The effect of altitude on dosing and response to erythropoietin in ESRD

For poorly understood reasons, patients with end-stage renal disease (ESRD) differ substantially in their response to treatment with recombinant erythropoietin (EPO). Because hypoxia influences many of the biologic pathways involved in erythropoiesis, the altitude at which a patient lives may affect the dose-response relationship of EPO. In this retrospective cohort study, clinical data from 341,737 incident hemodialysis patients registered in the U.S. Renal Data System were combined with elevation data from the U.S. Geological Survey to address this question. Higher altitude was associated with smaller EPO doses and higher hematocrit levels. For example, compared with patients at sea level, patients living above 6000 ft received 19% less EPO (12.9 versus 15.9 thousand units/wk) but had hematocrit levels 1.1 points higher (35.7% versus 34.6%). These associations were found within subgroups defined by sex, race, age, calendar time, cause of ESRD, and dialysis center profit status, and persisted after adjustment for various potential confounding factors. Furthermore, resistance to EPO decreased with elevation. Our results suggest that ESRD patients living at high altitude either increase endogenous EPO production or respond better to endogenous and exogenous EPO.     

Intraoperative contralateral pneumothorax during single-lung transplantation

Contralateral intraoperative tension pneumothorax is a rare complication of thoracic surgical procedures. Here we present three cases of tension pneumothorax that developed during single-lung transplantation for emphysema and pulmonary fibrosis. To the best of our knowledge, this is only the second report of contralateral intraoperative tension pneumothorax during single-lung transplantation. A high index of clinical suspicion is required for the detection of this potentially catastrophic complication.     

Esophageal perforation after catheterization of the subclavian vein

The insertion of a central venous catheter (CVC) via the subclavian vein is often associated with complications. We report a case in which a patient suffered an esophageal lesion with severe bleeding and a pneumothorax with mediastinal shift induced by the insertion of the dilator of a CVC. The pneumothorax had to be treated immediately by pleural drainage, and the esophageal lesion was successfully corrected by means of an endoclip. The patient survived the complication. However, he died 1 week later from multiple organ failure not associated with the CVC insertion.     

Primary care physicians' attitudes related to cognition enhancers in early dementia: a representative eight-year follow-up study in Lower Saxony, Germany

OBJECTIVE: By means of a representative follow-up survey, we investigated changes in family physicians' (FPs) attitudes towards cognition enhancers in early dementia during 1993 and 2001. METHODS: One hundred and twenty-two FPs (response rate 71.8%) in Lower Saxony, Germany, were randomly assigned to one of two written case samples presenting a patient with cognitive decline suggestive of early Alzheimer's disease (DAT; case A: female patient vs case B: male patient). Using a structured face-to-face interview, they were asked to suggest their potential drug treatment. The results were compared to corresponding data from our previous survey in 1993. RESULTS: FPs' readiness to start antidementia drug treatment decreased from 70.4% in 1993 to 43.4% at follow-up, although underlying DAT was significantly more frequently suggested (11.0% vs 26.2%, p < 0.05). Substances with questionable efficacy such as Piracetame were prescribed less frequently in 2001 whereas evidence-based medication like cholinesterase inhibitors (ChEIs) failed to compensate for this drop. Compared to 1993, when 55.2% of FPs expected no therapeutic impact, at follow-up, 75.4% expected slowdown of disease progression, stabilisation or improvement of symptoms (p < 0.05). CONCLUSIONS: Our results demonstrate a significant decrease of therapeutic nihilism in primary care within eight years. However, in patients with suspicion of DAT, this is not reflected accordingly in potential treatment.     

LRP1 modulates APP trafficking along early compartments of the secretory pathway

The amyloid beta peptide (Aβ) is a central player in Alzheimer's disease (AD) pathology. Aβ liberation depends on APP cleavage by β- and γ-secretases. The low density lipoprotein receptor related protein 1 (LRP1) was shown to mediate APP processing at multiple steps. Newly synthesized LRP1 can interact with APP, implying an interaction between these two proteins early in the secretory pathway. We wanted to investigate whether LRP1 mediates APP trafficking along the secretory pathway, and, if so, whether it affects APP processing. Indeed, the early trafficking of APP within the secretory pathway is strongly influenced by its interaction with the C-terminal domain of LRP1. The LRP1-construct expressing an ER-retention motif, LRP-CT KKAA, had the capacity to retard APP traffic to early secretory compartments. In addition, we provide evidence that APP metabolism occurs in close conjunction with LRP1 trafficking, highlighting a new role of lipoprotein receptors in neurodegenerative diseases.     

Multifactorial dysphagia complicated by esophago-bronchial fistula

Dysphagia in an elderly patient necessitates urgent clinical evaluation to exclude the possibility of an underlying esophageal malignancy. Atherosclerotic aortic aneurysms are common in old age, but dysphagia aortica resulting from compression of the esophagus by an aortic aneurysm is a rare cause for dysphagia. Development of a malignant esophago-airway fistula can occur from a variety of tumors, the most common of which is esophageal cancer. A case of longstanding dysphagia resulting from dysphagia aortica later developing an esophageal malignancy complicated by esophago-bronchial fistula is outlined in this unique case report.     

Comparison of 99mtechnetium-pertechnetate and 123iodide SPECT with FDG-PET in patients suspicious for breast cancer

PURPOSE: Breast carcinomas express the Na(+)/I() symporter and may-albeit not a routine procedure-be imaged with (123)iodide ((123)I) and (99m)technetium-pertechnetate ((99m)TcO(4)(-)) scintigraphy. The aim of our prospective study was the comparison of (99m)TcO(4)(-)--and (123)I-single-photon emission computed tomography (SPECT) with (18)F-2-fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) in patients suspicious for breast cancer. METHODS: Twenty-nine (29) untreated patients suspected of having breast carcinoma were prospectively examined with thorax SPECT with (99m)TcO(4)(-) (n=19) or (123)I (n=10), respectively, and FDG-PET (n=29) prior to biopsy. Tumor-to-background ratios (TBRs) were calculated for SPECT findings. Mean and maximum standardized uptake values (SUVs) were calculated for PET findings. Findings were compared in an intra-individual lesion-to-lesion analysis. RESULTS: In 28 of 29 patients, malignancy was verified with histopathology. In imaging the primary tumor, sensitivities of (99m)TcO(4)(-)-SPECT, (123)I-SPECT, and FDG-PET were 63%, 67%, and 89%, respectively. TBR maximum was 2.6+/-1.1 in (99m)TcO(4)()-SPECT and 2.3+/-0.6 in (123)I-SPECT. In FDG-PET, mean tumor SUV was 4.1+/-4 and maximum tumor SUV was 5.4+/-5.1. In contrast to FDG-PET, (99m)TcO(4)()-SPECT was ineffective in imaging nodal and distant metastases in the thorax, and (123)I-SPECT failed in imaging lymph node infiltrations. Distant metastases were not present in patients of the (123)I group, and the value of (123)I-SPECT was not evaluated. CONCLUSIONS: In contrast to FDG-PET, (99m)TcO(4)(-) and (123)I-SPECT are ineffective in imaging breast carcinoma in clinical practice.