Limited value of testing for intrinsic factor antibodies with negative gastric parietal cell antibodies in pernicious anaemia.

BACKGROUND: The appropriate testing strategy for diagnosing pernicious anaemia using gastric parietal cell (GPC) and/or intrinsic factor antibodies (IFA) is controversial. Intrinsic factor antibodies are found in only about 70% of cases. Indirect immunofluorescence screening for gastric parietal cell antibodies is more sensitive, labour intensive, and less specific. METHODS: The frequency of antibody positivity (IFA and/or GPC) was retrospectively examined in patients tested for both autoantibodies over a three-year period. It was investigated whether B12 levels were related to antibody status. These findings were validated in a prospective study of IFA in 91 GPC negative patients with low B12 levels. RESULTS: Of 847 samples identified in the retrospective study, 4 (0.47%) were positive for only intrinsic factor antibodies, 731 (86.3%) positive for GPC alone, and 112 (13.2%) for both. Student t test on log-transformed data showed B12 levels had no bearing on autoantibody status. 91 consecutive patients with low B12 levels were tested for both autoantibodies; all were negative for gastric parietal cell antibodies. Only one sample was positive for intrinsic factor antibody using the porcine intrinsic factor assay, but was negative by a human recombinant intrinsic factor-based ELISA. CONCLUSIONS: This study provides evidence that testing for gastric parietal cell antibodies is an appropriate screening test for pernicious anaemia, with intrinsic factor antibodies reserved for confirmatory testing or in patients with other autoantibodies that mask the GPC pattern; B12 levels are not related to autoantibody status.

Inducible nitric oxide synthase is involved in the mechanisms of cocaine enhanced neuronal apoptosis induced by HIV-1 gp120 in the neocortex of rat.

Cocaine, often abused by human immunodeficiency virus (HIV) infected patients, has been suggested to worsen the HIV associated dementia via unknown mechanisms. Here we report that subchronic treatment with a dose of cocaine (30 mg/kg i.p.), unable per se to cause neuronal death, increases the number of apoptotic cells typically observed in the neocortex of rats treated with HIV-1 gp120 (100 ng given i.c.v.). A pre-treatment with MK801 (0.3 mg/kg i.p.), a NMDA receptor antagonist, L-NAME (10 mg/kg i.p.) and 7-nitroindazole (50 mg/kg i.p.), two specific inhibitors of NOS, or with 1400 W (1 mg/kg s.c.), a selective inhibitor of inducible NOS (iNOS), minimized neurotoxicity by combined administration of cocaine and gp120 thus implicating iNOS. This conclusion is supported by the evidence that cocaine increases brain neocortical citrulline, the co-product of NO synthesis.

Intrahippocampal injection of paraquat produces apoptotic cell death which is prevented by the lazaroid U74389G, in rats.

Injection of paraquat, a redox-cycling compound, into the rat hippocampus produces limbic seizures and hippocampal damage. Here we report that a proportion of the neuronal cell death caused by the herbicide occurs via an apoptotic mechanism which appears to be mediated by oxygen free radicals. Adult male Wistar rats (n=12) received a single dose of paraquat (25 nmol/0.5 microl; 0.5 microl/min rate) and were sacrificed 24 h later. Paraquat caused DNA fragmentation, nuclear chromatin marginalization and compaction in all hippocampal subsectors, 24 h after its injection, as revealed by both the TUNEL procedure and hematoxylin eosin staining of coronal brain tissue sections. Pre-treatment with the free radical scavenger lazaroid U74389G (30 mg/kg given i.p. 30 min beforehand) significantly reduced paraquat-induced apoptosis, but did not protect against non apoptotic neuronal cell loss caused by the herbicide.

Sound-evoked electrocortical desynchronization is inhibited by N omega-nitro-L-arginine methyl ester microinfused into the inferior colliculi in rats.

In previous experiments we have shown that systemic or intracerebroventricular administration of N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthase, is able to significantly reduce sound-evoked electrocortical (ECoG) desynchronization in rats. The present experiments were aimed at identifying the site(s) of the brain through which these effects are mediated. L-NAME (200 and 300 nmol), oxyhaemoglobin (200 and 300 nmol), a NO-trapping agent, and methylene blue (100 and 150 nmol), an inhibitor of guanylate cyclase and NO synthase, given bilaterally into the inferior colliculi, but not in other relay stations of the acoustic pathway, prevented the reduction in ECoG amplitude induced by sound stimulation in rats. Significant reduction of sound-evoked ECoG desynchronization has also been observed in rats receiving injection of CGP37849 (125 and 500 pmol) and LY274614 (125 pmol), two competitive N-methyl-D-aspartate receptor antagonists into the inferior colliculi. The present results show that the inferior colliculus represents the main site where sound-evoked ECoG desynchronization is prevented by L-NAME and provide further support for the hypothesis that NO may play a role at this level in the control of the measured response.

Inhibition by N omega-nitro-L-arginine methyl ester of the electrocortical arousal response in rats.

In rats chronically implanted with cannulae into one lateral cerebral ventricle and recording electrodes onto the fronto-parietal cortex, the effects of systemic or intraventricular administration of the nitric oxide (NO) synthesis inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME), on electrocortical (ECoG) arousal response evoked by sound stimulation were studied. In control animals, a single acoustic stimulation (80 dB for 15 s) produced a significant decrease in ECoG total voltage power lasting approximately 25 s. No tolerance developed after repeating the same sound stimulation at 15, 30, 60 min and 24 h intervals. Under these experimental conditions, pretreatment with L-NAME, given systemically (10 mg kg-1, i.p.) or intracerebroventricularly (300 micrograms), significantly reduced the sound-evoked arousal response 1 h and 15 min later, respectively. In conclusion, the present data are in favour of a physiological role of NO in the control of arousal mechanisms.

[Role of sophisticated radiological technics in the diagnosis of lacrimal fistulas]. / Il ruolo delle techniche radiologiche sofisticate nella diagnostica delle fistole lacrimali.

Lacrimal fistulae are rare and not well known by radiologists. Four cases are illustrated, two congenital (a skin-canaliculous and a canaliculous-palpebral fistula) and two acquired (a rare case of sac-orbital fistula and a canaliculous-palpebral fistula arisen during dacryography). Fistulae are to be distinguished from pedunculated lacrimal diverticulous of which an interesting and rare case is presented. After a careful examination of the pathogenesis and symptomatology of lacrimal fistulae the authors agree that only macrodacryography carried out by means of sophisticated techniques (seriography, magnification, subtraction) enables a precise demonstration of the originating point, of the course and outlet (cutaneous and internal) and provides therefore indispensable data for surgery.