Infective endocarditis and stroke: when does it bleed? A single center retrospective study.

BACKGROUND: Infective endocarditis (IE) is a serious condition with a high mortality, represents a rare cause of stroke and an increased risk of intracranial hemorrhage. In this single center study, we characterize stroke patients with IE. We were interested in risk factors for intracranial hemorrhage and outcome of patients with intracranial hemorrhage compared to patients with ischemic stroke. METHODS: Patients with IE and symptomatic ischemic stroke or intracranial hemorrhage admitted to our hospital between January 2019 and December 2022 were included in this retrospective study. RESULTS: 48 patients with IE and ischemic stroke or intracranial hemorrhage were identified. 37 patients were diagnosed with ischemic stroke, 11 patients were diagnosed with intracranial hemorrhage. The intracranial hemorrhage occurred within the first 12 days after admission. We identified Staphylococcus aureus detection and thrombocytopenia as risk factors for hemorrhagic complications. An increased in-hospital mortality in patients with intracranial hemorrhage (63.6% vs. 22%, p = 0.022) was found, whereas patients with ischemic stroke and patients with intracranial hemorrhage do not differ regarding favorable clinical outcome (27% vs. 27.3%, p = 1.0). 27.3% patients with intracranial hemorrhage and 43.2% patients with ischemic stroke underwent cardiac surgery. Overall, 15.7% new ischemic strokes occurred after valve reconstruction, whereas no new intracranial hemorrhage was observed. CONCLUSIONS: We found an increased in-hospital mortality in patients with intracranial hemorrhage. Beside thrombocytopenia, we identified S. aureus detection as a risk factor for intracranial hemorrhage.

Analysis of the pinocytic process in rat kidney. I. Isolation of pinocytic vesicles from rat kidney cortex.

Pinocytosis was induced in rat kidney by exposure to horseradish peroxidase (HRP). Pinocytic vesicle preparations were enriched after homogenization of kidney cortex by differential centrifugation and free-flow electrophoresis with HRP as an exogenous marker. Vesicles were identified by enzymatic analysis and by electron microscopy, including specific staining procedures. Typical brush-border enzymes such as alkaline phosphatase, aminopeptidase, 5'-nucleotidase, lysosomal acid phosphatase, and mitochondrial succinic dehydrogenase were reduced in the vesicular fraction, compared to the kidney cortex homogenate. Glucose-6-phosphatase and Na(+)-K(+)-ATPase were only slightly increased in the fraction. These results indicate that preparations of pinocytic vesicles from rat kidney cortex can be enriched. They have biochemical characteristics that differ from those of the cell organelles and membranes previously purified from renal tissue.

The Use of a Helium-Oxygen Mixture during Maximum Expiratory Flow to Demonstrate Obstruction in Small Airways in Smokers.

We measured the response to breathing a mixture of 80% helium and 20% oxygen (He) during a maximum expiratory flow-volume (MEFV) maneuver in 66 nonsmokers and 48 smokers, aged 17-67. All of the subjects studied had (forced expiratory volume in 1 s/forced vital capacity [FEV(1.0)/FVC]) x 100 of greater than 70%. While the flow rates of the smokers were within +/-2 SD of those of the nonsmokers at 50% VC (Vmax(50)), both groups showed a reduction in flow with age (nonsmokers: r=-0.34, P<0.01; smokers r=-0.52, P<0.001). Nonsmokers showed no significant reduction with age in response to breathing He, while smokers showed a marked reduction with age (r=-0.63, P<0.001 at Vmax(50)). We also measured the lung volume at which maximum expiratory flow (Vmax) while the subject was breathing He became equal to Vmax while he was breathing air, and expressed it as a percent of the VC. This was the most sensitive method of separating smokers from nonsmokers. These results indicate that the use of He during an MEFV maneuver affords sufficient sensitivity to enable detection of functional abnormalities in smokers at a stage when Vmax while they are breathing air is normal.

Towards real-time MRI-guided 3D localization of deforming targets for non-invasive cardiac radiosurgery.

Radiosurgery to the pulmonary vein antrum in the left atrium (LA) has recently been proposed for non-invasive treatment of atrial fibrillation (AF). Precise real-time target localization during treatment is necessary due to complex respiratory and cardiac motion and high radiation doses. To determine the 3D position of the LA for motion compensation during radiosurgery, a tracking method based on orthogonal real-time MRI planes was developed for AF treatments with an MRI-guided radiotherapy system. Four healthy volunteers underwent cardiac MRI of the LA. Contractile motion was quantified on 3D LA models derived from 4D scans with 10 phases acquired in end-exhalation. Three localization strategies were developed and tested retrospectively on 2D real-time scans (sagittal, temporal resolution 100 ms, free breathing). The best-performing method was then used to measure 3D target positions in 2D-2D orthogonal planes (sagittal-coronal, temporal resolution 200-252 ms, free breathing) in 20 configurations of a digital phantom and in the volunteer data. The 3D target localization accuracy was quantified in the phantom and qualitatively assessed in the real data. Mean cardiac contraction was ⩽ 3.9 mm between maximum dilation and contraction but anisotropic. A template matching approach with two distinct template phases and ECG-based selection yielded the highest 2D accuracy of 1.2 mm. 3D target localization showed a mean error of 3.2 mm in the customized digital phantoms. Our algorithms were successfully applied to the 2D-2D volunteer data in which we measured a mean 3D LA motion extent of 16.5 mm (SI), 5.8 mm (AP) and 3.1 mm (LR). Real-time target localization on orthogonal MRI planes was successfully implemented for highly deformable targets treated in cardiac radiosurgery. The developed method measures target shifts caused by respiration and cardiac contraction. If the detected motion can be compensated accordingly, an MRI-guided radiotherapy system could potentially enable completely non-invasive treatment of AF.

Binding of lysozyme to brush border membranes of rat kidney.

The binding of 125I-labelled egg-white lysozyme to isolated brush border membranes of rat kidney cortex was investigated. The lysozyme binding was reversible and saturable. The Scatchard plot revealed a one-component binding type with a dissociation constant of 7.8 microM and 15.6 nmol/mg membrane protein for the number of binding sites. The binding of the basic lysozyme could be reduced by basic amino acids such as L-lysine, L-ornithine or L-arginine, while neutral amino acids such as L-citrulline or L-alanine had no effect. The inhibitory effect of lysine was competitive.

Kinetic studies of D-glucose transport in renal brush-border membrane vesicles of streptozotocin-induced diabetic rats.

Renal brush-border membrane vesicles prepared from streptozotocin-induced 4-day-diabetic rats possessed a Na+-dependent D-glucose transport system that exhibited apparent Kt and Vmax values about 2-fold greater than normal. Apparently, hyperglycemia and probably other stimuli cause the induction and membrane incorporation of a low-affinity transporter in these membranes; this increased sugar-transport capacity is retained for at least 4 weeks so long as the animals maintained or increased their body weight. Membranes prepared from 28-day-diabetic, severely ill ketoacidotic animals lose this enhanced transport ability and the decrease in Vmax was found to correlate directly with the weight loss. Furthermore, the transporter in brush-border membranes prepared from these cachectic animals had an even lower affinity for glucose than those from the acute hyperglycemic animals. That these changes in the diabetic animals represent major alterations in renal brush-border membrane construction is further supported by our observation that the specific activity of the marker enzymes, alkaline phosphatase and neutral alpha-glucosidase, are profoundly increased and decreased, respectively, in this condition.

Gadolinium decreases stretch-induced vulnerability to atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is frequently associated with atrial dilatation caused by pressure or volume overload. Stretch-activated channels (SACs) have been found in myocardial cells and may promote AF in dilated atria. To prove this hypothesis, we investigated the effect of the SAC blocker gadolinium (Gd(3+)) on AF propensity in the isolated rabbit heart during atrial stretch. METHODS AND RESULTS: In 16 isolated Langendorff-perfused rabbit hearts, the interatrial septum was perforated to equalize biatrial pressures. Caval and pulmonary veins were occluded. Intra-atrial pressure (IAP) was increased in steps of 2 to 3 cm H(2)O by increasing the pulmonary outflow fluid column. Vulnerability to AF was evaluated by 15-second burst pacing at each IAP level. At baseline, IAP needed to be raised to 8.8+/-0.2 cm H(2)O (mean+/-SEM) to induce AF. A dose-dependent decrease in AF vulnerability was observed after Gd(3+) 12.5, 25, and 50 micromol/L was added. AF threshold increased to 19.0+/-0.5 cm H(2)O with Gd(3+) 50 micromol/L (P<0.001 versus baseline). Spontaneous runs of AF occurred in 5 hearts on a rise of IAP to 13.8+/-3.3 cm H(2)O at baseline but never during Gd(3+). Atrial effective refractory period shortened progressively from 78+/-3 ms at 0.5 cm H(2)O to 52+/-3 ms at 20 cm H(2)O (P<0.05). Gd(3+) 50 micromol/L had no significant effect on effective refractory period. CONCLUSIONS: Acute atrial stretch significantly enhances the vulnerability to AF. Gd(3+) reduces the stretch-induced vulnerability to AF in a dose-dependent manner. Block of SAC might represent a novel antiarrhythmic approach to AF under conditions of elevated atrial pressure or volume.

The repolarization-excitability relationship in the human right atrium is unaffected by cycle length, recording site and prior arrhythmias.

OBJECTIVES: The goal of this study was to determine the relationship between repolarization and excitability in the human atrium under various conditions. BACKGROUND: Action potential duration (APD) measurements from monophasic action potential (MAP) recordings provide a surrogate for measuring the effective refractory period (ERP) in human ventricle. The relationship between repolarization and refractoriness in human atrium and the effect of prior atrial fibrillation/flutter on the ERP/APD correlation are unknown. METHODS: Seven patients with sinus rhythm and 15 patients after conversion of atrial flutter or fibrillation were evaluated. Monophasic action potentials were recorded at multiple right atrial sites and during different basic cycle lengths from 300 to 700 ms, while ERPs were determined by extrastimulus technique using the MAP recording-pacing combination catheter. RESULTS: There was a close correlation between ERP and APD at 70% repolarization (APD70, r = 0.97; p < 0.001) and 90% repolarization (APD90, r = 0.98; p < 0.001), respectively. Refractoriness occurred at a repolarization level of 72 +/- 8%. The ERP/APD70 and ERP/APD90 ratios averaged 1.06 +/- 0.10 and 0.86 +/- 0.08, respectively. These ratios were nearly constant over the entire range of basic cycle lengths, between different sites in individual patients and between different patients. Patients cardioverted from atrial fibrillation or flutter exhibited no significant differences in the ERP/APD relationship compared with patients with sinus rhythm. CONCLUSIONS: Effective refractory period and APD are closely related in the human right atrium. Using the MAP recording technique, atrial ERPs can be assessed by measurement of APDs. Effective refractory period is most closely reflected by APD70. Thus, MAP recordings allow investigation of the local activation and repolarization time course beat by beat, visualizing the excitable gap.

Course and prognostic implications of QT interval and QT interval variability after primary coronary angioplasty in acute myocardial infarction.

OBJECTIVES: The aim of this study was to determine the influence of early reperfusion on the course of QT interval and QT interval variability in patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) and its prognostic implications on major arrhythmic events during one-year follow-up. BACKGROUND: Although early coronary artery recanalization by primary angioplasty is an established therapy in AMI, a substantial number of patients is still threatened by malignant arrhythmias even after early successful reperfusion, which may be caused by an inhomogeneity of ventricular repolarization despite reperfusion. METHOD: Temporal fluctuations of ventricular repolarization were studied prospectively in 97 consecutive patients with a first AMI by measurements of QT interval and QT interval variability during and after successful PTCA (Thrombolysis in Myocardial Infarction flow grades 2 and 3). Continuous beat-to-beat QT interval measurement was performed from 24-h Holter monitoring, which was initiated at admission before PTCA. RESULTS: Reperfusion caused a significant continuous increase of mean RR interval (738 +/- 98 to 808.5 +/- 121 ms; p < 0.001) and a significant decrease of parameters of QT interval (QTc: 440 +/- 32 to 416.5 +/- 37ms; p < 0.001) and QT interval variability (QTcSD: 27.5 +/- 3 to 24.9 +/- 6 ms; p < 0.001) in the majority of patients. However, in patients with major arrhythmic events at the one-year follow-up (sudden cardiac death, ventricular fibrillation or sustained ventricular tachycardia, n = 15), parameters of QT interval remained unaltered after successful reperfusion (QTc: 447.3 +/- 41 to 432.9 +/- 45 ms, p = NS; QTcSD: 35.1 +/- 13.4 to 29.0 +/- 9.1 ms, p = NS). CONCLUSIONS: Reduction of QT interval and QT interval variability after timely reperfusion of the infarct-related artery may be a previously unreported beneficial mechanism of primary PTCA in AMI, indicating successful reperfusion.

Diagnosis of obstruction of the upper and central airways.

Patients with obstruction of the upper airways are often treated for long periods of time for other disorders. Correct diagnosis is important since treatment is quite specific. Such patients may present with a characteristic history and findings on physical examination. Certain physiologic tests such as flow-volume loops with and without helium help to prove the diagnosis. Patients with upper airway obstruction may also have sleep apneas and the sleep deprivation syndrome. Methods of diagnosis of upper airway obstruction are presented and three instructive cases are reviewed.

Reversibility of pulmonary function abnormalities in smokers. A prospective study of early diagnostic tests of small airways disease.

A prospective study of the reversibility of pulmonary function abnormalities in cigarette smokers was performed. Base line studies of 50 otherwise healthy cigarett smokers included lung volumes, static volume-pressure curves, closing volume, slope of phase III and maximum expiratory flow-volume curves while the subjects breathed air and while they breathed an 80 per cent helium-20 per cent oxygen mixture (He). Ten subjects, seven women and three men, ages 29 to 61, were restudied 6 to 14 weeks after they had stopped smoking. Two of these people had an abnormal closing volume, four had an abnormal slope of phase III and five had an abnormal response to helium. Static volume-pressure curves, slope of phase III and airflow rates were not improved on the repeat studies. There was increases in maximum expiratory flow rates with He at 50 and 25 per cent of vital capacity, reductions in the lung volume at which the maximum expiratory flow rate of air and He became identical, and decreases in closing volume. These reversible functional changes in smokers are thought to indicate improvement of peripheral airways obstruction.

Diagnostic accuracy in lung cancer; comparison of techniques used in association with flexible fiberoptic bronchoscopy.

Flexible fiberoptic bronchoscopic examination was performed 254 times in 228 patients in a prospective study to determine what specimens would give the greatest yield in the diagnosis of lung cancer. In addition, we questioned whether postbronchoscopic sputum specimens were still the most accurate method of diagnosing lung cancer, as they had been when only the rigid bronchoscope was available. Material for cytopathologic examination was obtained from bronchial brushings, bronchial biopsy, bronchial brushings in saline solution, bronchial washings, and three postbronchoscopie sputum specimens. In the latter part of the study, patients with peripheral tumors were studied with the aid of biplane fluoroscopic techniques. Bronchial brushings and bronchial biopsy each yielded the highest percentage of positive specimens (65 percent); postbronchoscopic sputum specimens were less frequently positive (40 percent). The combination of bronchial brushings and bronchial biopsies gave the optimum overall accuracy (79 percent). Bronchial washings and postbronchoscopic sputum specimens did not add significantly to diagnostic yield, and we conclude that they should no longer be part of the diagnostic procedures routinely ordered. In peripheral lesions, diagnostic accuracy was greatly enhanced in the cases where biplane fluoroscopic techniques were employed.

Double-blind crossover study of five bronchodilator medications and two delivery methods in stable asthma. Is there a best combination for use in the pulmonary laboratory?

The effects of five bronchodilator drugs and two methods of delivery (nebulizer vs metered-dose inhalers) on pulmonary function were studied in ten subjects with stable asthma. All subjects demonstrated statistically significant improvements (p less than 0.05) in pulmonary function relative to baseline and placebo effects after each medication, regardless of method of delivery; however, there was no statistically significant difference between the changes in pulmonary function caused by medication, method, or medication-method combination (p greater than 0.05). The choice of medication and device for delivery would appear to depend on the budget and time available in the laboratory.

Differential effects of defibrillation on systemic and cardiac sympathetic activity.

OBJECTIVE: To assess the effect of defibrillation shocks on cardiac and circulating catecholamines. DESIGN: Prospective examination of myocardial catecholamine balance during dc shock by simultaneous determination of arterial and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were applied in 30 patients after initiation of ventricular fibrillation for a routine implantable cardioverter defibrillator test. Another 10 patients were externally cardioverted (50-360 J) for atrial fibrillation. MAIN OUTCOME MEASURES: Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after the shock. RESULTS: After internal shock, arterial noradrenaline increased from a mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01), reflecting a shift from cardiac net release to net uptake. After external shock delivery, there was a similar increase in arterial noradrenaline, from 260 (112) to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01), outlasting the threefold rise following internal shock (p = 0.001). In both groups, a negative transmyocardial adrenaline gradient at baseline decreased further, indicating enhanced myocardial uptake. Cardiac lactate production occurred after ventricular fibrillation and internal shock, but not after external cardioversion, so the neurohumoral changes resulted from the defibrillation process and not from alterations in oxidative metabolism. CONCLUSIONS: A dc shock induces marked systemic sympathoadrenal and sympathoneuronal activation, but attenuates cardiac sympathetic activity. This might promote the transient myocardial depression observed after electrical discharge to the heart.

Development of sinus node disease in patients with AV block: implications for single lead VDD pacing.

OBJECTIVE: To investigate the incidence of sinus node disease after pacemaker implantation for exclusive atrioventricular (AV) block. DESIGN: 441 patients were followed after VDD (n = 219) or DDD pacemaker (n = 222) implantation for AV block over a mean period of 37 months. Sinus node disease and atrial arrhythmias had been excluded by Holter monitoring and treadmill exercise preoperatively in 286 patients (group A). In 155 patients with complete AV block, a sinus rate above 70 beats/min was required for inclusion in the study (group B). Holter monitoring and treadmill exercise were performed two weeks, three months, and every six months after implantation. Sinus bradycardia below 40 beats/min, sinoatrial block, sinus arrest, or subnormal increase of heart rate during treadmill exercise were defined as sinus node dysfunction. RESULTS: Cumulative incidence of sinus node disease was 0.65% per year without differences between groups. Clinical indicators of sinus node dysfunction were sinus bradycardia below 40 beats/min in six patients (1.4%), intermittent sinoatrial block in two (0.5%), and chronotropic incompetence in five patients (1.1%). Only one of these patients (0.2%) was symptomatic. Cumulative incidence of atrial fibrillation was 2.0% per year, independent of the method used for the assessment of sinus node function and of the implanted device. CONCLUSIONS: In patients undergoing pacemaker implantation for isolated AV block, sinus node syndrome rarely occurs during follow up. Thus single lead VDD pacing can safely be performed in these patients.

Is there any transtubular reabsorption of filtered proteins in rat kidney?

The bovine protease inhibitor aprotinin (Trasylol) has a high affinity to the kidney and is preferentially pinocytized in the proximal tubule. After i.v. injection of 1mug 124 I aprotinin the blood content decreases to 2.8% of the primary injected amount within 3 hrs, while simultaneously each kidney contains 29%. This substance was used to test whether or not a peptide which is pinocytized, is released in the intact form into the peritubular blood. By a cross circulation technique with two unilaterally nephrectomized rats we were unable to detect any transport of pinocytized, intact peptide through the proximal tubule cell over the observed cross circulation period of 1-8 hrs even when using 5000 times the above dosage. Since the total amount of aprotinin in the kidney is immunologically reactive (ca. 97%), and 65% of the radioactivity in the blood is not reactive after 6 hrs, we believe that the last step in the absorption process consists in digestion inside the lysosomes and instantaneous release of the split products into the blood.

Contraceptive efficacy and safety of DMPA-SC.

DMPA-SC 104 mg/0.65 mL is a new, low-dose subcutaneous (SC) formulation of Depo-Provera contraceptive injection (150 mg/mL medroxyprogesterone acetate injectable suspension) that provides efficacy, safety and immediacy of onset equivalent to Depo-Provera intramuscular (IM) injection. Two large, open-label, Phase 3 studies assessed the 1-year contraceptive efficacy, safety and patient satisfaction with DMPA-SC administered every 3 months (12-13 weeks). Zero pregnancies were reported in both studies, which included a total of 16,023 woman-cycles of exposure to DMPA-SC and substantial numbers of overweight or obese women. DMPA-SC was well-tolerated and adverse events were similar to those reported previously with Depo-Provera IM. Thus, DMPA-SC offers women a new, highly effective and convenient long-acting contraceptive option.

Angiosarcoma of the heart: review of the literature and report of two cases that illustrate the broad spectrum of the disease.

Two patients with primary angiosarcoma of the heart were treated. The first patient presented with spinal cord compression syndrome secondary to metastatic angiosarcoma of the lumbar spine. The primary tumour was found to be a right atrial mass. In contrast, the second patient presented with repeated episodes of pleural and pericardial hemorrhage resulting in effusive constrictive pericardial physiology. Repeated diagnostic attempts failed, and an open thoracotomy found an infiltrative type of pericardial angiosarcoma involving the right atrial wall. For both patients, the angiosarcoma proved to be rapidly fatal. The clinical spectrum of these two cases and a review of the literature suggest two major clinicopathological forms most commonly arising from the right atrium: a large obstructing mass and a less common, less symptomatic, locally infiltrative tumour, offering a greater diagnostic challenge. The prognosis is usually poor. However, a more aggressive diagnostic approach -- especially in the locally infiltrative tumours -- may offer hope for improving survival.

Giant cell arteritis in a 19-year-old woman associated with vertebral artery aneurysm and subarachnoid hemorrhage.

Giant cell arteritis (GCA) is a disease chiefly found in elderly patients. Intracranial vessels are rarely involved in GCA. Here we report the case of a 19-year-old woman with GCA in the basilar and vertebral arteries. Two weeks after the first symptoms, she developed an aneurysmatical dilatation of the right vertebral artery which ruptured leading to subarachnoid hemorrhage. Although the ruptured right vertebral artery was clipped neurosurgically, she died two days later. Autopsy revealed GCA with focal medial necrosis and intimal thickening of the vertebral arteries and the basilar artery. No other arteries were affected. In the involved vessels, the media exhibited C1q immunoreactivity. At the intimal site of the internal elastic lamina there were increased levels of elastase. Other arterial diseases showing the pattern of GCA were excluded. This case demonstrates that GCA is not necessarily restricted to elderly people. Moreover, this case shows that a GCA-induced aneurysm is a very rare reason for subarachnoid hemorrhage even in young adults.

Hemoptysis: a manifestation of pulmonary disease confidently managed by military physicians.

Military physicians can confidently manage hemoptysis with a systematic approach and optimal timing of consultation. Begin with a thorough history, physical examination, and chest x-ray. In our series of 177 cases, a cause for hemoptysis was found in 78% of those with abnormal chest x-rays but in only 21% of those with normal chest x-rays. All 36 cases of bronchogenic carcinoma were associated with an abnormal chest x-ray. A normal chest x-ray was associated with no cause found for the hemoptysis (44 cases) or bronchitis (25 cases), with no carcinomas developing upon a 2-year follow-up. Hospitalization is indicated with excessive bleeding or to allay patient or physician) anxiety. Diagnostic bronchoscopy is usually indicated, especially to localize the bleeding in massive hemoptysis (greater than 600 cc per 24 hours) when surgery may be indicated. Prompt referral should be the rule with bleeding from a mycetoma, diffuse bronchiectasis, or with recurrent significant hemorrhage (greater than 200 cc). In an active-duty population, these instances are fortunately rare, and conservative management and elective referral are the norm.