Atrioventricular valve function after single patch repair of complete atrioventricular septal defect in infancy: how early should repair be attempted?

BACKGROUND: Though repair of complete atrioventricular septal defect in infancy has become routine at most centers, it is not unusual for very young infants to be managed medically because of concerns about the fragility of the atrioventricular valve tissue. METHODS: Since July 1992, seventy-two infants have undergone primary repair of complete atrioventricular septal defects at a median age of 3.9 months (40% < 3 months). A single-patch technique was used in all patients. The cleft was closed completely in 61 patients and partially (n = 10) or not at all (n = 1) in select patients at risk for valve stenosis. Left atrioventricular valve annuloplasty was performed in 18 patients. On the basis of transesophageal echocardiographic findings, 10 patients were returned to bypass for revision of the valve repair. RESULTS: There was one early death in a patient with single left papillary muscle, no early reoperations, and no new permanent arrhythmias. Only three patients had moderate left atrioventricular valve regurgitation at discharge. During a median follow-up of 24 months, there was one late death and five reoperations for left atrioventricular valve regurgitation (n = 2) and/or systemic outflow obstruction (n = 4). Follow-up left atrioventricular valve regurgitation was moderate in three patients, mild in 14, and none/trace in 54. Age had no relation to postoperative atrioventricular valve regurgitation, death, or reoperation. CONCLUSIONS: Despite concerns about fragility of valve tissue in very young patients, excellent results can be achieved with meticulous techniques. From neonates to older infants, age at repair does not influence outcome or valve function.     

A haplotype and linkage disequilibrium analysis of the hereditary hemochromatosis gene region

Monoclonal antibodies were generated against serotonin (5-HT) and the C-terminal portion of the neuronal form of nitric oxide synthase (nNOS), the enzyme producing nitric oxide in neurons. These antibodies were used to compare the distribution of 5-HT- and nNOS-containing neurons in the raphe nuclei of four animal species (rat, mouse, guinea pig, and cat). It was found that the rat was the only species in which the raphe nuclei contain a substantial number of nNOS-immunoreactive (IR) cell bodies. In this species and as observed by other authors, all mesencephalic raphe nuclei contained nNOS-IR cells, the largest group being located in the nucleus raphe dorsalis. The coexistence of nNOS and 5-HT immunoreactivities in these nuclei was visualized by double labeling. In the medulla, the nuclei raphe magnus and obscurus displayed a rather low number of nNOS-IR neurons. In the other species, nNOS-IR cell bodies were found in very low numbers, whatever raphe nucleus was considered. The rostral pole of the nucleus raphe dorsalis and the nuclei raphe magnus and obscurus contained a few nNOS-IR neurons which did not show any coincidence with the 5-HT neurons. In addition, nNOS-IR axons were rare. It is concluded that in the mouse, guinea pig, and cat the involvement of nitric oxide in functions subserved by 5-HT within the raphe nuclei might be minimal.     

RAPD analysis reveals low genetic variability in the endangered light-footed clapper rail

After 4 hours of treatment with TNF, newly synthesized endothelial leukocyte adhesion molecule 1, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 molecules are diffusely expressed on the apical surface of cultured umbilical vein endothelial cells. Such cells maintain the epithelioid, cobblestone appearance of untreated endothelial cells and display cytoskeletal actin largely arranged in dense peripheral bands. After 24 to 72 hours of treatment with TNF, cells become elongated and rearrange their actin filaments into longitudinal stress fibers. At this time, intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 remain elevated but redistribute to the cell junctions. Intercellular adhesion molecule 2, beta 1 integrins, and beta 3 integrins also redistribute to cell junctions in TNF-treated cultures. IFN-gamma produces morphologic changes similar to those induced by TNF but does not cause surface protein redistribution. Cells treated with TNF plus IFN-gamma become even more elongated and display TNF-like redistributions. We conclude that TNF activates a program of membrane protein redistribution, and we speculate that this dynamic redistribution of adhesion molecules to cell junctions may contribute to the recruitment of leukocytes to sites of inflammation.     

An analysis of the effect of venous resistance on the performance of gravity-fed intravenous infusion systems

OBJECTIVE: Our objective was to assess the effect of venous resistance in a clinically relevant range on flow rates through intravenous (i.v.) cannulae. METHODS: Since resistances in series are additive, the sum of the resistance of the i.v. cannula and the vein equates to the total resistance to flow. Using resistance data from earlier work, the total resistance for various combinations of cannula and vein size was calculated, allowing a prediction to be made of the comparative flow rates between these combinations for a given driving pressure. Next, the clinical situation was simulated by measuring flow rates through i.v. cannulae connected in series to a variety of infusion devices with resistances known to be within the range of clinically relevant venous resistance. RESULTS: The effect of venous resistance was greatest on large-bore cannulae, with significant reductions in flow occurring when even low levels of venous resistance were added. Throughout much of the range of venous resistances encountered clinically, total flows through two small-gauge cannulae exceeded that through a single large-gauge cannula. CONCLUSION: To achieve maximum benefit from a large-bore cannula, a suitably large vein must be chosen. Further, where venous access is difficult and high flow potential from an infusion system is required, two separate infusions through small cannulae may be a preferable option to a single large bore.     

Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups

BACKGROUND: Exercise testing is useful in the assessment of symptomatic patients for diagnosis of significant or extensive coronary disease and to predict their future risk of cardiac events. The Duke treadmill score (DTS) is a composite index that was designed to provide survival estimates based on results from the exercise test, including ST-segment depression, chest pain, and exercise duration. However, its usefulness for providing diagnostic estimates has yet to be determined. METHODS AND RESULTS: A logistic regression model was used to predict significant (>/=75% stenosis) and severe (3-vessel or left main) coronary artery disease, and a Cox regression analysis was used to predict cardiac survival. After adjustment for baseline clinical risk, the DTS was effectively diagnostic for significant (P<0.0001) and severe (P<0.0001) coronary artery disease. For low-risk patients (score >/=+5), 60% had no coronary stenosis >/=75% and 16% had single-vessel >/=75% stenosis. By comparison, 74% of high-risk patients (score <-11) had 3-vessel or left main coronary disease. Five-year mortality was 3%, 10%, and 35% for low-, moderate-, and high-risk DTS groups (P<0.0001). CONCLUSIONS: The composite DTS provides accurate diagnostic and prognostic information for the evaluation of symptomatic patients evaluated for clinically suspected ischemic heart disease.     

Degradation kinetics of DMP 777, an elastase inhibitor

PURPOSE: The objective was to evaluate the degradation profile of the elastase inhibitor DMP 777 and lay the foundation for formulation development. METHODS: The pKa was determined by potentiometric titration in mixed-aqueous solvents. The degradation kinetics were studied as a function of pH, buffer concentration, ionic strength, methanol concentration and temperature using a stability-indicating HPLC assay. The degradation products were identified by LC-MS, NMR, and by comparison with authentic samples. RESULTS: The pKa for the protonated piperazine nitrogen was estimated to be 7.04. The pH-rate profile is described by specific acid-, water-, and specific base-catalyzed pathways. The pH of maximum stability is in the range of 4 to 4.5 where water is the principal catalyst in the reaction. Buffer catalysis, primary salt effects and medium effects were observed. The proposed mechanism for acid catalyzed degradation is the rarely observed AAL1 which involves alkyl-nitrogen heterolysis. The driving force for the reaction appears to lie in the stability of the benzylic carbocation. The proposed mechanism for base catalyzed degradation is BAC2 which involves beta-lactam ring opening. The beta-lactam ring of DMP 777, a monolactam, appears to be as reactive as that in benzylpenicillin in the KOH controlled region where a similar mechanism of hydrolysis should be operative. A contributing factor to this increased reactivity may lie in the reduced basicity of the beta-lactam nitrogen making it a good leaving group. CONCLUSIONS: The degradation profile indicates that development of a solution dosage form of DMP 777 with adequate shelf-life stability at room temperature is feasible.     

Tn10 transposition via a DNA hairpin intermediate

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder characterized by microcephaly, a birdlike face, growth retardation, immunodeficiency, lack of secondary sex characteristics in females, and increased incidence of lymphoid cancers. NBS cells display a phenotype similar to that of cells from ataxia-telangiectasia patients, including chromosomal instability, radiation sensitivity, and aberrant cell-cycle-checkpoint control following exposure to ionizing radiation. A recent study reported genetic linkage of NBS to human chromosome 8q21, with strong linkage disequilibrium detected at marker D8S1811 in eastern European NBS families. We collected a geographically diverse group of NBS families and tested them for linkage, using an expanded panel of markers at 8q21. In this article, we report linkage of NBS to 8q21 in 6/7 of these families, with a maximum LOD score of 3.58. Significant linkage disequilibrium was detected for 8/13 markers tested in the 8q21 region, including D8S1811. In order to further localize the gene for NBS, we generated a radiation-hybrid map of markers at 8q21 and constructed haplotypes based on this map. Examination of disease haplotypes segregating in 11 NBS pedigrees revealed recombination events that place the NBS gene between D8S1757 and D8S270. A common founder haplotype was present on 15/18 disease chromosomes from 9/11 NBS families. Inferred (ancestral) recombination events involving this common haplotype suggest that NBS can be localized further, to an interval flanked by markers D8S273 and D8S88.