Treatment of refractoriness to platelet transfusion by protein A column therapy

Ten thrombocytopenic patients (platelets < 10–24 × 10(9)/L) who were refractory to platelet transfusion were investigated for their responsiveness to staphylococcal protein A column therapy. Nine patients had previously been treated with steroids, intravenous immune globulin, and/or other forms of immunosuppressive therapy without improvement in their transfusion response. All patients were receiving multiple platelet transfusions without achieving 1-hour corrected count increments (CCIs) > or = 7500. Eight patients had antibodies that reacted with platelets and were directed against HLA class I antigens, ABO antigens, and/or platelet-specific alloantigens. Plasma (500-2000 mL) from each patient was passed over a protein A silica gel column and then returned to the patient. Patients received from 1 to 14 treatments. A positive response to protein A therapy was defined as at least a doubling of the pretreatment platelet count and/or two successive 10- to 120-minute posttransfusion CCIs > or = 7500. Following plasma treatments, 6 of 10 patients responded with daily platelet counts that averaged 48 +/− 11 × 10(9) per L as compared with counts of 16 +/− 7 × 10(9) per L (p < 0.0005) before treatment. Posttransfusion CCI values determined in four of these patients averaged 2480 +/− 810 and 10,010 +/− 3540 (p < 0.005) before and after treatment, respectively. In contrast, among the four unresponsive patients, platelet counts averaged 10 +/− 9 and 13 +/− 10 × 10(9) per L (p = NS), respectively, while posttransfusion CCIs were 700 +/− 1410 and 1520 +/− 2460 (p = NS), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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.     

Conformational analysis and molecular modeling of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines as D1 dopamine receptor ligands

Conformational studies on a series of 1-phenyl-, 4-phenyl-, and 1-benzyl-1,2,3,4-tetrahydroisoquinolines that possess an identical substituent pattern to the prototypical D1 dopamine receptor antagonist SCH23390 [(R)-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (1)] were performed with use of molecular mechanics calculations [MM2(85), with newly developed aromatic halide bending and torsional parameters that are now incorporated into MM2(87)], single-crystal X-ray analysis, and high-field NMR spectroscopy. The synthesis and biological testing of compounds 2-7 has been previously reported. The test compounds were compared both quantitatively and graphically to compound 1. Calculations on both the free-base and protonated forms of each compound were carried out. To insure that conformation space was adequately sampled, the test compounds were energy minimized from different starting geometries; ring inversion of the heterocycle was employed, as were dihedral driver calculations on the phenyl or benzyl rings. For N-methyl-6-chloro-7-hydroxy-1-phenyl-1,2,3,4-tetrahydroisoquinoline (2), it was determined that the torsion angle tau(C8a-C1-C12-C17) had energy minima at approximately 60 degrees and 240 degrees. This finding was corroborated by NMR studies that indicated a dramatic upfield chemical shift of ArH8 after ring cyclization. The nitrogen lone pair or hydrogen vector was approximately orthogonal to the plane of the substituted aromatic ring in the tetrahydroisoquinolines; this explained the upfield chemical shift of the vicinal chiral proton (H1). In all instances, the 6-membered heterocyclic ring in the energy-minimized structures preferred the half-chair conformation with the phenyl rings pseudo-equatorial. Distance comparisons of the proposed pharmacophoric atoms (Cl, N, O, centroid of the phenyl or benzyl ring) showed that the phenyl or benzyl centroid to ammonium H distance, Cl to N distance, and distance of the nitrogen above or below the plane of the isoquinoline aromatic ring are the distances most highly correlated with biological activity (r = 0.82, 0.75, 0.81, respectively). Resolution and single-crystal X-ray analysis of compound 2 showed the most active enantiomer to possess the S absolute configuration, in contrast to the benzazepine (R)-1. Least-squares fitting of the energy-minimized structures with SYBYL molecular modeling software showed (S)-(+)-2, rather than (R)-(-)-2, gave a better fit to (R)-1. Volume determinations derived from SYBYL multifit analyses aided in receptor mapping to qualitatively describe areas of "active" pharmacophore space as well as areas of "inactive" substituent space.(ABSTRACT TRUNCATED AT 400 WORDS)