Magnetic resonance imaging using hyperpolarized He-gas

Rationale and Objectives. Current imaging procedures of the lung concentrate on visualization of morphology. Computed tomography is the imaging method of choice for the majority of pulmonary diseases. Functional data are commonly obtained from arterial blood gas analysis, spirometry, and body plethysmography, which all suffer from lack of regional information.Materials and Methods. Magnetic resonance imaging (MRI) of the lung has been advanced recently by the use of hyperpolarized ³He as a new contrast mechanism. Four different image acquisition modes are performed during a typical patient study.Results. ³He-MRI yields functional information about the lung with a high spatial and temporal resolution, avoiding the risks of ionizing radiation. The method is currently limited by high costs and restricted availability of the gas.Conclusion. In this article, the experience obtained at the University of Mainz, being Europe’s most experienced center performing ³He-MRI in humans, is reviewed against the international background.     

Using a Personal Digital Assistant to Increase Independent Task Completion by Students with Autism Spectrum Disorder

In this study, a personal digital assistant (PDA) with picture, auditory, and video prompts with voice over, was evaluated as a portable self-prompting device for students with autism spectrum disorder (ASD). Using a multiple probe design across three cooking recipes and replicated with three students with ASD, the system was tested for its effectiveness in increasing independent performance across the multiple step tasks. In addition, data were recorded for the number and types of prompts used by the students across time. Results indicate that the students with ASD were able to adjust the prompt levels used on the PDA and to maintain their ability to use the device to independently complete recipes over time.     

Rectal endosonography in inflammatory bowel disease: differential diagnosis and prediction of remission

BACKGROUND AND STUDY AIMS: There are few and conflicting data on EUS features of the rectal wall in Crohn's disease (CD) and ulcerative colitis (UC). The aim of our study was to determine whether rectal EUS could first differentiate between CD and UC, and secondly predict remission in CD. PATIENTS AND METHODS: During a 14 month period we prospectively and blindly studied several parameters on rectal EUS (total wall thickness, mucosal appearance, submucosal thickness, number of enlarged vessels in the submucosa and number of pathological lymph nodes around the rectum and sigmoid colon) in 20 normal subjects, 26 patients with UC, 39 patients with CD, and four with infectious colitis. Comparisons were made between normal controls, patients with acute UC and those with acute CD, as well as between acute flare-ups and quiescent forms of CD and UC in the same patients. RESULTS: Normal subjects showed some features which were significantly different from those in CD or UC patients. A greater number of pathological lymph nodes was characteristic for acute UC, whereas the number of enlarged vessels was increased in acute CD. Quiescent CD showed a lower amount of wall thickening than acute CD. No significant alterations of the five parameters were found in quiescent UC compared to acute UC. CONCLUSIONS: This study suggests that EUS could be helpful in differentiating acute UC from CD, and to predict remission in CD.     

Phase I clinical study with multiple peptide vaccines in combination with tetanus toxoid and GM-CSF in advanced-stage HLA-A*0201-positive melanoma patients

Successful induction of functional tumor-specific T cells by peptide vaccination in animal models has resulted in many clinical trials to test this approach in advanced-stage melanoma patients. In this phase I clinical trial, 11 end-stage melanoma patients were vaccinated intradermally with 3 peptides: MART-1(26-35) E27L (ELAGIGILTV), tyrosinase(368-376) N375Q (YMDGTMSQV), and gp100(209-217) T210M (IMQVPFSV), admixed with tetanus toxoid and granulocyte-monocyte colony stimulating factor. The peptide vaccine was well tolerated at all tested doses, and led to grade 1-2 toxicity only. Although all patients did show a rise in antitetanus IgG titers, in only 3 patients peptide-specific CD8 T-cells were induced. In 2 cases, the response was directed against MART-1(26-35) and consisted of 0.2% and 3.3% of the CD8 population; however, in both instances these cells did not produce interferon-gamma on stimulation with the unmodified peptide. The third patient mounted a small (0.1%) response against gp100. In a fourth patient, a nonfunctional tyrosinase-specific response (0.6%) was found that was present before vaccination, but was not affected in size nor in function by the vaccine. None of the 11 patients responded clinically according to response evaluation criteria in solid tumors criteria. Although this study is a small scale phase I clinical trial, the efficacy that was observed was disappointingly low. In accordance with previously published peptide vaccination studies, these results add to the increasing evidence that peptide vaccination in itself is not potent enough as an effective melanoma immunotherapy in advanced-stage patients.     

Different from what the textbooks say: how GPs diagnose coronary heart disease

BACKGROUND: In patients with chest pain, GPs have to identify those with coronary heart disease (CHD) to arrange for further investigation and treatment. Previous studies have shown that only between 8% and 18% of patients have CHD. In primary care, the history is the most important diagnostic tool. However, there are only few studies exploring diagnostic criteria that GPs actually use in their daily practice. OBJECTIVE: To identify GPs' diagnostic criteria for diagnosing CHD in patients with chest pain. METHODS: In a semi-structured interview, 23 GPs were asked to describe their individual diagnostic criteria in two of their patients with chest pain they had prospectively identified. Interview data were taped, transcribed and analysed qualitatively. RESULTS: Histories of 39 patients were described, of which 17 patients were thought to have CHD and/or an indication for an emergency hospital admission. GPs mentioned the person-specific discrepancy, that is differences in behaviour or a different appearance of a patient in comparison to previous consultations, as an important diagnostic criterion. Known risk factors for CHD and past illness behaviour also influenced the GPs' diagnoses. CONCLUSION: Apart from classical textbook criteria, GPs make use of their prior knowledge of individual patients in a specific way. Discrepancies between previous and actual consultations alert the GPs for serious diseases. At the primary care level, medical practitioners use criteria that differ from secondary or tertiary care.     

Baclofen‐enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain: Long‐term outcome of a pilot study

In a previously published pilot study, we addressed the possibility to increase the effectiveness of spinal cord stimulation (SCS) applied for neuropathic pain by using adjunct pharmacological therapy. This combined treatment approach was a direct spin‐off from animal experiments aiming at the exploration of transmitter and receptor mechanisms involved in the pain relieving effect of SCS. Out of 48 patients with neuropathic pain of peripheral origin responding poorly to SCS, seven received pumps for intrathecal baclofen (GABA‐B receptor agonist) delivery together with SCS, and four had pumps alone. In order to assess the long‐term effect a follow‐up has been performed, with an average, total treatment time of 67 months. At the follow‐up the remaining nine patients still enjoy about the same pain relief as initially, but with a mean, further dose increase of about 30%. This study demonstrates that a deficient SCS effect in neuropathic pain may be considerably improved by intrathecal baclofen administration, and that this enhanced effect persists for a long‐time. On‐going and future animal studies may provide new and even more efficient pharmaceutical candidates for such combined therapy.     

Clinica chimica acta notice board

In order to study the three regulator enzymes of glycolysis, hexokinase (HK). phosphofructokinase (PFK) and pyruvate kinase (PK), in relation to lymphocyte maturation, lymphocytes of different origin were investigated. Lymphocytes from bone marrow, thymus, cord blood, adult peripheral blood and mitogen-stimulated lymphocytes were investigated. The enzyme activities were determined and the isozyme patterns were studied by means of electrophoresis, kinetic measurements and immunoprecipitation.The young lymphocytes from bone marrow and the mitogen-stimulated lymphocytes could be distinguished from the other lymphocytes by a higher residual HK activity in the presence of the inhibitor glucose-1,6-diphosphate.Peripheral blood T lymphocytes differed from non-T lymphocytes in the PK isozymes distribution. All the cells contained PK type K4 and the hybrid K₃M. In T cells a smaller amount of the K isozyme was seen than in non-T cells. The PK residual activity in the presence of alanine was significantly higher in peripheral blood T cells than in non-T cells.Thymocytes are characterised by a larger amount of PFK M-subunits than peripheral blood T and non-T lymphocytes. The stimulation of PFK by the positive effector glucose-1,6-diphosphate was higher in thymocytes than in the peripheral blood lymphocytes.     

Class- and subclass-specific antibody response to hemocyanin in nonmalignant paraproteinemia.

IgM, IgG, and IgA class-specific, as well as IgG subclass-specific antibody titers against the primary immunogen HPH were measured with ELISA in 19 patients with nonmalignant paraproteinemia (eight with IgG1, two with IgG2, two with IgG4, four with IgM, and three with IgA) and in a simultaneously studied age- and sex-matched control group. After primary immunization only IgM and IgA anti-HPH titers were significantly lower in the patient group. Four patients with relatively high IgG or IgA serum paraprotein levels did not produce antibodies in some Ig classes or IgG subclasses, whereas all other patients and all controls developed antibody titers in all classes and IgG subclasses. Low or absent antibody titers did not occur preferentially in the Ig (sub)classes to which the paraproteins belonged. After secondary immunization the patients could not increase or maintain their antibody titers as well as the controls, and this was most clear in the IgM and IgA antibody class. A direct correlation between polyclonal serum IgM levels and IgM anti-HPH titers was present in the patients. Such a correlation was absent for IgA in the patients and for all classes in the controls. It is concluded that humoral immunosuppression as measured with a newly encountered antigen in patients with nonmalignant paraproteinemia is most clearly expressed in the IgM and IgA antibody class and that the paraprotein (sub)class is not preferentially involved.     

Recovery of T cell subsets after autologous bone marrow transplantation is mainly due to proliferation of mature T cells in the graft

In 22 patients with malignancies, treated with high-dose chemoradiotherapy and autologous bone marrow transplantation (BMT), peripheral blood T cell subsets and functions were studied. In ten cytomegalovirus (CMV)-negative patients, CD4+ and CD8+ T cells (representing T cells of the helper/inducer phenotype and T cells of the suppressor/cytotoxic phenotype, respectively), recovered slowly and simultaneously. In 12 CMV-positive patients, however, CD8+ T cells recovered more rapidly than CD4+ T cells and rose to increased counts. No T cells with an immature phenotype (CD1+, OKT6+) were observed. Lymphocyte stimulation by herpes simplex virus infected fibroblasts (and by CMV-infected fibroblasts in CMV-positive patients) in contrast remained high and even increased after BMT in both groups. These data indicate that T cell recovery after autologous BMT is mainly due to proliferation of mature T cells present in the BM graft and not to generation of new T cells from T cell precursors.