Biomedical subjects
Publications and source records attributed to J S Doyle.
Orthopedics and neurosurgery offer multiple surgical modalities for improving the function, care, and well-being of children with spasticity. One surgical approach is not the best for all children with spasticity not adequately controlled with more conservative measures. For that reason, a multidisciplinary evaluation is important to optimize outcome for these children.
BACKGROUND & AIMS: Interleukin (IL)-10 gene-deficient mice, raised under germfree conditions, do not develop colitis, implying a role for bacteria. This study mapped the appearance of luminal colonic bacteria and, using antibiotic treatment, determined their association with colitis in IL-10 gene-deficient mice. METHODS: Mice were treated with ciprofloxacin or with neomycin and metronidazole. The intestine was harvested for histological scoring and bacterial assessment. RESULTS: At 2 weeks of age, before the development of colitis, IL-10 gene-deficient mice demonstrated an earlier appearance of Streptococcus and Clostridium sp., and had a greater proportion (P < 0.01) of bacteria adherent to the colonic mucosa. This pattern of increased adherent bacteria persisted for the 12 weeks of study. Treatment of mice before the onset of colonic inflammation, with either antibiotic regime, reduced mucosal adherent bacteria and prevented colitis (P < 0.01). In contrast, treatment of established colitis with neomycin and metronidazole did not reduce adherent bacterial levels, yet was more efficacious (P < 0.05) in treating established colitis than ciprofloxacin, which did reduce adherent colonic bacteria. CONCLUSIONS: In the IL-10 gene-deficient mouse model, the appearance and number of mucosal adherent colonic bacteria are altered before the onset of colitis. Antibiotics both prevent and treat the colitis through correction of this primary bacterial alteration.
BACKGROUND & AIMS: Intestinal luminal microflora, or their products, are likely an important initiating factor in the pathogenesis of inflammatory bowel disease. The aim of this study was to determine the role of colonic aerobic luminal bacteria and Lactobacillus species in the development of colitis in interleukin (IL)-10 gene-deficient mice. METHODS: Intestine from 2-16-week-old mice was scored histologically and cultured for bacteria. Lactobacillus sp. repopulation of the colonic lumen was achieved via daily rectal delivery of Lactobacillus reuteri or oral lactulose therapy. RESULTS: At 2 weeks of age, IL-10 gene-deficient mice showed no colonic injury but did display abnormal colonic bacterial colonization with increased colonic mucosal aerobic adherent and translocated bacteria in conjunction with reduced Lactobacillus sp. levels. In association with the abnormal colonic bacterial colonization, colitis developed by 4 weeks of age. Restoring Lactobacillus sp. to normal levels reduced levels of colonic mucosal adherent and translocated bacteria and attenuated the development of the colitis. CONCLUSIONS: In the neonatal period, IL-10 gene-deficient mice have decreased levels of colonic Lactobacillus sp. and an increase in colonic mucosal adherent and translocated bacteria. Normalizing Lactobacillus sp. levels reduced colonic mucosal adherent and translocated bacteria and prevented colitis.
The normal intestinal epithelium provides a barrier relatively impermeable to luminal constituents. However, patients with inflammatory bowel disease experience enhanced intestinal permeability that correlates with the degree of injury. IL-10 gene-deficient mice were studied to determine whether increased intestinal permeability occurs as a primary defect before the onset of mucosal inflammation or is secondary to mucosal injury. At 2 weeks of age, IL-10 gene-deficient mice show an increase in ileal and colonic permeability in the absence of any histological injury. This primary permeability defect is associated with increased mucosal secretion of interferon-gamma and tumor necrosis factor-alpha, and does not involve an increase in nitric oxide synthase activity. Colonic permeability remains elevated as inflammation progresses, while ileal permeability normalizes by 6 weeks of age. IL-10 gene-deficient mice raised under germ-free conditions have no inflammation, and demonstrate normal permeability and cytokine levels. This data suggests that the intestinal permeability defect in IL-10 gene-deficient mice occurs due to a dysregulated immune response to normal enteric microflora and, furthermore, this permeability defect exists prior to the development of mucosal inflammation.
2,4-Dichlorophenoxyacetic acid (2,4-D) is a selective weedkiller which works by uncoupling oxidative phosphorylation and is in widespread use. It is known as "agent orange". A 65 year old man had acute hepatitis, thought to be caused by exposure to 2,4-D. The patient ingested 2,4-D as a result of habitual licking of his golf ball. Clinical and histological data together with a challenge test confirmed the diagnosis of "golf ball liver".
STUDY DESIGN: A retrospective review of 15 patients with Down syndrome who had undergone arthrodesis of the upper cervical spine for instability. OBJECTIVES: To determine the complication rate and long-term outcome after posterior cervical arthrodesis for upper cervical instability in patients with Down syndrome. SUMMARY OF BACKGROUND DATA: Atlantoaxial instability is common in patients with Down syndrome, and fusion of the upper cervical spine has been recommended for patients who have instability, with or without myelopathy. Unfortunately, the results of posterior cervical arthrodesis are not well reported, and the natural history of this condition is unknown. METHODS: Fifteen patients with an average follow-up period of 74.6 months (range, 24-142 months) were reviewed after posterior arthrodesis of the upper cervical spine. Twelve patients were reexamined by the investigators specifically for the purpose of this study, and three patients had long-term follow-up results available from chart review. RESULTS: Eleven of 15 patients (73%) sustained 23 major complications including nonunion, loss of reduction, neurologic deterioration, late subaxial instability, infection, and wound dehiscence. Six patients (40%) required seven reoperations to address a complication. Ultimately, 12 patients (80%) obtained osseous union, but a definite clinical improvement was identifiable in only three patients, whereas two others had worsened neurologically at latest follow-up evaluation. CONCLUSIONS: A high complication rate should be anticipated after posterior arthrodesis of the upper cervical spine in patients with Down syndrome. A cautious approach to asymptomatic instability in this condition is advocated.
OBJECTIVE: To investigate the relationships between degradation of bone and activated blood polymorphonuclear leukocytes (PMNL) and mononuclear leukocytes (ML) as well as their soluble products in vitro. MATERIALS AND METHODS: A neonatal mouse calvarial bone model was used to assess the activity of degradation (by measuring the amount of 45Ca release) by normal human blood leukocytes, separated PMNL and ML following 24-hour incubation. The effects of conditioned culture medium obtained from Staphylococcus aureus-stimulated ML on PMNL-mediated calvarial bone loss were also studied. RESULTS: It was demonstrated that isolated human PMNL rapidly degraded bone in a dose and time dependent manner. The PMNL-mediated bone degradation was enhanced by conditioned medium obtained from Staphylococcus aureus-stimulated ML. CONCLUSION: These findings implicate PMNL as major contributors to early bone loss in infectious diseases such as acute haematogenous osteomyelitis.
An in vivo canine model was developed to investigate the histologic and biochemical parameters associated with aseptic loosening. Thirty-eight canines had cementless total hip arthroplasty. Experimental groups were designed specifically to investigate the relative contributions of implant motion and particulate debris (cobalt chrome alloy, titanium aluminum vanadium, and polyethylene) on the resultant periprosthetic tissues. Tissues from a stable, well-ingrown prosthesis provided a control. Importantly, the histologic and biochemical characteristics of the experimentally induced membranes consistently correlated with previous in vitro reports of tissues retrieved at revision surgery for aseptic loosening. Implant motion and all 3 particulate debris groups resulted in increased numbers of macrophages in the periprosthetic membranes. The histologic findings paralleled the increase in levels of biochemical mediators of bone resorption as measured by collagenase, gelatinase, prostaglandin E2, and interleukin-1 activity. The most striking results were seen in the histology and biochemistry of the particle groups with highly cellular membranes showing increased biochemical activity when compared with controls. The clinical relevance of this work lies in the description of an in vivo model of aseptic loosening that can be used to investigate the effects of numerous variables implicated in aseptic loosening. Ultimately, the model may serve as a basis for developing therapeutic interventions.
Explore the source record for details and available documents.
The previously unreported association of granulomatous gastritis and mononeuritis multiplex occurring in the setting of a vasculitic syndrome is described. The two conditions are considered to be associated and to be immune mediated. The previously accepted concept of isolated granulomatous gastritis is disputed.
A case of angiodysplasia, symptomatic for 18 years, is presented. This case highlights the difficulty of establishing a diagnosis. Associated findings included aortic stenosis and a carcinoid tumour of the ileum. Despite transfusion of a total of 1200 units of blood the liver was normal at necropsy.
Over a two year period 108 patients had cranial computerised tomographic (CCT) scans while under the care of a general medical team. Sixty eight scans showed 70 abnormalities. Completed stroke, transient ischaemic attacks (TIA), epilepsy and headache were the most common indications for CTT while infarct, atrophy, haemorrhage and tumour were the most common abnormalities. Eight tumours were identified comprising 12% of epileptics and 9% of stroke patients.
The behavioral effects of intracerebroventricular (ICV) injection of the brain-gut peptide vasoactive intestinal peptide (VIP) were quantified with a behavioral sampling technique in home-caged, nondeprived, male and female albino rats and golden hamsters. ICV VIP sex-dependently decreased observed resting behavior during 1 hr after injections in both rats and hamsters at 0.1-10.0 micrograms. Grooming behavior was increased in hamsters, and rearing and standing behaviors were increased in rats, sex-dependently at VIP doses that decreased resting. Drinking behavior was suppressed in rats by VIP at 10.0 micrograms. Intraperitoneal (IP) VIP (100.0 micrograms/kg) increased 5% ethanol intake and decreased eating behavior in fluid-deprived male rats. The increase in ethanol intake produced by IP VIP was prevented by IP cholecystokinin octapeptide (CCK, 4.0 micrograms/kg). VIP potently controls resting and ingestive behaviors, suggesting a role for this neuropeptide, along with CCK, in the feedback regulation of rodent behavior.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.