Biomedical subjects

Michael Duff

Publications and source records attributed to Michael Duff.

9 recordsLinked to original sources

PubMed2006

Paraneoplastic encephalomyelitis: a case report and review of the literature.

BACKGROUND: The incidence of paraneoplastic syndromes varies with tumor histology. Uterine sarcomas rarely cause paraneoplastic syndromes. Furthermore, paraneoplastic encephalomyelitis has never been reported to accompany a uterine leiomyosarcoma. CASE: A 44-year-old female developed an ANNA-1 paraneoplastic encephalomyelitis after a diagnosis of a uterine leiomyosarcoma. CONCLUSION: Paraneoplastic encephalomyelitis usually causes progressive neurologic decline. Treatment rarely alters this course.

Adult↗

PubMed2006

Radiation therapy for chronic vesicular hand dermatitis.

BACKGROUND: Chronic vesicular hand dermatitis is a chronic disease that can be debilitating for patients, and many treatment options do not provide lasting remission. OBJECTIVE: We attempted to determine the efficacy of megavoltage irradiation in the treatment of this disease. METHODS: Between July 2001 and March 2005, 9 patients with severe chronic vesicular hand dermatitis had megavoltage radiation therapy to their sites of disease. Eight pairs of hands and seven pairs of feet were irradiated (15 total sites). RESULTS: All patients had an improvement in their disease during the course of radiation therapy. Patients were followed after radiation therapy for a median follow-up time of 20.2 months (range, 1 to 45 months). The disease completely resolved in 7 of the 15 (47%) sites irradiated. There was a decrease in the severity or frequency of flare-ups at the other 8 sites (53%). CONCLUSION: Megavoltage radiation therapy may be effective in the treatment of chronic vesicular hand dermatitis and may provide durable remissions in some patients.

Adult↗

PubMed2005

Recognition of septanose carbohydrates by concanavalin A.

The ability of the jack bean lectin concanavalin A (ConA) to bind seven membered ring (septanose) monosaccharides has been investigated by isothermal titration calorimetry (ITC) and saturation transfer difference (STD) NMR spectroscopy.

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PubMed2005

Lysis-deficient bacteriophage therapy decreases endotoxin and inflammatory mediator release and improves survival in a murine peritonitis model.

BACKGROUND: Lysis-deficient (LyD) bacteriophages (phages) kill bacteria without endotoxin (Et) release. This may minimize systemic cytokine responses and limit inflammation in bacterial sepsis. We determined the effects of t amber A3 T4 LyD and virulent wild-type (WT) phages on mouse bacterial peritonitis. METHODS: Balb/c mice were injected with B40sul Escherichia coli, treated intraperitoneally with LyD, WT, or a beta-lactam antibiotic [latamoxef sodium (LMOX)], and followed for survival. We measured Et release, tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, as well as bacterial counts and peritoneal exudative cells (PECs) in peritoneal lavage fluid at 6 and 12 hours after infection. RESULTS: LyD mice showed significantly greater survival compared with other groups. Et levels were significantly lower in the LyD mice at 6 and 12 hours after infection. TNF-alpha and IL-6 levels were lower in LyD mice compared with control (untreated) mice at 12 hours. Compared with controls, bacteria counts in peritoneal lavage fluid were lower in all treatment groups (LyD, WT, or LMOX) at 6 and 12 hours. PEC counts were highest in LyD mice at 6 hours but significantly lower than that in WT phage- and LMOX-treated mice at 12 hours. CONCLUSIONS: LyD phage therapy significantly improves survival and attenuates the systemic effects of bacterial sepsis by minimizing Et release and pro-inflammatory mediators in murine bacterial peritonitis. Further studies may find phage therapy useful in treating peritonitis and multidrug-resistant bacterial infections.

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PubMed2004

Neuroendocrine responses mediate macrophage function after trauma.

BACKGROUND: Clearly understanding the interactions between macrophage (M phi)-generated inflammatory mediators and the neuroendocrine system in regulating immune function after traumatic injury may aid in reversing trauma-mediated immune dysfunction and diminish the incidence and severity of infection in the traumatized patient. METHODS: Trauma consisted of an open femur fracture and 40% retro-orbital hemorrhage (Trauma) or anesthesia alone (Control). Female Balb/C mice (6-8 weeks) with intact adrenal glands (Intact) or a bilateral adrenalectomy (ADX) were used. For glucocorticoid studies, corticosterone or a vehicle was administered via intraperitoneal (ip) injection 2 hours before the trauma. Splenic M phis were harvested and prostaglandin E(2) (PGE(2)) and interleukin-6 (IL-6) production, and mRNA, cyclooxygenase-2 (COX-2) protein, and nuclear factor kappa B (NF-kappa B) activity were measured. RESULTS: M phi, PGE(2) and IL-6 production in Trauma+Intact mice was significantly increased compared with Control+Intact mice. Adrenalectomy decreased these levels to Control levels. Similar changes were observed for COX-2 and IL-6 expression. M phi nuclear NF-kappa B levels were increased in Trauma+Intact mice compared with controls. Adrenalectomy abrogated this increase. Treating Trauma+Intact mice with RU-486 did not restore PGE(2) and IL-6 production or COX-2 and IL-6 messenger RNA to control levels. Administering exogenous glucocorticoid to Intact mice did not increase PGE(2) and IL-6 production or COX-2 and IL-6 mRNA to Trauma levels. CONCLUSIONS: The neuroendocrine system upregulates certain M phi inflammatory mediators, including PGE(2), IL-6, and NF-kappa B, after trauma. This upregulation does not seem to be mediated via glucocorticoids and possibly may be mediated via catecholamines. Elucidation of the interactions between the neuroendocrine system, the immune system, and inflammatory mediator secretion might provide novel therapeutic strategies for the injured patient.

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PubMed2004

Glucocorticoid pretreatment induces cytokine overexpression and nuclear factor-kappaB activation in macrophages.

BACKGROUND: Glucocorticoids are widely used in treating inflammatory diseases. The contribution of adrenal glucocorticoids to inflammatory regulation is unknown. Endogenous glucocorticoids, as distinct from synthetic analogues, not only suppress but also enhance immune functions. Elevated circulating cortisol levels are characteristic of injured patients. In a model of trauma, an early glucocorticoid surge occurs concomitantly with decreased cellular cytokine responses. Cytokine production elevated late after injury is associated with increased mortality. We hypothesized that this glucocorticoid surge mediates the later heightened macrophage responses. MATERIALS AND METHODS: The murine macrophage like cells RAW 264.7 were incubated with corticosterone (35 ng/mL), or vehicle control, for 1 h, after which the cells were washed and corticosterone-free medium added. At 0, 3, 6, 12, and 24 h after removal of the corticosterone, the cells were stimulated with lipopolysaccharide (LPS) and interferon-gamma. Supernatant tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and nitrite levels were measured. In separate experiments the effect of pretreatment with corticosterone on TNF-alpha, IL-6, and nitrite mRNA expression as well as nuclear factor-kappaB and glucocorticoid receptor activity was determined. CD14 receptor expression was determined by flow cytometry. RESULTS: Glucocorticoid pretreatment caused significantly increased RAW 264.7 cell production of nitrite, IL-6 and TNF-alpha. mRNA for these inflammatory mediators was induced 6 h after the corticosterone pretreatment, and was associated with activation of nuclear factor-kappaB in the presence of activated glucocorticoid receptor. Cell surface-expression of CD14 was likewise increased. CONCLUSIONS: The results of this study demonstrate a novel role for glucocorticoids and provide a mechanism for the late upregulation in macrophage function after injury.

Animals↗

PubMed2004

Altered cyclooxygenase-2 expression and nitric oxide metabolism following major elective surgery.

BACKGROUND AND AIMS: Postoperative variation in immune function leads to increased susceptibility to infections. Cyclooxygenase-2 (COX-2)-generated Prostaglandin-E(2) (PGE(2)), which signals through the PGE(2) receptor (EP receptor), as well as nitric oxide metabolites (NOx), appear to be important in postoperative immune dysfunction. It is unclear, however, how these substrates and receptors change over time. This study was conducted to evaluate postoperative changes in inflammatory mediator production and monocyte COX-2 and EP receptor expression. MATERIALS AND METHODS: Nineteen patients had blood drawn preoperatively and up to 1 week postoperatively. Plasma NOx levels were measured. Peripheral blood mononuclear cell (PBMC) COX-2 and EP receptor mRNA expression were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). PBMC PGE(2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and IL-10 productions were evaluated by enzyme-linked immunosorbent assay (ELISA) kits. Statistical analyses were by ANOVA and Student's t tests. RESULTS: Postoperatively, PBMC mean PGE(2) and IL-6 productions were significantly increased at all time points. Mean TNF-alpha production was maximal on postoperative day 2, while mean IL-10 production was unchanged. Mean circulating NOx levels demonstrated a biphasic response decreasing early postoperatively and normalizing at postoperative day (POD) 7. PBMC COX-2 enzyme and EP receptor mRNA expression were unchanged. CONCLUSIONS: Altered PBMC PGE(2) production and plasma NOx levels support a role for altered macrophage activity, which may contribute to immune dysfunction in the postoperative period.

Adult↗

PubMed2003

Cyclooxygenase-2 inhibition improves macrophage function in melanoma and increases the antineoplastic activity of interferon gamma.

BACKGROUND: Melanoma inhibits macrophage tumoricidal activity and increases the expression of cyclooxygenase-2 (COX-2). In this study, we sought to determine whether inhibition of COX-2 could restore macrophage function and hence maximize the antitumor activity of the immune stimulant interferon gamma (IFN gamma). METHODS: Peritoneal macrophages were exposed to B16 melanoma-conditioned medium for 24 hours with or without the COX-2 inhibitor NS-398 and then were stimulated with lipopolysaccharide and IFN gamma. Cytotoxic activity, nitrite production, and cytokine production by the stimulated macrophages were measured. In addition, B16 melanoma cells were implanted intradermally into mice treated with IFN gamma (14,000 U on alternate days) alone or with a combination of IFN gamma and a COX-2 inhibitor (NS-398 or nimesulide). Mice were assessed for tumor growth and survival. RESULTS: Macrophage cytotoxicity and nitrite production were significantly suppressed by melanoma-conditioned medium (P <.01). This was prevented by 200 micro M of NS-398 (P <.05). In vivo, combined treatment with IFN gamma and a COX-2 inhibitor caused a significant inhibition of tumor growth (P <.01) and improved survival (P =.02) compared with controls. CONCLUSIONS: COX-2 inhibition reversed melanoma-induced suppression of macrophage function, and combined treatment of IFN gamma plus a COX-2 inhibitor was maximally effective in reducing tumor growth and improving survival.

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PubMed2002

Crypt cell production rate in the small intestine of the zinc-supplemented mouse.

Zinc is a trace element which is necessary in the body and the daily requirement is usually provided mainly through food intake. The effects of zinc deficiency are multisystemic and in the gastrointestinal tract include ulceration and inflammation. Many of these effects in the mammalian small intestine are reversible by zinc replenishment in a manner that is thought to be linked to the effect of this element on intestinal mucosal cell kinetics. However, the effects of continued replenishment (supplementation) have not been closely examined. This study examined the effects of zinc supplementation on gut crypt cell production in zinc-replete animals. Fifteen CD-1 mice were given zinc sulphate (0.3 mmol/l) in tap water while a second (control) group of 15 mice received only tap water. After 14 days, the small intestine was removed, measured and divided into four equal lengths and then sampled at the midpoint of each of the resulting four segments. Whole crypt numbers and crypt cell production rate were determined for each intestinal site for both groups of mice. While crypt dimensions and crypt numbers in zinc-fed mice showed no significant change from control levels, the crypt cell production in zinc-fed mice was significantly increased and duration of mitosis reduced in the third (distal) intestinal segment when compared to values from control mice. These findings show that the addition of subtoxic quantities of zinc to diet in zinc-replete animals enhances cell production and indicate that the reversal of zinc deficiency-induced gut damage following dietary zinc replenishment may be due to a direct effect on cell kinetics.

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