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Biomedical subjects

P Galloway

Publications and source records attributed to P Galloway.

At least 19 recordsLinked to original sources

Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone.

BACKGROUND AND AIMS: Clinical adrenal insufficiency has been reported with doses of inhaled fluticasone proprionate (FP) > 400 microg/day, the maximum dose licensed for use in children with asthma. Following two cases of serious adrenal insufficiency (one fatal) attributed to FP, adrenal function was evaluated in children receiving FP outwith the licensed dose. METHODS: Children recorded as prescribed FP > or = 500 microg/day were invited to attend for assessment. Adrenal function was measured using the low dose Synacthen test (500 ng/1.73 m2 intravenously) and was categorised as: biochemically normal (peak cortisol response > 500 nmol/l); impaired (peak cortisol < or = 500 nmol/l); or flat (peak cortisol < or = 500 nmol/l with increment of < 200 nmol/l and basal morning cortisol < 200 nmol/l). RESULTS: A total of 422 children had been receiving FP alone or in combination with salmeterol; 202 were not investigated (137 FP within license; 24 FP discontinued); 220 attended and 217 (age 2.6-19.3 years) were successfully tested. Of 194 receiving FP > or = 500 microg/day, six had flat responses, 82 impaired responses, 104 were normal, and in 2 the LDST was unsuccessful. Apart from the index child, the other five with flat responses were asymptomatic; a further child with impairment (peak cortisol 296 nmol/l) had encephalopathic symptoms with borderline hypoglycaemia during an intercurrent illness. The six with flat responses and the symptomatic child were all receiving FP doses of > or = 1000 microg/day. CONCLUSION: Overall, flat adrenal responses in association with FP occurred in 2.8% of children tested, all receiving > or = 1000 microg/day, while impaired responses were seen in 39.6%. Children on above licence FP doses should have adrenal function monitoring as well as a written plan for emergency steroid replacement.

Adolescent↗

Investigation of global developmental delay.

The investigation of global developmental delay in preschool children varies between centres and between paediatricians. Following a literature search and review of the evidence base, guidelines were developed to assist in the assessment and management of such children presenting to secondary level services. Evidence supporting the use of genetic and biochemical investigations on a screening basis was found, but there was no evidence to support the use of metabolic investigations or neuroimaging in the absence of other positive findings on history or examination. Detailed history and examination are paramount in the assessment of children with global developmental delay. Investigations can be a useful adjunct in determining aetiology. Evidence based guidelines have been developed to assist doctors in the selection of appropriate investigations for this group of children.

Child, Preschool↗

Continuous wear silicone hydrogel contact lenses and microbial keratitis.

Like other lens types, the new generation of silicone hydrogel contact lenses can be associated with a spectrum of ocular complications. Most tend to be very minor, but serious and sight-threatening complications can occur. We present four such cases with microbial keratitis following extended wear of these lenses. Cultures were positive for Pseudomonas aeruginosa in three cases and all three of these suffered lasting visual impairment. We describe our findings and discuss possible risk factors.

Adult↗

Comparison of articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in cataract extraction.

BACKGROUND: Articaine is the most widely used local anaesthetic for dental anaesthesia in Germany, Italy and The Netherlands and has recently been introduced and licensed for dental use in the UK. We have previously shown articaine to be superior to a standard mixture of bupivacaine 0.5%/lidocaine 2% for peribulbar anaesthesia. Sub-Tenon's anaesthesia arguably provides a safer method of anaesthetic delivery for cataract surgery. A blunt cannula is used in this technique, thus greatly reducing the risk of globe perforation, intrathecal injection and sight-threatening periocular haemorrhage. METHODS: We compared articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in cataract surgery. RESULTS: Sub-Tenon's anaesthesia using articaine 2% resulted in a more rapid onset of motor block compared with a bupivacaine/lidocaine (P=0.0076). Ocular movement scores were significantly lower from 2 min after injection until the end of surgery (P=0.031 ANOVA). CONCLUSION: Articaine 2% is safe and effective for sub-Tenon's anaesthesia and is a suitable alternative to the traditional bupivacaine 0.5%/lidocaine 2% mixture.

Adult↗

Carotenaemia in children is common and benign: most can stay at home.

We identified children with elevated plasma carotene levels who attended the Royal Hospital for Sick Children, Glasgow, between July 1998 and April 2001 and carried out a retrospective case record review. Thirty-one children were identified (7 boys; 14 girls) with a median age at presentation of 13 months (range 7m- 11yrs). Twenty-seven (87%) children had simple diet-related carotenaemia and were well. In four cases the hypercarotenaemia reflected nutritional problems with associated failure to thrive. In only one case did the family doctor recognise the condition before referral. Many who attended hospital had laboratory confirmation of the benign diagnosis despite a clear dietary origin. Some had repeat laboratory tests to confirm resolution. Diet-related carotenaemia appears common in our community. The condition appears poorly recognised within primary care and hospital investigations may be over-enthusiastic.

Carotenoids↗

Decreased orocaecal transit time, as measured by the exhalation of hydrogen, in hyperthyroid cats.

Orocaecal transit time was assessed in healthy cats and cats with hyperthyroidism by means of the breath hydrogen test using a standard liquid meal with lactulose. The median transit time in 10 healthy cats was 98 minutes (range 60 to 150 minutes) and 90 minutes (range 75 to 150 minutes) in a repeated assessment. The median transit time in 10 cats with hyperthyroidism was 53 minutes (range 45 to 150 minutes) which was significantly more rapid (P < 0.05) than in the healthy cats.

Animals↗

Basic fibroblast growth factor binds to filamentous inclusions of neurodegenerative diseases.

The extracellular matrix protein heparin sulfate proteoglycans (HSPG) has been found in the neurofibrillary pathology of Alzheimer disease. This study was performed to determine if similar proteoglycans might be present in the fibrillary inclusions of other neurodegenerative diseases. Basic fibroblast growth factor (bFGF) binding to heparinase sensitive sites was used as an assay for HSPGs. We found that the inclusions of Pick and Parkinson diseases as well as progressive supranuclear palsy contained heparinase sensitive bFGF binding sites while the inclusions of diffuse Lewy body disease lacked bFGF binding sites. These findings indicate that HSPG's interactions and possible role in the formation of intraneuronal inclusions are not limited to Alzheimer disease.

Aged↗

Endoscopic and radiographic evaluation of the murine colon.

Endoscopic and radiographic techniques have not been widely applicable in the evaluation of chemically induced murine colon cancer. The authors investigated methods of cleansing the rat colon and refined endoscopic and radiographic techniques. They compared total colonoscopy (TC) and air-contrast (ACBE) and single-contrast barium enema (SCBE) findings with those obtained at necropsy in rats with 1,2-dimethylhydrazine (DMH)-induced colon cancer. Gastrograffin enemas with bisacodyl suppositiories showed complete evacuation of solid feces. Sprague-Dawley rats treated with DMH had their colons cleansed and then underwent TC (5.0-mm Olympus bronchoscope) and either SCBE or ACBE. Colonoscopy and ACBE were equally sensitive (81.5% and 76.3%, respectively), although SCBE was significantly insensitive in identifying lesions (P less than 0.001). This study demonstrates that: (1) mechanical cleansing of the rat colon is feasible, (2) TC and barium radiology can be done routinely after mechanical cleansing, and (3) TC and double-contrast BE are sensitive in identifying colon lesions. These techniques will provide a means for manipulation of murine tumors and in vivo surveillance.

1,2-Dimethylhydrazine↗

A new monoclonal antibody to study mouse macrophage antigen during BHT-induced lung injury and repair.

A rat monoclonal antibody 133-13A to a mouse lung carcinoma cell line was found to react with macrophages in mouse lung [1]. This monoclonal antibody is different from previously described antibodies to macrophages. Immunogold electron-microscopy and immunoperoxidase light microscopy have been used to show that MoAb 133-13A binds specifically to macrophages in normal and in BHT treated mouse lungs. This MoAb recognizes a protein of approximately 100 kDa (P100) on cultured lung carcinoma cells and a 87 kDa protein on macrophages from lung or the peritoneal cavity which is different from other macrophage antigens. The surface glycoprotein has been purified from cultured cells using immunoaffinity chromatography. The purified protein was radioiodinated and MoAb 133-13A was used to develop a competition radioimmunoassay to quantitate P100. Spleen, intestines, lung, skin and uterus all have high levels of P100. P100 on peritoneal macrophages has been determined to be about 94,000 molecules/cell. Analyses of lung lavage and whole lung homogenates from mice treated with BHT, BHT plus 70% O2, and 70% O2 alone show that treated animals have elevated P100 content compared to corn oil treated mice.

Animals↗

Alteration of neuritic cytoarchitecture in Alzheimer disease.

Individuals afflicted with Alzheimer disease (AD) demonstrate two prominent brain structural alterations: senile plaques and neurofibrillary tangles (NFT) (Selkoe, 1986). Not appreciated until recently is a third quantitatively significant structure, the dystrophic neurite. Many of these altered neurites are focally associated with amyloid deposits, and together they comprise the senile plaque. However, the great majority of the abnormal neurites in AD are independent of senile plaques (Braak, et al., 1986). Recent advances have yielded considerable information on the chemical nature of the extracellular amyloid (Kang, et al., 1987; Tanzi, et al., 1988) which comprises the central portion of the senile plaque, but there is much yet to be unraveled concerning both the nature of NFT and the relationship between senile plaques and NFT (Selkoe, 1987). While the NFT is principally comprised of 20 nm helically wound filaments, descriptively termed paired helical filaments (PHF) (Kidd, 1963; Wisniewski, et al., 1976) occasionally 12-15 nm straight filaments are also present (Perry, et al., 1987c). We have found that the predominant filaments in dystrophic neurites of AD are straight filaments which are morphologically indistinguishable from those found within NFT. The abnormal neuritic filaments and PHF share microtubule associated protein, tau, and ubiquitin immunoreactivity. The prevalence of altered neurites suggests that reorganization of neuritic cytoarchitecture in AD, as demonstrated by the formation of abnormal polymers structurally, and by inference functionally distinct from the normal cytoskeleton, may constitute a more important part of the cytopathological change of AD than previously appreciated.

Alzheimer Disease↗

Splenectomy and the induction of murine colon cancer.

The influence of a functional spleen on induction and growth of cancer is unknown. Both beneficial and detrimental results have been observed in tumor-bearing hosts following splenectomy. We examined the effect of splenectomy, splenic autotransplantation, and splenic preservation on the induction and growth of 1,2-dimethylhydrazine (DMH)-induced murine colon cancer. Following splenectomy there was a significant increase in malignant tumors but no increase in benign tumors. To rule out the possibility that splenectomy increased the carcinogenicity of DMH by decreasing the capacity for DNA repair in colon cells, the units of 06-alkylguanine DNA alkyltransferase were measured in tumor-free and malignant colon tissue from both splenectomized and control rats. This repair protein was chosen because it is known to protect cells from the mutagenic effects of methylating agents. There was no significant difference in the alkyltransferase activity of tumor-free colon vs malignant tumor or between treatment regimens. Thus, the ability of the spleen to protect rats from the induction of malignant colon tumors induced by DMH is most likely due to preservation of immunologic surveillance in the host.

Adenocarcinoma↗

Effects of muramyl dipeptide and core body temperature on peritoneal bacterial clearance.

To examine the interaction between muramyl dipeptide (MDP) and core body temperature in murine peritonitis, 120 Sprague-Dawley rats were randomized to receive either 0, 1, or 4 micrograms/g body weight of MDP. Twenty-four hours later a sublethal intraperitoneal inoculation of Escherichia coli was given after core body temperature regulation at 32 degrees C to 40 degrees C, which was maintained for 30 minutes. Killing of the rats at 1, 3, or 6 hours later allowed evaluation of peritoneal white blood cell and bacterial counts. Results demonstrated that MDP (independent of core body temperature) caused an increased peritoneal white blood cell response at one and six hours and an increased peritoneal bacterial clearance at three hours. Increasing core body temperature adversely affected peritoneal bacterial clearance. High-dose MDP was clearly significant in acceleration of peritoneal bacterial clearance. No interaction between MDP and core body temperature was seen.

Acetylmuramyl-Alanyl-Isoglutamine↗

Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of a family of glycoprotein hormones that stimulate the proliferation and differentiation of hemopoietic cells in vitro and in vivo. We now report that human GM-CSF can also stimulate the proliferation of two osteogenic sarcoma cell lines, a breast carcinoma cell line, a simian virus 40-transformed marrow stromal cell line, and normal marrow fibroblast precursors. These findings suggest a more general regulatory function of GM-CSF on nonhemopoietic cell types than previously anticipated. They also raise the possibility of adverse side effects of GM-CSF therapy in patients whose malignant cells may be directly stimulated by this molecule and suggest a previously unanticipated role of GM-CSF gene activation in the evolution of solid tumors and in the pathogenesis of myelofibrosis.

Animals↗