Einzelreferate und Buchbesprechungen

Ohne Zusammenfassung     

Rat polyvinyl sponge model for the study of infections: host factors and microbial proliferation.

Female rats were treated with several administration regimens of methylprednisolone, cobra venom anti-complementary factor, and cyclophosphamide in conjunction with polyvinyl sponge implantations. The effect of these drugs on host factors active against bacteria was evaluated with Staphylococcus aureus ATCC 25933, Escherichia coli K-12, and Pseudomonas aeruginosa CDC 7725. One of two implants in each animal was infected with 10(8) of one of the three bacteria, and bacterial and granulocyte content was determined in the infected and control sponges after 48 h. The single large dose of methylprednisolone decreased staphylococcal and E. coli clearance while promoting dissemination of P. aeruginosa. A low chronic dose of the steroid inhibited E. coli chemotaxis only. A higher dose of the steroid administered chronically interfered markedly with S. aureus and E. coli curtailment by the host while leading to enhanced dissemination of P. aeruginosa, accompanied by a precipitous decline in granulocytes. Results with cobra factor resembled the higher chronic dose of steroid enhancing, especially the dissemination of the pseudomonad and its anti-granulocytic propensity. Cyclophosphamide depression of granulocytes revealed the rat's ability to curtail the proliferation of particular S. aureus and E.coli strains even in the absence of leukocytes. This treatment resulted in the rapid spread of P. aeruginosa, leading to the death of some experimental animals. These experiments underline the versatility of this animal model in the study of host and microbial factors influential in infectious disease.     

Familial X-linked mental retardation with an X chromosome abnormality.

An X-linked pattern of transmission observed in four families with familial mental retardation in several generations was associated with a probable secondary constriction at the distal end of the q arms of the X chromosome. Twenty retarded males and no retarded females were observed. All available live retarded males and most of their normal mothers were found to have the abnormal X chromosome. The marker chromosome was shown to be the X chromosome in each case by Giemsa banding. In affected male and female carriers the marker chromosome varied in appearance and was not present in all metaphases. The significance of this study in relation to previously reported pedigrees showing non-specific X-linked mental retardation is discussed.     

Results of a high-resolution genome screen of 437 Alzheimer's disease families

Alzheimer's disease (AD) is a devastating neurodegenerative disorder of late life with complex inheritance. Mutations in three known genes lead to the rare early-onset autosomal dominant form of AD, while a common polymorphism (epsilon 4) in the gene encoding apolipoprotein E (APOE ) is a risk factor for more typical late-onset (>60 years) AD. A recent study concluded that there are up to four additional genes with an equal or greater contribution to the disease. We performed a 9 cM genome screen of 437 families with AD, the full National Institute of Mental Health (NIMH) sample, which has been carefully ascertained, evaluated and followed by our group over the last decade. Performing standard parametric and non-parametric linkage analyses, we observed a 'highly significant' linkage peak by Lander and Kruglyak criteria on chromosome 19q13, which probably represents APOE. Twelve additional locations-on 1q23, 3p26, 4q32, 5p14, 6p21, 6q27, 9q22, 10q24, 11q25, 14q22, 15q26 and 21q22-met criteria for 'suggestive' linkage [i.e. two-point lod score (TLS) >/=1.9 and/or multipoint lod score (MLS) >/=2.2] in at least one of our analyses. Although some of these will surely prove to be false positives, these linkage signals should provide a valuable framework for future studies aimed at identifying additional susceptibility genes for late-onset AD.     

Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses.

Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic Initiative sample indicates that the trait is heritable, and linkage studies of multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12. Associations with NRG1 SNPs have also been found in other schizophrenia populations from Scotland, Ireland, and China. Here, we report results demonstrating a significant linkage peak for ADP on 8p12 in the NIMH AD dataset, encompassing the NRG1 region. We also demonstrate that there is a significant association with a NRG1 SNP (single nucleotide polymorphism), rs392499, with ADP, chi2 = 7.0, P = 0.008. This same SNP is part of a 3-SNP haplotype preferentially transmitted to individuals with this phenotype. Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families.     

Blood pressure reaction to negative stimuli: Insights from continuous recording and analysis

Individuals with a tendency toward abnormally enhanced cardiovascular responses to stress are at greater risk of developing essential hypertension later in life. Accurate profiling of continuous blood pressure (BP) reactions in healthy populations is crucial for understanding normal and abnormal emotional reaction patterns. To this end, we examined the continuous time course of BP reactions to aversive pictures among healthy participants. In two experiments, we showed participants negative and neutral pictures while simultaneously measuring their continuous BP and heart rate (HR) reactions. In this study, BP reactions were analyzed continuously, in contrast to previous studies, in which BP responses were averaged across blocks. To compare time points along a temporal continuum, we applied a multi-level B-spline model, which is innovative in the context of BP analysis. Additionally, HR was similarly analyzed in order to examine its correlation with BP. Both experiments revealed a similar pattern of BP reactivity and association with HR. In line with previous studies, a decline in BP and HR levels was found in response to negative pictures compared to neutral pictures. In addition, in both conditions, we found an unexpected elevation of BP toward the end of the stimuli exposure period. These findings may be explained by the recruitment of attention resources in the presence of negative stimuli, which is alleviated toward the end of the stimulation. This study highlights the importance of continuous measurement and analysis for characterizing the time course of BP reactivity to emotional stimuli.     

When children tell their friends they have AIDS: possible consequences for psychological well-being and disease progression

OBJECTIVE: Past research has demonstrated that self-disclosure of traumatic or secretive information produces observable health benefits. Self-disclosure has also been linked, albeit less consistently, to improved psychological health. The present study examined the physiological and psychological consequences of children's self-disclosure of their HIV/AIDS status to friends. METHODS: Data were collected twice, one year apart, from 64 caregiver-child dyads in which all of the children were infected with HIV. Dependent variables included the child's CD4%, self-concept, and level of behavioral problems. RESULTS: Children who had disclosed their HIV+ diagnosis to friends during the 1-year course of the study had a significantly larger increase in CD4% than children who had told their friends before the study or those children who had not yet disclosed their HIV+ diagnosis to friends. This effect remained significant when the child's age and level of medication (protease inhibitors) were statistically controlled. Self-disclosure to friends did not impact the child's behavior or self-concept. CONCLUSIONS: This is the first study to investigate the effect of self-disclosure in children. The results were consistent with previous studies showing the positive health consequences of self-disclosure in adults, and suggest potentially important implications for professional and familial care givers of HIV/AIDS individuals.     

Vestibular evoked myogenic potentials and habituation to seasickness

Objective

Seasickness may impose severe limitations on the performance of ships’ crew. Cervical vestibular evoked myogenic potentials (cVEMP) assess the function of the saccule, the organ responsible for monitoring vertical linear acceleration, which has been found to be the most provocative motion stimulus in the evolution of motion sickness. We used the cVEMP test in a prospective evaluation of susceptibility and habituation to seasickness.

Methods

Forty-six naval recruits underwent the cVEMP test before exposure to sea conditions. After 6 months’ sailing experience, participants completed a questionnaire evaluating their initial and current seasickness severity. Based on their most recent experience, subjects were divided into three groups: non-vomiting non-habituating (NV-NH), vomiting (V), and non-vomiting habituating (NV-H).

Results

Statistically significant lower thresholds for cVEMP were found in subjects who habituated to sea conditions (NV-H), compared with those remaining severely susceptible (V) (77.0 dB HL vs. 84.9 dB HL; p < 0.01).

Conclusions

The ability to produce the cVEMP at lower thresholds represents a broader dynamic range, in which the reflex can respond to a wider array of stimuli amplitudes.

Significance

The present study demonstrates the potential of the cVEMP test for predicting future habituation to seasickness.     

Comparison of 16-slice MSCT and MRI in the assessment of squamous cell carcinoma of the oral cavity

The goal of this retrospective study was to assess the accuracy of 16-slice multislice CT (MSCT) and MRI in staging of patients with primary squamous cell carcinoma (SCC) of the oral cavity. Fifty-two patients with histologically proven primary SCC were examined with contrast enhanced MSCT and MRI at 1.5 T with a combined head and surface neck coil. Image modalities were evaluated in a blinded fashion by two radiologists and an oral-maxillofacial surgeon in consensus concerning tumour depiction, local tumour infiltration and cervical lymph node metastases. Results of the radiological assessment were correlated with the intraoperative and histopathological findings in all patients. 36 of 52 primary tumours (69.2%) were depicted by MSCT while 44 were localized by MRI (84.6%). Regarding muscle infiltration MRI versus MSCT had a sensitivity of 81.8% versus 72.7%, but a low specificity and an accuracy of 63.4% versus 61% and 67.3% versus 63.5%, respectively, were found. There was a trend towards a better detection of bony infiltration by MRI than MSCT with a sensitivity of 100% versus 71.4%, a specificity of 93.3% versus 95.5% and an accuracy 94.2% versus 92.3%, respectively. Detection of cervical lymph node involvement was similar for MRI and MSCT with a sensitivity of 84.2% and 78.9%, a specificity of 63.6% and 75.7% and an accuracy of 71.1% and 76.9%, respectively. For N-staging both methods failed to detect small metastasis. For T-staging MRI was superior to MSCT, because there was a tendency to underestimate the tumour size by MSCT more often (19.4% versus 6.8% by MRI). Therefore, pre-operative MRI is recommended as the basic imaging modality of choice for treatment planning of oral SCC. MSCT is a valid alternative imaging method especially in cases with low patient compliance.     

Regional variation in capillary permeability of ventricular myocardium

The transcapillary exchange of horseradish peroxidase (HRP) has been investigated in the principal layers of rat ventricular myocardium. Cardiac arrest was induced in rats by the intravenous (iv) administration of KCl at intervals of 4–180 sec after the iv injection of HRP. The coronary arteries of non-working hearts were perfused with peroxidase for 90–300 sec. Sections from both ventricles were processed for light and electron cytochemistry, and thin sections examined by electron microscopy. The capillaries in the subendocardial and intermediate regions of both ventricles exhibit greater permeability than the subepicardial capillaries, as manifested by the more rapid extravascular passage of HRP. This permeability gradient is detectable for at least 15 sec after iv injection of the tracer, and for as long as 5 minutes when the enzyme is perfused. The observations suggest that permeability differences in subendocardial and subepicardial capillaries have an ultrastructural basis and provide further evidence for the functional heterogeneity of ventricular myocardium.