Granulocyte antibodies in leukaemic chronic lymphoproliferative disorders

The anti-granulocyte activity of serum from patients with B-cell chronic lymphocytic leukaemia (CLL) and other lymphoproliferative disorders was investigated. Granulocyte-binding IgG was measured in 34 patients with CLL, 13 patients with hairy cell leukaemia, one patient with prolymphocytic leukaemia, two patients with Sézary cell leukaemia, and seven patients with chronic T-cell lymphocytosis who had a predominance of circulating large granular lymphocytes. Anti-granulocyte activity was absent in CLL and its variants, but present in the majority of granulocytopenic patients with chronic T-cell lymphocytosis. In one of these patients, granulocytopenia was associated with complement-activating IgG granulocyte antibody. Thus, antibody-mediated granulocyte injury appears to be an unusual occurrence in chronic lymphocytic leukaemia, but is a frequent complication of chronic T-cell lymphocytosis.     

Complement component C5a predicts restenosis after superficial femoral artery balloon angioplasty.

PURPOSE: To investigate whether balloon angioplasty of the superficial femoral artery (SFA) increases serum levels of C5a and whether C5a predicts risk of restenosis. METHODS: C5a antigen was measured at baseline and 8 hours after intervention in 131 consecutive patients (76 women; median age 72 years) with intermittent claudication who underwent successful primary SFA balloon angioplasty. Patients were followed for a median 10 months [interquartile range (IQR) 6 to 14] for the occurrence of >50% restenosis by duplex ultrasound. RESULTS: Median C5a levels increased significantly from 39.7 ng/mL (IQR 27.8 to 55.0) at baseline to 53.8 ng/mL (IQR 35.6 to 85.1, p<0.001) 8 hours post intervention. During the follow-up period, 70 (53%) patients developed restenosis. Increasing levels of C5a (quartiles) at baseline were significantly associated with an increased risk for restenosis (p=0.0092). Adjusted hazard ratios (95% confidence intervals) for restenosis with increasing quartiles of baseline serum C5a levels were 1.24 (0.60 to 2.58), 1.93 (0.95 to 3.93), and 2.08 (1.02 to 4.21), respectively, compared to the lowest quartile. This effect was independent of nonspecific inflammation as reflected by plasma levels of C-reactive protein. CONCLUSION: Inflammatory mechanisms play a major role in the development of restenosis after angioplasty. The complement component C5a exerts strong chemotactic and proinflammatory effects. Enhanced complement activation prior to PTA, as measured by higher levels of C5a, was significantly associated with restenosis after SFA balloon angioplasty. Pathways of complement inhibition thus may be worth investigating with respect to improving patency rates.     

Comparison of the detection of subtle changes in myocardial regional systolic function using qualitative and semi-quantitative techniques.

PURPOSE: To evaluate qualitative wall motion assessment vs. quantitative wall thickening for the assessment of subtle changes in myocardial systolic function using cine MRI. METHODS: Cine MR images were obtained in 5 canines with a significant coronary artery stenosis and in 2 controls on a 1.5T scanner. Qualitative results were obtained using a numerical scoring system; quantitative analysis was performed using a semi-automatic segmentation program. The techniques were matched and compared using Spearman correlations. RESULTS: All correlations in the experimental group revealed significant but weak to moderate relationships between the qualitative and quantitative results (e.g., at-risk tissue rho = 0.363, p < 0.0001; remote tissue rho = 0.275, p = 0.0002), with each identifying changes in regional function that ensued following creation of the stenosis. Intra-observer variability was reasonable in both methods when repeat analysis on a subset of the data was performed, with both techniques showing a significant correlation between the repeated measurements (quantitative - rho = 0.52, p < 0.0001; qualitative - rho = 0.54, p < 0.0001). CONCLUSION: Both methods were able to detect very limited wall motion abnormalities present in the canines with significant stenosis and either method gives comparable results.     

Visual acuity with reversed-contrast charts: I. Theoretical and psychophysical investigations.

When the contrast polarity of a visual acuity chart is reversed by using bright letters on a dark background instead of dark on light, the shape and height of the resolution feature in the retinal image is identical but inverted compared with the normal situation. However, the contrast is different in the two cases because the background light level, which is a dividing factor when contrast is calculated, is much less when only the letters are bright. To the extent that contrast is a limiting factor in visual acuity, reversed-contrast acuity would be expected to be better, and proportionally more so in eyes where light scatter and aberrations widen and flatten the point-spread function. In a careful psychophysical study of Landolt C resolution, the minimum angle of resolution was found to be significantly smaller for white letters on a dark background than for the traditional dark on bright situation.     

Der gesunde Patient mit Hypercholesterin?mie

Eine 71-jährige, gesundheitsbewusste, zu einer Medizinerfamilie gehörige Patientin stellt sich zur Bewertung einer seit 10 Jahren bekannten Cholesterinerhöhung und der an anderer Stelle begonnenen Behandlung mit Mevinacor^® (Lovastatin) vor.Im vorausgegangenen Jahr waren bei vielen Gelegenheiten Gesamtcholesterinkonzentrationen zwischen 289 und 345 mg/dl bestimmt worden. LDL wurde bis auf maximal 261 mg/dl erhöht gefunden, die HDL-Cholesterin-Werte lagen zwischen 40 und 48 mg/dl, die Triglyzeride zwischen 99 und 264 mg/dl.     

Recurrent Access Thrombosis

A substantial fraction of clotted polytetrafluoroethylene (PTFE) grafts undergoing thrombolysis and angioplasty clot again within a few months. Is there a place for routine follow-up fistulograms in these patients, or should we just retreat them as needed? Is there, perhaps, a subgroup that requires special management?     

Survival, mutagenesis, and host cell reactivation in a Chinese hamster ovary cell ERCC1 knock-out mutant

Positive selection-negative selection gene targeting was usedto disrupt the nucleotide excision repair gene ERCC1 in a Chinesehamster ovary cell line, CHO-K1. Southern and Northern analysisshowed that a cell clone isolated by this targeting approach,CHO-7-27, had an ERCC1 gene structure consistent with targeteddisruption of ERCC1 exon V, and did not express ERCC1 mRNA.CHO-7-27 was further characterized with respect to UV and mitomycinC sensitivities, and was shown to exhibit severe mutagen sensitivityphenotypes consistent with those of other CHO cell ERCC1 mutants.Mutation frequency experiments showed that CHO-7-27 was UV-hypermutableat the hypoxanthine-guanine phosphoribosyltransferase locus.Experiments assessing host cell reactivation of viral DNA synthesisfor UV-irradiated adenovirus showed that CHO7-27 exhibited aseverely deficient HCR phenotype similar to that of UV20 cells.Our results demonstrate that CHOK1 cells are hemizygous forthe ERCC1 gene, and show that the comparatively mild mutagensensitivities and lack of severely deficient HCR phenotypesof conventionally derived CHO-K1 ERCC1 mutants, in contrastto the severe phenotypes of CHO-AA8-derived mutants, are notdue to any intrinsic genetic differences between CHO-K1 andCHO-AA8 parental cell lines. ⁴To whom correspondence should be addressed     

Symptomatic and Clinical Improvement in Morbidly Obese Patients with Gastroesophageal Reflux Disease Following Roux-en-Y Gastric Bypass

Background: Patients who suffer with gastroesophageal reflux Disease (GERD) endure a worsening of symptoms as their weight increases. When medical treatment of this condition in the morbidly obese patients fails, surgical intervention may be indicated. Choosing a procedure which not only helps achieve weight control but which also relieves symptoms and complications of GERD is the goal. We present a review of patients who have undergone Roux-en-Y Gastric Bypass (RYGBP) and related procedures for this disease. Methods: One hundred eighty-eight patients undergoing surgery for morbid obesity and for GERD in 1992-1996 were contacted by mail or phone. All of these patients had undergone preoperative esophagogastroduodenoscopy to grade the severity of their disease. Their preoperative symptoms were compared to those experienced postoperatively. Results: One hundred thirty patients underwent a RYGBP with modified Hill fundopexy, 22 patients underwent a distal gastrectomy with modified Hill fundopexy, 8 patients underwent distal gastrectomy alone and 28 patients underwent RYGBP alone. There have been no deaths. There were nine surgical complications, eight early and one at 2.5 years postoperation. Follow-up is 4-48 months. The average BMI dropped from 43 to 30.2 kg/m². Whereas all patients were on some form of medical therapy before surgery, only 14 reported the need for medication postoperatively. Conclusions: Surgical intervention for weight control and treatment of GERD has been highly successful in our experience both with respect to weight control and to the reduction of reflux symptoms. Depending upon endoscopic and operative findings a RYGBP with or without an antireflux procedure can provide dramatic improvement. Gastrectomy with antireflux modifications is appropriate in selected cases.