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Biomedical subjects

M O'Reilly

Publications and source records attributed to M O'Reilly.

At least 73 records · Page 4Linked to original sources
PubMed1993

Bone marrow toxicity by silver sulfadiazine.

The effect of silver sulfadiazine (SSD) on the production of granulocytes and macrophages was studied in a murine model of cutaneous injury. Application of SSD daily to mice receiving a 10 percent full-thickness total body surface area burn injury failed to demonstrate consistent suppression of the bone marrow at one, four or seven days postinjury. Mice undergoing a 10 percent full-thickness skin excision (SE) and daily SSD application (SE plus SSD) had a near 50 percent reduction in total peripheral blood leukocyte counts in comparison with a control group and untreated mice that were skin-excised (SE-U) (p < 0.03) to 0.002) on day one postinjury and maintained this reduction compared with SE-U at days four and seven postinjury. The absolute number of granulocytes in SE plus SSD was only 10 percent of control or SE-U (p < 0.04 to 0.002) at day one postinjury and remained less than SE-U at four and seven days postinjury. Femoral bone marrow assay of granulocyte-macrophage progenitor cells (GM-CFC) revealed a marked reduction in nucleated bone marrow cells for SE plus SSD compared with respect to control at days one and seven and SE-U at days four and seven (p < 0.02 to 0.001). GM-CFC were significantly depressed in SE plus SSD on day one compared with C and SE-U and day four compared with SE-U (p < 0.01 to 0.001), but returned to control values by day seven. When SSD (0.5 to 500.0 micrograms per milliliter) was added to culture plates containing maximally stimulated normal murine or human bone marrow cells, the colony count was depressed in a dose-dependent manner. In vitro SSD is directly cytotoxic to myelopoietic tissue, and in vivo, alters the myeloid cell compartment. These observations in combination may explain the transient leukopenia frequently observed in patients receiving topical chemoprophylaxis with SSD.

Animals↗
PubMed1992

Interleukin 1 beta improves survival following cecal ligation and puncture.

Despite antibiotic therapy intra-abdominal sepsis following major surgery is a significant cause of mortality. We sought to determine if interleukin-1 beta (IL-1) could improve survival in a murine model of intra-abdominal infection. Groups of 10 BDF1 mice received a single subcutaneous (sc) injection of recombinant human IL-1 beta 24 hr prior to cecal ligation and puncture (CLP) and were assessed twice daily for survival. Mice that received a single injection of IL-1 beta 24 hr prior to CLP had a dose-dependent improval in survival compared to controls. The beneficial effect of IL-1 treatment may have been related to its ability to stimulate myelopiesis. The addition of indomethacin, in an effort to limit possible toxicity of IL-1, did not further improve survival. Appropriate timing of specific immunomodulators may provide an additional strategy for the treatment of infections.

Abdomen↗
PubMed1992

Treatment of intra-abdominal infection with granulocyte colony-stimulating factor.

Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Assessing the loneliness of workers with mental retardation.

This study was designed to determine whether a reliable instrument could be developed to measure the loneliness experienced by workers with mental retardation. In addition, supervisors were asked to rate subjects on loneliness and four other behavioral subtypes in order to determine whether there was a relation between these ratings and the loneliness questionnaire. Three groups of subjects were assessed: persons with mild, moderate, and severe mental retardation. Results indicated that the Worker Loneliness Questionnaire was a reliable instrument for use with persons with mild and moderate mental retardation. In addition, the results showed that some individuals were lonely; however, this was not a pervasive feeling. The implications for measuring the self-perceptions of individuals with mental retardation were discussed.

Adult↗
PubMed1991

Safe performance of difficult laparoscopic cholecystectomies.

Laparoscopic cholecystectomy has been advocated for the treatment of uncomplicated symptomatic gallstone disease, but has not been widely advocated for the management of more complicated gallbladder disease such as acute cholecystitis, previous surgery, or common duct stones. During the last 9 months, 360 patients underwent laparoscopic removal of their gallbladder. A total of 138 had a complicated presentation, making surgery more difficult. This article discusses the management of these patients with acute cholecystitis, previous surgery, or common duct disease. Using the described techniques, there were no complications or mortality. Laparoscopic management of difficult gallbladder problems is safe and effective.

Acute Disease↗
PubMed1990

The effect of interleukin 1 alpha on survival in a murine model of burn wound sepsis.

We examined the effects of human recombinant interleukin 1 alpha (IL-1 alpha) in a murine model of burn wound sepsis. The BDF1 male mice received a 15% burn injury, followed by burn wound inoculation with Pseudomonas aeruginosa. Improvement in survival was noted in the mice that received a single injection of 100 or 1000 ng of IL-1 alpha in comparison with the control animals (IL-1 alpha, 100 ng vs control, 60% vs 13%; IL-1 alpha, 1000 ng vs control, 40% vs 0%). The animals that received 1 ng twice daily for 7 days had improved survival in comparison with the controls (IL-1 alpha vs control, 70.8% vs 20.8%). The animals that received a single injection of 1000 ng after a bacterial challenge with 10(4) P aeruginosa of IL-1 alpha had fewer positive blood cultures at 48 hours compared with the controls (57% vs 89%). In addition, the animals that received 100 ng of IL-1 alpha had significantly increased absolute neutrophil counts at 6, 24, and 48 hours after thermal injury and bacterial challenge with 10(3) colony-forming units of P aeruginosa. The use of cytokines to modulate the host response to injury or infection may lead to additional strategies to improve the outcome following burn injury.

Animals↗
PubMed1990

Protective effect of recombinant human granulocyte colony-stimulating factor against pneumococcal infections in splenectomized mice.

Granulocyte colony-stimulating factor stimulates the proliferation and differentiation of progenitor cells committed to the neutrophil lineage, and it has been shown to improve survival to bacterial challenge in neutropenic mice. We studied recombinant human granulocyte colony-stimulating factor (rhG-CSF), cloned from bladder cell carcinoma line 5637, in a nonneutropenic infection model of Streptococcus pneumoniae pulmonary infection in splenectomized and sham-operated control mice. The rhG-CSF improved survival in the splenectomized mice but not in the sham-operated mice. Circulating leukocyte counts were greatest for the rhG-CSF-treated splenectomized mice compared with all other groups, presumably due to a loss of splenic sequestration. Clearance of live pneumococci from mouse lung pairs was impaired after splenectomy. The rhG-CSF improved lung clearance in both splenectomized and sham-operated mice compared with saline solution-treated controls. The number of live pneumococci recovered from tracheobronchial lymph nodes at 24 hours after aerosol challenge was greatest in the splenectomized mice vs sham-operated mice. Decreased numbers of viable pneumococci were recovered from tracheobronchial lymph nodes from the rhG-CSF-treated splenectomized mice and the sham-operated mice vs saline solution-treated controls. The rhG-CSF may be a useful adjuvant for treating infections in individuals with immunologic dysfunctions other than neutropenia.

Animals↗
PubMed1990

Tumor necrosis factor and wound healing.

Tumor necrosis factor alpha (TNF), 1 to 500 ng in saline (PBS) or collagen, was applied to the wounds of normal and Adriamycin-impaired mice and wound disruption strength (WDS) and histology were examined. Also wounded mice were administered TNF 25 to 75 micrograms/kg IP daily and WDS was determined. Wound histology was examined 6 months after wounding and local TNF application. Local TNF 5 to 500 ng in PBS did not significantly affect WDS. Local TNF 5 to 50 ng in collagen increased WDS 33% to 65% in Adriamycin-impaired animals (p = 0.05 to p less than 0.02). Local TNF 50 to 500 ng in collagen increased WDS 23% to 49% in normal animals (p = 0.08 to p less than 0.01). Adriamycin-impaired animals demonstrated improved wound histology with local TNF in collagen. Systemic TNF did not significantly affect WDS. Local TNF in collagen did not induce histologic pathology at 6 months. TNF may modulate macrophage function and local TNF in collagen can improve WDS in normal and Adriamycin-impaired animals.

Administration, Topical↗
PubMed1990

The coagulase of Staphylococcus aureus 8325-4. Sequence analysis and virulence of site-specific coagulase-deficient mutants.

The sequence of the coagulase gene (coa) from Staphylococcus aureus strain 8325-4 is reported. The deduced amino acid sequence of the coagulase protein is compared with previously reported sequences of coagulases from strains 213 and BB. The secreted mature forms of coagulase proteins are composed of three distinct segments: (i) the N-terminal 150-270 residues, which are c. 50% identical, (ii) a central region with high (greater than 90%) residue identities, and (iii) a C-terminal region composed of repeated 27-amino-acid residue sequences. The variable N-terminal sequences are probably responsible for antigenic differences among coagulases of different serotype. The region of coagulase which binds to prothrombin and activates it to form staphylothrombin is also located in the N-terminal half of the protein. A site-specific substitution mutation in the coa gene, which abolished plasma clotting activity, was isolated by recombinational allele-replacement in strains 8325-4 and M60. The Coa- mutants did not show diminished virulence in subcutaneous and intramammary infections of mice. No evidence for a role for coagulase in virulence of toxigenic or nontoxigenic strains was obtained. This contradicts findings of several groups using Coa- mutants generated by chemical mutagenesis and suggests that the earlier results were obtained with strains that had suffered additional mutations in virulence-related genes.

Alleles↗
PubMed1990

Cryptic alpha-toxin gene in toxic shock syndrome and septicaemia strains of Staphylococcus aureus.

The majority of clinical isolates of Staphylococcus aureus that produce toxic shock syndrome toxin-1 (TSST-1) fail to express alpha-toxin, despite having a copy of the hla gene in the chromosome. The hla gene was cloned from an Hla- TSST-1+ strain, Todd 555, which had been isolated from a case of toxic shock syndrome in the USA. Of the 630 bases of the Todd 555 gene sequenced, 46 differed from the hla gene sequence of strain Wood 46. The defect in alpha-toxin expression was shown to be due to a nonsense mutation which converted a CAG glutamine codon in the equivalent position in the functional Wood 46 sequence to a TAG stop codon. The same mutation was present in the hla gene cloned from a human septicaemia strain (V37) isolated in Dublin. The nonsense mutation of Todd 555 was suppressed by the supE44 mutation in Escherichia coli resulting in haemolytic activity in cell lysates. Hybrid hla genes were formed by splicing fragments of hla from Todd 555 and Wood 46. Expression of one such chimaeric hla gene in S. aureus demonstrated that the Todd 555 hla gene has a functional agr-regulated promoter. The silent hla gene may be a cryptic gene in S. aureus.

Animals↗
PubMed1990

Prophylaxis against postsplenectomy pneumococcal infection.

An excess risk of overwhelming sepsis following splenectomy is well established. In view of this, surgical responsibility must embrace the administration of pneumococcal prophylaxis. Current recommendations vary, but routine pneumococcal vaccination, together with penicillin prophylaxis in selected patients, is advocated widely. This retrospective review of 75 patients undergoing splenectomy was undertaken in order to evaluate the extent to which current practice complies with these recommendations. Among surviving patients, the incidence of vaccination with polyvalent pneumococcal vaccine (PPV) was found to vary according to operative indication. All haematological patients received pre-operative PPV. Two-thirds of multitrauma patients were vaccinated, while 42% of patients who required splenectomy following accidental intra-operative trauma received PPV. Only 11% of patients who underwent incidental splenectomy were vaccinated. Long-term antibiotic prophylaxis was commenced in 33% of surviving patients under 20 years of age, and in 8% with underlying malignancy. These results highlight a need for greater vigilance in the administration of pneumococcal prophylaxis, particularly following accidental or incidental splenectomy.

Adult↗
PubMed1990

Indomethacin augments granulocyte-macrophage colony-stimulating factor-induced hematopoiesis following 5-FU treatment.

We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF) given after the administration of 5-fluorouracil (5-FU) results in augmented hematopoietic recovery as evidenced by increased white blood cell and neutrophil counts. Mice receiving GM-CSF following 5-FU administration were observed to have a marked elevation in splenic granulocyte-macrophage colony-forming cells (GM-CFC) and a decrease in the femoral bone marrow GM-CFC. Because GM-CSF has been shown to increase prostaglandin synthesis and prostaglandins are thought to provide a negative feedback signal to down-regulate myelopoiesis, we sought to determine if the cyclooxygenase inhibitor, indomethacin, could prevent the reduction in the number of femoral bone marrow GM-CFC seen when GM-CSF was administered following 5-FU. Groups of mice received a single 60 mg/kg i.p. injection of 5-FU followed 24 h later by twice-daily injections of 1 micrograms GM-CSF and daily injections of 3, 5, or 6 mg/kg indomethacin; the hematopoietic assays were performed on day 7 following 5-FU. Compared to those animals that received GM-CSF alone following 5-FU, mice receiving 5 mg/kg indomethacin plus GM-CSF following 5-FU had increased numbers of GM-CFC in their bone marrow (3923 +/- 634 vs 971 +/- 138; p less than 0.001) as well as increased neutrophil counts (18,995 +/- 2872 vs 11,497 +/- 2476; p less than 0.01). Indomethacin alone was, in part, capable of facilitating hematopoietic recovery following 5-FU administration, but not to the extent seen when used in combination with GM-CSF. Prostaglandin inhibitors may have a role in combination with hematopoietic growth factors in accelerating hematopoietic recovery following cytoreductive chemotherapy.

Animals↗
PubMed1989

Roles of alpha-toxin and beta-toxin in virulence of Staphylococcus aureus for the mouse mammary gland.

Mutants of Staphylococcus aureus which fail to express alpha-toxin (Hly), beta-toxin (Hlb), or both have been constructed by site-specific mutagenesis. The virulence of the mutants was compared with that of wild-type toxigenic strains by intramammary inoculation of lactating mice. A bovine strain, M60, and a laboratory strain, 8325-4, caused acute mastitis and death within 48 h for 60% of the mice inoculated. Animals inoculated with Hly mutants also developed acute mastitis, but no deaths occurred. Comparisons of Hly- or Hlb-positive strains with the double mutation Hly Hlb showed that both toxins led to a significantly higher recovery of S. aureus from the gland 48 h postinfection. Histopathological examination of mammary glands showed that phagocytosis of bacteria occurred irrespective of toxigenicity, but toxigenic strains, particularly those which were Hly+, continued to multiply, invaded the interalveolar tissues, and produced severe lesions. Stimulation of an inflammatory response by inoculation of the mammary gland with endotoxin prior to challenge with S. aureus reduced recovery of the bacteria 10- to 100-fold and, under these conditions, neither alpha-toxin nor beta-toxin contributed significantly to growth and survival.

Animals↗
PubMed1989

The beneficial effect of granulocyte colony-stimulating factor (G-CSF) in combination with gentamicin on survival after Pseudomonas burn wound infection.

Inadequate granulopoiesis and decreased granulocyte function are thought to play a significant role in the burned victim's susceptibility to infection. In an attempt to determine whether the regulatory granulopoietic growth factor G-CSF could favorably affect survival when used in combination with antibiotics, we examined survival in a murine model of Pseudomonas aeruginosa burn wound infection. One hundred twenty male BDF1 mice received a 15% total body surface area burn and were randomized to one of five treatment groups: (1) burn only, (2) burn + infection, (3) burn + infection + G-CSF, (4) burn + infection + gentamicin, and (5) burn + infection + G-CSF + gentamicin. Infected mice received a 10(3) colony-forming units topical inoculum of Pseudomonas to the wound immediately postburn. Gentamicin animals received 6.0 mg/kg intraperitoneal gentamicin as a single dose immediately postburn. G-CSF was administered as 100 ng twice daily for 7 days. All treatment groups showed improved survival compared with the burn + infection group, which showed 100% mortality by day 9 (p less than 0.001 all groups; Cox-Mantel statistic). Group 5 (burn + infection + G-CSF + gentamicin) exhibited improved survival as compared with either group 3 (burn + infection + G-CSF, p = 0.054) or group 4 (burn + infection + gentamicin, p = 0.007). The use of hematopoietic growth stimulants in combination with antibiotic therapy may result in improved outcome after burn injury, and it suggests new treatment options in the management of postburn infectious complications.

Animals↗