Structural and ultrastructural characteristics of human pineal gland,and pineal parenchymal tumors

We have studied 20 pineal parenchymal tumors (PPT) and 4 normal or cystic pineal glands both by light and electron microscopy and immunohistochemistry with antibodies against glial markers [glial fibrillary acidic protein (GFAP) and protein S-100] or neural/neuroendocrine markers [neurofilaments (NF), synaptophysin and chromogranin A]. Light microscopy revealed the cellular organization of pinealocytes in the normal gland and in different morphological types of pineal tumors (typical pineocytomas, PPT with intermediate differentiation, mixed PPT exhibiting elements of both pineocytoma and pineoblastoma and pineoblastomas). Immunohistochemistry showed the presence of GFAP and protein S-100 in interstitial cells in nonneoplastic pineal gland. Cell processes were labeled with anti-synaptophysin and anti-NF antibodies. No immunoreactivity was found for chromogranin A in non-neoplastic pineal gland. In pineocytomas, GFAP and protein S-100 were observed in interstitial cells. Synaptophysin and NF were present in the large rosettes of pineocytomas. Synaptophysin, NF and chromogranin A were present in pineocytomas with a lobular arrangement of cells. Anti-chromogranin A immuno-reactivity was also seen in lobular areas of some PPT with intermediate differentiation. Analysis of normal human pineal gland by electron microscopy showed the presence of vesicle-crowned rodlets (VCR or synaptic ribbons), fibrous filaments (F), paired twisted filaments but few dense-core vesicles (DCV) in normal pinealocytes. Tumoral pineal cells appeared to differentiate either towards a neurosensory pathway characterized by the presence of sensory cells elements (VCR and F), or towards a neuroendocrine pathway, with the occurrence of many DCV. Immunogold labeling demonstrated the presence of chromogranin A in neurosecretory granules.Supported by grants from the Région Rhône Alpes and from INSERM (CJF 90-10)     

Value of AgNOR counts in cervical pathology.

Nucleolar organizer regions (NORs) were counted on normal tissue, condylomata, CIN 1, 2 and 3, to verify the possibility of a differentiation between the various grades of CIN and between them and condylomata. Counts were performed on the full thickness of the tissue, layer by layer (stratified counts). A significant difference (p < 0.05) was found between the mean of normal tissue in relation to condylomata and CIN 2 and 3 and between CIN 1, and CIN 2 and 3. There was no significance (p > 0.05) between normal tissue and CIN 1, between CIN 2 and 3 and between condylomata and CIN 2 and 3. The range of variations in the counts was associated with overlapping between the various cases. Our data showed also a progressive rise in mean NOR values from normal tissue to CIN 3. The stratified counts showed in all the groups a rise from basal to parabasal cells. Counts on parabasal and intermediate layers distinguished two groups of cases. In one there was either the same number of dots or a further rise while in the other a definite decrease was seen. The former pattern may be related to a potential for malignant evolution of the lesion. NORs should be counted in all cases of CIN and condylomata to treat more aggressively those lesions which present the patterns of a progressive rise of NORs from basal to intermediate cells.     

Changes in regional cerebral blood flow during brain maturation in children and adolescents.

Regional cerebral blood flow (rCBF) was studied by SPECT using 133Xe in 42 children, aged 2 days to 19 years, considered as neurologically normal. rCBF was measured on cortical regions and on the cerebellum and thalamus. Curves for reference values and standard deviation were defined for each region. At birth, cortical rCBFs were lower than those for adults; after birth they increased until 5 or 6 yr of age to values 50%-85% higher than those for adults and thereafter decreased, reaching adult levels between 15 and 19 yr. Neonatal values of rCBF on cerebellum and thalamus were slightly higher than adult level, but not significantly; after age 1, they followed the common pattern for cortical curves. When rCBFs were expressed in percent global CBF, they were lower at birth than adult levels in the cortex, then increased and reached a plateau corresponding to the adult value before the second year of age. The time needed to reach normal adult values differed for each cortical region. The shortest time was found on the primary cortex and the longest on the associative cortex. Cognitive development of the child seems to be related to changes in blood flow of the corresponding brain regions.     

Regimen-related toxicity in patients undergoing BMT with total body irradiation using a sweeping beam technique.

In our institution, total body irradiation (TBI) is performed by means of a sweeping beam technique. Toxicity of the procedure was evaluated according to the only grading system designed for high dose chemoradiotherapy. One hundred patients undergoing TBI and conditioned with a standard cyclophosphamide regimen before BMT were evaluated. Regimen-related toxicity was graded according to the Seattle transplantation toxicity system, from 0 to IV (fatal toxicity), in eight organs on days 0, 7, 14, 28 and 100 for lungs. Eighteen patients did not develop any toxicity. Grades III, IV toxicities were uncommon (9%) and were not influenced by dose of TBI, GVHD prophylaxis, disease status and allogenicity although no grade IV toxicity was observed among autologous marrow recipients. However, grade II toxicity was more common in patients receiving allogeneic vs autologous grafts (p < 0.01) because of increased mucosal (p = 0.002) and liver (p = 0.12) toxicities. Renal toxicity was unevaluable. When cumulative toxicity was equal or higher than 4, day 100 survival was worse (p = 0.05). These data confirm the safety of our TBI procedure and the validity of the grading system except for renal toxicity. We suggest that a more aggressive conditioning regimen may be tolerated by patients receiving autologous grafts.     

Brain macrophages synthesize interleukin-1 and interleukin-1 mRNAs in vitro

Amoeboid microglial cells (brain macrophages) were purified from early post-natal mouse brain cultures. The percentage of cells stained with an anti-Mac-1 antibody was greater than 95%. Stimulation of these brain macrophages by lipopolysaccharides induced the synthesis of interleukin-1 (IL-1), which, in part, remained associated with the cell surface and, in part, was released into the culture medium. In contrast, pure primary astrocyte cultures and cell lines of transformed or immortalised astrocytes did not synthesise significant amounts of IL-1, demonstrating that amoeboid microglia and not astrocytes synthesise IL-1 in vitro. These physiological data were confirmed by RNA hybridisation studies showing that, on LPS treatment, brain macrophages synthesise significant amounts of IL-1 alpha and IL-1 beta mRNAs.     

Hereditary colorectal cancer: observations of a family study]

Described in Switzerland in the early '60, the major features of hereditary non-polyposis colon cancer syndrome (HNPCCS) were established 20 years ago by H. T. Lynch. HNPCCS accounts for at least 60% of the colon cancer etiology. Cancer family syndrome is defined by the presence of extracolonic primary tumors in addition to colon cancer. Both syndromes are transmitted by an autosomic dominant pattern. None of the known biomarkers are specific and/or sensitive enough to rely on their predictive values of patient's risks. A typical Swiss family was investigated on the basis of the cancer-prone family history. 21% of the family members observed over 5 generations presented one or more (30% of the cases) colo-rectal neoplasms at the age of 50. 55% of the tumors were right sided. Histologically, half of the tumors were mucinous. 30% of metachronous cancer appeared within 10 years. Polyps (1-3) and flat adenomas were associated to the lesion in 57%. Extra-colonic tumors appeared in 18% of family members and in half of the colon cancer patients. The sites of these tumors were the urinary tract, ovary, small bowel, breast and stomach. Two fibroblast strains of affected individuals were established. No increased tetraploidy was noted. Preliminary results suggest that this two strains are rather sensitive to ionising radiation. Often neglected, family history of colon cancer remains the major diagnostic and decision-making tool of a such syndrome. It will necessitate special treatment of affected subjects and early screening of the relatives.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cystic meningiomas. Report of seven cases

Seven patients with cystic meningioma are reported. The computerized tomography appearance of these meningiomas may mimic that of a glial or metastatic tumor with cystic or necrotic changes, and lead to an incorrect presumptive diagnosis. Radiological evaluation and recognition are important for the surgical removal of these potentially curable neoplasms.     

Hypoxemia after heart surgery. An exception or a normal development?]

The course of respiratory exchange through arterial blood gas analysis after coronary bypass-grafting and valvular replacement has been investigated in a cohort of 62 patients. Arterial blood gases were measured at baseline (the day before surgery), and then 1, 2, 3 and 9 days after surgery; in a subset of 18 patients, randomly selected from the same population, pulmonary function tests were also performed at baseline and repeated on day 9. Arterial blood gases showed a remarkable prevalence of hypoxaemia (as defined as arterial PaO2 less than 60 mmHg): 31% on the first, 50% on the second, and 40% on the third post-operative day; anemia and desaturated mixed venous blood were also prominent findings during the first two days. Arterial PO2 resulted higher afterward, although its mean value then was significantly lower than baseline (81.5 +/- 8.8 vs 93.1 +/- 9 mmHg, p less than 0.005). Pulmonary function tests evidenced widespread restrictive changes, with alterated thoraco-pulmonary mechanics (loss of more than 40% of vital capacity and one second forced expiratory flow) and parenchimal lung damage (residual volume and CO diffusion capacity decrease). Some differences in PaO2 course between coronary patients and valvular patients have been releaved; the mean basal PaO2 value of valvular was significantly lower then the other one (86.7 +/- 10.8 vs 94.7 +/- 10.9, p less than 0.05).     

Hypercalcaemia and pancreatic ultrastructure in cats.

OBJECTIVE--To study the effects of local and systemic infusions of calcium on the ultrastructure of the pancreas in cats. DESIGN--Controlled study. INTERVENTIONS--Three groups of four cats each had local infusions (into the splenic artery) of calcium gluconate 0.6 mmol/kg.hour or potassium chloride 1.1 mmol/kg.hour, or sodium chloride 0.9%, for three hours. Two groups of eight cats each had systemic infusions (into the jugular vein) of either calcium gluconate 0.6 mmol/kg.hour or sodium chloride 0.9%, for twelve hours. In the group that was given calcium, the infusion rate was reduced after three hours to 0.3 mmol/kg.hour to maintain the hypercalcaemic state for a further nine hours. RESULTS--Local infusion of calcium caused destruction of acinar cells with hydropic degeneration of nuclei, discharge of cell organelles into the interstitial spaces, and extravasation of red blood cells but no apparent damage to the capillaries. There were no ultrastructural changes of any importance in the groups that received potassium or sodium chloride. Systemic infusion of calcium resulted in a 1.8 fold increase in the ionised calcium concentration in the serum, progressive signs of overstimulation of the Golgi apparatus with hypertrophy, fusion of condensing vacuoles, and disruption of the acinar cell polarization. This was followed by clumping of nuclear chromatin and destruction of acinar cells. CONCLUSION--Acute pancreatitis in cats can result from stimulation and destruction of acinar cells by hypercalcaemia.