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.     

EFFECTS OF FENTANYL-DIAZEPAM-NITRIOUS OXIDE ANAESTHESIA ON ARTERIAL BAROREFLEX CONTROL OF HEART RATE IN MAN

The effects of fentanyl 7.5 µg kg^–l (group I), 10.0µg kg^–1 (group Il) and 12.5 µg kg^–1(group lll) with diazepam 0.25 mg kg^–l and 70% nitrousoxide on baroreflex control of heart rate in humans were investigated.Phenylephrine (the pressor test), sodium nitroprusside (thedepressor test) and graded neck suction provoked baroreflexresponses. In group I the pressor, depressor and neck suctionbaroreflex slopes decreased during anaesthesia. In groups IIand III the depressor test slopes were also decreased duringanaesthesia. However, the slopes derived from the pressor andneck suction tests did not decrease. These data suggest thatbaroreflex control of heart rate is attenuated during low dosesof fentanyl (7.5 µg kg^–1). Baroreflex mediated tachycardiais decreased by higher doses of fentanyl (10.0 and 12.5 µgkg^–1). However, baroreflex-mediated bradycardia is maintainedduring the higher doses of fentanyl. We suggest this effectis the result of enhanced vagal efferent activity mediated byfentanyl.     

Effects of four orally administered analogues of prostaglandin E1 and E2 on glucose tolerance and on the secretion of pancreatic and gastrointestinal hormones in man

Oral glucose tolerance tests (75 g, 300 ml) were performed in 12 healthy volunteers, with prior administration of placebo, misoprostol (400 micrograms), rioprostil (300 micrograms), enprostil (70 micrograms), or nocloprost (200 micrograms), in a double-blind, randomized manner. None of the drugs significantly affected glucose tolerance, although with misoprostal some volunteers displayed an impaired glucose tolerance. Nocloprost was without effect on gastric inhibitory polypeptide (GIP) and did not influence insulin or C-peptide concentrations. Misoprostol and rioprostil reduced integrated incremental responses of GIP by 57% (P less than or equal to 0.001) and 45% (P less than or equal to 0.01), respectively, and both gave rise to an initial (approximately 10 min) delay of insulin and C-peptide responses, without a significant overall reduction in integrated incremental responses. Enprostil almost totally inhibited the GIP response (by 94%; P less than or equal to 0.001), delayed initial insulin and C-peptide responses, but reduced the integrated incremental C-peptide response (which corresponds to the overall release of insulin) by only 14% (P less than or equal to 0.05). Enprostil more substantially reduced the integrated incremental response of insulin by 36% (P less than or equal to 0.01), and also reduced the ratio of insulin and C-peptide incremental responses (P less than or equal to 0.001). In conclusion, prostaglandin E analogues which caused a reduction in GIP responses, and thereby disrupting the enteroinsular axis to varying degrees, delayed the time-course of insulin secretion without a significant impact on glucose tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)