RESUMO
BACKGROUND: Animals undergoing experimental manipulations, such as exposure to radiation, may exhibit physiologic and behavioral signs of pain and distress. Telemetry permits close monitoring of these parameters for early and effective management during procedures. METHODS: Radiotelemetric units were surgically implanted into 24 Macaca mulatta before 6.5-Gy cobalt-60 γ-photon irradiation. Each unit transmitted electrocardiogram, intrathoracic pressure, and body temperature leads. Primate irradiation-restraint boxes and housing cages were modified to collect telemetric signals before, during, and after irradiation. RESULTS: Differences in respiratory rate, heart rate, or body temperature in telemetric-collected recordings, which were observed during non-irradiation and irradiation sessions, were statistically insignificant. CONCLUSIONS: Insignificant changes in the physiological parameters during monitoring suggest that the animals experienced no detectable pain or distress during irradiation.
Assuntos
Macaca mulatta , Telemetria/veterinária , Irradiação Corporal Total , Aclimatação , Animais , Temperatura Corporal , Radioisótopos de Cobalto , Frequência Cardíaca , Masculino , Respiração , Telemetria/instrumentaçãoRESUMO
BACKGROUND: Microflora populations residing in oropharyngeal and gastrointestinal sites defend against pathogenic bacterial colonization. Perturbations in these microbial communities may allow opportunistic pathogenic bacteria to establish themselves and cause morbidity and mortality from sepsis particularly after stressful experimental procedures. This study determined the prevalent facultative bacteria in a resident population of Macaca mulatta prior to use in experimentally induced immunosuppressive radiation studies. METHODS: Standard microbiological methods were used to assess prevalent facultative bacteria in the oropharynx and rectum of 24 male M. mulatta. RESULTS: The majority of the bacteria isolated from the oropharyngeal and rectal sites were gram-positive cocci. Species of Staphylococcus and Streptococcus predominated in all samples. Few gram-negative bacteria were isolated. CONCLUSIONS: Bacteriological assessment is recommended to identify predominant bacterial species to be prepared to provide appropriate antimicrobial therapy in non-human primates that are expected to undergo stressful immunocompromising procedures.
Assuntos
Macaca mulatta/microbiologia , Orofaringe/microbiologia , Reto/microbiologia , Animais , Estudos Transversais , MasculinoRESUMO
The binding of human [125I]GH, ovine [125I]GH, bovine [125I]GH, and ovine [125I]PRL, to hepatic microsomal membranes (100,000 g) prepared from fetal, neonatal, and infant lambs and adult ewes has been examined. The specific binding of hGH increases (P less than 0.01) from 3.4 +/- 0.8% in the fetus (n = 7) to 20.0 +/- 2.1% (n = 6) in lambs at least 6 days postpartum. The binding of oGH is low in the fetus (0.7 +/- 0.2%; n = 13) and neonatal lamb (1.3 +/- 0.5%; n = 5) and increases (P less than 0.01) in older lambs (14.6 +/- 4.7%; n = 6) and adult sheep (14.9 +/- 5.3%; n = 4). Similarly, the binding of bGH is less (P less than 0.05) to fetal tissues. In contrast, the binding of oPRL is similar in fetal and postnatal preparations. Cross-reaction studies suggest that the binding of GHs is to a site with lactogenic characteristics in the fetus. In contrast, in lambs at least 4 days postpartum and in adult sheep, binding is to a site with somatogenic characteristics. The inability to detect somatogenic sites in the fetal liver is not due to saturation by endogenous GH or chorionic somatomammotropin, as the binding characteristics do not change after MgCl2 pretreatment of the membrane fractions. No change in binding is observed 25 days after fetal decapitation at 69 days (n = 3), suggesting that circulating GH does not down-regulate the fetal GH receptor. These observations suggest an immaturity of the somatogenic receptor in the ovine fetal liver and its appearance in the perinatal period. Immaturity of this receptor is likely to be the basis for the lack of a major effect of fetal GH on fetal somatic growth.
Assuntos
Fígado/crescimento & desenvolvimento , Receptores de Superfície Celular/metabolismo , Somatostatina/metabolismo , Envelhecimento , Animais , Animais Recém-Nascidos , Membrana Celular , Feminino , Feto , Cinética , Fígado/embriologia , Fígado/metabolismo , Magnésio/farmacologia , Cloreto de Magnésio , Receptores da Somatotropina , OvinosRESUMO
The effect of oral therapy with three quinolones (ofloxacin, ciprofloxacin, and pefloxacin) in the prevention of postirradiation bacteremia and mortality was tested in B6D2F1 mice given 9.5 Gy 60Co gamma radiation. Only 8 of 60 (13%) untreated mice survived for 30 days, compared to 47 of 60 (78%) mice treated with ofloxacin, 44 of 60 (74%) mice treated with ciprofloxacin, and 42 of 60 (70%) mice treated with pefloxacin (P less than 0.05). The organisms recovered from the mice were Streptococcus spp. and Enterobacteriaceae. More Enterobacteriaceae were recovered from the livers of untreated animals than from the mice treated with the quinolones. However, no reduction in the number of Streptococcus spp. was noted in the animals given quinolones when compared to controls. This study shows that quinolones prolonged survival and decreased systemic spread of Enterobacteriaceae up to 30 days after exposure of mice to lethal irradiation.
Assuntos
Anti-Infecciosos/uso terapêutico , Bacteriemia/prevenção & controle , Lesões Experimentais por Radiação/complicações , Animais , Bacteriemia/etiologia , Bacteriemia/mortalidade , Ciprofloxacina/uso terapêutico , Radioisótopos de Cobalto , Feminino , Raios gama , Camundongos , Ofloxacino/uso terapêutico , Pefloxacina/uso terapêuticoRESUMO
Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.
Assuntos
Ciprofloxacina/uso terapêutico , Infecções por Klebsiella/tratamento farmacológico , Ofloxacino/uso terapêutico , Pefloxacina/uso terapêutico , Lesões Experimentais por Radiação/complicações , Animais , Feminino , Infecções por Klebsiella/etiologia , Klebsiella pneumoniae , CamundongosRESUMO
When host antimicrobial defenses are severely compromised by radiation or trauma in conjunction with radiation, death from sepsis results. To evaluate therapies for sepsis in radiation casualties, we developed models of acquired and induced bacterial infections in irradiated and irradiated-wounded mice. Animals were exposed to either a mixed radiation field of equal proportions of neutrons and gamma rays (n/gamma = 1) from a TRIGA reactor or pure gamma rays from 60[Co sources. Skin wounds (15% of total body surface area) were inflicted under methoxyflurane anesthesia 1 h after irradiation. In all mice, wounding after irradiation decreased resistance to infection. Treatments with the immunomodulator synthetic trehalose dicorynomycolate (S-TDCM) before or after mixed neutron-gamma irradiation or gamma irradiation increased survival. Therapy with S-TDCM for mice irradiated with either a mixed field or gamma rays increased resistance to Klebsiella pneumoniae-induced infections. Combined therapy with S-TDCM and ceftriaxone for K. pneumoniae infections in mice exposed to a mixed radiation field or to gamma rays was more effective than single-agent therapy. In all irradiated-wounded mice, single therapy of acquired infections with an antibiotic or S-TDCM did not increase survival. Survival of irradiated-wounded mice after topical application of gentamicin sulfate cream suggested that bacteria colonizing the wound disseminated systemically in untreated irradiated mice, resulting in death from sepsis. In lethal models of acquired infections in irradiated-wounded mice, significant increases in survival were achieved when systemic treatments with S-TDCM or gentamicin were combined with topical treatments of gentamicin cream. Therapies for sepsis in all mice exposed to a mixed field were less effective than in mice exposed to gamma rays. Nonetheless, the data show a principle by which successful therapy may be provided to individuals receiving tissue trauma in conjunction with radiation injury.
Assuntos
Adjuvantes Imunológicos/uso terapêutico , Fatores Corda/uso terapêutico , Lesões Experimentais por Radiação/complicações , Infecção dos Ferimentos/complicações , Animais , Radioisótopos de Cobalto , Feminino , Raios gama , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae , Camundongos , Nêutrons , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Bacillus anthracis is a potential biological warfare agent. Its ability to develop resistance to antimicrobial agents currently recommended for the treatment of anthrax infection is a major concern. B. anthracis Sterne was grown from a live veterinary vaccine and used it to test for the development of resistance after 21 sequential subcultures in sub-inhibitory concentrations of doxycycline and three quinolones (ciprofloxacin, alatrofloxacin and gatifloxacin) and 15 sequential subcultures in sub-inhibitory concentrations of three macrolides (erythromycin, azithromycin and clarithromycin). After 21 subcultures the minimal inhibitory concentrations (MICs) increased from 0.1 to 1.6 mg/l for ciprofloxacin, from 1.6 to 12.5 mg/l for alatrofloxacin, from 0.025 to 1.6 mg/l for gatifloxacin and from 0.025 to 0.1 mg/l for doxycycline. After 15 passages of sequential subculturing with macrolides, the MICs increased from 12.5 to 12.5 or 50.0 mg/l for azithromycin, from 0.2 to 1.6 or 0.4 mg/l for clarithromycin and from 6.25 to 6.25 or 50 mg/l for erythromycin. After sequential passages with a single quinolone or doxycycline, each isolate was cross-tested for resistance using the other drugs. All isolates selected for resistance to one quinolone were also resistant to the other two quinolones, but not to doxycycline. The doxycycline-resistant isolate was not resistant to any quinolone.
Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Bacillus anthracis/efeitos dos fármacos , Doxiciclina/farmacologia , Bacillus anthracis/crescimento & desenvolvimento , Farmacorresistência Bacteriana , Fluoroquinolonas , Macrolídeos , Testes de Sensibilidade MicrobianaRESUMO
Infections in the immunocompromised host are difficult to treat. The local and systemic effect of penicillin therapy, supplemented by immunoglobulins, and pentoxifylline on wounds infected by Staphylococcus aureus was evaluated in mice irradiated with 6.5 Gy 60Co gamma-rays. Three days after irradiation a suspension of S. aureus was inoculated subcutaneously over the gluteus muscle of anesthetized mice. The skin and the muscle were incised at the site of the inoculation. Treatment with 62.5 mg/kg penicillin-G was administered for 10 days. Numbers of bacteria per mg muscle and presence of organisms in spleens and livers were determined. Numbers of bacteria were significantly reduced from 7.3 (+/- 0.3) to 5.3 (+/- 0.4) log10 CFU/mg (+/- SEM) muscle in treated animals. Administration of immunoglobulin G i.v. or pentoxifylline i.p. alone, or in addition to penicillin-G, did not further reduce the number of bacteria. Increase in the dose of penicillin to 250 mg/kg decreased the number of bacteria more than 62.5 mg/kg. Bacteria were recovered from spleens and/or livers of all 13 untreated mice, and only in six of the 13 penicillin-treated mice (P less than 0.05). Penicillin therapy reduced the systemic spread of S. aureus. The model provides a means to evaluate regimens for treatment of bacterial wound infections in irradiated animals. The data illustrated the ability of antimicrobial agents to contain but not cure the infection in the immunocompromised host, and the lack of efficacy of immunoglobulins in neutropenic mice.
Assuntos
Pentoxifilina/uso terapêutico , Lesões Experimentais por Radiação/complicações , Infecções Estafilocócicas/terapia , Teobromina/análogos & derivados , Infecção dos Ferimentos/terapia , Animais , Radioisótopos de Cobalto , Feminino , Raios gama , Imunidade/efeitos da radiação , Imunoglobulina G/uso terapêutico , Camundongos , Penicilina G/uso terapêutico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológico , Infecção dos Ferimentos/complicações , Infecção dos Ferimentos/tratamento farmacológicoRESUMO
Bacterial infection of simple wounds was studied directly and quantitatively in adult mice given 6.5 Gy 60Co. Three days later, when neutropenia was evident, the skin and the medial gluteus muscle of anaesthetized mice were incised. A suspension of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Streptococcus pyogenes was inoculated into the wound. Bacteria per mg muscle were enumerated 3, 4 or 7 days later. The geometric means of bacteria per mg were greater in irradiated than in non-irradiated mice. Phagocytic cells were present in the wounded tissue. Hence sublethal ionizing radiation enhanced the susceptibility of mice to infections of wounds by these four bacterial species.
Assuntos
Efeitos da Radiação , Infecção dos Ferimentos/microbiologia , Animais , Escherichia coli/isolamento & purificação , Feminino , Klebsiella pneumoniae/isolamento & purificação , Contagem de Leucócitos , Camundongos , Músculos/microbiologia , Radiação Ionizante , Pele/microbiologia , Pele/patologia , Staphylococcus aureus/isolamento & purificação , Streptococcus pyogenes/isolamento & purificação , Trombocitopenia/etiologia , Infecção dos Ferimentos/patologiaRESUMO
PURPOSE: To determine the efficacy of WR-151327 (WR) [S-3-(3-methylaminopropylamino) propylphosphorothioic acid; (CH3-HN-(CH2)3-NH-(CH2)3-S-PO3H2)] in increasing resistance to bacterial infection after a sublethal dose of gamma-photons or mixed-field neutrons plus gamma-photons. MATERIALS AND METHODS: B6D2F1/J female mice received 200 mg/kg WR i.p. or saline vehicle 20-30 min before or after sham (0 Gy) or 7.0 Gy 60Co gamma-photon irradiation. WR or saline vehicle was given only before 3.5 Gy TRIGA-reactor-produced mixed-field [n/(n+y) = 0.67] irradiation. Four days after drug treatment or drug treatment and irradiation, graded doses of Klebsiella pneumoniae were injected s.c. into mice, and 30-day survival was recorded. To assess haemopoietic changes other unirradiated and irradiated mice not injected with bacteria were given WR or saline. Peripheral blood (PB) and femoral bone marrow (BM) cells were measured 1, 3 or 4, 7, 10 and 14 or 15 days later. RESULTS: WR pretreatment increased resistance to infection in irradiated but not in unirradiated mice. Bacterial CFU-LD50/30 values for 0 Gy saline-treated mice were 1.20x10(6); for 0 Gy WR-treated mice 1.16x10(6); for gamma-photon-irradiated saline-treated mice 3.02x10(1); for gamma-photon-irradiated WR-treated mice 1.24x10(4); for mixed-field-irradiated saline-treated mice 1.94x10(2); and for mixed-field-irradiated WR-treated mice 6.13x10(3). WR-induced resistance to infection paralleled increased numbers of PB white cells, neutrophils, platelets, femoral BM cells and granulocyte macrophage colony-forming cells (GM-CFC) in irradiated mice not given bacteria. CONCLUSIONS: These studies quantify the resistance to bacterial infection in mice treated with WR before sublethal irradiation. The findings suggest that WR treatment increases resistance to infection in immunocompromised hosts.
Assuntos
Imunidade Inata/efeitos da radiação , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Compostos Organotiofosforados/farmacologia , Protetores contra Radiação/farmacologia , Animais , Contagem de Células Sanguíneas , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/efeitos da radiação , Feminino , Raios gama , Imunidade Inata/efeitos dos fármacos , Infecções por Klebsiella/mortalidade , Camundongos , Eficiência Biológica RelativaRESUMO
High doses of radiation induce septicaemia, from bacterial translocation, and death in animals. Mice were exposed to either comparable lethal (LD90/30) or sublethal (LD0/30) doses of mixed-field [n/(n + y) = 0.67] or pure 60Co gamma-photon radiation. The relative biological effectiveness of these comparable doses of radiation was 1.82, determined by probit analysis. Mice given a lethal dose of mixed-field radiation developed a significant (p < 0.01), 10(9)-fold increase in Gram-negative facultative bacteria in their ilea over values in control mice. In contrast, mice given a lethal dose of gamma-photon radiation developed a significant (p < 0.01) increase in only Gram-positive bacteria in their ilea, while the number of Gram-negative bacteria remained near values in control mice. Data correlated with bacteria that were isolated and identified from the livers of mice that were given comparable lethal doses (LD99/30) of mixed-field or gamma-photon radiation. In sublethally irradiated mice, fluctuation in the total number of bacteria was detected in their ilea during the first week following irradiation, after which the number approximated the value in control mice. This difference in the predominant facultative bacteria in ilea resulting from different qualities of radiation has important implications for the treatment of septicaemic-irradiated hosts.
Assuntos
Infecções Bacterianas/etiologia , Raios gama , Íleo/efeitos da radiação , Nêutrons , Sepse/microbiologia , Animais , Relação Dose-Resposta à Radiação , Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Íleo/microbiologia , Camundongos , Fatores de TempoRESUMO
Irradiation increases susceptibility to bacterial infection. Exogenous proinflammatory cytokines can alter the response of mice to gamma radiation, but the role of endogenous inflammatory cytokines after bacterial infection in irradiated animals is not known. Gene expression of hematopoietic (GM-CSF) and proinflammatory (IL-1 beta, IL-6 and TNF-alpha) cytokines were examined in spleens of B6D2F1/J female mice after irradiation alone (1.0- and 7.0-Gy), and after irradiation followed by Klebsiella pneumoniae s.c. challenge 4 days postirradiation by using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization. At 4, 8, and 24 h after bacterial challenge in 7.0-Gy-irradiated mice, GM-CSF mRNA increased (p < 0.05). TNF-alpha mRNA in irradiated mice were slightly decreased, whereas after bacterial challenge, TNF-alpha mRNA elevated at 30 h in 7.0-Gy-irradiated mice; at 4, and 8 h in 1.0-Gy-irradiated mice, and at 1 h in sham-irradiated mice (p < 0.05). IL-6 mRNA displayed a biphasic response in 7.0-Gy-irradiated mice, and, after bacterial challenge, in both irradiated mice (1.0- and 7.0-Gy) and sham-irradiated mice. IL-1 beta mRNA remained at or below normal for 8 h and increased at 24 h after bacterial challenge on day 4 in 7.0-Gy-irradiated mice. These results indicate that sublethal gamma radiation alters the patterns of the hematopoietic and proinflammatory cytokine responses to bacterial challenge in vivo. Consequently, treatment protocols may need to take into account changes in cytokine gene responses to resolve infection after irradiation.
Assuntos
Citocinas/imunologia , Regulação da Expressão Gênica/efeitos da radiação , Infecções por Klebsiella/imunologia , Klebsiella pneumoniae , Baço/imunologia , Baço/efeitos da radiação , Animais , Citocinas/genética , Regulação da Expressão Gênica/imunologia , Infecções por Klebsiella/genética , Camundongos , Baço/microbiologiaRESUMO
Spaceflight personnel need treatment options that would enhance survival from radiation and would not disrupt task performance. Doses of prophylactic or therapeutic agents known to induce significant short-term (30-day) survival with minimal behavioral (locomotor) changes were used for 180-day survival studies. In protection studies, groups of mice were treated with the phosphorothioate WR-151327 (200 mg/kg, 25% of the LD(10)) or the immunomodulator, synthetic trehalose dicorynomycolate (S-TDCM; 8 mg/kg), before lethal irradiation with reactor-generated fission neutrons and gamma-rays (n/gamma=1) or 60Co gamma-rays. In therapy studies, groups of mice received either S-TDCM, the antimicrobial ofloxacin, or S-TDCM plus ofloxacin after irradiation. For WR-151327 treated-mice, survival at 180 days for n/gamma=1 and gamma-irradiated mice was 90% and 92%, respectively; for S-TDCM (protection), 57% and 78%, respectively; for S-TDCM (therapy), 20% and 25%, respectively; for ofloxacin, 38% and 5%, respectively; for S-TDCM combined with ofloxacin, 30% and 30%, respectively; and for saline, 8% and 5%, respectively. Ofloxacin or combined ofloxacin and S-TDCM increased survival from the gram-negative bacterial sepsis that predominated in n/gamma=1 irradiated mice. The efficacies of the treatments depended on radiation quality, treatment agent and its mode of use, and microflora of the host.
Assuntos
Anti-Infecciosos/uso terapêutico , Raios gama , Nêutrons , Ofloxacino/uso terapêutico , Compostos Organotiofosforados/uso terapêutico , Lesões Experimentais por Radiação/mortalidade , Tolerância a Radiação/efeitos dos fármacos , Protetores contra Radiação/uso terapêutico , Adjuvantes Imunológicos/uso terapêutico , Animais , Ceftriaxona/uso terapêutico , Cefalosporinas/uso terapêutico , Fatores Corda/uso terapêutico , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/etiologia , Fígado/imunologia , Fígado/microbiologia , Camundongos , Camundongos Endogâmicos , Lesões Experimentais por Radiação/tratamento farmacológico , Lesões Experimentais por Radiação/prevenção & controle , Taxa de SobrevidaRESUMO
After arterial reconstruction, patients have traditionally been followed up in clinic in the long term. We have pursued a policy of limited clinic follow-up, with an 'open access' service for suspected graft failure (and latterly duplex scanning surveillance for vein grafts). This policy was assessed by measurement of the success of self-referral, graft patency and patient satisfaction after operation for lower limb ischaemia in 173 patients. At median follow-up of 50 months, 61 (35%) patients had died and 45 (25%) had required amputation. Of those with salvaged limbs and available for follow-up, 55 (86%) patients reported continuing symptomatic improvement with a graft patency rate of 80%. During the review period, 27 (42%) patients had presented themselves on suspicion of graft occlusion and 14 (52%) of these had required surgical intervention. Of the patients, 45 (70%) found a single postoperative clinic visit helpful, and the majority thought that further visits would not have been helpful to them. Limited clinic appointments seem especially desirable for elderly patients for whom journeys are an imposition, as well as reducing travel costs, and giving surgeons more time to deal with new referrals. These results suggest that properly educated patients present themselves when signs of graft occlusion occur, and there is little to be gained by regular long-term clinic follow-up in vascular surgical practice.
Assuntos
Assistência Ambulatorial/métodos , Arteriopatias Oclusivas/cirurgia , Prótese Vascular , Oclusão de Enxerto Vascular/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inglaterra , Feminino , Seguimentos , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Ambulatório Hospitalar , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
Ionizing radiation could increase morbidity from common bacterial infections in military personnel on the modern battlefield. The combined effects of a sublethal dose of ionizing radiation and the bacterial diarrheal agent Shigella sonnei on body weight and forelimb grip strength in mice were assessed over a 30-day period. Individually housed B6D2F1 female mice were divided into four groups: control, sham irradiation + gavage with saline vehicle; 3 Gy 60Co gamma radiation at 0.4 Gy/min radiation + saline gavage; sham irradiation + 1.3 x 10(8) colony-forming units (CFUs) S. sonnei via gavage, administered 4 days postirradiation; and the combination of 3 Gy 60Co gamma radiation + 1.3 x 10(8) CFUs S. sonnei. Behavioral tests were conducted 3 days preirradiation and on days 9, 14, and 22 postirradiation. Body weight was significantly reduced in the radiation + Shigella group on days 5 to 10 postirradiation. Forelimb grip strength was reduced for mice in the radiation + Shigella group on days 9 and 14 postirradiation. These data demonstrate that an exposure to gamma radiation in combination with the bacterial agent S. sonnei can lead to a synergistic loss of body weight and degradation in performance.
Assuntos
Disenteria Bacilar/complicações , Raios gama/efeitos adversos , Shigella sonnei/patogenicidade , Redução de Peso , Animais , Peso Corporal/efeitos da radiação , Extremidades/fisiopatologia , Extremidades/efeitos da radiação , Feminino , Força da Mão/fisiologia , CamundongosAssuntos
Androstenodiol/administração & dosagem , Raios gama , Lesões por Radiação/prevenção & controle , Protetores contra Radiação/administração & dosagem , Androstenodiol/uso terapêutico , Animais , Feminino , Raios gama/efeitos adversos , Células Matadoras Naturais , Contagem de Leucócitos , Masculino , Camundongos , Monócitos , Neutropenia/etiologia , Neutropenia/prevenção & controle , Protetores contra Radiação/uso terapêutico , Trombocitopenia/etiologia , Trombocitopenia/prevenção & controle , Irradiação Corporal TotalRESUMO
Casualties of radiation dispersal devices, nuclear detonation or major ionizing radiation accidents, in addition to radiation exposure, may sustain physical and/or thermal trauma. Radiation exposure plus additional tissue trauma is known as combined injury. There are no definitive therapeutic agents. Cyclooxygenase-2 (COX-2), an inducible enzyme expressed in pathological disorders and radiation injury, plays an important role in inflammation and the production of cytokines and prostaglandin E(2) (PGE(2)) and could therefore affect the outcome for victims of combined injury. The COX-2 inhibitors celecoxib and meloxicam were evaluated for their therapeutic value against combined injury in mice. In survival studies, the COX-2 inhibitors had no beneficial effect on 30-day survival, wound healing or body weight gain after radiation injury alone or after combined injury. Meloxicam accelerated death in both wounded and combined injury mice. These drugs also induced severe hepatic toxicity, exaggerated inflammatory processes, and did not enhance hematopoietic cell regeneration. This study points to potential contraindications for use of COX-2 inhibitors in patients undergoing therapy for radiation injury and combined injury.
Assuntos
Inibidores de Ciclo-Oxigenase , Pirazóis , Lesões por Radiação/tratamento farmacológico , Sulfonamidas , Animais , Peso Corporal , Celecoxib , Contraindicações , Inibidores de Ciclo-Oxigenase/uso terapêutico , Citocinas/sangue , Dinoprostona/sangue , Feminino , Camundongos , Pirazóis/uso terapêutico , Sulfonamidas/uso terapêuticoRESUMO
OBJECTIVES: Sublethal ionizing doses of radiation increase the susceptibility of mice to Bacillus anthracis Sterne infection. In this study, we investigated the efficacy of clindamycin in 60Co-gamma-photon-irradiated and sham-irradiated mice after intratracheal challenge with B. anthracis Sterne spores. Clindamycin has in vitro activity against B. anthracis and inhibits the production of toxin from other species, although no direct evidence exists that production of B. anthracis toxin is inhibited. METHODS: Ten-week-old B6D2F1/J female mice were either sham-irradiated or given a sublethal 7 Gy dose of 60Co-gamma-photon radiation 4 days prior to an intratracheal challenge with toxigenic B. anthracis Sterne spores. Mice were treated twice daily with 200 mg/kg clindamycin (subcutaneous or oral), 100 mg/kg moxifloxacin (oral), 50 mg/kg ciprofloxacin (subcutaneous) or a combination therapy (clindamycin + ciprofloxacin). Bacteria were isolated and identified from lung, liver and heart blood at five timed intervals after irradiation. Survival was recorded twice daily following intratracheal challenge. RESULTS: The use of clindamycin increased survival in gamma-irradiated and sham-irradiated animals challenged with B. anthracis Sterne in comparison with control mice (P < 0.001). Ciprofloxacin-treated animals had higher survival compared with clindamycin-treated animals in two experiments, and less survival in a third experiment, although differences were not statistically significant. Moxifloxacin was just as effective as clindamycin. Combination therapy did not improve survival of sham-irradiated animals and significantly decreased survival among gamma-irradiated animals (P = 0.01) in comparison with clindamycin-treated animals. B. anthracis Sterne was isolated from lung, liver and heart blood, irrespective of the antimicrobial treatment. CONCLUSIONS: Treatment with clindamycin, ciprofloxacin or moxifloxacin increased survival in sham-irradiated and gamma-irradiated animals challenged intratracheally with B. anthracis Sterne spores. However, the combination of clindamycin and ciprofloxacin increased mortality associated with B. anthracis Sterne infection, particularly in gamma-irradiated animals.
Assuntos
Antraz/tratamento farmacológico , Antibacterianos/uso terapêutico , Compostos Aza/uso terapêutico , Ciprofloxacina/uso terapêutico , Clindamicina/uso terapêutico , Quinolinas/uso terapêutico , Lesões Experimentais por Radiação/complicações , Administração Oral , Animais , Antraz/complicações , Antraz/patologia , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Compostos Aza/administração & dosagem , Compostos Aza/farmacologia , Bacillus anthracis/efeitos dos fármacos , Bacillus anthracis/genética , Bacillus anthracis/isolamento & purificação , Sangue/microbiologia , Ciprofloxacina/administração & dosagem , Ciprofloxacina/farmacologia , Clindamicina/administração & dosagem , Clindamicina/farmacologia , Modelos Animais de Doenças , Quimioterapia Combinada , Feminino , Fluoroquinolonas , Raios gama , Injeções Subcutâneas , Fígado/microbiologia , Pulmão/microbiologia , Camundongos , Moxifloxacina , Quinolinas/administração & dosagem , Quinolinas/farmacologia , Análise de SobrevidaRESUMO
A new technique of balloon-assisted laparoscopic lumbar sympathectomy is described and the results of the initial three cases are described. The procedure is technically straightforward and was accomplished without any complications. It should be compared with other techniques of lumbar sympathectomy in comparative trials; however, this early experience is most encouraging.
Assuntos
Laparoscopia/métodos , Simpatectomia/métodos , Adolescente , Idoso , Feminino , Humanos , Hiperidrose/cirurgia , Laparoscópios , Região Lombossacral , Masculino , Doenças Vasculares Periféricas/cirurgia , Peritônio , Simpatectomia/instrumentaçãoRESUMO
BACKGROUND: The objective of this study was to audit the presentation and outcome for patients admitted with an acute complication of diverticular disease. METHODS: This study was a retrospective review of 418 admissions with an acute complication of diverticular disease over a 5-year interval. RESULTS: Of the 418 admissions, 15 patients were eventually found to have an alternative diagnosis. Some 403 patients were studied further. The overall mortality rate in this group was 5.7 per cent. A total of 113 patients (28.0 per cent) required an operation and in this group the mortality rate was 17.7 per cent. All deaths occurred in patients who had surgery for septic complications or bowel obstruction. Of the patients who had surgery, 90.2 per cent had a resection of the involved colon. One-third of these had a primary anastomosis; the remainder underwent Hartmann's procedure. Some 83 patients had a stoma fashioned and of these 72 went on to have the stoma closed. The median age of those who died after operation was 80 years. An American Society of Anesthesiologists (ASA) score of 3 or more, concurrent medical disease and shock on admission were all associated with a high mortality rate (P < 0.001). Some 30 per cent of patients were readmitted during this study with a further complication of diverticular disease. CONCLUSION: The mortality rate after surgery for acute diverticular disease remains excessive and a high-risk group can be identified before operation. A policy of resection and anastomosis appears justified for selected patients. Adopting a practice of interval elective sigmoid colectomy after admission with acute diverticulitis might prevent readmission with further complications.