defined as showing a clockwise orientation with early annular break and wave-front collision over the isthmus. Two patients had atypical right AFL around low voltage areas ("scars") in the posterolateral right atrium. CONCLUSIONS: Atypical right AFL is most commonly associated with an isthmus-dependent mechanism (ie, LLR or subeustachian isthmus breaks). Non-isthmus-dependent circuits include upper loop reentry or scar-related circuits.

New algorithm for the localization of accessory atrioventricular connections using a baseline electrocardiogram.

OBJECTIVES: In this study, we propose a new algorithm for accessory atrioventricular pathway localization using a 12-lead electrocardiogram (ECG). BACKGROUND: Radiofrequency catheter ablation produces a very discrete lesion, and ECG localization based on surgical dissection is obsolete. METHODS: Stepwise discriminant analysis was used to assess the relation of 18 pre-excited ECG (QRS duration > 100 ms) variables to the site of successful ablation in 93 patients. The most discriminating variables were combined to form rules for each location. The ECGs were retested by these rules to determine predictive accuracy. RESULTS: If the precordial QRS transition was at or before lead V1, the pathway had been ablated on the left side. If it was after lead V2, the pathway had been ablated on the right side. If the QRS transition was between leads V1 and V2 or at lead V2, then if the R wave amplitude in lead I was greater than the S wave by > or = 1.0 mV, it was right-sided; otherwise, it was left-sided (p < 0.0001, sensitivity 100%, specificity 97%). Right-side pathways. If the QRS transition was between leads V2 and V3, the pathway was right septal; if after lead V4, it was right lateral. If it was between leads V3 and V4, then if the delta wave amplitude in lead II was > or = 1.0 mV, it was right septal; otherwise, it was right lateral (p < 0.0001, sensitivity 97%, specificity 95%). In right lateral locations, if the delta wave frontal axis was > or = 0 degrees, or if it was < 0 degrees but the R wave amplitude in lead III was > or = 0 mV, it was anterolateral; otherwise, it was posterolateral (p < 0.0001, sensitivity 100%, specificity 87.3%). Anteroseptal pathways had a sum of delta wave polarities in leads II, III and aVF > or = +2(p < 0.0001, sensitivity 100%, specificity 100%). Posteroseptal pathways (inferior delta wave sum < or = -2) were less well discriminated from right midseptal pathways (inferior delta wave sum < or = 1 > or = -1) (p < 0.0001, sensitivity 76.5%, specificity 71%) [corrected]. Left-sided pathways. Two or more positive delta waves in the inferior leads or the presence of an S wave amplitude in lead aVL greater than the R wave, or both, discriminated left anterolateral pathways from posterior pathways (p < 0.001, sensitivity and specificity 100%). If the R wave in lead I was greater than the S wave by > or = 0.8 mV, and the sum of inferior delta wave polarities was negative, the location was posteroseptal; otherwise, it was posterolateral (p < 0.05, sensitivity 71.4%, specificity 100%). CONCLUSIONS: Using the algorithm derived, a right-sided accessory pathway can be reliably distinguished from one that is left-sided, right free wall from right septal, right anterolateral from posterolateral and anteroseptal from other right septal pathways. Left anterolateral pathways can be distinguished from left posterior pathways and left posterolateral pathways from left posteroseptal pathways.

Bone mass continues to increase at the hip after parathyroid hormone treatment is discontinued in glucocorticoid-induced osteoporosis: results of a randomized controlled clinical trial.

Glucocorticoid-induced osteoporosis is the most common secondary cause of osteoporosis. In this 24-month study, we report changes in bone turnover and bone mass after 12 months of daily injections of human parathyroid hormone 1-34 [hPTH(1-34)] and 12 months off treatment in postmenopausal women (mean age, 63 years) with osteoporosis treated with glucocorticoid and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy X-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SEM) change in BMD of the lumbar spine by QCT and DXA in the PTH group at 24 months was 45.9+/-6.4% and 12.6+/-2.2% (p < 0.001). The change in total hip and femoral neck BMD was not significant at 12 months but increased to 4.7+/-0.9% (p < 0.01) and 5.2+/-1.3% at 24 months, respectively, as compared with a relatively small change of 1.3+/-0.9% and 2.6+/-1.7% in the estrogen-only group. The mean percent differences in BMD of the lumbar spine by QCT and DXA between the groups at 24 months were 43.1% and 11.9%, respectively (p < 0.001). The mean percent differences over the estrogen-only group in hip BMD were 3.4% for total hip (p < 0.01) and 2.6% for femoral neck at 24 months. Biochemical markers of bone turnover increased to more than 150% during the first 6 months of therapy, remained elevated throughout the 12-month treatment period, and returned to baseline values within 6 months of discontinuing the PTH treatment. These results suggest that PTH dramatically increases bone mass in the lumbar spine and hip in postmenopausal women with glucocorticoid-induced osteoporosis who are taking hormone replacement therapy. However, the maximum effect of this anabolic agent on bone mass at the hip after 12 months of treatment requires at least 6-12 months after the PTH treatment is discontinued.

Acute changes in trabecular bone connectivity and osteoclast activity in the ovariectomized rat in vivo.

Estrogen deficiency results in a loss of trabecular bone mass and structure that leads to an increased incidence of osteoporotic fractures. The purpose of this study was to determine the time course for trabecular structure deterioration and changes in bone turnover just after ovariectomy in the rat. Six-month-old female virgin Sprague-Dawley rats had their right proximal tibia scanned by X-ray tomographic microscopy (XTM) at baseline (day 0). Animals were then randomized into two groups, and in each group 9 were sham-operated and 11 were ovariectomized and had repeat XTM scans on days 5, 13, 29, and 42 postovariectomy in group 1 and on days 8, 13, 33, and 50 postovariectomy in group 2. Urine was collected for deoxypyridinoline (DPD) cross-link measurements 24 h before each XTM scan and analyzed by ELISA. Trabecular bone structural variables and bone turnover endpoints were calculated from XTM data and standard histomorphometry. Trabecular connectivity decreased 27% by days 5 and 8 postovariectomy (p < 0.01) and continued to decrease up to day 50 postovariectomy (p < 0.01). The trabecular bone volume decreased 25% by 8 days postovariectomy (p < 0.01), and it continued to decrease through day 50. DPD cross-link excretion had increased 37% on day 13 (p < 0.01) and by over 100% of baseline by day 50 postovariectomy. Trabecular bone connectivity and volume deteriorate rapidly while DPD cross-link excretion increased more slowly in acute estrogen deficiency. These data suggest that if an agent is to preserve fully trabecular bone structure, it must be instituted very early in the estrogen-deficient state. They also suggest that a lag time exists before DPD excretion properly mirrors newly induced conditions of high bone turnover in this rat model.

Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat.

To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes in trabecular bone volume (BV/TV) and connectivity beginning either at ovariectomy (OVX) or 5-13 days after OVX in adult female rats, the right proximal tibial was examined by three-dimensional X-ray tomographic microscopy (XTM) in vivo. Animals had XTM scans of the right tibia and then were randomized into six groups (n = 9). Groups 2-6 had bilateral (OVX), while group 1 was sham-ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and 2) or 17beta-estradiol therapy (ERT) at 10 microg/kg three times per week starting at days 0, 5, 8, and 13 post-OVX (groups 3, 4, 5, and 6), until day 50 when they were rescanned by XTM and sacrificed. Trabecular bone structural variables were calculated from XTM data (BV/TVx and beta1/BV/TVx) and standard histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections per cubic millimeter of trabecular bone (beta1/BV/TVx) were maintained in both sham-OVXd animals and OVX animals given ERT from the time of OVX. However, OVX + vehicle-treated animals lost 54% BV/TVx and 46% beta1/BV/TVx (p < 0. 01 from day 0). BV/TVx and beta1/BV/TVx decreased rapidly post-OVX to -22% and -25% at day 13 (p < 0.01 from day 0). ERT initiated at day 5, 8, and 13 post-OVX restored BV/TVx to baseline values at day 50 by modestly increasing trabecular plate thickness; however, beta1/BV/TVx was reduced in all OVX groups when compared with their baseline values. ERT also caused a significant reduction in bone turnover compared with OVX + vehicle; however, resorption was suppressed more than formation. These results demonstrate that ERT can restore the lost trabecular bone, but not trabecular connectivity, that occurs soon after OVX by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which prompt intervention with estrogen and other antiresorptive agents can restore bone mass that has been lost from the increase in remodeling space, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.

Prevention of glucocorticoid-induced osteoporosis: provider practice at an urban county hospital.

PURPOSE: We sought to determine the frequency and types of prophylaxis for osteoporosis that were prescribed to outpatients who were receiving chronic glucocorticoid treatment and to identify the patient and provider characteristics that were associated with the use of prophylaxis. SUBJECTS AND METHODS: We identified 215 adult outpatients at San Francisco General Hospital who had received a prescription for prednisone (or its equivalent) at a daily dose of at least 5 mg for at least 1 month. Patient demographic characteristics, the diagnosis for which glucocorticoids were prescribed, comorbid illnesses, and medications were determined by chart review. Characteristics of the patients who were prescribed prophylaxis were compared with those of patients who were not prescribed prophylaxis. RESULTS: Prophylaxis for glucocorticoid-induced osteoporosis was prescribed to 58% of patients. Patients prescribed prophylaxis were older (mean [+/-SD] age of 50.0 +/- 13.9 versus 44.5 +/- 13.6 years, P = 0.004), more likely to be female (69% versus 40%, P <0.0001), postmenopausal if female (84% versus 56%, P = 0.002), have more comorbid illnesses (63% versus 29%, P = 0.001), and take multiple medications (66% versus 45%, P = 0.002). Patients attending the rheumatology clinic were 1.6 times more likely to receive prophylaxis than those attending other clinics (P <0.0001). The strongest predictor of prophylaxis was postmenopausal state. In premenopausal women, the independent predictors of prophylaxis were being treated in the rheumatology clinic and the presence of comorbid illnesses, whereas comorbid illnesses was the only independent predictor of prophylaxis in men. CONCLUSIONS: Educational efforts should be directed toward increasing awareness of the importance of glucocorticoid-induced osteoporosis and its prevention.

Graded exercise testing in patients with sinus node dysfunction.

Serial measurements of heart rate and oxygen uptake were obtained before and during maximal upright graded bicycle stress testing in 16 patients, 10 to 77 years old (mean 46 years), with sinus node dysfunction; five had permanent and two had temporary demand ventricular pacemakers. In 15 patients, including those with pacemakers, maximal exercise was performed before and after the intravenous administration of 1 mg atropine. Maximal exercise was terminated because of cerebral symptoms in seven (three had effort-induced tachyarrhythmias and one had autonomic insufficiency), fatigue in five (one had effort-induced heart block), heart failure in three and angina pectoris in one. With maximal exercise, patients with sinus node dysfunction were unable to obtain maximal heart rates or oxygen uptakes comparable to age- and sex-matched control subjects. Additionally, maximal oxygen uptake did not differ significantly between patients with or without pacemakers even when ventricular pacing rates were increased (two instances). The administration of atropine increased the resting heart rate, but the maximal heart rate and oxygen uptake achieved during maximal exercise did not differ significantly from those obtained before the administration of atropine in the patient and control groups. Physically active patients with sinus node dysfunction have diminished exercise capacity due in part to cardiac arrhythmia, latent or overt cardiac failure, or autonomic dysfunction.

Atrial pacing in patients with sinus node dysfunction.

Sinus nod recovery time (SNRT) at paced atrial rates of 100 (SNRT100) and 120 (SNRT120) beats/min, atrial effective refractory periods at spontaneous heart rates (AERP) and at paced rates of 100 (AERP100) and 120 (AERP120) beats/min, and premature atrial stimulation were among the studies in evaluating 33 patients with symptomatic sinus node disease and 42 normal subjects. Although mean SNRT100 and SNRT120 were statistically significantly greater in patients than in control subjects, there was a significant overlap between patient and control groups, and SNRT100 or SNRT120 was associated with a 30.3 per cent false-negative and 5 per cent false-positive incidence. Correction for heart rate (SNRT-spontaneous cycle length) failed to improve the sensitivity or specificity of this test. There was no significant difference in mean AERP, AERP100 or AERP120, or in sinoatrial conduction time in patients compared with control subjects. Analyses of curves derived from plots of test and return cycles showed abnormal curves in only five of the 24 patients studied by progressively premature atrial stimulation. Two of these five patients showed normal zone I and II phenomena followed by a progressive linear increase in the return cycle that was thought to be due to abnormal refractoriness of the perinodal fibers.

A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate.

PURPOSE: The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels. RESULTS: Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.

Electrophysiologic effects of cigarette smoking in patients with and without chronic beta-blocker therapy.

After refraining from smoking for at least 8 hours, 22 adult male habitual smokers underwent baseline electrophysiologic study including atrial and ventricular burst pacing and programmed premature stimulation with single extrastimuli. After smoking 2 of their usual brand of cigarettes in rapid succession, the electrophysiologic protocol was repeated. Nicotine, catecholamine and carbon monoxide concentrations all increased significantly. Smoking increased heart rate and improved atrioventricular conduction in the 13 patients receiving chronic beta-blocker therapy (mostly for angina pectoris); increases in heart rate and improvement in atrioventricular conduction were not different statistically from those seen in patients not receiving beta-blocker therapy, suggesting the possibility of a direct effect of nicotine or other components of tobacco smoke. Ventricular refractoriness was not altered and atrial and ventricular arrhythmias were not increased by smoking. Persistent sympathomimetic actions of cigarette smoking may explain in part the failure of beta-blocking drugs to reduce cardiac mortality risk in smokers after myocardial infarction.

Quantitative effects of functional bundle branch block in patients with atrioventricular reentrant tachycardia.

Changes in the retrograde conduction time (ventriculoatrial [VA]) interval during functional bundle branch block (BBB) have been used to separate septal from free wall accessory pathways (APs), but different values of the VA interval prolongation (deltaVA) have been described in different reports. A total of 95 patients with single nondecremental APs who developed BBB during atrioventricular reentrant tachycardia were studied. Free wall APs were found in 60 patients, and 35 had septal APs. For patients with free wall APs, complete and incomplete BBB ipsilateral to the atrial insertion site of APs were observed in 39 of 60 patients (65%) and 31 of 60 patients (52%), respectively. For patients who had both complete (QRS > or = 120 ms) and incomplete (QRS <120 ms) BBB during atrioventricular reentrant tachycardia, deltaVA for patients with complete BBB was significantly greater than in those with incomplete BBB, 59 +/- 19 ms versus 30 +/- 11 ms, p <0.001. For patients with septal APs and complete and incomplete BBB during tachycardia, the mean deltaVA for those with complete BBB was 31 +/- 20 ms and was significantly longer than in patients with incomplete BBB (14 +/- 6 ms), p <0.001. There was no significant difference in deltaVA between those with free wall APs and incomplete BBB compared with those with septal APs and complete BBB. The criteria of QRS > or = 120 ms associated with deltaVA > or =40 ms served to best separate free wall from septal APs with a sensitivity of 88% and a specificity of 89%. Left anterior fascicular block was associated with marked lengthening of deltaVA for those with left free wall APs, whereas a left posterior fascicular block pattern resulted in a marked increase in the deltaVA for patients with posteroseptal APs. In the absence of fascicular block patterns, a deltaVA > or =40 ms provides strong evidence of a free wall AP, with a sensitivity of 95% and a specificity of 100%. The left posterior fascicle appears to provide predominant innervation of the posterior septum.

Survival in severe left ventricular failure treated with the new nonglycosidic, nonsympathomimetic oral inotropic agents.

Survival in severe left ventricular failure is poor but has not been widely assessed since the introduction of several new nonglycosidic, nonsympathomimetic oral inotropic agents for long-term therapy. We examined retrospectively the survival of 82 patients with severe left heart failure during long-term treatment with oral milrinone (17 patients), posicor (12 patients), enoximone (47 patients), and piroximone (6 patients). Sixty-five patients were in New York Heart Association (NYHA) functional class 4, 15 patients were in class 3, and two patients were in class 2. There were 57 patients with ischemic and 25 patients were in class 2. There were 57 patients with ischemic and 25 patients with nonischemic etiology of left heart failure. Most patients were referred for inotropic therapy after failing to respond to conventional agents, including vasodilators. However, in almost all patients, marked hemodynamic and clinical improvement occurred initially. Overall survival was 36 percent at six months, the majority of deaths occurring during the first three months. Survival in relation to etiology of heart failure showed a trend toward increased mortality in patients associated with ischemic heart disease vs non-ischemic dilated cardiomyopathy. Sudden death mortality was also higher in the ischemic group (28 percent at six months vs 5 percent at six months; p less than 0.05). There was a trend toward reduced sudden death mortality in patients on antiarrhythmic agents during inotropic therapy (p = 0.06). We conclude that overall survival in symptomatic patients with severe left ventricular failure remains very low during long-term therapy with several new oral inotropic agents. Sudden death appears higher in patients with an ischemic etiology during therapy with these agents.

Transfusion significantly increases the risk for infection after splenic injury.

OBJECTIVES: To determine if splenectomy results in an increased risk for perioperative infection when analyzed against splenic repair and to identify factors associated with perioperative infection, respiratory complication, and admission to the intensive care unit following surgery for splenic trauma. DESIGN: Data were collected retrospectively from hospital records and analyzed using stepwise multiple logistic regression. SETTING: San Francisco (Calif) General Hospital, an urban level 1 trauma center. PATIENTS: All patients (n = 252) undergoing operation for traumatic splenic injury at San Francisco General Hospital from 1984 through 1990. Patients who died within 24 hours of presentation were excluded from the study. MAIN OUTCOME MEASURES: Perioperative infection, respiratory complications, and admission to the intensive care unit. RESULTS: Infection rates and the types of organisms yielded in cultures were similar between patients who underwent splenectomy and repair. Gram-negative and gram-positive organisms were found in equal numbers, and in no group did encapsulated organisms predominate. Splenectomy had no independent impact on any of the three outcome measures. Total blood transfusion was found to be the only independently significant variable associated with perioperative infection and respiratory complication. Total blood transfusion of more than 2 U and Injury Severity Score of greater than 25 were independently significantly associated with admission to the intensive care unit. CONCLUSIONS: The choice between splenectomy and splenic repair does not affect the risk for perioperative infection following injury, whereas blood transfusion significantly increases the risk for perioperative infection, respiratory complication, and admission to the intensive care unit.

Echocardiography in serial evaluation of left ventricular systolic and diastolic function: importance of image acquisition, quantitation, and physiologic variability in clinical and investigational applications.

Quantitative echocardiography is frequently used for serial evaluation of left ventricular performance. This prospective study was designed to determine the extent to which the acts of image acquisition and quantitation, and the subjects themselves, affect total variability in two-dimensional and Doppler echocardiographic indexes of left ventricular morphology and performance. Therefore, two technicians and two readers acquired and analyzed 60 echocardiograms from 15 normal subjects, each of whom was studied four times (twice on each of two visits). Analysis of variance based on generalizability theory was used to estimate the magnitude of these variability sources by calculating standard deviations (SD) and used to estimate their contribution to total variability. Of the two-dimensional echocardiographic indexes tested, ejection fraction varied least (SD, 6.6%) and left ventricular mass varied most (SD, 35.3 gm). Of the Doppler indexes, normalized early diastolic filling velocity integral varied least (SD, 8.4%) and deceleration time varied most (SD, 48.6 msec). Technical (image acquisition and quantitation) variability contributed most (and subject variability least) to total variability of stroke volume (68%) and deceleration time (67%). Technical variability contributed least (and subject variability most) to variability of ejection fraction (43%) and diastolic filling time (25%). The acts of image acquisition and quantitation varied more between than within technicians and readers. Peak atrial filling velocity and the ratio of peak early to atrial filling velocity significantly differed between technicians. Left ventricular ejection fraction, left ventricular mass, peak atrial filling velocity, early filling integral, and deceleration of early filling differed significantly between readers. Therefore the acts of image acquisition and quantitation, and subject variability itself, all contribute to total variability in echocardiographic indexes. Changes seen on clinical studies should be interpreted as abnormal only when exceeding the total variability originating from these sources. Generalizability theory allows one to tailor strategies to reduce variability. These strategies include increasing the number of observations, readers, and technicians for any given "baseline" study and using the same readers and technicians for sequential follow-up studies.

[Reocclusion following thrombolytic treatment in acute myocardial infarct]. / Reocklusion efter trombolytisk behandling vid akut hjärtinfarkt.

Currently there are five thrombolytic substances undergoing evaluation: streptokinase, tissue plasminogen activator, acylated plasminogen streptokinase activator complex, urokinase and single chain urokinase plasminogen activator. Equal results for mortality reduction (25 per cent) and reocclusion (6-24 per cent) has been reported in the literature for the five substances. Reocclusion can be divided into an early (greater than 24 hours) and a late phase. The early phase is most likely due to an imbalance between thrombolysis and the formation of a thrombus. During late reocclusion there is formation of a thrombus on the underlying coronary plaque or residual thrombotic mass, following thrombolytic therapy. The residual stenosis following thrombolysis seems to be the most important prognostic factor for reocclusion. A residual stenosis of over 75 per cent is unfavourable. Early reocclusion is prevented through simultaneous antithrombotic and thrombolytic therapy. Patients with a residual stenosis of over 75 per cent should be considered for some sort of active intervention to prevent late reocclusion.