Premature failure of small-sized Shelhigh No-React porcine pulmonic valve conduit model NR-4000.

OBJECTIVE: Given the limited availability of small-sized cryopreserved pulmonary homografts, we implanted a series of Shelhigh No-React porcine pulmonic valve conduits (SPVC). The aim of this study was to evaluate the short-term performance following implantation. METHODS: From February 2000 to September 2000, the SPVC was implanted 25 times in 24 patients in the right ventricular outflow tract (RVOT) to correct congenital anomalies. The anatomical malformations were TOF/PA in eight patients, TGA/VSD/PS in four, truncus arteriosus in four, IAA/VSD/AS or AA in four, l-TGA/VSD in two and other in two. Age at operation was 2.8+/-3.9 years (mean+/-SD), including 12 patients under 1 year. The median conduit size was 14mm (range, 10-18). RESULTS: At a mean follow-up of 23+/-5 months, two late deaths (8%) have occurred. Although they were not primarily conduit related, both showed severe conduit stenosis. Twenty-one conduits (84%) showed mild to severe conduit stenosis, regurgitation or both. Two patients underwent balloon dilatation for distal conduit stenosis. Twelve conduits (48%) in 11 patients were removed at a median of 12 months (range, 2-18 months) due to RVOT obstruction in 11 and free conduit insufficiency with pseudoaneurysm in one. The typical findings of the explanted conduits were prominent intimal peel formation at the distal anastomosis without calcification. The actuarial freedom from reintervention at 18 months was 48+/-10%. CONCLUSIONS: Our experience of the SPVC with the diameter of 14mm or less has revealed a high incidence of distal conduit stenosis due to intimal peel formation resulting in early conduit failure. These findings have led us to abandon its use when other options are available.     

Postoperative functional assessment of a modified surgical approach to repair of tetralogy of Fallot

Since February 1982, we have used a modified technique to repair tetralogy of Fallot with transatrial closure of the ventricular septal defect, a short infundibular incision with avoidance of muscle resection, and anterior expansion of the right ventricular outflow tract using a patch in every case. The pulmonary anulus is approached in the usual manner. Twenty-six patients have had repair with this technique without mortality, and 20 patients (Group 1) have been evaluated 1 to 3 years postoperatively. Their results are compared with those of all patients followed up in our division who had had repair by the traditional technique in the 5 years before February 1982, with the same evaluation within 4 years of operation (Group 2, n = 22). Ten of 20 patients in Group 1 and 14 of 22 in Group 2 required a transannular patch. At cardiac catheterization, right ventricular outflow tract obstruction was effectively relieved in both groups (right ventricular systolic pressure [mean +/- standard error], Group 1 versus Group 2, 45 +/- 5 versus 49 +/- 4 mm Hg). No patient with the modified technique had a residual ventricular septal defect. By M-mode echocardiography, right ventricular-left ventricular end-diastolic dimension ratio was significantly lower for Group 1 patients (0.58 +/- 0.03 versus 0.78 +/- 0.04; normal less than 0.45; p less than 0.001). With radionuclide ventriculography, right ventricular ejection fractions were significantly higher for Group 1 patients with the modified repair (38% +/- 2.2% versus 33% +/- 1.8%; normal greater than or equal to 45%; p less than 0.05). Because the incidence of obligatory pulmonary insufficiency caused by transannular patch is similar in both groups, these results cannot be directly attributed to the presence of pulmonary insufficiency alone. With ambulatory electrocardiographic monitoring, no patient in Group 1 had any ventricular premature contractions whatsoever, whereas six of 22 patients in Group 2 had demonstrable ventricular premature contractions. These results suggest that in children with tetralogy of Fallot, right ventricular outflow tract obstruction can be effectively relieved with this modified approach with improved early preservation of right ventricular function.     

A specific DNA probe for detecting Mycoplasma hyopneumoniae in experimentally infected piglets.

Mycoplasma hyopneumoniae is the primary agent of swine enzootic pneumonia. Because of fastidious growth requirements and its serological cross-reactions with other porcine mycoplasmas, we developed a specific DNA probe for its detection. A partial genomic library of M. hyopneumoniae was constructed in plasmid pBR 322 using Hind III chromosomal fragments. The recombinant plasmids were screened by differential hybridization with M. flocculare and M. hyorhinis genomic DNA probes. One non-hybridizing recombinant plasmid was selected and its 1.65 kbp insert (designated I141) tested for specificity against genomic DNA from numerous mycoplasmas, other bacteria species and DNA from lung tissue of specific pathogen free (SPF) piglets. The 32P labelled I141 could detect specifically down to 400 pg of M. hyopneumoniae genomic DNA. To test the suitability of the I141 probe for the laboratory diagnosis of M. hyopneumoniae infections, we used clinical tracheobronchial specimens from piglets which were experimentally infected with M. hyopneumoniae. The results with hybridization on each specimen were compared to findings with an immunofluorescence test. Of the clinical specimen tested, there was agreement in the two tests of 63%.     

Effect of cognitive and motor tasks on postural stability in Parkinson's disease: a posturographic study.

To analyse the effect of concomitant cognitive or motor task performance on balance control in Parkinson's disease (PD), we performed a posturographic study in 24 PD patients and in 20 sex- and age-matched control subjects. Postural sway was measured with eyes open (EO) and eyes closed (EC) during quiet stance and during performance of calculation or motor sequence of thumb opposition to the other fingers. No difference of centre of foot pressure (COP) parameters was observed during quiet standing (either EO or EC) between patients and controls, but visual deprivation induced in both groups a worsening of postural stability. COP area was significantly increased in PD patients during dual task performance, whereas no difference of COP path and x-y axes was observed. The effects induced by the performance of cognitive or motor task were significantly more evident in PD patients with clinical evidence of postural instability (presence of prior falls in the history). This study demonstrates that dual task interference on postural control can be observed in PD patients during performance of cognitive as well as motor tasks. The balance deterioration during dual task performance was significantly enhanced in patients with history of prior falls. These findings have some implications for the strategies to be used in reducing the risk of fall in PD.     

Communication of BRCA1 and BRCA2 results to at-risk relatives: a cancer risk assessment program's experience

We describe results from a survey designed to assess patterns of communication within families shortly after an individual receives results of BRCA1 and BRCA2 mutation carrier status. Shortly after disclosure of BRCA1 and BRCA2 genetic test results, the proband was contacted by phone to administer the post disclosure survey. Questions asked included whether they had shared their results with their siblings or adult children, if there were difficulties in communicating the test results, and if there was any distress associated with the sharing of results. A total of 162 women who have received results from BRCA1 and BRCA2 genetic testing participated in the survey. The probands shared their results more often with their female than their male relatives (P < 0.001). Probands who had tested positive for a mutation in the BRCA1 or BRCA2 gene shared their results more often with their relatives than did probands who were not carriers (P = 0.002). Probands reported more often that their siblings rather than their adult children had difficulties understanding the results (P = 0.001). The probands who were carriers more often reported having difficulties explaining their results to their relatives (P < 0.001) and their relatives were upset on hearing the result more often than were the relatives of probands who were not carriers (P < 0.001). The probands who were carriers reported more often that they were upset explaining their results to their relatives than did the probands who were not carriers (P < 0.001). Individuals are disclosing their test results to their relatives. Probands who are BRCA1- or BRCA2-positive are more likely to experience difficulty and distress with the communication of their test results to family members.     

Comparison of DNA- and RNA-based methods for detection of truncating BRCA1 mutations

A number of methods are used for mutational analysis of BRCA1, a large multi-exon gene. A comparison was made of five methods to detect mutations generating premature stop codons that are predicted to result in synthesis of a truncated protein in BRCA1. These included four DNA-based methods: two-dimensional gene scanning (TDGS), denaturing high performance liquid chromatography (DHPLC), enzymatic mutation detection (EMD), and single strand conformation polymorphism analysis (SSCP) and an RNA/DNA-based protein truncation test (PTT) with and without complementary 5' sequencing. DNA and RNA samples isolated from 21 coded lymphoblastoid cell line samples were tested. These specimens had previously been analyzed by direct automated DNA sequencing, considered to be the optimum method for mutation detection. The set of 21 cell lines included 14 samples with 13 unique frameshift or nonsense mutations, three samples with two unique splice site mutations, and four samples without deleterious mutations. The present study focused on the detection of protein-truncating mutations, those that have been reported most often to be disease-causing alterations that segregate with cancer in families. PTT with complementary 5' sequencing correctly identified all 15 deleterious mutations. Not surprisingly, the DNA-based techniques did not detect a deletion of exon 22. EMD and DHPLC identified all of the mutations with the exception of the exon 22 deletion. Two mutations were initially missed by TDGS, but could be detected after slight changes in the test design, and five truncating mutations were missed by SSCP. It will continue to be important to use complementary methods for mutational analysis.     

Reye's syndrome simulacra in liver of mice after treatment with chemical agents and encephalomyocarditis virus

In children with Reye's syndrome, liver specimens exhibit the following characteristics: mitochondrial dysfiguration, fatty infiltration, decreased activity of carbamyl phosphate synthetase and of ornithine transcarbamylase, histochemically reduced activity of succinic dehydrogenase and cytochrome oxidase, and depletion of glycogen. We intended to create an animal model for Reye's syndrome by treating mice with encephalomyocarditis virus, and/or salicylate, fructose, Atlox, butylated hydroxytoluene, pentachlorophenol, and an equal mixture of butylated hydroxytoluene and monosodium stearate. Liver specimens were then examined for the listed characteristics as well as for the activity of argininosuccinic lyase, arginase, phosphorylase, and glucose-6-phosphatase. Results of interest in regard to the experimental intention were obtained in livers of mice treated with virus and Atlox (A) or virus and butylated hydroxytoluene (B). In these specimens, we found a significant reduction (p less than 0.05)--except for ornithine transcarbamylase (A)--to the following levels (in percentage of normal mean): carbamyl phosphate synthetase (A, 79 per cent; B, 57 per cent); ornithine transcarbamylase (A, 91 per cent; B, 75 per cent); glycogen (A, 26 per cent; B, 37 per cent). Simultaneous morphologic analysis of these liver specimens indicated mitochondrial dysfiguration, absence of dense granules, fatty infiltration, and normal activity of succinic dehydrogenase and cytochrome oxidase. The induction of Reye's syndrome-like features in mouse liver may be useful for the study of disease mechanisms and therapy.     

Enhanced myocardial protection during global ischemia with 5'-nucleotidase inhibitors.

Depletion of adenosine triphosphate precursors, such as myocardial adenosine, during global ischemia results in poor postischemic adenosine triphosphate repletion and functional recovery. Neonatal hearts may be more resistant to this deleterious effect of ischemia, because they are characterized by low 5'-nucleotidase activity, which may result in higher sustained endogenous myocardial adenosine triphosphate precursor levels during ischemia. Adult hearts, however, have high levels of 5'-nucleotidase activity leading to depleted precursors during ischemia and poor postischemic functional recovery. Augmenting myocardial adenosine exogenously during ischemia in adult hearts has a beneficial effect on recovery. The present study tested if preservation of nucleotide precursors, better adenosine triphosphate repletion, and enhanced postischemic myocardial recovery in adult hearts could be achieved with a "neonatal" strategy. Therefore 5'-nucleotidase inhibitors were administered to isolated, perfused adult rabbit hearts subjected to 120 minutes of ischemia (at 34 degrees C) to determine if this improved functional recovery. Hearts received St. Thomas' Hospital cardioplegic solution (control hearts) or cardioplegic solution containing 5'-nucleotidase inhibitors: pentoxifylline, thioinosine, [s-(p-nitrophenyl)-4-thioinosine], or thioinosine's dimethyl sulfoxide vehicle alone. After ischemia and reperfusion, recovery of systolic function, diastolic function, and myocardial oxygen consumption was significantly better with 5'-nucleotidase inhibition. No changes in coronary flow were noted. We speculate and are pursuing the theory that the mechanism of 5'-nucleotidase inhibition's favorable action is due to preventing the catabolism, transport, and loss of nucleotide precursors during ischemia, maintaining adenosine triphosphate precursor availability.     

Plasmapheresis using the IBM 2991 blood cell processor

The IBM 2991 Blood Cell Processor, normally used to wash or deglycerolize red blood cells, has been modified to permit serial plasmapheresis using a small roller pump, an adapter line and the disposable processing set usually used for cell washing. Blood is withdrawn from the donor, pumped into the plastic centrifuge bag and the plasma removed after centrifugation. Donor erythrocytes are pumped from the processing bag to a reservoir bag from which they are returned to the donor by gravity. Multi-unit plasmapheresis to harvest plasma for transfusion or to remove plasma as a therapeutic measure is possible using the modified system. A four-unit plasmapheresis can be done in 65 to 75 minutes at a cost of $27.61, including disposables and technologist labor. This modification allows the IBM 2991 to function for red blood cell washing and as an efficient instrument for plasmapheresis.     

Normal rate of ventricular emptying in valvular aortic stenosis.

The delayed upstroke of the arterial pulse in valvular aortic stenosis has been attributed, in part, to prolonged left ventricular emptying. Left ventricular emptying rate, however, has not been measured in aortic stenosis. We assessed the rate of left ventricular emptying by computer analysis of biplane cineangiograms in seven normal subjects, six patients with mild to moderate aortic stenosis, and 12 patients with severe aortic stenosis. As an indicator of delayed arterial pulse rise, T time index (time to half maximum aortic pressure corrected for heart rate) was measured in each group. T time index averaged 0.07 +/- 0.01 units in normal subjects, 0.14 +/- 0.04 units in the patients with mild to moderate aortic stenosis, and 0.13 +/- 0.05 units in those with severe aortic stenosis. Patients with mild to moderate and severe aortic stenosis differed significantly from normal subjects. Relative emptying rates were defined as the percentage of initial systolic volume ejected divided by the percentage of systole elapsed. These relative emptying rates were determined during the first, second, and third thirds of systole in all three groups. No significant decrease in the relative rate of left ventricular emptying was noted when each group of patients with aortic stenosis was compared with the normal subjects. Neither was there slowing in the actual rate of ejection of blood in ml per second throughout systole. We conclude that the rate of ventricular emptying is normal in aortic stenosis and does not explain the arterial pulse delay in this disease.