Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia

Summary Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg · kg^-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg · kg^-1 i.p., followed by an i.v. infusion of 225 g · kg^-1 · min^-1 for 6 h), with dizocilpine 0.33 mg · kg^-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40116 [D-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid] 10 mg · kg^-1 given i.p.. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist. We conclude that neuronal damage continues to develop in the striatum and in cortical brain regions in the posthypoglycemic period and that both NMDA- and AMPA-receptors contribute to this process, possibly by a change in the cellular response to both AMPA- and NMDA-receptor stimulation.     

Efficiency of adjuvant immunochemotherapy following curative resection in patients with locally advanced gastric cancer

Background Despite curative resection, 50%–90% of gastric cancer patients die of disease relapse. Although some clinical trials have indicated that chemotherapy and immunochemotherapy may be effective modalities, more recent studies have not been able to define the standard treatment for advanced gastric cancer. The present study evaluated the effect of adjuvant immunochemotherapy with the use of BCG (bacille Calmette-Guérin) and FAM (5-fluorouracil, adriamycin, mitomycin C) chemotherapy on the survival of patients with locally advanced resectable gastric cancer.Methods A total of 156 patients with stage III or IV gastric cancer who had undergone curative resection were randomly assigned to three treatment groups: BCG + FAM (immunochemotherapy), FAM (chemotherapy), and control (surgery only). Treatment was continued for 2 years or until death. Further postsurgical follow up was carried on for up to 10 years.Results Overall 10-year survival was 47.1% for the immunochemotherapy group (P < 0.037 vs FAM and P < 0.0006 vs control), 30% for the chemotherapy group (vs control, NS), and 15.2% for the control group. In patients with pT2/T3 primary tumors, 10-year survival was 55.3% for BCG + FAM vs 28.2% for FAM (P < 0.01) and 14.6% for the control group (P < 0.00018). BCG + FAM signifi-cantly improved the survival of patients with intestinal-type but not diffuse-type cancer. Immunochemotherapy was well tolerated.Conclusion This study, based on a limited number of patients, indicates that adjuvant immunochemotherapy (BCG + FAM) may prolong the survival of gastric cancer patients after curative gastrectomy; in particular, in patients with pT2/T3 tumors and intestinal-type primary tumors. There was no survival benefit from FAM adjuvant chemotherapy.     

Jansen type of spondylometaphyseal dysplasia

Metaphyseal dysplasia, type Jansen (JMD), is a rare skeletal dysplasia with characteristic radiographic abnormalities. Of the various types of metaphyseal dysplasia, JMD shows the most severe alteration in metaphyseal architecture. All of the long tubular bones, including those of the hands and feet, show metaphyseal irregularity with a fragmented appearance and slight widening. The adjacent physes are abnormally widened, while the epiphyses tend to be slightly enlarged, rounded but otherwise normal. The spine in infancy and childhood usually appears normal. This report describes a young girl with metaphyseal changes typical of JMD except for the hands and feet, which appeared normal. She also showed very unusual abnormalities of the spine. This appears, therefore, to represent a unique osteochondrodysplasia for which we propose the term spondylometaphyseal dysplasia, type Jansen. Received: 4 April 1999 Revision requested: 6 April 1999 Revision received: 29 November 1999 Accepted: 1 December 1999     

Accumulation of Cadmium in and Its Effect on the Midgut Gland of Terrestrial Snail Helix pomatia L. from Urban Areas in Poland

The objectives of this study were (1) to determine cadmium (Cd) accumulation in the midgut gland of a land snail Helix pomatia L. inhabiting residential areas of the 14 largest cities in Poland, and (2) to examine whether the accumulated Cd exerted any toxic effects. The average accumulation of Cd in the midgut gland of snails, weighing 16–18 g, ranged from 7.00 to 87.3 µg/g dry weight (0.06–0.77 µmol/g) and differed significantly among animals from the various urban areas. This difference in Cd accumulation was not related to city population, but was associated with the topsoil Cd (R² = 0.868, p < 0.0001). The tissue Cd was not found to produce toxicity (histopathology, programmed cell death, lipofuscin formation or lipid peroxidation), probably due to the induction of sufficiently high quantities of metallothionein and glutathione, well-known protective molecules.     

Renal artery aneurysm as a cause of resistant hypertension in a young female--case report

A case of a 19-year-old woman suffering for 5 years from pharmacologically resistant hypertension, is presented. During invasive diagnostic procedures left renal artery aneurysm was found. Surgical resection with vessel prosthesis implantation was successfully performed. Examination carried-out 6 months later revealed good response to pharmacological treatment with normal levels of blood pressure.     

Carcinoma, a fibrolamellar variant--immunohistochemical analysis of 4 cases

BACKGROUND/AIMS: To analyze, by means of immunocytochemistry, the cases of fibrolamellar variant of hepatocellular carcinoma (FLC), diagnosed in our Department. METHODOLOGY: The material comprised 4 FLC cases of tumors resected surgically. Besides the routine morphological assessment, we used a panel of immunohistochemical stainings including: hepatocellular cytokeratin, CK7, CK19, Ki67, PCNA, chromogranin A, synaptophysin, NSE, insulin, calcitonin, parathormon, CD34, EBV (LMP), Bcl2, cyclin D1. RESULTS: In 3 out of 4 cases, we observed co-expression of CK7 with hepatocellular CK. In addition, there was positive staining with some endocrine markers in the majority of patients. In one case, we found strong cyclin D1 immunoreactivity which correlated with EBV (LMP) immunoreactivity, in the same patient. The score of PCNA positivity varied between 15 and 90%. In all cases Ki67 was negative. CONCLUSIONS: The incidence of FLC, among all hepatocellular carcinomas diagnosed in our Department was 5.1%. In accordance with other reports, all our FLC cases were young patients without underlying liver disease. We were unable to find a correlation between FLC cellular immunophenotype, and histological and clinical markers of malignancy. In addition, it appears that PCNA is a better marker of cell-proliferation in FLC than Ki67. The significance of EBV infection in FLC requires further study.     

Assessment of flow changes in the circle of Willis after stenting for severe internal carotid artery stenosis.

PURPOSE: To assess flow velocities in the cerebral arteries after carotid artery stenting (CAS) in patients with unilateral versus bilateral lesions and analyze velocities in patients with neurological complications after CAS. METHODS: Ninety-two patients (68 men; mean age 63.2 +/- 8.4 years, range 44-82) with internal carotid artery (ICA) stenoses were divided according to unilateral (group I, n = 72) or bilateral (group II, n = 20) disease. Fifty age- and gender-matched patients without lesions in the extra- or intracranial arteries served as a control group. Transcranial color-coded Doppler ultrasound was performed prior to and within 24 hours after CAS in the test groups; systolic velocities were assessed ipsilateral (i) and contralateral (c) to the CAS site in the middle cerebral artery (MCA) and anterior cerebral artery (ACA). RESULTS: Collateral flow via the anterior communicating artery (ACoA) was found in all group-II patients and 90% of group-I patients. After CAS, collateral flow through the ACoA ceased, and the velocity increased by 26% in the iMCA in group I compared to controls (p < 0.001). In group II, iMCA flow increased by 30% (p < 0.001) and flow via the ACoA (p < 0.001) increased, resulting in normalization of cMCA velocities (p = 0.928). In 89 (96.7%) subjects, CAS was uncomplicated. Hyperperfusion syndrome occurred in 2 (2.2%) patients, both with bilateral ICA stenoses; 1 (1.1%) transient ischemic attack was seen in a patient with unilateral disease. In the patients with hyperperfusion syndrome, the MCA velocities were 2.7- and 7.4-fold higher, respectively, versus before CAS and 2-fold higher than in controls. CONCLUSION: Uncomplicated CAS results in an iMCA velocity increase >25% compared to controls. MCA velocities in hyperperfusion syndrome were greatly increased versus before CAS and in controls.