Estimation of the DNA sequence discriminatory ability of hairpin-linked lexitropsins

Three- and four-ring polyamides containing N-methylimidazole and N-methylpyrrole, and their hairpin-linked derivatives, bind side-by-side in the minor groove of DNA in a sequence-specific manner. The sequences recognized by side-by-side molecules are dependent on the pairings of the polyamide rings to the bases. In this study we report a mathematical model for estimating the free energies of binding for γ-aminobutyric acid-linked polyamides to 5- and 6-bp DNA sequences. The model parameters are calibrated by a least-squares fit to 35 experimental binding constants. The model performs well in cross-validation experiments and the parameters are consistent with previously proposed empirical rules of polyamide–DNA binding. We apply the model to the design of targeted polyamides, evaluating the ability of the proposed polyamides to bind to a DNA sequence of interest while minimizing binding to the remaining DNA sequences.     

A study of patients referred from A&E for coroners post-mortem.

A review of 179 autopsies was undertaken over a 1-year period to determine if clinically useful information was obtainable from coroners post mortems performed on patients referred from the A&E department. Fifty-six patients had undergone unsuccessful resuscitation. The leading causes of death were heart disease and trauma. Discrepancies between the diagnosis made during resuscitation and the cause of death found at autopsy were revealed especially in those dying from noncardiac causes. Iatrogenic trauma from resuscitation attempts occurred in a significant number of cases. It is suggested that review of selected Coroners post mortems should be part of departmental audit, with a view to improving clinical skills.     

Traumatic esophageal rupture: unusual cause of acute mediastinal widening

We have presented the case of a 32-year-old man who sustained blunt trauma to the chest in a motor vehicle accident. Plain roentgenograms showed a widened mediastinum and pneumomediastinum, and an esophagogram with water-soluble contrast material showed an esophageal laceration at the T-4 level.     

Segmental intestinal muscular thinning: a possible cause of intestinal obstruction in the newborn

Intestinal obstruction proximal to a transition zone without an interposed physical barrier usually indicates Hirschsprung disease. The authors report one case of focal small bowel muscular thinning just distal to a transition zone that produced clinical and radiographic findings that simulated long-segment Hirschsprung disease in a 2-day-old infant.