A 90-Day Inhalation Toxicity Study with Benomyl in Rats

A 90-Day Inhalation Toxiaty Study with Benomyl in Rats. WARHEIT,D. B., KELLY, D. P., CARAKOSTAS, M. C., AND SINGER, A. W. (1989).Fundam Appl Toxicol./ 12, 333-345. Benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazolecarbamate,CAS Registry No. 17804-35-2] is a fungicide and the possibilityfor inhalation exposure exists for field workers. To assessthe toxicity of benomyl, groups of 20 male and 20 female CDrats were exposed nose-only 6 hr a day, 5 days a week, to concentrationsof 0, 10, 50 or 200 mg/m³ of a benomyl atmosphere. At the midpoint(approximately 45 days on test) and at the end of the exposureperiod, blood and urine samples for clinical evaluation werecollected from 10 rats/group/sex, and these animals were sacrificedfor pathological examination. Similar evaluations were performadon all remaining rats at the end of the 90-day test period.After approximately 45 days on test, compoundrelated degenerationof the olfactory epithelium was observed in all males and in8 of 10 female rats exposed to 200 mg/m³ benomyl. Two male ratsexposed to 50 mg/m³ had similar, although less severe, areasof olfactory epithelial degeneration. After approximately 90days of exposure, the remaining 10 rats/group/sex were sacrificedand examined. Of these rats, all of the males and females exposedto 200 mg/m³ had olfactory degeneration, along with 3 malesexposed to 50 mg/m³ of benomyl. No other observed lesions wereinterpreted to have been caused by the benomyl exposure. Inaddition, male rats exposed to 200 mg/m³ benomyl had depressedmean body weights compared to controls and this finding correlatedwith a reduction in food consumption. Based on pathologicalobservations, 10 mg/m³ represents the no-observable-effect level(NOEL) for the male rats, and 50 mg/m³ is the NOEL for the femalerats.     

Use of Telemetered Electrograms in the Assessment of Normal Pacemaker Function

The facility of direct real-time endocardial electrogram recording offered by newer pacemaker models can be helpful in the assessment of normal pacemaker function. Confirmation of the main hallmarks of sensing (amplitude, slew rate, and timing of the electrogram) can be achieved. Assessment of pacing capture also can be made; techniques for further analysis using external signal averaging can enhance this. The measurement of atrial and ventricular electrograms by telemetry has led to alterations in the protocol used at implantation to allow for the input impedance of the sensing circuit of the pacemaker. Accurate measurements of retrograde VA conduction times and confirmation of normal upper rate limit behavior of ODD pacemakers can be achieved simply and reliably using telemetered electrograms from the permanent pacemaker system.     

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.     

Meta-analysis of placebo-controlled studies of the efficacy of Epogam in the treatment of atopic eczema. Relationship between plasma essential fatty acid changes and clinical response

Gamma-linolenic acid in the form of a particular variety of evening primrose oil (Epogam) has been reported of value in the treatment of atopic eczema. Nine controlled trials of evening primrose oil were performed in eight centres. Four of the trials were parallel and five cross-over. Doctors and patients assessed the severity of eczema by scoring measures of inflammation, dryness, scaliness, pruritus and overall skin involvement. Individual symptom scores were combined to give a single global score at each assessment point. In the analysis of the parallel studies, both patient and doctor scores showed a highly significant improvement over baseline (P less than 0.0001) due to Epogam: for both scores the effect of Epogam was significantly better than placebo. Similar results were obtained on analysis of the cross-over trials, but in this case the difference between Epogam and placebo in the doctors' global score, although in favour of Epogam, failed to reach significance. The effects on itch were particularly striking. There was no placebo response to this symptom, whereas there was a substantial and highly significant response to Epogam (P less than 0.0001). When the improvements, or otherwise, in clinical condition were related to changes in plasma levels of dihomogammalinolenic and arachidoni acids, it was found that there was a positive correlation between an improvement in clinical score and a rise in the fatty acid levels.     

Incremental Value of Three-Dimensional Echocardiography Over Transesophageal Multiplane Two-Dimensional Echocardiography in Qualitative and Quantitative Assessment of Cardiac Masses and Defects

In the present study, we compared three-dimensionally (3-D) reconstructed images with multiplane two-dimensional (2-D) transesophageal echocardiographic (TEE) images in 17 patients with various cardiac masses and defects. To overcome the problem of making measurements from 3-D reconstructed images, we carefully "dissected" the 3-D dataset using paraplane and anyplane 2-D sections, which were then used to obtain the maximum sizes of the cardiac masses and defects. Of the 15 vegetations and 9 abscesses detected by 3-D TEE in 7 patients, only 8 (53%) vegetations and 4 (44%) abscesses were detected by multiplane 2-D TEE (P < 0.02). Also, the exact anatomical location, shape, geometry, and extent of various cardiac masses and defects were more clearly delineated by 3-D than 2-D TEE. The maximum dimensions of cardiac masses and defects were larger by 3-D than by 2-D TEE in 17 (89%) of the 19 lesions available for comparison (P < 0.002). In addition, 3-D TEE correlated more closely than 2-D TEE when compared to surgical measurements in three patients in whom they were available. Thus, it would appear that in several instances, the exact size of the cardiac lesion could only be assessed by analysis of the 3-D volumetric dataset. Out preliminary study has demonstrated the superiority of transesophageal 3-D reconstruction over multiplane 2-D TEE in both qualitative and quantitative assessment of various cardiac mass lesions and pathological defects.     

Surgical Treatment of Double Inlet Ventricle ("Single Ventricle")

The surgical techniques described are the result of an evolution over a number of years in the performance of the septation operation and the modified Fontan-Kreutzer repair for patients with double inlet ventricles. Those with associated pulmonary stenosis are best palliated by a classical Blalock-Taussig or Goretex shunt if an operation is required during the first few years of life and later, between two and four years of age, definitive repair by the modified Fontan-Kreutzer operation is advised. Although controversial, we prefer the use of a large nonvalved right atrial-pulmonary artery connection. Ventricular septation remains the best definitive surgical option when pulmonary stenosis is absent or mild. It is contraindicated by severe pulmonary vascular disease and also by less than moderate ventricular enlargement. The need for concomitant AV valve replacement and the use of an extracardiac conduit are associated with increased hospital mortality in our experience. Infants identified during the first year of life who do not have pulmonary stenosis are a difficult subset to manage. If the VSD and subaortic area is large and unobstructed, pulmonary artery banding early in life will control pulmonary vascular resistance and from this standpoint, permit these patients to become ultimately suited to a modified Fontan-Kreutzer repair. Unfortunately, ventricular hypertrophy usually results from pulmonary artery banding and has been associated with higher hospital mortality at the time of definitive repair. When pulmonary artery banding is undertaken for this subset, debanding and definitive repair seems best advised at about two years of age. Pulmonary artery banding is well known to accelerate the development of subaortic stenosis by spontaneous progressive restriction of the VSD. This results in small ventricular cavity size and increased ventricular hypertrophy, which are incremental risk factors for increased hospital mortality by either definitive procedure. When the VSD or subaortic area is narrow and the patient is identified during the first year of life, isolated pulmonary artery banding is inappropriate. The surgical options for these patients include Ebert's two-stage management program consisting of the initial placement of a loose partial septation patch with concomitant pulmonary artery banding, and later debanding and complete septation. Alternatively, a trial of primary complete septation may be warranted, or the use of a procedure consisting of division of the main pulmonary artery with distal closure and anastomosis of the proximal portion to the side of the ascending aorta, coupled with a systemic-pulmonary artery shunt.