Effects of chronic administration of alcohol on neural mechanisms of arterial blood pressure regulation]

Metaphor comprehension was studied in schizophrenics as compared to psychiatric and nonpsychiatric controls. Subjects were asked in a two-condition forced-choice response task to detect the metaphor similar or contrary to a proverb with an abstract meaning. Schizophrenic patients were impaired in both conditions. However, the paranoid patients' performances did not differ from psychiatric and nonpsychiatric controls. These results are consistent with the hypothesis that the ability of metaphorizing is preserved in some schizophrenic patients.     

A review of orthodontic appliance problems in general dental practice

Data from the literature, as well as our previous work, indicate a protective effect of superoxide dismutase (SOD) in topical application against UV-induced cutaneous damage. In the present article we show that pre-treatment of the skin with SOD protects against PUVA-induced inflammatory reactions not only in murine, but also in human skin. Using fluorescently labelled Cu,Zn SOD, epifluorescence microscopy and digital image processing, we demonstrate that the FITC fluorescence localizes in the stratum corneum and upper granulosa, as well as in the epidermal cell layer surrounding the lumina of the hair follicles. These findings were similar for murine and human skin. Since autofluorescence was eliminated by a special filter, it can be ascertained that the fluorescence observed in the tissues was due to FITC-labelled SOD.     

Hair analysis does not support hypothesized arsenic and chromium exposure from drinking water in Woburn, Massachusetts

We hypothesized that residents of Woburn, Massachusetts, had been exposed to as much as 70 microg/l of arsenic (As) and 240 microg/l of chromium (Cr) in drinking water from municipal supply wells G and H. To test this hypothesis, we measured the concentrations of As and Cr in 82 hair samples donated by 56 Woburn residents. Thirty-six samples were cut between 1964 and 1979, the period during which wells G and H were in operation. The remainder were cut either before 1964 (1938-1963; n = 26) or after 1979 (1982-1994; n = 20). Washed hair samples were analyzed by instrumental neutron activation. Exposure to the well water--measured as access--was estimated using well pumping records and a model of the Woburn water distribution system. Our results show that access to wells G and H water was not significantly correlated (95% confidence interval) with As and Cr concentrations measured in the hair of Woburn residents, but As concentrations have declined significantly over the last half century. Linear regression of As concentrations (micrograms per gram) upon year of hair cut and access to wells G and H water yielded a standard coefficient for year of -0. 0074 +/- 0.0017 (standard error; p = 2.5 -multiple- 10(-5)) and -0.12 +/- 0.10 (p = 0.22) for access. The r2 value for the model was 0.19. The geometric mean concentrations (geometric standard deviation) of As and Cr in the hair of residents who had access (i.e., relative access estimate >0) to wells G and H water (n = 27) were 0.14 (2.6) and 2.29 (1.8) microg/g, respectively; the geometric mean concentrations of As and Cr in all of the hair samples from residents who did not have access (1938-1994; n = 55) were 0.13 (3.0) and 2.19 (2.0) microg/g, respectively.     

Basic fibroblast growth factor augments podocyte injury and induces glomerulosclerosis in rats with experimental membranous nephropathy

Podocyte injury is believed to contribute to glomerulosclerosis in membranous nephropathy. To identify the factors involved, we investigated the effects of basic fibroblast growth factor (bFGF), a cytokine produced by podocytes, on rats with membranous nephropathy (passive Heymann nephritis [PHN]). All rats received a daily i.v. bolus of 10 microg bFGF or vehicle from days 3-8 after PHN induction. In proteinuric PHN rats on day 8, bFGF injections further increased proteinuria. Podocytes of bFGF-injected PHN rats showed dramatic increases in mitoses, pseudocyst formation, foot process retraction, focal detachment from the glomerular basement membrane, and desmin expression. bFGF injections in PHN rats did not alter antibody or complement deposition or glomerular leukocyte influx. bFGF-injected PHN rats developed increased glomerulosclerosis when compared with control PHN rats. Also, bFGF induced proteinuria and podocyte damage in rats injected with 10% of the regular PHN-serum dose. None of these changes occurred in bFGF-injected normal rats, complement-depleted PHN rats or rats injected with 5% of the regular PHN serum dose. These divergent bFGF effects were explained in part by upregulated glomerular bFGF receptor expression, induced by PHN serum. Thus, bFGF can augment podocyte damage, resulting in increased glomerular protein permeability and accelerated glomerulosclerosis. This bFGF action is confined to previously injured podocytes. Release of bFGF from glomerular sources (including podocytes themselves) during injury may represent an important mechanism by which podocyte damage is enhanced or becomes self sustained.     

Reproductive and thyroid hormone levels in rats following 90-day dietary exposure to PCB 28 (2,4,4''-trichlorobiphenyl) or PCB 77 (3,3''4,4''-tetrachlorobiphenyl)

It has been reported that suramin, an anthelminthic, trypanocidal agent and an inhibitor of P2 receptors, may antagonise N-methyl-D-aspartate (NMDA) subtype of the excitatory amino acid receptors. Both NMDA receptors and P2X subclass of P2 receptors are ligand-gated Ca2+-selective channels and, since the increased influx of Ca2+ into neurons has been linked to neurotoxicity, simultaneous inhibition of P2X and NMDA receptors in vivo by suramin could represent an effective neuroprotective treatment. We have found that suramin inhibited the binding of [3H]CGP 39653 to NMDA receptor binding sites in vitro and reduced the frequency of NMDA channel openings in patch-clamp studies. Suramin (1 mM) had no effect on [3H]kainate binding in vitro. In vivo, intracerebroventricular (I.C.V.) injections of suramin (70 nmol/brain) antagonised convulsive effects of the NMDA agonist (RS)-(tetrazol-5-yl)-glycine (TZG, LY 285265). Suramin, however, did not prevent neurotoxic lesions in the hippocampus caused by I.C.V. administration of TZG. Increasing the dose of suramin resulted in death from severe respiratory depression.     

Characterization of protein kinase A and protein kinase C phosphorylation of the N-methyl-D-aspartate receptor NR1 subunit using phosphorylation site-specific antibodies

Modulation of N-methyl-D-aspartate receptors in the brain by protein phosphorylation may play a central role in the regulation of synaptic plasticity. To examine the phosphorylation of the NR1 subunit of N-methyl-D-aspartate receptors in situ, we have generated several polyclonal antibodies that recognize the NR1 subunit only when specific serine residues are phosphorylated. Using these antibodies, we demonstrate that protein kinase C (PKC) phosphorylates serine residues 890 and 896 and cAMP-dependent protein kinase (PKA) phosphorylates serine residue 897 of the NR1 subunit. Activation of PKC and PKA together lead to the simultaneous phosphorylation of neighboring serine residues 896 and 897. Phosphorylation of serine 890 by PKC results in the dispersion of surface-associated clusters of the NR1 subunit expressed in fibroblasts, while phosphorylation of serine 896 and 897 has no effect on the subcellular distribution of NR1. The PKC-induced redistribution of the NR1 subunit in cells occurs within minutes of serine 890 phosphorylation and reverses upon dephosphorylation. These results demonstrate that PKA and PKC phosphorylate distinct residues within a small region of the NR1 subunit and differentially affect the subcellular distribution of the NR1 subunit.     

Extensively coated femoral components in young patients

A review of 174 hips in 154 patients younger than 50 years of age who underwent primary total hip arthroplasty with a cementless acetabular component and an extensively coated femoral component done by one surgeon was performed to determine whether this method of fixation improves the results of previously reported comparable series using different methods of fixation. The average age was 37.6 years. The average followup was 8.3 years (range, 2-13 years). Eighty-eight hips had at least 10 years followup. Sixteen (9%) hips had severe stress shielding. There were 13 (7.5%) acetabular failures. Of 144 porous coated cups, three were revised for wear and one for dislocation. Another was revised 11 years postoperatively for late loosening secondary to catastrophic acetabular lysis. Excluding the bipolar and threaded components (30 hips), five (3.4%) porous coated cups were revised for failure. Of the 174 fully coated stems, 99.4% had stable fixation, 167 (96%) were ingrown, six (3.4%) had stable fibrous fixation, and one (0.6%) was unstable. Two (1.1%) femoral stems were revised. The total rate of osteolysis was 4%. Cementless extensively porous coated stems and porous coated acetabuli give excellent lasting results in young patients.     

Pretreatment evaluation of chronic hepatitis C: risks, benefits, and costs

CONTEXT: Chronic hepatitis C (CHC) infection affects nearly 4 million people in the United States. Treatment with interferon alfa-2b has been limited by its cost and low likelihood of long-term response. OBJECTIVE: To examine the cost-effectiveness of alternative pretreatment management strategies for patients with CHC. DESIGN: Decision and cost-effectiveness analysis using a Markov model to examine prevalence of genotypes, viral load, and histological characteristics in relation to the sustained response rate with treatment. Data were based on a previously published decision model and a MEDLINE literature search for hepatitis C, biopsy, and liver from 1966 to 1996. PATIENTS: A hypothetical population of patients with CHC infection and elevated serum alanine aminotransferase level. INTERVENTIONS: Combinations of liver biopsy, genotyping, and quantitative viral load determination prior to a single 6-month course of interferon alfa-2b; empirical interferon treatment; and conservative management. MAIN OUTCOME MEASURES: Proportion of sustained responders, lifetime costs, life expectancy, and quality-adjusted life expectancy. RESULTS: Strategies involving hepatitis C virus (HCV) RNA testing had marginal cost-effectiveness ratios up to $4400 per discounted quality-adjusted life-year gained but would miss up to 36% of sustained responders. Empirical interferon treatment had a marginal cost-effectiveness ratio of $12400 per discounted quality-adjusted life-year gained and reached all potential sustained responders. Strategies involving liver biopsy were more expensive and would miss 6% of sustained responders and yield slightly lower life expectancies. CONCLUSIONS: Routine liver biopsy before treatment with interferon increases the cost of managing patients with CHC without improving health outcomes. Using quantitative HCV RNA testing to guide therapy misses some potential sustained responders. Empirical interferon treatment has a marginal cost-effectiveness ratio within the bounds of other commonly accepted therapies and misses none of the sustained responders.