Radiologic appearance of non-traumatic intracranial hemorrhage]

The diagnosis of nontraumatic intracranial hemorrhage is currently made by computed tomography and is rarely problematic. The causes of bleeding are very numerous. It is important to determine the cause of the hemorrhage promptly, because there may be a recurrence of bleeding. Guidelines for radiologists are proposed and discussed here.     

Agreement between staff and service users concerning the clientele's mental health needs: a Quebec study.

OBJECTIVES: This article examines the differences found between clientele with severe mental health problems and their key health workers in terms of assessing service users' needs in 6 Quebec service areas. METHOD: We questioned 165 pairs of users and staff, using the Camberwell Assessment of Needs questionnaire. The profile of serious and overall problems encountered by clientele from each of the sites was compared. RESULTS: The sites with the greatest degree of user-staff agreement in identifying problems were also the ones where users considered that local services best met their needs. CONCLUSIONS: The study demonstrated that, in needs assessment, major differences exist between the perceptions of users and their key workers in the various sites. These differences can be explained in part by users' individual characteristics, by types of needs, by local particularities, and by service use.     

An HLA-DRB α-helix motif shared by DR11 and DR8 alleles is implicated in the pluriallelic restriction of peptide-specific T-cell lines

The T-cell recognition of HLA-DR-peptide complexes is generally restricted by the polymorphism of the DRB molecules but pluriallelic restriction has been described. The molecular basis of restriction and promiscuity of such peptide-specific responses is poorly understood. We isolated a panel of T-cell lines specific for the tetanus toxin peptide p2 (TT830-843) exhibiting pluriallelic restriction by DR11 and DR8 alleles. Fine restriction specificity of the T-cell lines was examined in functional assays against DR oligotyped APCs expressing different variants of DR11 and DR8 alleles. Our results show that (a) polymorphisms between serologically related alleles are relevant in terms of restriction of the peptide-specific T-cell response; in some instances, a single amino acid substitution can determine the restriction of a T-cell line; (b) different patterns of restriction are not the result of specific differences in DR-p2 binding as p2 peptide binds to all DR11 and DR8 alleles tested (DRB1^* 1101, -1102, -1103, -1104, 110X, -0801, -0802, -0803, and -0806); and (c) pluriallelic restriction of the peptide-specific T-cell responses correlates with the presence of a DRB1 α-helix motif (67-71-86) shared by some DR11 and DR8 alleles. Possible implications of pluriallelic restriction of peptide-specific T-cell response in autoimmune disorders associated with DR11 and DR8 are discussed.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Bone mass and bone cellular variations after five months of physical training in rhesus monkeys: Histomorphometric study

Summary Five Rhesus Monkeys (Maccaca mulatta), a suitable nonhuman model, performed 5 months of ropeclimbing exercise. Duration of the training sessions was progressively increased to reach 1 hour/day after 1 month of training and was maintained until the end of the experiment. Bone mass parameters, bone resorption, and bone formation activity were measured by histomorphometric analysis on iliac crest bone biopsies before and after the experiment. Mineral apposition rate was measured in cortices and trabecular bone after double calcein labeling. Five months of rope-climbing exercise had determined a significant decrease of bone volume with a slight decrease of the number and thickness of trabeculae. This might induce an alteration of biomechanical properties of bone. These architectural modifications were associated with a nonsignificant decrease of bone resorption activity. But the main effect of training was an important decrease of bone formation activity without change of the mineral apposition rate. Endurance exercise at low intensity has determined a decreased bone turnover with osteoblastic depression. This animal experiment points out that exercise modalities might be important in the bone response to training and should be carefully defined for preventive use in humans.     

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Thymidylate synthase activity,folates, and glutathione system in head and neck carcinoma and adjacent tissues

Background. Head and neck squamous cell carcinomas (HNSCC) present variable aggressiveness and chemosensitivity. Because the glutathione (GSH) system and thymidylate synthase (TS) are involved in the resistance to the main drugs used in HNSCC (cisplatin and 5-FU), we studied these systems in tumors and normal mucosae. Methods. Tumor samples and normal adjacent mucosae were collected from 37 untreated HNSCC patients. GSH and glutathione S-transferase (GST) activity were assayed by spectrophotometry, whereas TS activity and folates were determined by radioassays. Results. Mean GSH levels were higher in tumors (15.2 ± 8.2 nmol/mg protein) than in mucosae (8.3 ± 4.1 nmol/mg protein) (p = 0.005, paired t test). GST activity was also higher in tumors (394 ± 194 nmol/min/mg protein) than in mucosae (261 ± 132 nmol/min/mg protein) (p = 0.0003). TS activity was markedly higher in tumors (9.2 ± 21.5 pmol/min/mg protein) compared to that of mucosae (0.9 ± 1.2 pmol/min/mg protein) (p = 0.0001). Folate levels in tumors and mucosae were similar (1.2 ± 1.1 and 0.8 ± 0.9 pmol/mg protein, respectively; p = 0.1, NS). In relation to clinical stage and tumor size, a statistical difference was found in GSH and GST values between tumors and mucosae for stage IV and T3/T4. The increase in tumor TS compared to that of mucosae was significant for all clinical stages, tumor sizes, and nodal involvement. Conclusions. These data enhance our understanding of the enzymatic systems involved in cisplatin and 5-fluorouracil (5-FU) resistance in HNSCC and normal mucosae and may help to elucidate tumor behavior and interpatient differences in drug sensitivity. © 1994 John Wiley & Sons, Inc.