Identification and characterization of a pyrantel pamoate resistant cyathostome population

Three fecal egg count reduction assays (FECR) and one critical trial were performed to determine the efficacy of pyrantel pamoate (PP) at 6.6 mg base kg-1 on a well managed stud farm in Louisiana where a loss of efficacy was suspected. Efficacy of PP based on FECR varied from 25% in mares to 83% in yearlings. Second treatments with PP 2 weeks following an initial treatment failed to reduce eggs per gram (EPG). A critical trial was performed to determine the cyathostome species resistant to PP. Three strongyle-naive ponies which acquired infections on the farm were used for this purpose. Following treatment with PP at the recommended dose, 11 species of cyathostomes remained in the intestine of the tracer ponies. Reduced efficacies (62%-88%) were noted for seven species. Resistance to oxibendazole (OBZ), which was > 90% effective on this farm in 1982, was also evaluated by FECR and found to exist. The results of one experiment indicate that dual resistance of parasites to PP and OBZ also exists.     

Determinants of reoperation after 960 valve replacements with Carpentier-Edwards prostheses

During the period of 1977 to 1990, 960 Carpentier-Edwards standard prostheses (Baxter Healthcare Corp., Santa Ana, Calif.) were placed in 875 operations. Freedom from reoperation at 10 years was 57% +/- 4%, 76% +/- 3%, and 95% +/- 5% for mitral, aortic, and tricuspid valve replacement, respectively. Age was the only independent determinant of reoperation for both aortic and mitral valves. Likelihood of reoperation decreased with age, with freedom from reoperation after 10 years in patients aged less than 60 years versus 60 or more years being 65% +/- 5% versus 90% +/- 4% after aortic valve replacement and 48% +/- 5% versus 75% +/- 6% after mitral valve replacement. For mitral valve replacement, larger valve size made reoperation more likely, with freedom from reoperation at 10 years being 71% +/- 6% for sizes median less than 31 mm and 57% +/- 5% for sizes 31 mm or larger. For aortic valve replacement, prior median sternotomy reduced freedom from reoperation at 10 years from 80% +/- 3% to 25% +/- 5%. The low prevalence of reoperation affirms the suitability of the Carpentier-Edwards prosthesis for selected elderly patients and for tricuspid valve replacement. Because of their influence on the probability of reoperation, valve size and prior cardiac procedures also merit consideration in the choice of valvular prosthesis.     

Quantitative trait locus mapping of human blood pressure to a genetic region at or near the lipoprotein lipase gene locus on chromosome 8p22

Resistance to insulin-mediated glucose disposal is a common finding in patients with non-insulin-dependent diabetes mellitus (NIDDM), as well as in nondiabetic individuals with hypertension. In an effort to identify the generic loci responsible for variations in blood pressure in individuals at increased risk of insulin resistance, we studied the distribution of blood pressure in 48 Taiwanese families with NIDDM and conducted quantitative sib-pair linkage analysis with candidate loci for insulin resistance, lipid metabolism, and blood pressure control. We found no evidence for linkage of the angiotensin converting enzyme locus on chromosome 17, nor the angiotensinogen and renin loci on chromosome 1, with either systolic or diastolic blood pressures. In contrast, we obtained significant evidence for linkage or systolic blood pressure, but not diastolic blood pressure, to a genetic region at or near the lipoprotein lipase (LPL) locus on the short arm of chromosome 8 (P = 0.002, n = 125 sib-pairs, for the haplotype generated from two simple sequence repeat markers within the LPL gene). Further strengthening this linkage observation, two flanking marker loci for LPL locus, D8S261 (9 cM telomeric to LPL locus) and D8S282 (3 cM centromeric to LPL locus), also showed evidence for linkage with systolic blood pressure (P = 0.02 and 0.0002 for D8S261 and D8S282, respectively). Two additional centromeric markers (D8S133, 5 cM from LPL locus, and NEFL, 11 cM from LPL locus) yielded significant P values of 0.01 and 0.001, respectively. Allelic variation around the LPL gene locus accounted for as much as 52-73% of the total interindividual variation in systolic blood pressure levels in this data set. Thus, we have identified a genetic locus at or near the LPL gene locus which contributes to the variation of systolic blood pressure levels in nondiabetic family members at high risk for insulin resistance and NIDDM.     

Apoptosis and expression of inducible nitric oxide synthase are mutually exclusive in renal mesangial cells

Nitric oxide (NO) is a multipurpose messenger molecule, important for blood vessel relaxation, neuronal communication, and antimicrobial activities. The generation of NO from L-arginine is catalyzed by NO synthase (NOS). An inducible form of NOS, iNOS, was first characterized in macrophages and then in many other tissues and cells, including renal mesangial cells. Mesangial cells play a crucial role in the regulation of the glomerular filtration rate as well as in the pathophysiology of certain forms of glomerulonephritis in which mesangial cells and macrophages produce NO in high amounts. Because reports have associated NO production with apoptotic cell death in macrophages and we recently demonstrated NO-mediated apoptosis in mesangial cells, we searched for the relationship between in situ iNOS induction and apoptosis by iNOS immunocytochemistry and terminal desoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. RAW 264.7 macrophages exhibited homogeneous iNOS expression and apoptotic nuclei in the iNOS-containing cells upon stimulation with interferon-gamma and lipopolysaccharide. In contrast, stimulated rat mesangial cells stained heterogeneously for iNOS, depending on cell passage and iNOS-stimulating pathway. Mesangial cells expressing iNOS did not display signs of apoptosis and, vice versa, cells showing characteristic features of apoptosis did not stain for iNOS. Thus, our study suggests that mesangial cells react to stimulation by interleukin-1 and/or cAMP-elevating compounds with mutually exclusive responses, either by expression of iNOS or by undergoing programmed cell death.     

Selective loss of pallidal dopamine D2 receptor density in hepatic encephalopathy

The binding parameters of [3H]SCH 23390 and [3H]spiperone (radioligands for dopamine D1 and D2 receptors, respectively) were investigated in autopsied frontal cortex, caudate nucleus and globus pallidus/putamen of cirrhotic patients who died in hepatic coma as well as in age- and sex-matched controls. Specific [3H]SCH 23390 binding site densities were unchanged in all regions; in contrast, specific [3H]spiperone binding site density was decreased (by 44%, P < 0.001) in the globus pallidus/putamen of patients with HE. Decreased densities of pallidal D2 binding sites could relate to the motor dysfunctions commonly encountered in human HE.     

Sustained ventricular tachycardia in older children. Spontaneous regression in 3 cases]

Extensively described since Gallvardin's reports, the electrical features of salves of ventricular tachycardia in an apparently healthy heart are now well known. The usual benign nature of this arrhythmia is acknowledged, seldom contradicted by isolated clinical cases. Although chronicity is the rule in young adults, there have been a few publications concerning the natural history of these tachycardias in the paediatric age group. The authors report three cases of episodic sustained ventricular tachycardia in older children, presenting at an average of 7 years of age (range 5 to 9 years) and followed up for an average of 7 years (range: 5.5 to 9 years). These three children were treated for an average of 4.5 years (range: 3 to 5.5 years). All treatment was finally withdrawn when stable permanent sinus rhythm without ventricular extrasystoles was restored and confirmed over an average period of 2 years (range 10 months to 3.5 years), an average of 4 (range 3 to 7) successive normal Holter recordings at several months' interval. The outcome in children to spontaneous regression after several years would seem to make radiofrequency ablation more dangerous than useful given the benign nature of the arrhythmia and its good response to pharmacological intervention.