Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

Time course of vascular prostanoid production in the fructose‐hypertensive rat

1 There is a relationship between hypertension, insulin resistance and an altered plasmatic lipid profile known as ‘metabolic syndrome’. Fructose (F) overload induces in the rat a mild hypertension associated with metabolic alterations such as hyperglycemia, hypertriglyceridemia and insulin resistance, resembling such syndrome. 2 Prostanoids (PR), metabolites of arachidonic acid, include vasoactive substances synthesized and released by the vessel wall. An altered pattern of PR release has been previously found in mesenteric vessels of experimental diabetic rats. 3 This study analyzed the effects of F‐overload during different periods (4, 9, 15 and 22 weeks) on PR release in aorta (A) and mesenteric vascular beds (MVB). Animals received tap water (control) or F solution (10% w/v) to drink. 4 Rats with F overload showed significantly higher systolic blood pressure, glycemia and triglyceridemia than controls; but no differences in this parameters were found among periods of treatment either in controls or experimental animals. 5 In A, prostacyclin was decreased at 9, 15 and 22 weeks of treatment when compared to 4 weeks and controls. In MVB, prostacyclin showed different patterns of release in the studied periods of F overload. Prostaglandin (PG) E₂ diminish in MVB at the same extent in all periods. No changes were observed in A. The vasoconstrictor thromboxane was elevated in the MVB at 9 weeks. PGF₂α, also a vasoconstrictor, remains unchanged. 6 In conclusion, F overload provokes in the rat a decrease in the vascular production of vasodilator PR and, in one of the studied periods, an increase in the release of the vasoconstrictor thromboxane, leading to a negative imbalance in the prostacylin/thromboxane ratio. This could be involved in the blood pressure alterations found in this experimental model of metabolic syndrome.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.     

Sequence comparison of human and yeast telomeres identifies structurally distinct subtelomeric domains

We have sequenced and compared DNA from the ends of three human chromosomes: 4p, 16p and 22q. In all cases the pro-terminal regions are subdivided by degenerate (TTAGGG)n repeats into distal and proximal sub- domains with entirely different patterns of homology to other chromosome ends. The distal regions contain numerous, short (<2 kb) segments of interrupted homology to many other human telomeric regions. The proximal regions show much longer (approximately 10-40 kb) uninterrupted homology to a few chromosome ends. A comparison of all yeast subtelomeric regions indicates that they too are subdivided by degenerate TTAGGG repeats into distal and proximal sub-domains with similarly different patterns of identity to other non-homologous chromosome ends. Sequence comparisons indicate that the distal and proximal sub-domains do not interact with each other and that they interact quite differently with the corresponding regions on other, non- homologous, chromosomes. These findings suggest that the degenerate TTAGGG repeats identify a previously unrecognized, evolutionarily conserved boundary between remarkably different subtelomeric domains.