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Biomedical subjects

M Hitchcock

Publications and source records attributed to M Hitchcock.

At least 19 recordsLinked to original sources
PubMed2006

Long-term effects of antidepressants on cognition in patients with Alzheimer's disease.

PURPOSE: Approximately 25-40% of patients with Alzheimer's disease (AD) may develop depression. Antidepressants are typically used to treat depression in this population. However, their effect on cognition has been rarely studied and the results are conflicting. In addition, the long-term effects of antidepressants on cognition have not been studied. Therefore, the objective of the study was to evaluate the effects on cognition in patients with AD treated with antidepressants for at least 9 months. METHODS: Data on antidepressant use over a minimum period of 9 months were retrospectively collected for patients with AD receiving cholinesterase inhibitors. Data on cognition were analyzed to compare those taking antidepressant therapy and those not receiving antidepressants. RESULTS: Ninety-nine of 210 patients met our inclusion criteria. Fifty-eight patients were prescribed an antidepressant (e.g. selective serotonin reuptake inhibitors (SSRIs), newer generation antidepressants). Sertraline (mean dose: 82 mg/day) and citalopram (mean dose: 35 mg/day) were the most commonly prescribed antidepressants. The baseline mean Mini Mental State Examination (MMSE) score was 16.32 with an average annual rate of cognitive decline of 2.55 for patients receiving antidepressants compared with 16.59 (P = NS) and 2.27 (P = NS) for those not taking antidepressants. CONCLUSIONS: Our small sample data indicate no differences in baseline MMSE scores and cognitive decline between the two groups, suggesting antidepressants did not contribute significantly to cognitive decline over a utilization period of at least 9 months.

Aged↗
PubMed1996

Dermatofibrosarcoma protuberans treated with Mohs surgery. A case with CD34 immunostaining variability.

BACKGROUND: Immunohistochemical stains for CD34 antigen can help in differentiating dermatofibrosarcoma protuberans (DFSP) from other fibrohistiocytic tumors and in demarcating its surgical margins during Mohs surgery. However, variable expression of CD34 antigen in nodular areas can sometimes result in negative staining of tissue sections creating diagnostic and therapeutic dilemmas. OBJECTIVE: To show the variable expression of CD34 antigen in a DFSP tumor. METHODS: Case presentation of DFSP with immunohistochemical staining using the ABC peroxidase macromolecular complex. RESULTS: Microscopic examination of paraffin-embedded sections showed CD34-negative DFSP tumor cells with positive staining of endothelial cells. On frozen sections at the time of surgery the tumor cells stained strongly positive for CD34. CONCLUSION: This case demonstrates the variable expression of CD34 antigen by DFSP tumors and emphasizes the need to interpret with caution the results of these immunostains during Mohs surgery.

Adult↗
PubMed1993

Blood loss following tonsillectomy in children. A blind comparison of diclofenac and papaveretum.

One hundred and ninety-eight children, aged 3 to 12 years, who were scheduled for tonsillectomy were randomly allocated to receive either diclofenac 1.0 mg.kg-1 or papaveretum 0.2 mg.kg-1 by intramuscular injection after induction of anaesthesia. There were no significant differences between the treatment groups in operating theatre blood loss, the frequency of bleeding on the ward, or the need for operative haemostasis. However, the incidence of above average bleeding in the recovery room was significantly higher in the diclofenac group (p < 0.05). Similarly, marked restlessness in the recovery room was more frequent in the diclofenac group (p < 0.01). In both treatment groups there was an association between bleeding and restlessness during recovery so the increased bleeding in the diclofenac group may not be a direct effect.

Akathisia, Drug-Induced↗
PubMed1993

Alcoholic hepatitis.

Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis of alcoholic hepatitis can be made in alcoholics with associated fever, leukocytosis, jaundice and tender hepatomegaly. Associated laboratory abnormalities may include leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes, including aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. An AST-to-ALT ratio greater than 2 is common in patients with alcoholic hepatitis. Liver biopsy may be required to establish the diagnosis and to identify other pathology, such as cirrhosis. Histologic diagnosis of alcoholic hepatitis requires the presence of liver cell damage, an inflammatory infiltrate and fibrosis. Biopsy-proven cirrhosis with alcoholic hepatitis or a significantly elevated total bilirubin level and prolonged prothrombin time are associated with a worse prognosis. Abstinence from alcohol, nutritional supplementation and corticosteroids are the mainstays of treatment for severe alcoholic hepatitis.

Hepatitis, Alcoholic↗
PubMed1992

Suppression of murine retroviral disease by 2',3'-didehydro-2',3'-dideoxythymidine (D4T).

The thymidine analog, 2',3'-didehydro-2',3'-dideoxythymidine (D4T), and 3'-azido-3'-deoxythymidine (AZT) were evaluated for activity against Friend virus complex (FV) in Mus dunni cells using a focal immunoenzyme assay. The 50% effective doses were, respectively, 1.2 and 0.1 microM for the two compounds; the 50% cytotoxic doses using trypan blue dye exclusion were 25.4 and > 100 microM. Four FV inhibition experiments with D4T were run in F1 hybrid mice containing the Rfv-3r/s genotype. This mouse strain allows the study of treatment effects on development of specific neutralizing antibodies and on splenomegaly, splenic and plasma virus titers, and splenic viral RNA. In the first experiment, D4T was given by oral gavage (p.o.) three times daily (t.i.d.) for 14 days beginning 4 h post-virus inoculation. All dosages used (187.5, 375, 750 mg/kg/day) significantly inhibited all viral parameters. Other experiments used D4T p.o. twice daily, with dosages of 46.9, 93.8, 187.5 and 375 mg/kg/day or four times daily with a dose of 375 mg/kg/day. No significant disease inhibition was seen using the twice daily treatment schedule, but efficacy was apparent using the four times daily treatment. The final experiment repeated the initial study, extending the t.i.d. treatments to 25 days and using dosages of 46.9, 93.8, 187.5 and 375 mg/kg/day. All but the lowest dose reduced each virus parameter. None of the D4T treatment regimens caused death in toxicity controls, although moderate host weight loss or less weight gain was seen, and variable hematocrit decreases occurred, particularly in mice receiving the highest drug dosage. Inhibition of natural killer (NK) cell activity also was seen in these same animals, but in infected mice, FV-induced decrease in NK cell activity was prevented by D4T treatment. Virus-specific neutralizing antibodies developed in all infected, treated animals. These data indicate D4T has potential as a possible candidate for anti-human immunodeficiency virus evaluations in the clinic.

Animals↗
PubMed1985

Cerebral amyloid angiopathy presenting as transient ischemic attacks. Case report.

Cerebral amyloid angiography can cause ischemic stroke and transient ischemic attacks (TIA's), as illustrated by this case report and literature review. It is possible that the use of anticoagulant or platelet-antiaggregant drugs in elderly patients with TIA's but no angiographic abnormalities may increase the risk of hemorrhage from unsuspected amyloid angiopathy.

Aged↗
PubMed1984

IgE immune complexes induce immediate and prolonged release of leukotriene C4 (LTC4) from rat alveolar macrophages.

Alveolar macrophages obtained by lung lavage from rats were incubated with monoclonal mouse anti-DNP IgE and specific antigen (DNP-HSA) and were found to release a slow reacting substance (SRS), which was characterized by high performance liquid chromatography as leukotriene C4 (LTC)4. Alveolar macrophages incubated with 1 microM A23187 (calcium ionophore) released similar amounts of SRS (6.0 +/- 2.2 and 5.7 +/- 3.7 X 10(-10) mol of LTC4 per 5 X 10(6) alveolar macrophages, respectively). The optimal conditions and mechanism of LTC release by IgE and antigen were examined. LTC4 release was maximal when freshly retrieved alveolar macrophages were incubated for 20 min with 10 micrograms/ml IgE and then for 20 min with 100 ng/ml antigen or for 20 min with IgE and antigen that had been preincubated together for 30 min at room temperature. In addition, LTC4 release was maximal when cells were challenged with IgE and antigen in a protein-free balanced salt solution and when the cells were tumbled to prevent adherence. Dose response experiments revealed that macrophages released LTC4 when stimulated with as little as 10 ng IgE and 100 ng DNP-HSA. Alveolar macrophages did not release LTC when challenged with IgE or DNP-HSA alone. Activation of LTC4 release by IgE and antigen was rapid in onset (2.5 to 5 min), and washing to remove fluid phase IgE and antigen revealed that once activated, alveolar macrophages were capable of prolonged and continuous release of LTC4. Peritoneal lavage cells stimulated with IgE and antigen did not release SRS but could release SRS when incubated with A23187 (5.7 +/- 1.3 X 10(-10) mol LTC4/5 X 10(6) macrophages). A large variability existed between individual rats in the ability of their alveolar macrophages to be activated by IgE and antigen to release LTC4. DNP-HSA labeled with 125I was used to show formation of immune complexes of IgE and antigen when IgE and antigen were incubated together before macrophage challenge. IgE immune complexes containing as little as 2 ng of antigen elicited the release of LTC4 from alveolar macrophages. These data indicate that rat alveolar macrophages release primarily LTC4 when challenged with IgE immune complexes, and that the alveolar macrophage may differ in this respect from peritoneal macrophages that do not release detectable quantities of LTC4 when challenged under identical conditions.

Animals↗
PubMed1983

Effects of ascorbic acid deficiency on the in vitro biosynthesis of cyclooxygenase metabolites in guinea pig lungs.

Endogenous levels of ascorbic acid may play a role in regulating the biosynthesis of cyclooxygenase metabolites in lungs of male guinea pigs. The in vitro biosyntheses of prostaglandins, prostacyclin and thromboxane were examined using isolated microsomal membranes from control and ascorbic acid deficient guinea pigs, under conditions in which the substrate concentration ( [3H]-arachidonic acid) was varied from 10-100 microM. Maintenance of guinea pigs for two weeks on an ascorbic acid deficient diet did not alter lung/body weight ratios, nor protein content of the lungs. Lung microsomes from ascorbic acid deficient guinea pigs demonstrated a greater biosynthesis of total cyclooxygenase metabolites at low substrate concentrations. A significant increase in the PGF2 alpha synthesis was observed in the scorbutic microsomes at 20 microM arachidonic acid. At higher substrate concentrations the production of PGF2 alpha was significantly reduced in ascorbic acid deficient animals. By contrast, biosynthesis of thromboxane or prostacyclin in treated animals was not significantly different from control microsomes. At a substrate concentration of 100 microM, there was equivalent synthesis of total cyclooxygenase metabolites in control and vitamin C deficient animals. The changes in prostaglandin biosynthesis were not due to an interaction of ascorbic acid with glutathione levels in the lung. These results support the hypothesis that ascorbic acid may modulate cyclooxygenase activity in the lung in a substrate dependent nature.

Animals↗
PubMed1981

Arachidonic acid metabolism and modulation of in vitro anaphylaxis by 5,8,11,14-eicosatetraynoic acid and 9a,12a-octadecadiynoic acid.

1. 5,8,11,14-Eicosatetraynoic acid (ETYA) inhibited the antigen-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. Consistent data were obtained only when the spirals were treated with indomethacin. 2. ETYA did not affect histamine-induced contractions of indomethacin-treated tracheal spirals. 3. 9a, 12a-Octadecadiynoic acid (Ro-3-1314) a potential inhibitor of linoleic acid metabolism, stimulated the antigen-induced contraction of guinea-pig tracheal spirals and the immunological release of slow reacting substances of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments. 4. Both ETYA and Ro-3-1314 inhibited the immunological release of malondialdehyde from guinea-pig lung fragments. 5. The data indicate that the effects of ETYA were due to inhibition of lipoxygenase and the effects of Ro-3-1314 were due to inhibition of cyclo-oxygenase. 6. The results suggest that products of lipoxygenase contribute to the antigen-induced contraction of guinea-pig lung, particularly when cyclo-oxygenase is inhibited. Under these conditions there may be redirection of the metabolism of arachidonic acid to favour production of constrictor products of lipoxygenase such as SRS-A.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1980

Stimulation of the antigen-induced contraction of guinea-pig trachea and immunological release of histamine and SRS-A from sensitized guinea-pig lung by (2-isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin.

1 (2-Isopropyl-3-indolyl)-3 pyridyl ketone (L8027) and indomethacin reduced basal tension and enhanced the antigen- and histamine-induced contractions of tracheal spirals obtained from actively sensitized guinea-pigs. The stimulating effect of L8027 required the presence of the drug, while that of indomethacin persisted after its removal from the organ bath. 2 L8027 and indomethacin stimulated the immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) and inhibited the de novo synthesis and release of malondialdehyde from actively sensitized guinea-pig lung fragments. 3 L8027 was 2,800 times more potent than indomethacin in both in vitro models of anaphylaxis. 4 A selective antagonist of SRS-A (FPL 55712) inhibited contractions produced by antigen, but had no effect on contractions produced by histamine. 5 Prostaglandins E and F2 alpha were continuously released into the organ bath fluid by the resting trachea. Contractions induced by antigen or histamine increased the rate of prostaglandin efflux. 6 L8027 had no effect on the efflux of prostaglandins E and F2 alpha at rest and during contraction. Indomethacin inhibited prostaglandin efflux at rest and during contraction while present in the organ bath. Prostaglandin efflux was restored to 80% of control after removal of indomethacin. 7 The results suggest that prostaglandins E and F2 alpha have no role in the stimulation by L8027 and indomethacin of the contractile responses of guinea-pig trachea. The possible mechanism for the effects of these drugs is discussed.

Airway Resistance↗
PubMed1980

Effect of variation in endogenous levels of ascorbic acid on the in vitro immunological release of histamine and slow reacting substance of anaphylaxis from actively sensitized guinea-pig lung fragments.

1. The in vitro immunological release of histamine and slow reacting substance of anaphylaxis (SRS-A) from actively sensitized guinea-pig lung fragments was greatly reduced when the animals were maintained on an ascorbic acid-deficient diet. Excessive dietary levels of ascorbic acid did not increase mediator release above normal levels. 2. Restoration of ascorbic acid in the diet of scorbutic guinea-pigs restored in vitro immunological histamine to normal levels. 3. Variation in dietary levels of ascorbic acid had no effect on lung histamine content. 4. The lung ascorbic acid content was proportional to the dietary intake. Approximately 60% of the total lung ascorbic acid was removed by the process of chopping and washing of the tissue. This relationship was independent of dietary intake. 5. The results indicate that the immunological release of mediators of inflammation from guinea-pig lung is dependent on adequate endogenous levels of ascorbic acid.

Animals↗
PubMed1978

Effect of inhibitors of prostaglandin synthesis and prostaglandins E2 and F2alpha on the immunologic release of mediators of inflammation from actively sensitized guinea-pig lung.

Histamine and slow reacting substance of anaphylaxis (SRS-A) were released from actively sensitized guinea-pig chopped lung fragments (100 mg) in a concentration dependent manner by 0.2 to 100 microgram/ml of antigen. Individual variation between lungs in the proportion of the total histamine released by antigen (20 microgram/ml) showed a normal frequency distribution (n = 95). The effect of inhibitors of prostaglandin (PG) synthesis on the release of histamine and SRS-A was examined. Indomethacin (0.03--13 micrometer), racemic 6-chloro-alpha-methylcarbazole-2-acetic acid (0.03--3 micrometer) and sodium salicylate (0.8--8 micrometer) stimulated histamine release by high concentrations of antigen (more than 10 microgram/ml) but had no effect at low concentrations of antigen. These agents stimulated the release of SRS-A at all antigen concentrations tested. In contrast, 5,8,11,14-eicosatetraynoic acid (0.04--42 micrometer) had no effect on the release of histamine but inhibited the release of SRS-A. Histamine release was stimulated by exogenous PGF2alpha (0.01--1 micrometer) in lungs which had control releases in the 25th percentile of the frequency distribution, but was unaffected by exogenous PGE2 (0.01--10 micrometer). In the presence of blockade of PG synthesis by indomethacin (13 micrometer), the stimulatory effect of PGF2alpha was enhanced while PGE2 antagonized the stimulatory effect of indomethacin. These results suggest that 1) histamine and SRS-A release from guinea-pig lung is regulated in part by the de novo synthesis of prostaglandins and 2) that SRS-A synthesis and release is influenced by a metabolite of arachidonic acid produced by a metabolic pathway other than cyclooxygenase.

Animals↗
PubMed1977

Reduction in basal adenylate cyclase activity during the immunologic release of histamine from guinea pig lung.

Cyclic AMP has been implicated in the regulation of the immunologic release of histamine from lung and other tissues and cell types. The mechanism whereby intracellular levels of cAMP are altered during mediator release was investigated. Measurements of histamine, adenylate cyclase, and cAMP phosphodiesterase activities were made in actively and passively sensitized guinea pig lung after challenge with antigen. A transient decrease in basal adenylate cyclase activity occurred which returned to control levels after histamine release. There was no change in cAMP phosphodiesterase activity determined at substrate concentrations of 1 mM and 0.01 mM. The adenylate cyclase response did not occur under the following conditions: 1) incubation of nonsensitized lung with antigen, 2) incubation of sensitized lung with antigen in the absence of extracellular calcium, and 3) incubation of nonsensitized lung with compound 48/80. These observations indicate 1) the adenylate cyclase response and the immunologic release of histamine are intimately related, and 2) the reduction in intracellular levels of cAMP which have been reported to occur during immunologic histamine release are mediated via adenylate cyclase.

3',5'-Cyclic-AMP Phosphodiesterases↗