Alzheimer's disease: identical phenotype of familial and non-familial cases

Summary Ninety outpatients with Alzheimer's disease according to ICD-10 diagnostic draft criteria were studied to test the hypothesis that cases with a familial aggregation are different from cases without such an aggregation with respect to cognitive impairment. In all cases the diagnosis of Alzheimer's disease was confirmed by prospective observation within 12 months of initial evaluation. Patients were divided into two groups: one consisting of 23 patients with a familial aggregation, the other consisting of 67 patients without secondary cases among first-degree relatives. By means oft-tests differences in impairment of cognitive functions between the groups were calculated. The results did not yield statistically significant differences between the groups for any of the neuropsychologically investigated cognitive deficits. Thus the hypothesis that the presence of a familial aggregation may lead to a distinct phenotype in Alzheimer's disease was not confirmed.     

Receptive field scatter,topography and map variability in different layers of the hindpaw representation of rat somatosensory cortex

We recorded neurons extracellularly in layers II/III, IV, and V of the hindpaw representation of primary somatosensory cortex in anesthetized rats and studied laminar features of receptive fields (RFs) and representational maps. On average, RFs were smallest in layer IV and largest in layer V; however, for individual penetrations we found substantial deviations from this rule. Within the hindpaw representation, a distinct rostrocaudal gradient of RF size was present in all layers. While layer V RFs were generally largest independent of this gradient, layer IV RFs recorded caudally representing the proximal portions of the paw were larger than layer II/III RFs recorded rostrally representing the digits. The individual scatter of the locations of RFs across laminar groups was in the range of several millimeters, corresponding to about 25% of the average RF diameter. The cutaneous representations of the hindpaw in extragranular layers were confined to the areal extent defined by responsive sites in layer IV. Comparison between RFs determined quantitatively and by handplotting showed a reliable correspondence. Repeated measurements of RFs revealed spontaneous fluctuations of RF size of no more than 5% of the initial condition over an observation period of several hours. The topography and variability of cortical maps of the hindpaw representation were studied with a quantitative interpolation method taking into account the geometric centers of RFs and the corresponding cortical recording sites. On average, the overall topography in terms of preservation of neighborhood relations was present in all layers, although some individual maps showed severe distortions of topography. Factors contributing to map variability were overall position of the representation on the cortical surface, internal topography and spatial extent. Interindividual variability of map layout was always highest in the digit representations. Local topographic orderliness was lowest in layer V, but comparable in layers II/III and IV. Within layer IV, the lowest orderliness was observed in the digit representations. Our data emphasize a substantial variability of RF size, overlap and position across layers and within layers. At the level of representational maps, we found a similar degree of variability that often co-varied across layers, with little evidence for significant layer specificity. Laminar differences are likely to arise from the specific input-output pattern, layer-specific cell types and the connectivity between different layers. Our findings emphasizing similarities in the variability across layers support the notion of tightly coupled columnar interactions between different layers.     

Study of neu-protein expression in mammary Paget's disease with and without underlying breast carcinoma and in extramammary Paget's disease.

Correlation between neu/c-erbB-2/Her-2 gene amplification and overexpression of the neu gene product has been reported in tumors of glandular origin, especially ductal breast carcinomas. Formalin-fixed and dewaxed sections from 23 cases of mammary (MPD) and 9 cases of extramammary (EPD) Paget's disease were immunohistochemically stained by means of the monoclonal antibody 3B5 directed against an intracellular domain of the neu gene protein. All MPDs exhibited a distinct membrane staining of tumor cells independent of the presence of ductal breast carcinomas found in 18 cases. All these breast carcinomas also were positive for neu staining. In contrast to MPD, all EPDs were negative. Normal epidermis was always negative. Northern blot analysis sustained the immunohistologic findings in that the presence of neu mRNA could be demonstrated in two of three cases with MPD. Negativity in one case was due to dilution effects by nontumor cells. Our results suggest that Paget cells of mammary and extramammary localization, although very similar phenotypically, derive from different genetic accidents. Furthermore neu positivity in all MPDs and all underlying ductal carcinomas suggests common genetic alterations for both tumors. However the finding of five neu protein-positive MPDs without associated ductal breast carcinomas may suggest a somewhat different transformation process.     

Encoding of visceral noxious stimuli in the discharge patterns of visceral afferent fibres from the colon

Afferent fibres, in the inferior splanchnic nerves and lumbar white rami, which supply the colon and its mesentery in the cat, were investigated for their responses to distension and contraction of the colon and to local pressure applied to colon and its mesentery. 1) 63% (177 out of 287) of the axons had resting activity (median 0.3 imp/s). These axons were either unmyelinated (conduction velocity below 2 m/s) or thin myelinated (conduction velocity below 18 m/s). Most axons without resting activity (N=95 out of 106 axons) conducted at less than 1.4 m/s, and most were probably sympathetic efferents. 2) 76 out of 80 afferent units with resting activity (95%) and 8 out of 27 units without (30%) were excited by distension of the colon. The thresholds were largely at intraluminal pressures of around 25 mm Hg or higher. 3) Most afferent units (87%) responded with an increased steady state discharge throughout the distension with or without initial dynamic response. The rest of the afferent units responded only with a transient discharged to distension. 4) Most afferent units reacted in a graded manner to variable intraluminal pressures. 5) In only 43% of the distension-sensitive afferent units could mechanoreceptive sites be located on the wall of the colon or in the mesentery. The majority of the afferent units had one mechanoreceptive site only, some had two. 6) Afferent units reacting to colon distension were also excited by contraction of the colon. 7) The excitability spectrum of visceral afferent fibres in the inferior splanchnic nerves, which are activated by colon distension, suggests that these units are involved in visceral nociception from the colon.     

Pathways Linking Treatment Intensity and Psychosocial Outcomes among Adult Survivors of Childhood Leukemia

To determine the pathways between treatment intensity (age at diagnosis, dosage of chemotherapy [intrathecal methotrexate; IT-MTX] and cranial radiation [CRT]) and various psychosocial outcomes, review of medical records and structured interviews were carried out in 510 adult survivors of childhood leukemia. Structural equation modeling revealed that higher treatment intensity during childhood (indicated by treatment with high-dose CRT, low-dose IT-MTX, and adjusted by younger age at diagnosis) predicted more health- compromising behaviors as adults through lower educational achievement. Additionally, higher childhood treatment intensity predicted current negative mood both directly and via changes in perceived limitations. The present study's findings suggest that higher treatment intensity during childhood may serve as a risk factor for adult survivors' health-compromising behaviors through neuropsychological deficits that arise from cancer treatment.     

Colorectal adenocarcinoma with micropapillary pattern and its association with lymph node metastasis.

Micropapillary carcinoma has been reported as an aggressive variant of carcinoma in several organs, where it is associated with frequent lymphovascular invasion and poor clinical outcome. This study explored the clinicopathological features of colorectal adenocarcinoma with a micropapillary carcinoma component and compared them with those of conventional colorectal adenocarcinoma. One hundred seventy-eight consecutive cases of surgically resected colorectal carcinomas were studied for tumor size, type, depth of invasion, nodal and distant metastases, tumor stage, and percentage and extent of micropapillary component. Among 178 cases of colorectal carcinoma, 34 (19.1%) cases had a micropapillary component, which ranged from 5 to 60% of the entire tumor. Lymph node metastasis was identified in 25 of 34 (73.5%) carcinomas with micropapillary component, whereas they were detected in 61 of 144 (42.4%) cases without micropapillary component (P=0.001). Lymphovascular invasion was identified more frequently in carcinoma with micropapillary component (41.2%) than carcinoma without micropapillary component (20.1%; P<0.05). Distant metastases occurred in 4 of 34 cases (11.7%) with micropapillary component and in 10 of 144 cases (6.9%) without micropapillary component (P=0.311). Multivariate regression analysis demonstrated that the presence of micropapillary component, as well as tumor stage and lymphovascular invasion are independent predictors of regional nodal metastasis.     

The Effect of Presleep Focal Attention Load on Subsequent Sleep Patterns

The hypothesis that a load on focal attention prior to sleep results in subsequent changes in sleep patterns was investigated. Eight females and 2 males slept in the laboratory for 4 nights: 2 adaptation nights, 1 experimental night preceded by a focal attention load, and 1 control night preceded by relaxed activity. On the experimental night, time in bed, total sleep time, and stage REM sleep were significantly longer than on the control night. The results support the hypothesis and suggest that attention during REM sleep has a unique character.