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.     

Intravenous streptokinase in acute myocardial infarction (I.S. A.M.): assessment of left ventricular function 1 and 7 months after infarction by radionuclide ventriculography

l.S.A.M. was a prospective, placebo-controlled, double-blindmulticentre trial of high-dose short-term intravenous streptokinasein acute myocardial infarction (AMI) within 6 h of the onsetof symptoms. Determination of left ventricular ejection fraction(LVEF) by radionuclide ventriculography was performed 1 and7 months after AMI in a subset of 192 patients at rest and,in 140 of them, also during exercise. Regional myocardial functionwas analysed in all 145 patients with neither a history of aprevious myocardial infarction nor revascularization proceduresor reinfarction within the 7-month follow-up period. One month after AMI, mean LVEF was higher in the streptokinasegroup in patients with anterior AMI (50±15% vs 42 ±16%,P = 0.013). This difference was more marked in the subgrouptreated within 3 h (53 ± 14% vs 42 ± 15%, P =0.004), whereas patients treated 3–6 h after the onsetof symptoms did not differ from respective controls (41 ±16%vs 41 ±18%). In patients with inferior A MI, the differencein mean LVEF was small (57±11% vs 55 ±12%, P =0.47). After anterior AMI benefit due to streptokinase therapywas preserved up to 7 months (52 ±14% vs 44 ±17%,P = 0.013). During exercise, the increase of mean LVEF was greaterin the streptokinase group at both dates, especially 7 monthsafter AMI (41 ±61% vs l.2±6.3%, P = 0.015). Instreptokinase-treated patients with anterior AMI, regional LVEFat rest was higher at both dates compared with controls, withinthe infarct zone as well as in remote myocardium. No treatment-controldifferences were demonstrable in patients with inferior AMI.During exercise, regional contractile reserve was better inthe streptokinase group within the infarct zone as well as inremote myocardium, irrespective of the site of infarction. Thus, intravenous streptokinase within 3 h after the onset ofA MI preserves global left ventricular function m anterior AMIover a period of at least 7 months. Intravenous streptokinaseimproves regional myocardial function within the infarct zoneas well as in remote areas. In inferior AMI investigation solelyat rest may underestimate the benefit of streptokinase therapy.     

Evaluation of three methods for quantifying valvular regurgitation using gated equilibrium radionuclide ventriculography

The non-invasive quantification of mitral and aortic regurgitationusing the left-to-right stroke count ratio (SCR) calculatedwith gated equilibrium radionuclide ventriculography (RNV),is affected by the overlap of atria and ventricles and the consequentdifficult definition of the ventricular regions of interest(ROI). Various solutions of the problem have been proposed.In this study we evaluated the results obtained with a techniquebased on visual inspection of the RNV images (variable ROI method—VRI)and those of two approaches which utilize functional images(stroke volume image method—SVI—and Fourier amplituderatio—FAR), by comparing them with the invasive quantificationof valvular regurgitation according to Sandier et al.^[1] (strokevolume ratio — SVR). Forty patients (15 controls and 25valvular patients) were studied.In the control group the rangeof the SVR wasO.81±1.11 (mean±lSD=1.01±0.08).The SCR was O.83–1.28 (1.03±0.15) with VRI, 1.10–1.15(1.30±0.14) with SVI and 1.11–1.58 (1.35±0.17)with FAR. The correlations between SVR and SCR were r=0.47 (P<0.05),r=0.62 (P<0.001) and r=0.55 (P<0.01) respectively withVRI, SVI and FAR. The SCR of valvular patients fell in the rangeof controls in 11/25 using VRI, 6/25 using SVI and in 4/25 usingFAR. This overlap was present in 2/25 with the invasive quantification.Irrespective of the method used, a reliable assessment of thevalvular regurgitation was not possible in two patients withseverely depressed left ventricular function. We conclude thatthe use of techniques based on functional images clearly improvesthe effectiveness of the non-invasive quantification of valvularregurgitation with the SCR even if this cannot be regarded asa substitute for invasive quantification and has a limited reliabilityin particular groups of patients.     

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.