Inadequate Erythropoietin Response to Anaemia in HIV Patients: Relationship to Serum Levels of Tumour Necrosis Factor-Alpha, Interleukin-6 and Their Soluble receptors

Severe anaemia is a frequent complication in advanced HIV infection. In our study we investigated the interaction between cytokine network, HIV infection and erythropoietin (Epo) response with increasing anaemia levels. No correlations could be established between circulating tumour necrosis factor (TNF)-alpha and any of the examined parameters. However, a negative correlation was found between haemoglobin values and soluble TNF receptor levels (sTNF-R-I: r  = −0.54; P  < 0.001; sTNF-R II: r  = −0.47; P  < 0.001) as well as interleukin-6 levels ( r  = −0.29; P  < 0.001). In contrast, no significant increase in log[Epo], counterbalancing haemoglobin decline and paralleling the rise in sTNF receptors, was found. In patients classified as stage III, according to the Centers for Disease Control (CDC) classification, the erythropoietin response was significantly more impaired than in patients from CDC groups I and II ( P  < 0.001). The results of this study suggest that similar to its action in vitro , activation of the TNF/TNF-R system may impair erythropoietin production in HIV-associated anaemia. Due to the brief half-life of TNF-α, this activation is particularly reflected by elevations of soluble TNF receptor levels.     

Randomized Evaluation of an Inflatable Femoral Artery Compression Device After Cardiac Catheterization

Mechanical femoral artery compression devices have several limitations. We compared a novel disposable beltheld pneumatic compression device to manual compression alone in 213 patients randomized into two equal groups. Both were comparable for age, gender, current therapy with aspirin (ASA) and warfarin, diameter of the arterial sheath, previous procedures via the same artery, procedure duration, and blood pressure. Manual compression time was 12 ± 3 minutes. Pneumatic compression was reduced during 60 minutes. Patient discomfort was assessed as none (82% vs 88%), mild (13% vs 8%), moderate (3% vs 4%), or severe (2% vs 0%) for the manual versus pneumatic group, respectively. Bleeding and hematoma occurred in 7.5% of patients with no difference between the treatment groups. However, manual compression was significantly more effective in the higher range of systolic blood pressure, and pneumatic in the lower range, with a cut point of approximately 170 mmHg. Predictors for bleeding were systolic blood pressure and dose of ASA. Among 113 patients with systolic blood pressure < 160 mmHg and low dose (75 mg) or no ASA, only / patient (0.9%) experienced bleeding while 31% of 16 patients with both elevated systolic blood pressure and high dose ASA (150–330 mg) bled. We conclude that pneumatic femoral artery compression does not reduce bleeding and hematoma compared with manual compression. The use of low dose (75 mg) or no ASA, as well as giving special attention to patients with elevated systolic blood pressure, may reduce the risk of bleeding after cardiac catheterization .     

A 6-Month Multispecies Inhalation Study with Maleic Anhydirde

A 6-Month Multispecies Inhalation Study with Maleic Anhydride.SHORT, R. D., JOHANNSEN, F. R., AND ULRICH, C. E. (1988). Fundam.Appl. Toxicol. 10, 517–524. This study was initiated toassess the safety of atmospheres containing maleic anhydride.Accordingly, rats (15/sex/group), hamsters (15/sex/group), andmonkeys (3/sex/group) were treated 6 hr a day 5 days a weekfor 6 months. Atmospheres were generated by subliming maleicanhydride and were monitored using Tenax collection columnsand gas chromatography to detect total maleic; i.e., maleicanhydride plus maleic acid. The mean analytical concentrationswere 0, 1.1,3.3, and 9.8 mg/m³ of total maleic. Dose-relatedsigns of nasal and ocular irritation were observed at each testlevel in all three species; signs included discharge, sneezing,gasping, and coughing. No significant treatment-related mortalitywas observed in any species. While reduced weight gains wereobserved only in mid- and high-dose rats, their terminal bodyweights were greater than 90% of control values. No treatment-relatedeffects were observed in hematology. clinical chemistry, urinalysis,and pulmonary function tests. Although microscopic evaluationof tissue revealed evidence of nasal irritation in all species,there was no evidence of systemic toxicity which was directlyattributed to maleic anhydride. While the results of this studysupport the current ACGIH TLV and OSHA PEL of 1 mg/m³ regardingsystemic toxicity, continuous exposure at this level duringthe day may produce some signs of irritation.     

Invasive electrophysiological evaluation of patients with sleep apnoea-associated ventricular asystole—methods and preliminary results

SUMMARY  Twelve patients (aged 48 ± 12 y) with ventricular asystole of >3s due to complete atrioventricular (AV) block ( n = 8), sinoatrial (SA) block or sinus node arrest ( n = 3) or both ( n = 1) associated with obstructive sleep apnoea underwent invasive electrophysiological evaluation of sinus node function and AV conduction properties before and after administration of atropine (0.02 mg kg^-1). Ventricular asystole lasted for 5.9 ± 2.8 s (range 3.1–13 s). Sinus node function was assessed by measurement of sinus node recovery time, sinoatrial conduction time, and the response of sinus rate to atropine. Parameters of AV-conduction assessment included AH- and HV-intervals, AV- and VA-Wenckebach periods, and effective refractory period of the AV node before and after atropine. Sinus node function was normal in 11 of the 12 study patients and moderately abnormal in 1 patient. AV-nodal function was normal in 8 patients and moderately abnormal in 4 patients. A slightly prolonged HV-interval (59–63 ms) was present in 6 patients. Intra- or infra His block was not observed in any patient. In conclusion, normal or only moderately abnormal electrophysiological findings in patients with sleep apnoea-associated ventricular asystole suggest that a neurally mediated cardioinhibitory reflex may cause ventricular asystole in these patients. This sleep apnoea-triggered 'vasovagal' reflex may unmask pre-existing mild to moderate structural abnormalities of the AV conduction system.     

Acute Inhalation Toxicity of Aliphatic (C1-C5) Nitrites in Rats

Acute Inhalation Toxicity of Aliphatic (C₁–C₅) Nitritesin Rats. KLONNE, D. R., ULRICH, C. E., WEISSMANN, J., and MORGAN,A. K. (1987). Fundam. Appl. Toxicol. 8, 101–106. The 4-hrinhalation LC50 was determined for methyl-, ethyl-, n-propyl-,n-butyl-, isobutyl-, and isopentyl nitrite in Sprague-Dawleyrats. LC50 values were 176, 160, 300, 420, 777, and 716 ppm,respectively. The dose-mortality curves were characterized byextremely steep slopes. Toxic signs observed during exposureincluded cyanosis, prostration, and rarely, convulsions. Therewere no effects of exposure on body weight gain during a 14-daypostexposure observation period. Signs of pulmonary hemorrhagewere apparent in rats which died during exposure but were muchless prominent in rats sacrificed at study termination. No animalsdied after cessation of exposure, and rapid recovery was apparentafter exposure. Concentration x Time (CT) relationships suggestedthat the actual concentration was more important than the "dose"in determining the lethal effects of inhalation exposure tonitrites. Because of the extremely steep dose-mortality curves,the aliphatic nitrites are more hazardous than the LC50 valueswould indicate.     

Antibodies to Human Sinus Node in Sick Sinus Syndrome

The incidence of autoantibodies against human conducting tissue was studied in 45 pacemaker patients with sick sinus syndrome (SSS), in 17 patients with bradyarrhythmia, and jive patients with hypertensitive carotid sinus syndrome. Antibodies against the human sinus node were demonstrated in 29% of patients with SSS and in 24% of patients with bradyarrhythmia; a tenfold risk of SSS could be calculated in patients with this antibody as compared to age-matched controls. At least two subtypes of anti-sinus node antibodies were demonstrated: an antibody absorbable and another one not absorbable with ventricular myocardium. Patients with SSS and prior myocarditis of rheumatic fever have a threefold incidence of that antibody, demonstrating that anti-conducting tissue antibodies are etiologic indicators for former inflammatory heart disease. These antibodies may play a role in the secondary immunopathogenesis of sick sinus syndrome. This hypothesis emerges as an interesting new pathogenetic concept.     

Management of Patients with Acute Coronary Syndrome: Should We Rely on Cardiac Markers?

Early diagnosis and risk stratification of patients presenting to the emergency room for a suspected acute coronary syndrome is an emerging problem. In general, diagnosis is based on an ECG, clinical presentation, and elevated cardiac markers. In the past decade cardiac troponins and myoglobin have been identified as important markers for the global assessment and treatment of patients with acute coronary syndromes. Recent studies have identified patients with increased troponin I and T levels as a high risk population gaining benefit from the adjunctive treatment with glycoprotein (GP) IIb/IIIa receptor antagonists or low molecular weight heparin. Myoglobin was introduced as a sensitive marker of successful or failed reperfusion following thrombolytic therapy. These studies indicate that cardiac markers are important tools in the risk stratification of patients with acute coronary syndromes allowing adequate treatment decisions. However, certain limitations of cardiac markers have to be considered. These limitations mainly refer to the delay in time from presentation to the emergency room to the availability of the results of the blood sample. Thus, in the individual case, especially if an ECG and clinical presentation are unspecific or there is doubt concerning the success of thrombolytic therapy, early angiography remains the gold standard for diagnosis and establishment of adequate therapy. In this setting, early reperfusion by percutaneous coronary interventions will increase myocardial salvage, and therefore, should be preferred to the delayed confirmation of the diagnosis by repeated determination of cardiac markers.