Comparison of Renal Hemodynamic Effect of Ramiprilat to Captopril: Possible Role of Kinins

Sincetheintroductionofthefirstlineofangiotensinconvertingenzyme(ACE)inhibitors,ofwhichcaptoprilistheprototype,morepotentlonger-lastingagentshavebecomeavailable[l].AmongtheseisramipriIat,anonsL1lfhydrylACEinhibitorsimilarchemicallytoenalaprilatbutcontaininginadditionapentanering.Benderetal[2Jdemonstratedinvitrothatramiprilatisatleast23timesmorelipophilicthanenalaprilatwithanaffinityforACE47timesgreatc'rthanthatofcaptopril.ItwaspostulatedthatthemorelipophiIicanACEinhibitor,thebetteraccessi…     

Recurrent arthritis as presenting symptom of osteomyelitis

We present a patient who had one episode of prepatellar bursitis and subsequently several episodes of arthritis of his right knee. Cultures of several punctures of his knee remained sterile, but the patient had been taking oral antibiotics on each of these occasions against our medical advice. Ultimately a diagnostic puncture revealed growth of Staphylococcus aureus. An X-ray demonstrated an osteolytic lesion of the patella, but no defect in the articular surface of the patella could be visualised. MRI demonstrated a communication between the osteomyelitic focus through the medial retinaculum to the bursa suprapatellaris and the knee joint. Osteomyelitis of the patella is mainly a disease of childhood. This case is, to our knowledge, the first report on the association between bursitis, osteomyelitis of the patella and recurrent septic arthritis of the knee in an adult. The literature is reviewed and discussed briefly.     

The beta-globin gene on the Chinese delta beta-thalassemia chromosome carries a promoter mutation

A new type of delta beta-thalassemia characterized by decreased expression of the beta-globin gene and increased expression of both G gamma and A gamma globin gene in the absence of a detectable deletion has recently been described in the Chinese population. In this study we characterize the mutant beta-globin gene from this delta beta- thalassemia chromosome. An A to G transversion is identified in the "ATA" sequence of the promoter region that leads to decreased expression of the beta-globin gene in vivo and in vitro. We also demonstrate the presence of this mutation in every individual with a high fetal hemoglobin phenotype in this family and its absence in every individual with a normal hemoglobin phenotype. This same promoter mutation has recently been detected in Chinese beta-thalassemia genes where it is present on chromosomes of the same haplotype as that of the delta beta-thalassemia chromosome we are studying. These data support the hypothesis that an as yet unidentified mutation occurred on the ancestral chromosome carrying the promoter mutation and subsequently gave rise to the delta beta-thalassemia phenotype.     

Risk and significance of endoscopic/radiological evidence of recurrent Crohn's disease

BACKGROUND & AIMS: The aim of this study was to determine the risk of endoscopic/radiological recurrence of Crohn's disease postoperatively and the long-term outcome. METHODS: A randomized placebo-controlled trial was performed to determine the effectiveness of mesalamine in preventing recurrent Crohn's disease postoperatively. Patients in the control group were examined endoscopically/radiologically before entry into and annually during the trial. Findings were classified as minimal or severe. RESULTS: There were 76 patients (49 men and 37 women; mean age, 37.1 +/- 13.2 years). Fifty (61.7%) had terminal ileal resections. Overall, 55 endoscopic/radiological recurrences were observed in 51 patients (67.1%). Expressed actuarially, the recurrence rate was 27.5% at 1 year (95% confidence interval [CI], 15.8%-37.6%), 60.8% at 2 years (95% CI, 46%-71.3%), and 77.3% at 3 years (95% CI, 62.7%-86.3%). Nineteen (37%) were symptomatic and 12 (24%) were initially asymptomatic but later became symptomatic (mean, 13.0 +/- 8.8 months), whereas 20 (39%) remained asymptomatic (mean, 16.9 +/- 17.4 months). Patients with severe endoscopic/radiological disease were significantly more likely to be or become symptomatic than those with minimal disease (23 of 32 vs. 8 of 19, respectively; P = 0.0437). CONCLUSIONS: This study suggests that postoperative endoscopic/radiological recurrences occur later than previously reported. Furthermore, many of these patients, especially with minimal disease, will remain asymptomatic. (Gastroenterology 1997 Dec;113(6):1823-7)     

Beta-thalassemia due to two novel nucleotide substitutions in consensus acceptor splice sequences of the beta-globin gene

We have identified two novel RNA-splicing mutations affecting a critical nucleotide (nt) in the acceptor consensus sequences at both the IVS-1/exon 2 and IVS-2/exon 3 junctions of the human beta-globin gene. Both mutations are single nt substitutions, T to G and C to A, at position -3 adjacent to the invariant AG dinucleotide. For the IVS- 2/exon 3 mutation abnormal splicing into the cryptic splice site at IVS- 2 nt 579 is documented. Identification of these two mutations provides further support for the importance of the location of specific nucleotides within the consensus sequences in splice site selection and RNA processing.     

Platelet modulation of polymorphonuclear leukocyte shear induced aggregation

A cone and plate viscometer and Coulter Counter were used to study platelet modulation of polymorphonuclear leukocyte (PMNL) aggregation caused by controlled shear stress. As an index of aggregation, the large-particle percentage (LPP) was calculated. This represents the ratio of aggregated cell count to total cell count. PMNL suspensions in buffer (1.0 X 10(7) cells per milliliter, final concentration) did not show any aggregate formation at shear stresses below 150 dynes/cm2 for one minute exposure time (LPP less than 3%). However, there was PMNL aggregation in mixed PMNL and platelet-rich plasma suspensions in this shear stress range. Supernatant plasma from sheared platelets initiated PMNL aggregation at moderate shear stress (150 dynes/cm2 for one minute; LPP, 20.3% +/- 2.5%). In contrast, platelet release factors, such as adenosine diphosphate (2 mumol/L) and serotonin (2 mumol/L) did not cause PMNL aggregation (LPP, 2.9% +/- 1.2% and 3.3% +/- 0.8%, respectively). The use of a cyclo-oxygenase inhibitor (acetylsalicylic acid, 50 mumol/L) did not suppress the aggregation of PMNLs after shear (LPP, 20.1% +/- 2.4%). However, preincubation with nordihydroguaiaretic acid (10 mumol/L), an inhibitor of C-5 and C-12 lipoxygenase, and 6,9- deepoxy-6,9-(phenylimino)-6,8-prostaglandin I1 (U-60257, 10 mumol/L), an inhibitor of C-5 lipoxygenase in human leukocytes, suppressed this aggregation (LPP, 9.1% +/- 2.5% and 10.4% +/- 3.2%, respectively). Also, the formation of lipoxygenase products (5-HETE, 12-HETE, 15-HETE, and LTB4) activated by shear stress was documented by reversed phase- high-performance liquid chromatography (RP-HPLC). These data support the possibility of a cooperation between platelets and leukocytes in shear-induced PMNL aggregation that is dependent on C-12 or C-5 lipoxygenase activity, or both.     

Platelet refractoriness and alloimmunization in pediatric oncology and bone marrow transplant patients

BACKGROUND: The purposes of this study were to determine the overall incidence of platelet refractoriness and alloimmunization among multiply transfused children on a medical oncology and bone marrow transplant service and to evaluate the effect of routine white cell reduction in blood components on that incidence. STUDY DESIGN AND METHODS : The platelet transfusion records of 128 consecutive children admitted to the hospital and requiring blood component support for the treatment of disease were evaluated retrospectively. Mean corrected count increments (CCIs) for each patient were calculated for all random- donor platelet transfusions given within 7 days of the routine weekly testings of the patient's serum for lymphocytotoxic antibodies (LCTAbs). Mean CCIs for HLA-matched platelet transfusions were calculated separately for the patients receiving them. RESULTS : Thirty- one patients (24%) had or developed persistently positive LCTAbs (patient's serum reacted with > or = 3/10 panel lymphocytes); 22 (71%) of these patients had a mean CCI < 7.5 to random-donor platelet transfusions. In contrast, of the 97 patients with negative or transiently positive LCTAbs, only 25 (26%) had a mean CCI < 7.5. The overall incidence of platelet refractoriness (CCI < 7.5) was 37 percent. Patients with acute myelogenous leukemia had a significantly (p < 0.01) reduced incidence (17%) of low CCIs, with or without positive LCTAbs, as compared to patients with other malignant or nonmalignant disorders (41%). No difference in the incidence of LCTAbs or low CCIs was seen in patients undergoing allogeneic or autologous bone marrow transplant or receiving drug therapy only. Among the 24 patients who received HLA-matched platelets, only those with positive LCTAbs showed a significant improvement in CCIs over that achieved with random-donor platelet transfusions. Routine white cell reduction in red cell and platelet components with third-generation white cell filters was performed prior to transfusion in 73 of the patients. There was no significant difference between the incidence of LCTAbs and/or low CCIs in this group and that in the 55 children receiving unfiltered transfusions. CONCLUSION : Alloimmunization and platelet refractoriness occur in pediatric oncology and bone marrow transplant patients, but the incidence-particularly in children with acute myelogenous leukemia- -appears to be low. The detection of LCTAbs predicts a poor response to random-donor platelet transfusion, but most such patients show improved CCIs with HLA-matched platelets. Routine use of white cell-reduction filters has thus far failed to eliminate alloimmunization in children requiring prolonged blood component support.