PubMed Health⌕ Search

Biomedical subjects

Kenneth Thompson

Publications and source records attributed to Kenneth Thompson.

12 recordsLinked to original sources

Initial adjustments within a new river channel: Interactions between fluvial processes, colonizing vegetation, and bank profile development.

A conceptual model of the morphological development of the riparian margins of newly cut river channels is presented, suggesting early feedbacks between vegetation growth and bank form. To test the model, observations of long and cross profiles, bank sediment and seed deposition, and bank vegetation development were collected over the first 2 years of river flows through a reach of the River Cole, West Midlands, UK. The newly created channel had a sinuous planform and varying asymmetric trapezoidal cross section in sympathy with the planform. No imposed bedforms or bank reseeding were included in the design. Over the 2 years, development of bedforms was rapid, with bed sediment sorting and bank profile adjustment occurring more steadily and progressively. Six classes of bank profile were identified by the end of the study period, illustrating close associations with sediment aggradation, vegetation colonization, and growth patterns. Vegetation colonization of the banks was seeded predominantly from local sources during the summer and from hydrochory (transport by the river) during the winter. Colonizing vegetation on the riverbanks appeared to act as a significant propagule source by the second summer and as an increasingly important roughness element, trapping both propagules and sediment, within the second year and providing early feedback into bank evolution. As a result, the time required for riparian margin development in the conceptual model was found to be considerably longer than observed in the study river. In addition, the role of surface wash/bank failure in modifying the bank profile and transporting seeds onto the upper bank face during the first year of bank development was found to be important in initiating rapid bank vegetation colonization and surface stabilization. This set of processes had not been incorporated in the initial conceptual model. In relation to channel restoration, this research illustrates that in small temperate rivers of modest energy the provision of an initial, sinuous corridor is sufficient to induce rapid development of fluvial features and vegetation cover without the need to construct bed forms or to seed the banks.

Conservation of Natural Resources↗

The effect of treatment with moxifloxacin or azithromycin on acute bacterial rhinosinusitis in mice.

OBJECTIVE: Acute bacterial rhinosinusitis, which is a major health problem, is treated with antibiotics. We developed a mouse model of acute bacterial rhinosinusitis to gain a better understanding of the pathophysiology of the disease. Our goal was to investigate the response to acute rhinosinusitis when treated with either a bactericidal or a bacteriostatic antibiotic. METHODS: C57BL/6 mice were infected intranasally with Streptococcus pneumoniae. One day after inoculation, the mice were treated with either moxifloxacin (bactericidal) or azithromycin (bacteriostatic). Different groups were euthanized during the first five days post-inoculation. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were evaluated by flow cytometry. RESULTS: Azithromycin led to rapid clearance of the bacteria and of the inflammation in contrast to placebo. Surprisingly, moxifloxacin showed a limited effect. Investigations of this limited effect of moxifloxacin suggested a high metabolic clearance, a low concentration at the site of infection, and low persistent post-antibiotic effects of moxifloxacin in mice. CONCLUSION: Our animal model of acute sinusitis has great utility for studying the disease, but the difference between mice and man must always be considered in making extrapolations from animal experiments to the human experience.

Acute Disease↗

Effect of genetic background on the response to bacterial sinusitis in mice.

OBJECTIVE: To study the importance of ongoing allergen exposure and TH1/TH2 genetic background in augmented bacterial and inflammatory responses in allergic and infected mice. DESIGN: BALB/c and C57BL/6 mice were made allergic to ovalbumin. After 1 day of intranasal allergen exposure, they were inoculated intranasally with Streptococcus pneumoniae. The numbers of bacteria and inflammatory cells in the sinuses were determined, and nasal responsiveness to histamine was assessed. RESULTS: Infected BALB/c and C57BL/6 mice that received ongoing ovalbumin challenge following intraperitoneal sensitization showed significantly greater bacterial load and phagocyte level compared with the infected-only mice. Differences were diminished after the allergen challenge was stopped. Allergic and infected C57BL/6 mice showed fewer bacteria and phagocytes compared with the allergic and infected BALB/c mice. Surprisingly, in contrast to the nonallergenic C57BL/6 mice, the infected BALB/c mice showed a larger number of bacteria 28 days after infection. CONCLUSIONS: Ongoing allergic reaction augments bacterial load in both BALB/c and C57BL/6 mice and induces nasal hyperreactivity to histamine. Allergic and infected C57BL/6 mice show less allergic inflammation and bacterial load compared with allergic and infected BALB/c mice. Stopping allergen exposure reduces the response. Infected BALB/c mice, which favor a TH2 response, were less able to clear infection than C57BL/6 mice, which favor a TH1 response. Inflammation and bacterial load are affected by genetic background of mice and ongoing allergen stimulation.

Allergens↗

Effect of montelukast on bacterial sinusitis in allergic mice.

BACKGROUND: In mice, allergic rhinitis augments the infectious and inflammatory response to Streptococcus pneumoniae-induced sinusitis. OBJECTIVE: To investigate the effects of cysteinyl leukotriene antagonism on the severity of bacterial infection. METHODS: We performed 3 parallel, placebo-controlled experiments. In the first, mice were ovalbumin sensitized and ovalbumin challenged to show the effects of montelukast on the allergic inflammation; in the second, we evaluated the effect of montelukast on S. pneumoniae infection; in the third, we used mice that were both allergic and infected. Montelukast was given starting 2 days after sensitization until the day before euthanasia. One day after drug treatment began, the mice were inoculated intranasally with S. pneumoniae in the infected groups. Nasal hypersensitivity was measured with histamine challenges before the first sensitization and on the day before euthanasia. On the fifth day after infection, mice were euthanized, nasal lavage was performed, bacteria were cultured, and inflammatory cells in the sinuses were quantified. RESULTS: Mice that were infected only tended toward having increased bacterial counts from nasal lavage in the montelukast-treated group. The mice that were allergic and infected experienced significantly higher bacterial counts (P < .05). All 3 montelukast treatment groups had significantly decreased eosinophil counts as well as T-lymphocyte counts. CONCLUSIONS: Montelukast reduces the manifestations of allergic rhinitis in mice. Surprisingly, montelukast led to an increase in bacterial growth in infected mice. This suggests an effect of the cysteinyl leukotrienes on the innate response to bacterial infection.

Acetates↗

Persistent inflammation and hyperresponsiveness following viral rhinosinusitis.

OBJECTIVES: To develop a murine model of viral rhinosinusitis. STUDY DESIGN: Randomized, controlled, animal model. METHODS: Mice were intranasally inoculated with Sendai virus (SeV) or ultraviolet (UV)-inactivated virus. On days 3 and 10 postinfection, nasal lavage fluid was obtained for viral culture. On days 4, 10, and 38 postinfection, sinus mucosa was harvested and analyzed by flow cytometry for CD3-, CD4-, CD8-, CD25-, CD11b-, CCR3-, and GR1-positive cells. Nasal hyperresponsiveness to histamine challenge was measured on days 8 and 36 postinoculation. RESULTS: On day 3, viral cultures were positive from all SeV-inoculated mice but from none of the UV-inactivated mice (P<or=.0039). There was no growth of virus from either group on day 10. On day 4, flow cytometry on SeV-infected sinus cells showed a significant increase in macrophages (P<or=.03) and neutrophils (P<or=.02) compared with controls. This inflammation resolved by day 10. On day 38, mice inoculated with SeV had significantly more CD8+ (P<or=.044) and CD4+CD25+ (P<or=.017) cells than did controls. On day 8, there was a significant increase in both sneezing (P<or=.002) and nasal rubbing (P<or=.002) in the SeV-infected group to histamine challenge compared with controls. This difference continued to day 36. CONCLUSIONS: Inoculation with SeV results in an acute infection that resolves spontaneously within 10 days. Infected mice develop a significant increase in T-suppressor and T-regulatory cells after resolution of the acute infection, which persists for at least 38 days. The persistence of these T cells is associated with hyperresponsiveness to histamine. This mouse model has some parallels to chronic rhinosinusitis after a viral infection in humans and should allow us to clarify the pathophysiology of this disease.

Animals↗

Role of type 1 T helper cells in the resolution of acute Streptococcus pneumoniae sinusitis: a mouse model.

BACKGROUND: We examined the importance of the adaptive and innate immune responses in the resolution of an acute bacterial sinus infection in mice. METHODS: Recombinase-activating gene knockout (RAG-1(-/-)) (no lymphocytes) and C57BL/6 (wild-type) mice were infected with Streptococcus pneumoniae. For determination of the cell type involved, lymphocytes from mice were adoptively transferred into RAG-1(-/-), C57BL/6 (all lymphocytes), B cell-deficient, and T cell-deficient mice. The degree of infection and inflammation was determined by quantification of S. pneumoniae from nasal lavage and analysis of sinus tissue, respectively. RESULTS: In C57BL/6 mice, both the infection and inflammation resolved in 21 days, whereas neither resolved in RAG-1(-/-) mice. When C57BL/6 lymphocytes were adoptively transferred into RAG-1(-/-) mice, resolution of the infection and inflammation occurred. Mice without B cells were able to clear the infection, whereas mice without T cells could not clear it. In vitro stimulation of the draining lymph nodes of the infected mice by use of heat-killed S. pneumoniae led to the production of interferon (IFN)- gamma. Flow-cytometric analysis of lymphocytes obtained from sinus mucosa and draining lymph nodes showed an increase in the number of type 1 T helper cell-like cells over that in control mice. CONCLUSIONS: RAG-1(-/-) mice with innate immunity but no lymphocytes contain--but cannot clear--a bacterial sinus infection. Lymphocytes transferred to RAG-1(-/-) mice clear the infection. The sinus mucosa and draining lymph nodes show an increase in T cells generating IFN- gamma. These data demonstrate that T cells are essential in clearing an acute S. pneumoniae bacterial sinus infection.

Acute Disease↗

Evaluation of importance of Toll-like receptor 4 in acute Streptococcus pneumoniae sinusitis in mice.

OBJECTIVES: To investigate the effect of RC-527, a synthetic toll-like receptor 4 (TLR4) agonist, on stimulating the immune response before acute Streptococcus pneumoniae sinusitis in a mouse model, and to determine the importance of TLR4 in modulating the response to S. pneumoniae. Toll-like receptor 4 agonists have been shown to induce protective innate immune responses when administered before some bacterial or viral challenges in mice. DESIGN: We intranasally inoculated BALB/c, TLR4 complex-deficient C3H/HeJ, and wild-type C3H/HeOuJ mice with S. pneumoniae 24 hours after treatment with 10 or 1 microg of RC-527 or vehicle. Bacterial counts from nasal lavage culture and the cell markers GR1, CD11b, CD3, CD4, and CD8 in sinus tissue were quantified at postinoculation days 2, 5, and 14. MAIN OUTCOME MEASURE: Immune response induced by RC-527. RESULTS: Treatment with RC-527 induced an immune response through TLR4, as demonstrated by recruitment of phagocytes in uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. The immune response was also demonstrated by a significant increase of CD3+, CD4+, and CD8+ T cells in infected and uninfected wild-type C3H/HeOuJ mice, but not in TLR4 complex-deficient C3H/HeJ mice. However, the enhancement of the immune response induced by the TLR4 agonist showed a limited effect on bacterial clearance. CONCLUSIONS: Our studies in mice suggest that stimulation of TLR4 plays a minor role in the overall response to S. pneumoniae infection of the upper airway, and stimulating this receptor before infection does not significantly enhance the immune response of immunocompetent mice to clear S. pneumoniae infection.

Acute Disease↗

Antigen stimulation of TH2 cells augments acute bacterial sinusitis in mice.

BACKGROUND: Previously, we showed that an ongoing nasal allergic response augmented bacterial sinusitis in mice. In those experiments mice were sensitized to ovalbumin (OVA) by means of intraperitoneal injections of OVA-alum and then exposed to OVA intranasally before being infected with Streptococcus pneumoniae. OBJECTIVE: We sought to study the importance of TH2 cells and to eliminate potential alum effects. METHODS: In this study we sensitized mice by adoptively transferring OVA-specific TH2- or TH1-skewed cells. RESULTS: TH2 passive sensitization followed by intranasal OVA showed a robust local eosinophilic response (5-fold increase) compared with that seen in mice with only TH2 passive sensitization alone (P <.001). Mice with TH2 passive sensitization and intranasal OVA exposure followed by infection showed an increase in the number of recovered S pneumoniae (P <.05) and an increase in sinus inflammation compared with that seen in those with infection alone (P <.01). In contrast, mice passively sensitized with TH1 followed by intranasal OVA exposure and infection showed no significant increase in the recovery of S pneumoniae and sinus inflammation compared with those with infection alone. CONCLUSIONS: These data support the importance of antigen-stimulated TH2 cells in the augmented response to infection in allergic mice. Whether the increased infection is related to the direct effect of TH2 cells and their cytokines or subsequent recruitment of other cells, such as eosinophils, will be determined in further studies.

Acute Disease↗

Residue depletion study and withdrawal period for flunixin-N-methyl glucamine in bovine milk following intravenous administration.

The objective of this study was to establish a withdrawal period for flunixin in milk by quantifying 5-hydroxyflunixin, the marker residue, in bovine milk as a function of time, following intravenous treatment of lactating dairy cows with flunixin-N-methyl glucamine (Banamine or Finadyne). Lactating dairy cows were dosed on three consecutive days at 2.2 mg of flunixin free acid/kg of body weight/day. Milk was collected twice daily and assayed using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) procedure. The method was validated at concentrations in the range 0.5-250 ppb. The concentrations for 5-hydroxyflunixin measured 12 h after the last administration of drug ranged from 1.56 to 40.6 ppb for all cows. Milk concentrations for 5-hydroxyflunixin were used to establish withdrawal periods of 36 h using guidelines established by the U.S. Food and Drug Administration/Center for Veterinary Medicine and 24 h using guidelines established by the European Medicinal Evaluation Agency/Committee on Veterinary Medicinal Products.

Animals↗

Flunixin residues in milk after intravenous treatment of dairy cattle with (14)C-flunixin.

Flunixin meglumine is used in veterinary medicine as an alternative to narcotic analgesics and as an antiinflammatory agent. Eight Holstein dairy cows were dosed intravenously once daily on three consecutive days with (14)C-flunixin meglumine at approximately 2.2 mg of flunixin free acid/kg of body weight. Milk was collected twice daily to determine the decline of the total radioactive residues (TRR) in milk and to identify or characterize residue components. TRR in milk declined rapidly and averaged 66, 20, and 14 ppb, respectively, for the first, second, and third milkings after administration of the last dose. Milk was extracted, and the extracts were examined for radioactive residues. Mean extractability of milk TRR was always greater than 80%. Flunixin and 5-hydroxyflunixin were identified by coelution with analytical standards using reverse phase HPLC. These two residues were the main radioactive residues found in milk and together accounted for 64, 37, and 44% of the extractable residues, for the first, second, and third milkings, respectively, after administration of the last dose. The presence of 5-OH flunixin in milk was confirmed by HPLC/MS/MS.

Animals↗

Efficacy of two 65 % permethrin spot-on formulations against canine infestations of Ctenocephalides felis and Rhipicephalus sanguineus.

The efficacy of two formulations of a topically applied 65% permethrin spot-on for dogs (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp.) was evaluated against experimental infestations of the cat flea, Ctenocephalides felis, and the brown dog tick, Rhipicephalus sanguineus. Thirty dogs were randomly allocated to treatment with 65 % permethrin in diethylene glycol monomethyl ether (original formulation), 65 % permethrin in propylene glycol monomethyl ether (test formulation), or to an untreated control group. Dogs assigned to treatment with a permethrin formulation received either 1 or 2 ml of the formulation in accordance with label directions on Day 0. One hundred unfed, adult cat fleas and 50 unfed, adult ticks were placed on each dog on Days -1, 5, 12, 19, 26, 33, and 40. Live fleas and ticks were counted on each dog on Days 2, 7, 14, 21, 28, 35, and 42. Treatment of dogs with either formulation of 65 % permethrin significantly (P <.05) reduced the number of live fleas and ticks from Days 2 through 42. No statistical differences were noted between the formulations regarding efficacy against C. felis or R. sanguineus.

Administration, Topical↗