“Occult” hydrocephalus in children

The authors describe 32 children between 2 and 15 years of age who had hydrocephalus that was only clinically manifest late in life. The clinical picture of these children did not suggest an obvious increase in intracranial pressure; instead, the presenting signs were rather nonspecific and included macrocrania, mild psychomotor retardation, unsteady gait, increased muscle tone and deep tendon reflexes in the lower limbs, impaired ocular movement, epilepsy, and endocrine dysfunction. Their histories suggest the possible causes of the ventricular dilation in about one third of the cases were: perinatal hemorrhage, leptomeningitis, neurofibromatosis, and untreated aneurysm of the great vein of Galen. In 20 patients, however, no positive anamnestic findings were reported. CT scan revealed triventricular dilation in more than half of the cases; tetraventricular dilation was present in 6 patients, and biventricular dilation in the remaining subjects. All children underwent CSF shunting, which resulted in complete recovery in all but 2 cases. The most frequently recorded surgical complication was postoperative subdural effusion (7 subjects), which required surgical treatment in only 2 cases.Presented at the 15th Annual Scientific Meeting of the International Society for Pediatric Neurosurgery, New York, 1987     

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.     

Molecular pathologic diagnosis in solid tumors. What is clinically relevant?

There are only a few clinically relevant applications of molecular pathology assays in solid tumors. Among the findings which may influence therapy decisions are the amplification of Her-2/new in breast cancer and specific translocations in sarcomas. Mutation analyses of p53 may be helpful for only a very few cases, e.g. for confirming high grade dysplasia in the upper gastrointestinal tract or for diagnosing malignant soft tissue tumors in isolated cases. Microsatellite analyses are important for HNPCC screening or distinguishing tissue specimens of questionable identity. Other applications of molecular pathology assays such as detection of minimal residual disease or tumor cell dissemination and FISH analysis of urine and effusion specimens, may be increasingly applied in the future.     

CK20 expression in the gastrointestinal tract of the embryo and fetus]

A novel type of cytokeratin, cytokeratin 20 (CK20), was added in 1990 to the classic catalog of human cytokeratins, a heterogeneous group of proteins present in almost all epithelia. In man, the expression of CK20 is almost entirely confined to the gastro-intestinal epithelium, to the urothelium and to Merkel cells. Since only few data are available regarding the expression of CK20 in the developing human intestinal mucosa, we studied CK20 immunoreactivity in fetal and neonatal human gut. Immunoreactivity for CK20 was tested in fetuses and newborns, from the twelfth up to the fortieth week of gestation. In each subject, a specimen from the oesophagus, stomach, small intestine, colon, appendix was studied. Tissue samples were routinely processed and paraffin sections were stained with the CK20-specific antibody IT-Ks 20.8. CK20 immunoreactivity was absent in the oesophageal epithelium and it was unevenly distributed in the gastrointestinal mucosa. Three main patterns of immunoreactivity were observed during normal development: the first, found in the stomach and in the small bowel, is characterized by a progressive increase in CK20 expression during gestation; the second pattern, found in the duodenum, shows a progressive decrease in CK20 expression during gestation; in colon and appendix (third pattern), we did not find significant changes in the degree of immunoreactivity for CK20 during gestation. CK20 is unevenly expressed in developing human intestinal mucosa. The degree of positivity for CK20 appears to be related to the epithelial maturation stage only in gastric and small bowel mucosa. Further studies are needed to verify if the uneven CK20 immunoreactivity in the gastrointestinal tract persists even in adulthood.     

Focal electroretinograms and fundus appearance in nonexudative age-related macular degeneration

· Background: The aim of this study was to evaluate the focal electroretinogram (FERG), an objective indicator of outer retinal function, in nonexudative age-related macular degeneration (NE-AMD), and to compare FERG results with morphological lesions assessed by stereoscopic fundus photographs and fluorescein angiograms. · Methods: Twenty-five patients (25 eyes) with bilateral NE-AMD (visual acuity of the study eyes ≥0.4) as well as 10 age- and sex-matched control subjects (10 eyes) were evaluated. FERGs were recorded from the macular region (9°) in response to sinusoidal stimuli flickered at 32 Hz. Amplitude and phase angle of the Fourier-analyzed FERG fundamental component were measured. Fundus lesions were graded from color slides according to the Wisconsin age-related maculopathy grading system [15]. Fluorescein angiograms were evaluated by an image analysis technique to compute the area with pathological hyperfluorescence (associated with drusen and/or retinal pigment epithelial atrophy) within the macular (approximately 9°×9°) region. · Results: Compared to control eyes, NE-AMD eyes had a reduction in the mean FERG amplitude (57% loss, P<0.001) with no phase changes. Amplitudes of individual affected eyes were negatively correlated with either the Wisconsin grading score (r=–0.63, P<0.001) or the percentage area of pathological hyperfluorescence (r=–0.70, P<0.01). Eyes with minimal NE-AMD lesions (Wisconsin score ≤6) and normal acuity had a lower mean amplitude (47% loss, P<0.05) than that of control eyes. · Conclusions: The results indicate that, in NE-AMD, the FERG is altered in parallel with the extent and severity of fundus lesions. However, a functional impairment of outer macular layers, which is detected by FERG losses, could precede morphological changes typical of more advanced disease. Received: 6 March 1998 Revised version received: 5 June 1998 Accepted: 17 June 1998     

Olfactory dysfunction and extent of white matter abnormalities in multiple sclerosis: a clinical and MR study

BACKGROUND: The relative contribution to the olfactory dysfunction of the lesions in the specific brain regions involved in olfaction compared with the lesions scattered all over the rest of the brain has not been fully clarified yet in patients with multiple sclerosis (MS). The concurrent use of Magnetic Resonance Imaging (MRI) and a standardized test of odor identification ability now permits to study the relation between smell loss and the extent of white matter abnormalities. METHODS: We tested the olfactory function of 40 patients with definite MS and of 40 age-sex- and smoking-habit-matched healthy controls by using the Cross Cultural Smell Identification Test. We measured also the lesion load on T2-weighted images in the inferior-frontal and temporal lobes and in the rest of the brain in MS patients. Therefore, we tried to correlate measures of lesion load and smell test scores. RESULTS: A robust correlation was demonstrated between MR measures of lesion load in the white matter of the olfactory brain region and smell loss (r=-0. 739, P<0.0001). A significant relationship has been found even after taking potential confounding factors, such as sex, age, disease duration, disability, anxiety and depression, into account (r=-0.90, P<0.0001). CONCLUSIONS: Our findings show, in MS patients with stable neurological impairment and no recent disease exacerbation, a correlation between smell loss and the lesion load in the regions of the brain involved in olfaction and support the theory that the extent and severity of MRI abnormalities in specific brain regions are related to the presence of selective neurologic and neuropsychologic impairment.     

Differentiation of human adult CD34+ stem cells into cells with a neural phenotype: role of astrocytes

It has recently been reported that adult hematopoietic stem cells can differentiate into neural cells, opening new frontiers in therapy for neurodegenerative diseases. In this study, adult human hematopoietic stem cells (HSCs) were isolated via magnetic bead sorting, using a specific CD34 antibody and cultured with human astrocyte culture conditioned medium (ACM). In order to evaluate their differentiation into neurons and/or astrocytes, ACM-treated cultures were probed for the expression of several neural markers. We observed morphological modifications and, after 20 days of treatment, cell morphology displayed extending processes. Immunocytochemistry, Western blotting and RT-PCR showed the expression of neuronal markers such as neurofilaments, neuron specific enolase (NSE) and NeuN in ACM-treated HSCs cultured in poly-L-lysine-coated dishes. On the contrary, when the same ACM-treated cells were grown on a plastic substrate, they expressed high levels of glial fibrillary acidic protein (GFAP), with only weak expression of neuronal markers. Nestin, a neural progenitor cell marker, was present in treated cells, regardless of the substrate. These results demonstrate that astrocytes can generate a suitable microenvironment for inducing HSCs to differentiate into neural cells. Therefore, adult bone marrow may represent a readily accessible source of cells for treating neurodegenerative diseases.