In vivo induction of HLA molecules in patients with myeloproliferative syndrome during IFNα treatment

Summary Eighteen patients with myeloproliferative syndrome (14 with chronic myeloid leukemia, four with essential thrombocytosis) were investigated for modulation of HLA antigens on peripheral blood lymphocytes, monocytes, and hematopoietic precursors during IFN therapy as a sign of potentially increased immune recognition of malignant cells. After 1 month of IFN therapy, an increased number of monocytes and hematopoietic precursor cells, but not of lymphocytes, expressed HLADQ antigens. In addition, a strong induction of HLA class-I antigens was found on both hematopoietic progenitors and normal peripheral blood mononuclear cells. With daily injections of IFN in the first month of therapy stimulation continuously increased, suggested a major effect of IFNa on hematopoietic progenitors with sustained enhanced expression of HLA class-I antigens during differentiation of myelomonocytic cells. HLA class-I antigen expression was consistently augmented by IFN in all patients, irrespective of their hematological response.This work was supported by theElse Übelmesser Stiftung and theDeutsche Forschungsgemeinschaft, Sonderforschungsbereich 120, projects A3 and D4     

Heparin-induced thrombocytopenia and thrombosis following subarachnoid hemorrhage. Case report

The authors present a case of heparin-induced thrombocytopenia and thrombosis (HITT) that occurred after aneurysmal subarachnoid hemorrhage (SAH), and they review the relevant literature. An immune-mediated syndrome, HITT is characterized by moderate thrombocytopenia and paradoxical vascular thromboses. Although it has been estimated in prospective studies that HITT occurs in between 1 and 3% of patients receiving heparin, it is underrecognized in the neurosurgical literature. In the present case, a 49-year-old woman underwent clipping of a right posterior communicating artery aneurysm after suffering a Hunt and Hess Grade III SAH. She had an uncomplicated postoperative course with good clip positioning and no vasospasm observed on a cerebral angiogram obtained on Day 7. On Day 23, the patient developed a right hemiparesis and experienced a grand mal seizure. A head computerized tomography scan revealed a hemorrhagic infarct in the left middle cerebral artery distribution. Repeated cerebral angiograms did not show vasospasm. She was thrombocytopenic (platelet count as low as 46 x 10(9)/L on Day 28 compared with 213 x 10(9)/L on Day 1) and had been receiving heparin flushes to maintain intravenous catheter patency. An assay for HITT-associated antibodies was positive. The heparin flushes were discontinued and the platelet count recovered (121 x 10(9)/L). She improved neurologically, but was left with a significant right hemiparesis at discharge. This patient had assay-proven heparin-induced thrombocytopenia despite minimal exposure to heparin. Because there was no evidence of vasospasm or other factors to account for her delayed hemorrhagic infarction, an HITT-related disorder seemed most likely. Despite a large body of literature describing HITT in nonneurosurgical patients, only three previous neurosurgical cases have been published. This case report may serve to heighten awareness of this disorder.     

Posterior cerebral artery territory infarcts: clinical features, infarct topography, causes and outcome. Multicenter results and a review of the literature

Only a few large series of posterior cerebral artery (PCA) stroke exist, and clinical features and causes have not been studied as extensively as in other vascular territories. The PCA syndrome includes more clinical signs than the well-known visual field deficits. Concomitant findings are frequently sensory, slight motor and neuropsychological deficits. Unilateral headaches are the common presenting symptom making complicated migraine an important differential diagnosis. Combined deep and superficial PCA territory infarcts involving the lateral thalamus are more frequent than commonly assumed and are mostly associated with sensory and reversible slight motor deficits. Occlusion of the precommunal PCA segment with associated paramedian midbrain infarction causes severe motor deficits, oculomotor signs, and decreased consciousness and has a poorer outcome than other PCA territory infarcts. Embolism from a cardiac or undetermined source is the leading mechanism accounting for up to half of the cases, whereas arterial embolism from significant proximal vertebrobasilar disease is less frequent. Local atherothrombotic stenosis or occlusion of the PCA is uncommon. In spite of thorough diagnostic evaluation, the etiology of PCA territory infarction cannot be determined in at least one quarter of patients. Among the rare causes of PCA territory infarction carotid artery disease is important while the significance of migraine remains controversial.     

Quality assurance of sphincterotomy: A prospective single-centre survey

Quality assurance becomes an increasingly important part of clinical medicine and of the field of endoscopy. Endoscopic sphincterotomy is associated with a fairly high complication rate. We aimed to assess our quality of sphincterotomy for benchmarking by using a prospective electronic database registry, and to identify potential risk factors for post-interventional complications. Over 2 years, 471 sphincterotomies were performed in a single tertiary referral centre. Patient- and procedure-related variables were prospectively recorded with the support of a multi-centre international sphincterotomy registry. Multivariate analysis was performed. The overall post-interventional complication rate was 9.3%. Pancreatitis happened in 5.5%, bleeding in 2.1%, perforation in 1.3%, and cholangitis in 0.4%. In the multivariate analysis following variables remained highly significant and predictive for complications: ‘papilla only in lateral view’ (p=0.001), antiplatelet therapy (p=0.024), and opacification with contrast up to the pancreatic tail (p=0.001). The primary success rate of sphincterotomy was 95.1%. The rate of post-interventional pancreatitis did not differ significantly regardless of the presence of prophylactic pancreatic stent (p=0.56). The outcome of sphincterotomy in our centre matches with literature data. The extent of pancreatic duct opacification has an influence on the pancreatitis rate. Prevention of pancreatitis by inserting pancreatic stents is not confirmed.     

Right ventricular pacing is an independent predictor for ventricular tachycardia/ventricular fibrillation occurrence and heart failure events in patients with an implantable cardioverter-defibrillator

Aims: There is increasing evidence that right ventricular (RV) pacingmay have detrimental effects by increasing morbidity and mortalityfor heart failure in implantable cardioverter–defibrillator(ICD) patients. In this study we prospectively tested the hypothesisthat cumulative RV pacing increases ventricular tachycardia/ventricularfibrillation (VT/VF) occurrence (primary endpoint) and hospitalizationand mortality for heart failure (secondary endpoint) in a predominantlysecondary prophylactic ICD patient population. Methods and results: Two hundred and fifty patients were divided into two groupsaccording to the median of cumulative RV pacing (2 vs. >2%)and prospectively followed-up for occurrence of primary andsecondary endpoints for 18 ± 4 months. Established predictorsfor VT/VF occurrence and heart failure events such as age, leftventricular ejection fraction (EF), QRS duration, history ofatrial fibrillation, and NT-proBNP were collected at enrolment.Multivariate Cox regression analysis revealed that cumulativeRV pacing > 2% and EF < 40% were independent predictorsfor VT/VF occurrence and heart failure events. Kaplan–Meieranalysis showed that patients with >2% cumulative RV pacingmore frequently suffered from VT/VF occurrence and heart failurehospitalization. Conclusion: Cumulative RV pacing > 2% and EF < 40% are independentpredictors for VT/VF occurrence and mortality and hospitalizationfor heart failure in predominantly secondary prophylactic ICDpatients. Our data show that algorithms capable of reducingcumulative RV pacing should be used more frequently in clinicalpractice.     

Head-to-head comparison of B-type natriuretic peptide (BNP) and NT-proBNP in daily clinical practice

B-type natriuretic peptide (BNP; Abbott Diagnostics) and N-terminal proBNP (NT-proBNP, Roche Diagnostics) were compared in consecutive samples of 458 patients (mean age 60 years+/-16 years; 159 female, 299 male) sent for NT-proBNP measurement to investigate influences on both markers. BNP and NT-proBNP showed a close correlation with each other (r=0.89, p<0.0001). Using age- and gender-adjusted upper reference values the inter-rater agreement of both parameters was satisfactory (83%, Cohen's kappa coefficient=0.7). The combination of normal BNP and elevated NT-proBNP was significantly more frequent than vice versa (61 vs. 16 patients), and a calculated glomerular filtration rate<60 ml/min/1.73 m(2) was found in 39% of these patients. Multiple linear regression analysis revealed a significant influence of a reduced ejection fraction (<50%), renal dysfunction (calculated glomerular filtration rate<60 ml/min/1.73 m(2)), anemia, hypertension, age, and gender on both BNP and NT-proBNP. In conclusion, despite a close correlation and a satisfactory agreement between both markers in classification, frequent discrepancies in individual patients demonstrate that both markers are clinically not completely equivalent.