Transition from enhanced T cell infiltration to inflammation in the myelin-degenerative central nervous system

Myelin degeneration in the central nervous system (CNS) is often associated with elevated numbers of T cells in brain and spinal cord (SC). In some degenerative diseases, this T cell immigration has no clinical relevance, in others, it may precede severe inflammation and tissue damage. We studied T cells in the myelin-degenerative SC of transgenic (tg) Lewis rats overexpressing the proteolipid protein (PLP). These lymphocytes are T(H)1/T(C)1 cells and represent different T cell clones unique to individual animals. The SC-infiltrating CD8(+) T cell pool is more restricted than its CD4(+) counterpart, possibly due to constrictions in the peripheral CD8(+) T cell repertoire. Some SC-infiltrating T cells are highly motile and cover large distances within their target tissue, others are tethered to MHC class II(+) microglia cells. The activation of the tethered cells may trigger the formation of inflammatory foci and could pave the way for inflammation in degenerative CNS disease.     

Fatal leukoencephalopathy after reduced-intensity allogeneic stem cell transplantation

BACKGROUND: Toxicity associated with immunosuppression and conditioning regimens represents a common cause of neurological complications after allogeneic stem cell transplantation. CASE REPORT: We present a 56-year-old female patient with refractory acute lymphoblastic leukemia undergoing reduced-intensity conditioning with fludarabine, BCNU and melphalan followed by matched-sibling allogeneic stem cell transplantation. Under immunosuppressive treatment with cyclosporine A (CSA) the patient developed early-onset (day +33) and ultimately fatal leukoencephalopathy. DISCUSSION: As fludarabine and CSA represent two key substances of today's reduced-intensity conditioning regimens we raise the question of whether CSA, fludarabine or a combination of both led to this outcome and discuss differential diagnoses.     

Apoptosis of peripheral blood neutrophils in COPD exacerbation does not correlate with serum cytokines

The study investigated the relationship between apoptosis of peripheral blood neutrophils during exacerbation of chronic obstructive pulmonary disease (COPD) and the inflammatory response that characterises this condition. Twenty-six hospitalised patients with COPD exacerbation and 13 controls were included. Three sequential blood and sputum samples were obtained from patients at admission, after 3 days and at discharge. Blood apoptotic neutrophils were measured by flow-cytometry and light microscopy. Serum and sputum levels of IL-6, IL-8 and TNF-alpha were determined by an immunoassay technique. We found a significantly reduced percentage of apoptotic neutrophils at the onset of COPD exacerbation which increased over time (1.1+/-0.4% at admission vs. 2.4+/-0.4% at discharge, P<0.0001). Patients presented no changes in serum cytokines neither during exacerbation nor in comparison to controls. In contrast, sputum levels of cytokines were significantly increased compared to serum levels. There was no significant correlation between the apoptotic neutrophils and the cytokine concentrations in serum or sputum. None of the clinical parameters, such as smoking, microbial infection, corticosteroids or hypoxemia showed a correlation with neutrophil apoptosis. No relationship could be found between the reduced percentage of apoptotic neutrophils in blood and serum concentration of IL-6, IL-8 and TNF-alpha or other clinical parameters in patients with COPD exacerbation.     

Hemolysis, high-intensity transient signals (HITS) and hemodynamic results after aortic valve replacement with the Medtronic Hall Easy-Fit heart valve prosthesis

BACKGROUND AND AIM OF THE STUDY: Previous studies have shown a correlation between type, orientation and valve size of mechanical heart valve prostheses and the incidence of high-intensity transient signals (HITS). The study aim was to investigate the presence of HITS and hemolysis and the impact of valve size and hemodynamic parameters following aortic valve replacement (AVR) using the new Medtronic Hall Easy-Fit prosthesis. METHODS: A total of 150 patients (120 males, 30 females; mean age 62 +/- 8 years; range: 32-78 years) underwent AVR (n = 94; 63% concomitant procedures) with the Easy-Fit valve in its optimal orientation. Patients were investigated at between three and 36 months after AVR using transcranial Doppler examination of the right and left middle cerebral artery, and the incidence of HITS was determined. For evaluation of hemolysis, serum lactate dehydrogenase (LDH), hemoglobin and bilirubin were measured. These parameters were related to valve size. Transthoracic echocardiography was performed in all patients. RESULTS: Among the patients, 112 (75%) showed no or low HITS (34% none, 41% < 30/h), while only 38 (25%) had elevated HITS (range 31-100/h, 14%; range > 100/h, 11%). Statistical analysis showed a linear association between the HITS count and valve size. A positive correlation between valve size and LDH was observed; hemoglobin and bilirubin showed normal values. CONCLUSION: The valve size-dependent increase in LDH after AVR corresponds with the observation that the presence of HITS increases with valve size. In light of these findings, the surgical approach to implant the largest size Easy-Fit valve possible should be discussed, given the excellent hemodynamic results provided by the valve, even in smaller sizes.     

Neuropsychiatric disorders in HIV infection: impact of diagnosis on economic costs of care

BACKGROUND: HAART is associated with a growing prevalence of HIV-associated neuropsychiatric disorders (NPD) despite improved overall survival. OBJECTIVE: To investigate the added direct costs of medical care for patients with and without NPD. METHODS: Nine dimensions of patient-specific costs [as costs per patient per month (CPM)] were followed prospectively between 1997 and 2003 in a community-based HIV/AIDS clinic for HIV-1-seropositive patients with a diagnosis of NPD (n = 188) and without (n = 153). Patients with NPD were stratified into subgroups of cognitive impairment (CI), peripheral neuropathies (PN), or other neuropsychiatric disorders (OND). RESULTS: Compared with the non-NPD group ($916), patients in the NPD group showed an increased mean CPM during the 12-month intervals immediately preceding and subsequently following NPD diagnosis [$1371 (P < 0.001) and 1463 US dollars (P < 0.001), respectively], but not at 18 months prior to diagnosis (1061 US dollars; P > 0.05). Intragroup comparisons between 12 month post-diagnosis and 18 month pre-diagnosis showed a mean CPM increased of 67% (1613 US dollars; P < 0.001) with CI, 31% (1490 US dollars; P < 0.01) with PN, and 33% (1362 US dollars; P < 0.01) with OND. Increased numbers of clinic and physician visits, non-antiretroviral drugs and home care accounted for the higher mean CPM (P < 0.05) both pre-and post-diagnosis within the NPD group. CONCLUSIONS: Neuropsychiatric disorders in patients with HIV/AIDS increase medical costs both before and after diagnosis, primarily owing to the management of the neuropsychiatric illness. Cost analyses offer useful measures of evolving patient needs, and provide a basis for allocation of healthcare resources.     

Akute kardiopulmonale Dekompensation einer 39-Jährigen mit chronischer Zyanose

A 39-year-old female patient with a history of chronic cyanosis was admitted to our intensive care unit with acute heart failure. Echocardiography revealed signs of chronic pulmonary hypertension. Contrastenhanced computed tomography (CT) showed multiple pulmonary artery aneurysms with thrombotic obstructions. Post mortem examination showed complete necrosis of vessel walls with adherent thrombus formation. Therefore, a vascular Behçet was diagnosed. Immunosuppressive therapy at an early stage of disease can achieve (partial) remissions. Complications, e.g. large aneurysms, may be treated surgically.     

Specifying computer-based counseling systems in health care: A new approach to user-interface and interaction design

Computer-based counseling systems in health care play an important role in the toolset available for medical doctors to inform, motivate and challenge their patients according to a well-defined therapeutic goal. The design, development and implementation of such systems require close collaboration between users, i.e. patients, and developers. While this is true of any software development process, it can be particularly challenging in the health counseling field, where there are multiple specialties and extremely heterogeneous user groups. In order to facilitate a structured design approach for counseling systems in health care, we developed (a) an iterative three-staged specification process, which enables early involvement of potential users in the development process, and (b) a specification language, which enables an author to consistently describe and define user interfaces and interaction designs in a stepwise manner. Due to the formal nature of our specifications, our implementation has some unique features, like early execution of prototypes, automated system generation and verification capabilities.