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Biomedical subjects

J Grigg

Publications and source records attributed to J Grigg.

At least 37 records · Page 2Linked to original sources

Bronchoalveolar lavage fluid cellularity and soluble intercellular adhesion molecule-1 in children with colds.

Viral colds are an important cause of respiratory symptoms in normal children. Studies in adults suggest that inflammation in the lower respiratory tract is associated with viral colds, but there are no data regarding inflammation and viral infection in the lower airway of normal children with colds. We, therefore, studied the lower airway of two groups of children: Group I, those with active coryzal symptoms and a respiratory virus isolated from bronchoalveolar lavage fluid (BALF); and Group II: asymptomatic children who had had a clinical cold within the previous 2 weeks and no respiratory virus in BALF. Both groups were compared to age- and weight-matched normal noninfected controls, who had had no coryzal symptoms for at least 8 weeks. Viruses isolated from BALF of Group I (n = 7) were: respiratory syncytial virus (n = 2), rhinovirus (n = 3), parainfluenza I (n = 1), and echovirus 11 (n = 1). Compared to normal controls, Group I had an increased BALF lymphocyte and neutrophil differential count (P < 0.05), a concomitant depressed alveolar macrophage differential count (P < 0.05), and increased BALF concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) (P < 0.05, n = 6), total protein (P < 0.05, n = 6) and albumin (P < 0.05, n = 7). Similar changes were seen in Group II (n = 22), with an increased BALF neutrophil (P < 0.05) and lymphocyte (P < 0.01) differential count, and increased concentrations of sICAM-1 (P < 0.01, n = 15), total protein (P < 0.0001, n = 9) and albumin (P = 0.05, n = 17). Our results suggest that inflammation and viral infection in the lower airway are present during active colds, and that inflammation is also present during the convalescent period.

Adolescent↗

Soluble intercellular adhesion molecule-1 in the bronchoalveolar lavage fluid of normal children exposed to parental cigarette smoke.

This study sought to test the hypothesis that normal children exposed to parental cigarette smoke have increased bronchoalveolar lavage (BAL) fluid levels of soluble intercellular adhesion molecule (sICAM)-1. Cells and solutes from the lower airway of normal children were obtained by nonbronchoscopic BAL using three aliquots of 1 mL x kg body weight(-1) normal saline, prior to elective orthopaedic surgery. Children with evidence of recent or ongoing infection, atopic disease, previous history of wheeze, and chronic respiratory symptoms were excluded. Twelve children with parents who smoked (group 1) were paired with 12 age- and weight-matched controls with self-reported nonsmoking parents (group 2). There was no significant difference (group 1 versus 2) in the volume of BAL fluid recovered (median 29.0 versus 28.7 mL), the percentage of alveolar macrophages (92.5 versus 91.8%), neutrophils (1.1 versus 2.1%), lymphocytes (5.3 versus 5.6%) and eosinophils (0 versus 0%), and the total BAL fluid leukocyte concentration (80 versus 61 x 10(3) cells x mL(-1)). BAL fluid albumin concentration was similar between the two groups (0.033 versus 0.020 mg x mL(-1)). sICAM-1 was detected in all BAL fluid samples, and was significantly increased in group 1 (39.2 versus 22.5 ng x mL(-1), p<0.01). It was concluded that exposure of children to parental cigarette smoke is associated with increased soluble intercellular adhesion molecule-1 concentrations in the bronchoalveolar lavage fluid and this may reflect an altered activation of pulmonary immune cells.

Adolescent↗

Alveolar macrophage immaturity in infants and young children.

Very little is known about alveolar macrophage (AM) immunological function in early childhood. Using nonbronchoscopic bronchoalveolar lavage (BAL), this study sought to compare the proportion, number, and function of AM between very young and older children. BAL fluid (BALF) leukocyte parameters were determined in 63 children, and data divided into 3 age groups: group 1 (<2 yrs), group 2 (> or =2-< or =5 yrs) and group 3 (> or =6-< or =17 years). In a further subgroup of children, AM function and immune receptor expression were assessed, and data categorized into two age groups: <2 yrs and > or =2 yrs of age. Compared to groups 2 and 3, the AM percentage in the BAL in group 1 was significantly increased (median: 98% versus 92% and 91%), as was the albumin-adjusted AM concentration. AM from children <2 yrs expressed less human leukocyte antigen (HLA)-DR (versus > or =2 yrs of age), were less effective in reducing nitro blue tetrazolium, and released less interleukin (IL)-1 and tumour necrosis factor on lipopolysaccharide stimulation. There was no difference in release of IL-6, expression of intercellular adhesion molecule-1 (CD54), and AM stimulation of allogeneic T-cells, between children <2 yrs and > or =2 yrs of age. It was concluded that the capacity of alveolar macrophage to stimulate T-cells is not enhanced in early childhood, and that immaturity of alveolar macrophage function may contribute to an increased susceptibility to respiratory infections in this age group.

Adolescent↗

Choroidal melanoma: a review of the experience of the Sydney Eye Hospital Professorial Unit 1979-1995.

PURPOSE: This study examines 90 patients presenting with choroidal or ciliochoroidal melanoma to the Professorial Unit at the Sydney Eye Hospital. The indications for treatment, and the outcome for the eye and vision are presented together with an account of mortality and the incidence of metastases. METHODS: A retrospective analysis of 90 choroidal melanoma patients managed by one surgeon over a 16-year period was undertaken. Initial findings, investigations performed, incidence of metastatic disease, treatment received and complication rates and mortality, where applicable, were recorded. RESULTS: The group was followed for an average of 64 months (range, 5-172 months). Primary treatment was with either iodine125 (125I) brachytherapy, local excision or enucleation. Radiation retinopathy was prominent in 125I cases resulting in poor visual acuity when the tumour resided in the posterior pole. Local excision even of large tumours was effective particularly if peripheral. Overall metastatic disease was seen in 11% with 5-year survival rates for the metastatic group being 10%. Prognosis after diagnosis of metastases was poor. CONCLUSIONS: Specific therapy for choroidal melanoma must relate to the size and location of the tumour at the time of diagnosis. Visual outcome relates directly to the proximity of the tumour to the optic nerve and fovea. Metastatic disease latency can be prolonged; therefore caution about prognosis is required long after therapy is given. The 5-year survival is encouraging with all forms of therapy. However, as the natural history of ocular melanoma is variable and not fully delineated it is important to monitor the effects of conservative therapy. Further long-term survival data is required to distinguish whether one form of treatment is advantageous over the others, although case-control studies are difficult for ethical and practical reasons. In this regard the Collaborative Ocular Melanoma Study (COMS) will provide further evidence for the safety and efficacy of conservative therapy with brachytherapy compared to enucleation.

Adult↗

Effectiveness of budesonide aerosol in ventilator-dependent preterm babies: a preliminary report.

The aim of this randomized, double-blind, placebo-controlled trial was to assess the short-term effect of a topical glucocorticoid (budesonide 600 mu g twice daily) vs. placebo administered by metered dose inhaler (MDL) and spacer (Aerochamber MV15) directly into endotracheal tube of intubated infants for 7 days. Twenty preterm infants (mean birthweight, 1,030 g; mean gestational age, 27.3 weeks)who still needed assisted ventilation at 14 days of age were randomly assigned to receive budesonide (n=9) or placebo (n=11) and completed the study. The primary outcome was the need for mechanical ventilation after 7 days of treatment. Other outcome variables included ventilator settings, blood gases, serum cortisol levels, and bronchoalveolar lavage inflammatory cell counts. No ventilated infant was extubated during the study period. The treatment group showed significant improvements in mean peak inspiratory pressure, ventilator efficiency index, and (A-a) oxygen difference. There were no changes in the placebo group. Serum cortisol levels and bronchoalveolar lavage cell counts did not change significantly during study period. There was no difference in side effects between the groups. This trial demonstrates that topical budesonide administered by MDL and Aerochamber produces clinical improvement in ventilated preterm infants, without glucocorticoid side effects.

Administration, Inhalation↗

Alveolar epithelial lining fluid cellularity, protein and endothelin-1 in children with congenital heart disease.

This study applied bronchoalveolar lavage (BAL) to children with congenital heart disease (CHD) prior to elective cardiac catheterization (n = 48), to determine the influence of pulmonary blood flow and viral infection on the alveolar epithelial lining fluid (ELF) concentration of leucocytes, protein and endothelin-1 (ET-1). Lower respiratory tract (LRT) viral infection was defined as either a positive immunofluorescence for virus, or a virus cultured from the bronchoalveolar lavage fluid (BALF). Haemodynamic status was determined at cardiac catheterization. Normative data for BALF, but not ELF parameters, were obtained from 26 asymptomatic, noninfected normal children undergoing elective surgery. In the absence of LRT infection, the BALF macrophage, lymphocyte and neutrophil differential in CHD was not significantly different from the normal controls. In CHD, both increased pulmonary-to-systemic flow ratio (Q'p/Q's) and increased pulmonary artery-to-left ventricular pressure ratio PAP/LVP were associated with a decrease in ELF protein (rs = -0.59; p < 0.0001; and rs = -0.50; p < 0.0001 respectively). A respiratory virus was isolated from the BALF in 8 (17%) of CHD children. Virus isolation was associated with an increased ELF total protein (p < 0.05 vs no infection), a decreased alveolar macrophage differential count (p < 0.01), and an increased neutrophil differential count (p < 0.05). ET-1 was detected in the BALF of 83% of the noninfected CHD children compared to only 23% of the controls (p < 0.001). ELF ET-1 concentrations did not correlate with haemodynamic status in CHD, but were up to 100 times higher than paired plasma levels. We conclude that, in congenital heart disease, both lower respiratory tract viral infection and increased pulmonary blood flow and/or pulmonary vascular pressure influence the alveolar milieu. High alveolar epithelial lining fluid concentrations of endothelin-1 occur in congenital heart disease, but the stimulus for pulmonary endothelin-1 production is unclear.

Bronchoalveolar Lavage Fluid↗

Inflammatory markers of outcome.

A significant proportion of early childhood wheezing appears not to be due to atopy-induced pulmonary inflammation, and mediator studies in atopic adults and older children may not be relevant to this age group. The usefulness of inflammatory markers in young children is related to 1) whether atopic and nonatopic wheezing are associated with different patterns of pulmonary inflammation, and 2) whether indirect measurements truly reflect the inflammatory milieu within the lung. Both assumptions remain unproved. Bronchoalveolar lavage (BAL) directly samples the alveolar milieu and is a potential tool for defining both the pulmonary mediator profile, and to validate plasma mediator concentrations. BAL fluid (BALF) eosinophil cationic protein (ECP) concentrations accurately reflect pulmonary eosinophil activation, and the BALF interleukin-2 to interleukin-4 ratio may be helpful in defining those children with established pulmonary sensitization to allergen. Of the mediators that have been measured in the plasma, ECP eosinophil protein X (EPX) and major basic protein (MBP) correlate well with atopy-induced wheezing. However atopic activation in other sites may also increase the plasma concentrations of eosinophil-specific mediators. The profile of adhesion molecules in the plasma (e.g. soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 and E-selection) reflects transmigration of specific types of leucocytes across the pulmonary endothelium. To date, the potential of this group of soluble markers to define the nature of pulmonary inflammation is unclear. More information is therefore required on pulmonary inflammation in early childhood to guide the future use of plasma markers.

Asthma↗

Resiting Molteno implant tubes.

The authors describe a surgical technique for resiting Molteno implant tubes. The indications for this intervention are a blockage of the tube that cannot be resolved by other means; erosion of the scleral flap and conjunctiva by the tube; and pediatric cases in which enlargement of the eye causes retraction of the tube from the anterior chamber.

Filtering Surgery↗

Neuronal basis of amblyopia: a review.

Amblyopia is an acquired defect in vision due to an abnormal visual experience during a sensitive period of visual development. The neuronal basis of amblyopia is the study of the effects of "abnormal" environmental influences on the genetically programmed development of the visual processing system. Visual pathway development commences with ganglion cells forming the optic nerve. The process that guides these neurones initially to the lateral geniculate nucleus (LGN) and then onto the visual cortex is genetically programmed. Initially this process is influenced by spontaneously generated impulses and neurotrophic factors. Following birth, visual stimuli modify and refine the genetically programmed process. Exposure to the visual environment includes the risk of abnormal inputs. Abnormal stimuli disrupt the formation of patterned inputs allowing alteration of visual cortical writing with reduction in ocular dominance columns driven by the abnormal eye. Correction of the abnormal visual input and penalisation of the "normal" input is the mainstay of therapy for amblyopia. Further understanding of the mechanisms involved in the development of a normal visual processing system will allow trialing therapies for amblyopia not responding to occlusion therapy. Levodopa is one agent providing insights into recovery of visual function for short periods in apparently mature visual systems.

Amblyopia↗

Retinal detachments in patients with AIDS and CMV retinopathy: a role for laser photocoagulation.

A retrospective review of all patients with a cytomegalovirus (CMV) related retinal detachment and HIV infection managed at the ocular immunology clinic at St Vincent's Hospital between January 1985 and June 1992 was performed. Over this period 142 patients with CMV retinopathy were managed and 17 eyes from 14 of these patients developed a retinal detachment related to CMV retinopathy. Fourteen eyes from 11 of these patients were treated surgically with combinations of laser photocoagulation, cryopexy, scleral buckling, vitrectomy, and silicone oil tamponade. The use of laser photocoagulation alone in five patients resulted in an excellent visual outcome. The majority of patients (90.9%) benefited from surgery in that vision was either stabilised or improved.

Acquired Immunodeficiency Syndrome↗

Bronchoalveolar lavage cellularity in healthy children.

The role of bronchoalveolar lavage (BAL) in children remains to be defined, and to date there has been no standardization of acquisition and processing of the BAL fluid. The aim of the present study was to evaluate a standardized protocol for obtaining, processing, and analyzing BAL fluid and to establish reference values for healthy children. Eighteen children 3 mo to 10 yr of age were lavaged with three 1-ml/kg aliquots of normal saline, using a flexible bronchoscope into the right middle lobe. The first aliquot was processed separately; the second and the third were pooled. There was a higher percentage of neutrophils and epithelial cells in the first aliquot. The number of total cells per milliliter (median, Q1 to Q3) in the first aliquot was 60 (45 to 90) x 10(3)/ml; in the pooled sample it was 155 (75 to 257) x 10(3)/ml. Percentages (median, Q1 to Q3) of different cell types in the pooled sample were: macrophages, 91% (84 to 94); lymphocytes, 7.5% (4.7 to 12.8); neutrophils, 1.7% (0.6 to 3.5); eosinophils, 0.15% (0.0 to 0.3). The ratio of helper/cytotoxic T-cells was 0.58 (0.4 to 1). The results of this study demonstrate that BAL, using a standardized protocol adjusting instilled fluid volume by weight, appears to be appropriate in children and that cellular and protein values from healthy children are, apart from differences in lymphocyte subsets, similar to those found in healthy adults.

Age Factors↗

Role of bronchoalveolar lavage in children with lung disease.

The aim of the present study was to evaluate the clinical role of bronchoscopic and nonbronchoscopic bronchoalveolar lavage (BAL) in the diagnosis of infectious and interstitial lung disease in children. BAL was performed using three 1 mL.kg-1 aliquots of normal saline, with the flexible bronchoscope (Olympus 3.6 or 4.8 mm) wedged in a segmental or subsegmental bronchus of the lobe that showed most abnormality on chest radiograph. In seven children with severe diffuse lung disease who were intubated, a nonbronchoscopic suction catheter lavage was performed. Fluid cultures and cellularity were evaluated using identical methods for both techniques. Between January 1993 and April 1994, 41 BAL were performed in 32 children aged 2 months to 17 yrs (median 8 yrs). Of these lavages, 14 were in heart and heart-lung transplant recipients, 11 in children known to be immunocompromised, and 16 in children who had a lung biopsy for interstitial lung disease or who had presumed infective lung disease. Transbronchial biopsies (TBB) or open lung biopsies were performed coincident with 19 BAL procedures. In all transplant recipients without clinical symptoms, BAL and TBB cultures were negative and BAL cellularity was normal. TBB did not reveal infection or rejection in any of these patients. A diagnosis of infection was made by BAL in 1 out of 8 transplant recipients with clinical symptoms, and a diagnosis of rejection was made by TBB in 3 out of 8 patients. In 6 out of 11 BAL in immunocompromised children, an infectious agent was found in the BAL fluid. In three other patients who had an open lung biopsy, an interstitial lung disease was diagnosed. In these patients, BAL was abnormal but not diagnostic. In summary, BAL proved helpful in the diagnosis of infective lung disease, but had little value in the diagnosis of rejection or parenchymal noninfective lung disease in children.

Adolescent↗

Induction of intercellular adhesion molecule-1 by lipopolysaccharide in canine alveolar macrophages.

Previous studies have demonstrated that alveolar macrophages (AMphis) adherent to plastic release interleukin-8 in response to lipopolysaccharide (LPS). We sought to determine whether LPS could also alter surface adhesion molecule expression and thus modulate additional AMphi adhesive interactions. Canine AMphis obtained by bronchoalveolar lavage of excised lung were adhered onto tissue culture plastic and exposed to LPS (0.01 to 100 ng/ml). Expression of beta 2 integrins and intercellular adhesion molecule-1 (ICAM-1) was subsequently determined by flow cytometry, a cDNA probe to canine ICAM-1 was used to quantify ICAM-1 mRNA, and changes in adhesion molecule function were assessed by evaluating the extent of homotypic aggregation. ICAM-1 and CD11a/CD18 were present on freshly isolated AMphis. CD11b/CD18 and CD11c/CD18 were expressed at lower levels. Nonadherent AMphis expressed a pattern of beta 2 integrin and ICAM-1 comparable to adherent cells. During short-term LPS stimulation (3 h), adherent AMphis increased both the synthesis and expression of ICAM-1. CD18 expression was either decreased or remained unchanged with LPS stimulation. LPS stimulation in vitro (> 0.01 ng/ml) enhanced the homotypic aggregation of adherent AMphis. Aggregation was blocked by monoclonal antibodies to ICAM-1 (CL18/6) and CD11a (R7.1) and CD18 (R15.7). Similar kinetics were found for expression of ICAM-1 and homotypic aggregation, suggesting that up-regulation of ICAM-1 is a major determinant of the LPS-stimulated aggregation of AMphis.

Animals↗