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.     

Toxicity Sudies of Acetone Administered in the Drinking Water of Rodents

Toxicity Studies of Acetone Administered in the Drinking Waterof Rodents. DIETZ, D. D., LEININGER, J. R., RAUCKMAN, E. J.,THOMPSON, M. B., CHAPIN, R. E., MORRISSEY, R. L., AND LEVINE,B. S. (1991). Fundam Appl. Toxicol 17, 347–360. Two- andthirteen-week toxicity studies were conducted using male andfemale F344/N rats and B6C3F1 mice. Animals were exposed tothe following concentrations of acetone in their drinking water:two-week studm 0; 5000; 10,000; 20,000; 50,000; or 100,000 ppmacetone. Thirteen-week rat and female mouse studies 0; 2500;5000; 10,000; 20,000; or 50,000 ppm acetone. Thirteen week malemice were exposed to 0; 1250; 2500; 5000; 10,000; or 20,000ppm acetone. Depressed body weight gain was restricted to the50,000 and 100,000 ppm exposure groups. Male and female miceexposed respectively to 20,000 or 50,000 ppm acetone for 2 weeksdeveloped hepatocellular hypertrophy. This change was not apparentafter 13 weeks of exposure although relative and alsolute liverweight was increased in high dose female mice. Bone marrow hypoplasiawas observed In 5/5 high dose (100,000 ppm) male rats duringthe 2-week studies. Treatment of male rats for 13 weeks resultedin a variety of mild and subtle hematological changes that oftenoccurred at relatively low levels of exposure (5000 ppm) andresembled those seen during the clinical condition of megaloblasticanemia Changes characteristic of hypogonadism (depressed spermmotility and cauda epididymal and epididymal weight and elevatedincidence of abnormal sperm) were observed in male rats raceiving50,000 ppm acetone for 13 weeks. The incidence and severityof a kidney laion that is morphologically similar to the spontaneouslyoccurring nephropathy among aging F-344 rats were increasedat 20,000 and 50,000 ppm acetone, respectively, in 13-week malerats. In summary, the effects of acetone were either subtlein nature or occurred during very high levels of exposure confirmingacetone's low level of toxicity. The daily levels of acetoneexposure were often several-fold greater than possibly encounteredby humans during the accidental consumption of contaminatedgroundwater (250 ppm; 5 mg/day) and frequently exceeded maximumlevels reported following acute toxic exposures (2,500 mg/kg).     

Subchronic (13-Week) Toxicity Studies of Oral Phenolphthalein in Fischer 344 Rats and B6C3F1 Mice

Phenolphthalein is a cathartic agent that is widely used inover-the-counter laxatives. Thirteen-week toxicity studies ofphenolphthalein were performed using F344/N rats and B₆C₃F₁mice. Rats and mice were fed ad libitum with a NIH 07 diet containing0; 3000; 6000; 12,000; 25,000; or 50,000 ppm phenolphthalein.On a milligram per kilogram body weight basis, rats and micefed 50,000 ppm phenolphthalein ingested more drug than wouldbe expected during human laxative abuse. Phenolphthalein producedlittle evidence of toxicity in rats. There was slightly lowerweight gain among the 25,000 and 50,000 ppm groups. Treatedrats showed elevated relative kidney weights (males only) andelevated absolute and relative liver weights at 12,000–50,000ppm phenolphthalein. Rat serum bile acids were depressed early(Days 5 and 6) by phenolphthalein treatment. Several treatment-relatedtoxic effects, however, were identified in mice who receivedmore phenolphthalein per unit body weight than rats. Althoughthere were no effects on body weight gain, elevated liver weightswere noted in female mice receiving 6000–50,000 ppm phenolphthalein.The primary treatment-related findings that occurred duringthe mouse studies involved the reproductive and hematopoieticsystems. Reproductive changes including depressed testis andright epididymal weights and sperm density, an elevated productionof abnormal sperm, and morphologic alterations in seminiferoustubules occurred at all levels of exposure (3000–50,000ppm). Hematopoietic changes included bone marrow hypoplasia(12,000–50,000 ppm), increased splenic hematopoiesis (malesonly, 25,000 and 50,000 ppm), and an elevated incidence of micronucleatederythrocytes (6000–50,000 ppm).     

To mesh or not to mesh

We are in the midst of an increasingly acrimonious discussion regarding the use of mesh in pelvic reconstructive surgery. Modern mesh kits, aggressively marketed by biotech companies, have become widespread. At times, they are used inappropriately, and significant complications such as pain syndromes and erosion are not uncommon. While conventional alternatives such as sacrospinous colpopexy and Burch colposuspension are not without their problems either, the discussion surrounding mesh use has a character never encountered before in urogynaecology. Many colleagues feel that the resolution of this conflict may be found in large randomised controlled trials such as the PROSPECT trial currently being planned in the UK. I feel that such a trial may well do more harm than good, unless certain precautions are taken. In this opinion piece I'll try and explain why.