Contrast enhancement for the myocardium.

The potential of MR imaging and spectroscopy in ischemic heart disease is substantial. MR contrast media have the potential to improve the differential tissue characterization among normal, ischemic, and infarcted myocardium. Several reports in animals and patients have revealed that MR contrast media can improve the delineation of acute myocardial infarctions (1–7). Studies from several centers in Europe and Asia have demonstrated that the contrast between the normal and acutely infarcted myocardium substantially increased with the use of gadolinium-DTPA administered intravenously (1, 2, 4, 5). In these studies, the acutely infarcted myocardium on delayed MR scans demonstrated greater enhancement with the paramagnetic contrast media than normal myocardium, producing a greater percentage contrast between the two regions. These studies are consistent with previous reports using gadolinium-DTPA contrast media to enhance the differential in signal intensity between the normal and infarcted myocardium in animal models (3, 6, 7). The expanded use of MR in ischemic heart disease will likely depend upon employing contrast media to enhance regional myocardial signal in proportion to regional blood flow. Such contrast media are needed for using MRI to demonstrate regions of myocardial ischemia and to depict reperfusion of a myocardial region after an ischemic event. © 1991 Academic Press, Inc.     

Molecular epidemiology and population genetics in Leishmania

Polymorphic DNA sequences have been amplified using different PCR-based techniques and used for species identification, strain discrimination and population genetic studies in Leishmania. A PCR fingerprinting method that uses single non-specific primers generates species-specific banding patterns with some intraspecies variation. This approach can be used to identify Leishmania species and also to discriminate strains of different Leishmania species. Cultivation of the parasites is, however, mandatory. PCR-restriction fragment length polymorphism of the internal transcribed spacer (ITS) in the ribosomal operon differentiates all Leishmania species, except members of the L. donovani and L. brasiliensis complexes. ITS-single-strand conformation polymorphism or ITS sequencing can detect strain specific-variation (except in L. infantum); culturing is not required. Species of Leishmania exhibit different degrees of genetic variation (L. tropica > L. aethiopica > L. major > L. donovani). Population analysis using co-dominant DNA markers developed by sequence-confirmed amplified region analysis revealed a primarily clonal structure in a L. donovani population from Sudan and suggested that occasional recombination events may occur in this population.     

Occlusive and reperfused myocardial infarcts: MR imaging differentiation with nonionic Gd-DTPA-BMA

To increase the time during which effective contrast exists between normal and infarcted myocardium, a high dose (0.6 mmol/kg) of the nonionic contrast medium gadolinium diethylenetriaminepentaacetic acid bismethylamide (Gd-DTPA-BMA) was used to distinguish between occlusive and reperfused myocardial infarctions in rats. After administration of Gd-DTPA-BMA, there was clear and persistent demarcation of both occlusive and reperfused infarcts on T1-weighted MR images. In occlusive infarcts, normal, infarcted, and periinfarcted myocardium could be identified. High signal intensity was evident for 60 minutes in a band straddling the border between infarcted and normal myocardium, namely, the periinfarction zone. In the reperfused infarct, normal and infarcted myocardium could be identified. The reperfused zone was immediately enhanced after injection of Gd-DTPA-BMA. A differential pattern of enhancement between occlusive and reperfused myocardial infarcts was evident for 1 hour. Thus, Gd-DTPA-BMA has the potential to allow (a) depiction of occlusive and reperfused acute myocardial infarcts, (b) documentation of reperfusion of myocardial infarction, and (c) distinction between occlusive and reperfused infarction.     

Chemokine receptor CCR9 contributes to the localization of plasma cells to the small intestine

Humoral immunity in the gut-associated lymphoid tissue is characterized by the production of immunoglobulin A (IgA) by antibody-secreting plasma cells (PCs) in the lamina propria. The chemokine CCL25 is expressed by intestinal epithelial cells and is capable of inducing chemotaxis of IgA+ PCs in vitro. Using a newly generated monoclonal antibody against murine CCR9, we show that IgA+ PCs express high levels of CCR9 in the mesenteric lymph node (MLN) and Peyer's patches (PPs), but down-regulate CCR9 once they are located in the small intestine. In CCR9-deficient mice, IgA+ PCs are substantially reduced in number in the lamina propria of the small intestine. In adoptive transfer experiments, CCR9-deficient IgA+ PCs show reduced migration into the small intestine compared with wild-type controls. Furthermore, CCR9 mutants fail to mount a regular IgA response to an orally administered antigen, although the architecture and cell type composition of PPs and MLN are unaffected and are functional for the generation of IgA PCs. These findings provide profound in vivo evidence that CCL25/CCR9 guides PCs into the small intestine.     

Tolerance induction towards cardiac allografts under costimulation blockade is impaired in CCR7-deficient animals but can be restored by adoptive transfer of syngeneic plasmacytoid dendritic cells

Deficiency of transplant recipients for the chemokine receptor CCR7 was originally described to slightly increase the survival time of vascularized solid organ grafts, probably due to a reduced priming of alloreactive T cells. Using a model of allotolerance induction by donor-specific splenocyte transfusion (DST) in combination with anti-CD40L mAb-mediated costimulation blockade (CSB), we show here a striking failure of CCR7-deficient (CCR7(-/-) ) recipients to tolerate cardiac allografts. Furthermore, in addition to the recently described lack of Treg, CCR7(-/-) mice were found to harbor significantly reduced numbers of plasmacytoid dendritic cells (pDCs) within peripheral as well as mesenteric lymph nodes (LNs), but not the bone marrow or spleen. pDCs had previously been suggested to function as tolerogenic APC during allograft transplantation, and a single transfer of syngeneic WT pDCs, but not conventional DCs, was indeed sufficient to rescue graft survival in DST+CSB-treated CCR7(-/-) recipients in a dose-dependent manner. We therefore conclude that the nearly complete absence of pDCs within LNs of CCR7(-/-) mice prevents the successful induction of DST+CSB-mediated allotolerance, leading to the observed acute rejection of cardiac allografts under tolerizing conditions.     

A Psychometric evaluation of the German version of the 'Health of the Nation Outcome Scales, HoNOS-D': on the feasibility and reliability of clinician-performed measurements of severity in patients with mental disorders

BACKGROUND: The assessment of the severity of a mental illness is a central component in the treatment of patients with mental disorders in both the in- and outpatient settings. In Great Britain, the 'Health of the Nation Outcome Scales, HoNOS' were developed to assess the health and social functioning of patients with mental disorders. AIMS: To examine the psychometric properties, especially the feasibility and reliability, of a German version of the HoNOS (HoNOS-D) and to thus provide international data for the comparison of different mental health services. SAMPLING AND METHODS: The HoNOS was translated into German (HoNOS-D) in an extensive and multilayered consensus procedure. The HoNOS-D was then reviewed within the framework of a pilot study on quality assurance measures implemented by the German statutory health insurance institutes in 11 hospitals. Assessments were made of the psychometric qualities of feasibility and reliability using a representative sample of patients with mental and behavioral disorders. RESULTS: An analysis of the feasibility of the HoNOS-D showed a range of missing values between 1.3 and 4.5% for 11 of the 12 items. An item analysis showed that three items of the HoNOS-D are particularly positively skewed. In most instances, the individual items of the rating scale exhibited only slight correlations to each other. With regard to retest reliability, satisfactory intraclass correlations between 0.80 and 0.91 were seen for 9 of the 12 items. CONCLUSIONS: The authors of the original version of the HoNOS [Wing et al.:Br J Psychiatry 1998;172:11-18] primarily emphasized the feasibility of the instrument and the independence of the individual items and dimensions. The analysis of the missing values showed satisfactory results for feasibility. The intercorrelation matrix of the individual items also exhibited only few correlations >0.30. The retest reliability also proves to be satisfactory for the majority of the items. The narrow distribution of some of the items must be critically discussed in comparison to analyses of results in other countries (e.g. Great Britain) and other settings (e.g. inpatient psychiatric hospitals or outpatient psychotherapy).     

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.     

Leukemia inhibitory factor differentially regulates capsaicin and heat sensitivity in cultured rat dorsal root ganglion neurons

Thermal hyperalgesia is one hallmark of neuropathic pain conditions. Although the exact pathophysiological mechanisms remain elusive, nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are considered key mediators. Their local availability or synthesis are altered by nerve damage and, in turn, they entail changes in phenotype of affected neurons. We examined the effects of LIF on capsaicin sensitivity, heat responsiveness, and galanin immunoreactivity in rat dorsal root ganglion neurons cultured for up to 6 days without supplemented NGF. Using double labeling, the proportions of heat-sensitive/galanin-immunoreactive (GAL-IR) and capsaicin-sensitive/GAL-IR neurons were compared over time in culture with galanin immunoreactivity being a marker for nociceptive neurons. The time course of the proportions of neurons responding to heat (44 degrees C) or capsaicin (1 microM) which also were GAL-IR was differently affected by LIF. In the absence of LIF, within the population of heat-sensitive neurons, the proportion of neurons also GAL-IR increased from 17% to 32% between 6h and 1 day in culture to stay at this level. For the capsaicin-sensitive neurons, the proportion of neurons also GAL-IR increased from 10% after 6h to 18% at day 2 and then decreased to 4% at day 4. In contrast, LIF prevented the increase in the proportion of heat-sensitive/GAL-IR neurons and the decrease of capsaicin-sensitive/GAL-IR neurons. The results suggest that LIF partially prevents TRPV-1 downregulation in NGF-deprived nociceptive galaninergic DRG neurons. Furthermore, there is evidence that LIF regulates the expression of a heat receptor distinct from TRPV-1.