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Expanded ensembles were used to obtain the association free energy, in which the number of ideal basepair contacts formed served as the order parameter, for DNA oligonucleotides of varying composition, chain length, and ionic strength. Although free energy profiles are unique to each sequence, all exhibit a pronounced response for low contact numbers dominated largely by an increase in system entropy. Short oligonucleotides with sequence periodicity exhibit a rather smooth free energy profile that increases in complexity as chain length increases. The complexity in non‐periodic sequences arises even in short oligonucleotides. Taking intact dsDNA with an extent of reaction ξ = 1.0, the maximum of the free energy profile appears at ξ≈0.1, representing two to four basepair contacts. In terms of chain length, the free energy barrier of longer oligonucleotides is higher and slightly narrower, due to the ensuant sharpness of the single‐to‐double stranded transition. Low ionic strength conditions induce an insta...

Detailed restriction maps of microbial genomes are a valuable resource in genome sequencing studies but are toilsome to construct by contig construction of maps derived from cloned DNA. Analysis of genomic DNA enables large stretches of the genome to be mapped and circumvents library construction and associated cloning artifacts. We used pulsed-field gel electrophoresis purified Plasmodium falciparum chromosome 2 DNA as the starting material for optical mapping, a system for making ordered restriction maps from ensembles of individual DNA molecules. DNA molecules were bound to derivatized glass surfaces, cleaved with NheI or BamHI, and imaged by digital fluorescence microscopy. Large pieces of the chromosome containing ordered DNA restriction fragments were mapped. Maps were assembled from 50 molecules producing an average contig depth of 15 molecules and high-resolution restriction maps covering the entire chromosome. Chromosome 2 was found to be 976 kb by optical mapping with NheI, and 946 kb with BamHI, which compares closely to the published size of 947 kb from large-scale sequencing. The maps were used to further verify assemblies from the plasmid library used for sequencing. Maps generated in silico from the sequence data were compared to the optical mapping data, and good correspondence was found. Such high-resolution restriction maps may become an indispensable resource for large-scale genome sequencing projects.

We compared the dimensions of the aorta obtained by two-dimensional transthoracic echocardiography (echo) (median, 2.5 mo preangioplasty) and magnetic resonance imaging (MRI) (median, 4.2 mo preangioplasty) to those obtained by angiography (cath) in 13 patients (age, 7.7 +/- 1.6 yr; mean +/- SEM) who underwent evaluation for coarctation balloon angioplasty between April 1993-January 1996. Echo measurements were obtained from the suprasternal and subcostal sagittal planes, MRI measurements from axial and sagittal oblique views, and cath measurements from the straight lateral or oblique views. Measurements of the diameters of the aortic isthmus, coarctation, descending aorta at the diaphragm, and isthmus length were made by all three modalities. Presence of aorto-aortic collaterals was determined, and the coarctation length was delineated. Investigators were blinded to other measurement data prior to statistical analysis. Data analysis by repeated analysis of variance (ANOVA) and Student-Newman-Keuls testing revealed no statistically significant difference between systolic pressure gradient by clinical examination (32.2 +/- 5.9 mm Hg), peak instantaneous Doppler evaluation (37.5 +/- 2.9 mm Hg), or preangioplasty systolic pressure gradient (32.1 +/- 3.3 mm Hg). With the exception of measurements of the descending aorta (echo, 11.7 +/- 0.9 mm vs. MRI, 13.3 +/- 0.8 mm vs. cath, 14.0 +/- 1.3 mm; P = 0.04), there was no statistically significant difference in dimensions of the aortic isthmus (9.2 +/- 0.6 mm vs. 10.5 +/- 0.9 mm vs. 10.8 +/- 0.9 mm), coarctation site diameter (4.8 +/- 0.6 mm vs. 5.6 +/- 0.9 mm vs. 5.3 +/- 0.8 mm), or isthmus length (12.4 +/- 2.1 mm vs. 12.1 +/- 2.2 mm vs. 10.9 +/- 1.7 mm). The correlation coefficients derived from comparisons of MRI vs. cath to echo vs. cath were similar for all dimensions except for isthmus length (P0.01). MRI demonstrated aorto-aortic collaterals more frequently than echo, while echocardiography better demonstrated cardiac function and intracardiac anomalies. Both modalities detected the single patient with a long segment coarctation. We conclude that echocardiography and MRI provide similar definition of the coarcted thoracic aorta, and either test may be individually advantageous in specific clinical situations.

At our institution, 55 infants and children (ages 0.3-21 yr, median 2.5 yr) underwent pulmonary balloon valvuloplasty between August 1983 and May 1993. Systolic pressure gradients fell acutely following balloon valvuloplasty from 63.5 +/- 24.8 mmHg (mean +/- standard deviation) to 26.7 +/- 12.9 mmHg (P0.001) with a decrease in systolic pressure ratio from 0.81 +/- 0.25 to 0.42 +/- 0.12 (P0.0001). Fifty of the 55 patients had long-term echocardiographic evaluation performed2 yr following balloon valvuloplasty. Thirty-four of the 50 patients (Group A; 68%) were classified as having successful (residual systolic gradients25 mmHg, ventricular systolic pressure ratios0.6) long-term outcomes. Their peak systolic gradients fell acutely from 58.8 +/- 16.6 mmHg to 22.7 +/- 11.2 mmHg (P0.001). At 4.6 +/- 2.3 yr postvalvuloplasty, peak instantaneous pressure gradients were 17.8 +/- 5.7 mmHg (P = ns vs. acute postvalvuloplasty). Fifteen of the 50 patients (Group B; 30%) had unsuccessful (residual systolic gradientsor = 25 mmHg and/or ventricular systolic pressure ratios0.6) long-term outcomes. Their peak instantaneous systolic gradients fell acutely from 76.5 +/- 33.1 mmHg to 36.6 +/- 11.4 mmHg (P0.05). At 3.8 +/- 1.7 yr postvalvuloplasty, peak instantaneous pressure gradients were 35.1 +/- 9.1 mmHg (P = ns vs. acute postvalvuloplasty). One 3-yr-old patient (Group C, 2%) required repeat balloon valvuloplasty on two separate occasions for recurrent stenosis. There was no significant prevalvuloplasty difference between Groups A and B with regard to age, weight, or Z scores of the pulmonary annuli or balloon/annulus ratio; however, patients in Group A had significantly lower prevalvuloplasty gradients and lower systolic pressure ratios than patients in Group B. Total systolic gradient reduction between patients with successful and unsuccessful outcomes was not significantly different (Group A: 36.1 +/- 16.6 mmHg; Group B: 41 +/- 22.3 mmHg). At long-term follow-up, patients in Group A had fewer symptoms and a significantly lower rate of electrocardiographic right ventricular hypertrophy than Group B patients. Successful outcomes defined by our criteria following balloon valvuloplasty were achieved in 68% of patients with greatest long-term success in patients with prevalvuloplasty systolic gradients60 mmHg and systolic pressure ratios0.8. Intervention at lesser systolic gradients (40-60 mmHg) appears indicated to achieve lower long-term gradients and fewer symptoms as total systolic gradient reduction by this technique is limited.

Changes in pulmonary function were studied via standard spirometry in 30 patients after laparoscopic cholecystectomy (LC) and compared with those in nine patients after traditional open cholecystectomy (OC). Studies performed presurgery and the morning after surgery included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and forced expiratory flow (FEF25%-75%). Age (43.9 +/- 2.6 years for LC and 42.3 +/- 3.2 for OC), sex, reasons for cholecystectomy, and smoking history were similar in both groups. The mean FVC decreased 23% after LC (3.57 +/- 0.18 L presurgery, range 0.56-5.62, versus 2.68 +/- 0.17 postsurgery, range 0.65-5.14) and 35.2% after OC (mean 3.52 +/- 0.29 presurgery, range 2.38-4.99, versus 2.24 +/- 0.24, range 1.23-3.49 postsurgery). FEV1 showed similar changes, with LC decreasing pulmonary function by 24.3% (2.76 +/- 0.14 L presurgery versus 2.01 +/- 0.12 postsurgery) compared with a 36.2% reduction in FEV1 after OC (2.86 +/- 0.29 L presurgery versus 1.81 +/- 0.21 L postsurgery). Forced expiratory flow decreased by 24.3% after LC and 40% after OC. Laparoscopic cholecystectomy provides less decrement in pulmonary function than traditional open cholecystectomy.

It has been suggested by several authors that the prevalence of mitral valve prolapse and aortic root dilation is increased in individuals with the fragile X syndrome. The prevalence of these abnormalities in young children with fragile X has not been established. Sixteen boys and 1 girl 13 years or younger were studied. Only 1 child (6%) had the typical examination findings of mitral valve prolapse, although his echocardiogram was normal. From this study it appears that cardiac abnormalities in fragile X syndrome develop in late childhood and adolescence. It seems important to follow these children carefully so that these cardiac abnormalities can be documented when they do develop.

From 1985 to 1990, 89 patients underwent placement of 41 aortic and 54 pulmonic cryopreserved allograft valved conduits between the right ventricle and the pulmonary arteries. Six patients underwent replacement with a second allograft conduit. Median age at operation was 4.3 years, and 20 patients were infants less than 1 year of age. Conduit sizes averaged 11 mm in the conduits placed in 20 infants and 20 mm in the 75 placed in patients more than 1 year of age. There were 7 early deaths in 89 patients (7.8%, 70% confidence levels 5.4% to 11.3%) and 9 late deaths in 82 hospital survivors (11%, 70% confidence levels 8% to 15%). Actuarial survival was 81% (70% confidence levels 75% to 86%) at 33 months, and no deaths were due to conduit problems. Late reoperation was required in 13 patients (7 for conduit obstruction, 1 for conduit valve insufficiency, and 5 for nonconduit-related problems). Six of the eight reoperations were done in patients who had small (or = 13 mm) conduits placed during infancy. Conduit failure was similar between pulmonic and aortic allografts. There were no deaths in the eight patients who required conduit reoperation. Actuarial freedom from reoperation for conduit dysfunction was 80.5% (70% confidence levels 72% to 86%) at 53 months for the entire group and 94% (confidence levels 88% to 97%) at 44 months for patients more than 1 year of age. Cryopreserved allograft conduits have good early and midterm results and are comparable to porcine xenograft conduits. Despite a likely need for replacement within 3 years, we continue to favor the use in infants of an allograft valved conduit over a xenograft Dacron conduit. The need to replace a cryopreserved allograft conduit appears similar for conduits of aortic or pulmonic origin.

It has been shown that an epidural test dose with adrenaline does not always detect an intravascular injection in halothane-anaesthetized children. To ascertain whether test dosing with other agents might be more useful, we sought to determine if and at what dose levels three different intravenous drugs (adrenaline, isoprenaline and 1% lignocaine with 1/200,000 adrenaline) produced an increase in heart rate (HR) in halothane-anaesthetized lambs. Eight 2-week-old lambs were anaesthetized with 1% halothane in oxygen. The lambs were intubated and ventilated in order to maintain end-tidal and arterial CO2 within normal limits; HR and blood pressure before and 15-180 s after the injection of four increasing doses of each drug were recorded. The same set of measurements was repeated after the intravenous injection of atropine 10 micrograms kg-1. Adrenaline-containing doses produced a more sustained increase in HR (P less than 0.05, ANOVA) at lower doses of adrenaline when atropine was injected first. This increase did not occur in all lambs, and dysrhythmias were manifest in some. Isoprenaline always produced a significant increase in HR without dysrhythmias whether atropine was given or not. We conclude that in halothane-anaesthetized lambs, isoprenaline is a more reliable indicator of intravascular injection than adrenaline.

The usefulness of measuring both alpha-fetoprotein and hCG in following the progress of patients with testicular cancers and germ cell tumors is demonstrated. In almost half the cases of testicular cancers studied, only one tumor marker was elevated; in at least one instance, the source of alpha-fetoprotein was eliminated while the source of hCG persisted. A comparison of the hCG method in use at Memorial Sloan-Kettering Cancer Center ( MSKCC ) with a commercial kit (Corning) showed that the methods were equivalent for monitoring both testicular cancers and gestational trophoblastic disease. All 17 patients with hepatocellular carcinoma had elevated levels of alpha-fetoprotein.

Tetralogy of Fallot with absent pulmonic valve is a rare but life-threatening syndrome. Children with this complex may have aneurysmally dilated pulmonary arteries which compress the tracheobronchial tree and cause airway compromise and death. This paper reviews the course of 10 children with this syndrome who were seen at our institution from 1962 until the present. Two infants with respiratory distress secondary to tetralogy plus absent pulmonary valve were treated with early aggressive medical intervention followed by operation. After closure of the ventricular septal defect and reconstruction of the right ventricular outflow tract, the pulmonary artery aneurysms were resected. Both children are growing and are well more than 1 year after the operations. Our experience with these two patients suggests that such infants may benefit from this form of therapy.