Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

Delayed hemorrhage following endoscopic retrograde sphincterotomy for choledocholithiasis

To define the clinical significance of delayed postsphincterotomy hemorrhage, we reviewed 476 consecutive ERCP procedures performed over a three-year period. Of 250 patients who underwent endoscopic sphincterotomy (ES), five (2%) developed postprocedure hemorrhage, two of whom had immediate, self-limited bleeding that resolved after endoscopic injection of epinephrine and did not require transfusion. The other three had delayed hemorrhage characterized by: onset 20–48 hr after the procedure, melena without hematemesis as the index clinical manifestation of bleeding, and atraumatic balloon extraction of common duct stones. Transfusion of 2–6 units of packed erythrocytes was necessary in each and one patient required surgical hemostasis. Delayed hemorrhage following ERS is an important, frequently severe complication to remember when contemplating performing ERS as an outpatient procedure.     

Ciliary central microtubular orientation is of no clinical significance in bronchiectasis

It has been suggested that patients with bronchiectasis might have increased central microtubular orientation angle (CMOA), which leads to poor coordination of ciliary beating, and consequently impairment of airway defence. We have employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82). There was no significant difference in CMOA among patients according to the etiology of bronchiectasis, presence of nasal symptoms, or sputum status of Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e. those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had significantly lower CMOA than their counterparts (P<0.05). There was no correlation between CMOA with age, 24h sputum volume, exacerbation frequency, FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated with ciliary beat frequency (negative), and the percent of cilia showing ultrastructural or microtubular defects (P<0.05). Central microtubular orientation angle does not correlate with clinically important parameters, in contrary to the results reported by previously published smaller scale studies.     

Both heterozygous and homozygous alpha+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya

Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous alpha+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality-coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.