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Biomedical subjects

D Hill

Publications and source records attributed to D Hill.

At least 55 records · Page 3Linked to original sources

Long-term follow-up of surgically treated AIS patients.

The aim of this study was to determine the long-term changes in spine and trunk alignment in patients who have undergone scoliosis surgery. Twenty-three (16F; 7M; at age of surgery 15.7 +/- 4.9 years) patients with adolescent idiopathic scoliosis agreed to participate and had posterior-anterior radiographs and surface topography prior to derotation surgery, within 6 months of surgery, at 2 years post-operatively and 5-10 years (mean follow-up period 6.11 +/- 1.6 years) after surgery. Cobb angles, surface trunk rotations, and cosmetic scores were measured at each visit. A questionnaire assessed back appearance and pain at the 5-10 year follow-up. The results of the questionnaire were compared to 25 patients with idiopathic scoliosis who had recently undergone surgery. A paired two-tailed Student's t-test with p=0.05 was used to compare the deformity between visits. The Cobb angle and cosmetic score improved after surgery while the change in trunk rotation was insignificant (p=0.37). Between the two-year and 5-10 year review, the Cobb angle, cosmetic score, and surface trunk rotation significantly increased. Self-perception of appearance and pain were similar to the control group. Surgical correction of scoliosis is not completely maintained during adulthood although the radiographic and surface deterioration does not appear to be clinically significant.

Adolescent↗

Assessing the impact of pelvic obliquity in post-operative neuromuscular scoliosis.

The goal of this pilot study was to explore the relationship between pelvic obliquity and patient pain, sitting tolerance, pressure sores, and function. Five neuromuscular patients who underwent spinal surgery 6-26 weeks prior to assessment took part in this on-going study (4F; 1M); age at surgery (14.6 +/- 2.6 years). Pelvic obliquity was measured from pre- and post-operative anterior-posterior radiographs. A force-sensing pad with a grid of sensors was placed on a flat surface and the weight distribution pattern was recorded. The pressures were divided into left and right sides and peak levels were noted on each side. The parents or caregivers completed a questionnaire on their child's pain, sitting tolerance, pressure sores, and functional abilities. Pelvic obliquity was reduced after surgery by approximately 50% depending on the method used to assess pelvic obliquity. The major curve was reduced from 64 degrees(10 degrees) to 39 degrees (10 degrees). Post operatively, the average pressure (left/right side) ranged from 1.2 to 2.0 (average 1.6). The peak pressure ratio ranged from 1.1 to 1.9 (average 1.4). The ratio of left/right pressure correlated with improvement in pelvic obliquity (r2=0.9). Pain was moderate/severe in the 2 patients with the least correction as measured with the Cobb angle from surgery; both improved following surgery. Two patients suffered pressure sores pre-operatively and one post-operatively. Only 3/5 felt sitting endurance had increased. All parents felt their child sat straighter after surgery. The outcome measures of pain, pressure sores, sitting tolerance, and function were not well related to the amount of pelvic obliquity. More candidates and a longer follow-up may shed light on the many relationships.

Activities of Daily Living↗

IL-18-binding protein protects against lipopolysaccharide- induced lethality and prevents the development of Fas/Fas ligand-mediated models of liver disease in mice.

IL-18-binding protein (IL-18BP) is a natural IL-18 inhibitor. Human IL-18BP isoform a was produced as fusion construct with human IgG1 Fc and assessed for binding and neutralizing IL-18. IL-18BP-Fc binds human, mouse, and rat IL-18 with high affinity (K(D) 0.3-5 nM) in a BIAcore-based assay. In vitro, IL-18BP-Fc blocks IL-18 (100 ng/ml)-induced IFN-gamma production by KG1 cells (EC(50) = 0.3 microg/ml). In mice challenged with an LD(90) of LPS (15 mg/kg), IL-18BP-Fc (5 mg/kg) administered 10 min before LPS blocks IFN-gamma production and protects against lethality. IL-18BP-Fc administered 10 min before LPS blocks IFN-gamma production induced by LPS (5 mg/kg) with ED(50) of 0.005 mg/kg. Furthermore, IL-18BP-Fc (5 mg/kg) abrogates LPS (5 mg/kg)-induced IFN-gamma production even when administered 6 days before LPS but shows no effect when administered 9 or 12 days before LPS. Given 10 min before LPS challenge to mice primed 12 days in advance with heat-killed Propionibacterium acnes, IL-18BP-Fc prevents LPS-induced liver damage and IFN-gamma and Fas ligand expression. Given at the moment of priming with P. acnes, IL-18BP-Fc decreases P. acnes-induced granuloma formation, macrophage-inflammatory protein-1alpha and macrophage-inflammatory protein-2 production and prevents sensitization to LPS. IL-18BP-Fc also prevents Con A-induced liver damage and IFN-gamma and Fas ligand expression as well as liver damage induced by Pseudomonas aeruginosa exotoxin A or by anti-Fas agonistic Ab. In conclusion, IL-18BP can be engineered and produced in recombinant form to generate an IL-18 inhibitor, IL-18BP-Fc, endowed with remarkable in vitro and in vivo properties of binding and neutralizing IL-18.

Animals↗

Functional annotation of a full-length mouse cDNA collection.

The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.

Animals↗

Radon: a likely carcinogen at all exposures.

BACKGROUND: Radon is a well-established lung carcinogen that has been extensively studied. Very high concentrations can occur in some underground mines. Concentrations also tend to build up in homes. MATERIALS AND METHODS: Epidemiological studies of radon-exposed miners and of residential radon and lung cancer are reviewed. Quantitative estimates of the risk of lung cancer, based on the experience of the miners, are applied to residential radon exposures in the United Kingdom. Strategies for the prevention of lung cancer induced by residential radon are discussed. RESULTS: Estimates are uncertain, but residential radon is probably responsible for about 2000 lung cancer deaths per year in the United Kingdom, or around 6% of the total, making it the second biggest cause after smoking. Over 80% of the deaths are estimated to occur at ages less than 75 and over 80% in smokers or ex-smokers. Around 90% of radoninduced deaths in the United Kingdom probably occur as a result of exposures to radon concentrations below the currently recommended action level of 200 Bq m(-3). CONCLUSIONS: Further work is needed to obtain more reliable estimates of the risk of lung cancer associated with residential radon and on the cost-effectiveness of various intervention strategies before the most appropriate policies can be developed for managing exposure to this natural carcinogen.

Air Pollution, Indoor↗

The -590C/T and -34C/T interleukin-4 promoter polymorphisms are not associated with atopic eczema in childhood.

Susceptibility to the development of asthma and other atopic diseases is known to have a genetic component. To date, several studies have linked chromosome 5q31 to asthma and atopy in human beings. This region harbors a cluster of cytokine and growth factor genes, IL-4 presenting as a prime atopy candidate gene, inasmuch as it plays a pivotal role in the atopy pathway. Our approach was to identify polymorphisms within the promoter regions of IL-4 and test their association with atopic eczema. Polymorphisms were typed in a cohort of 76 small nuclear families and 25 triads with childhood atopic eczema. The genotypes were used to test for linkage in the presence of association with atopic eczema. A new polymorphism, -34C/T, was identified and studied with a known polymorphism, -590C/T. On its own, each polymorphism showed no association with atopic eczema. The 2 polymorphisms were used to generate haplotypes, and a significant result was found for the -590C/-34C haplotype. However, after Bonferroni correction for multiple testing, the association became nonsignificant. Neither polymorphism predisposes to early-onset atopic eczema by itself, but suggestive linkage was found for the -590C/-34C haplotype in this study.

Child↗

Intrathecal ropivacaine or bupivacaine with fentanyl for labour.

Combined spinal-epidural (CSE) is widely used to provide pain relief in labour while minimizing motor blockade. Aiming to further reduce associated motor weakness, we compared ropivacaine 2.5 mg in the intrathecal injection with a standard bupivacaine CSE in a double-blind study. Forty women were randomized to receive either bupivacaine 2.5 mg or ropivacaine 2.5 mg intrathecally, both with fentanyl 0.025 mg. There were no significant differences between the groups regarding the onset, duration or quality of analgesia or the level of sensory block attained. Forty per cent of the women (8/20) receiving bupivacaine developed detectable motor block compared with only 5% (1/20) in the ropivacaine group (P<0.05). Vibration sense was impaired in one woman in each group. Adverse effects did not differ between groups. We conclude that intrathecal ropivacaine 2.5 mg in combination with fentanyl 0.025 mg as part of a CSE technique provides rapid and safe analgesia for labour as effective as that achieved with bupivacaine 2.5 mg and with significantly less motor block.

Adolescent↗

How is the liver primed or sensitized for alcoholic liver disease?

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

Animals↗

Ten-year review of hysterectomy morbidity and mortality: can we change direction?

The medical records of all women who underwent hysterectomy for benign disease performed between 1986 and 1995 were reviewed to ascertain the incidence of morbidity and mortality of abdominal, vaginal, and laparoscopically assisted vaginal hysterectomy at a university teaching hospital. A total of 1940 hysterectomies were performed during this period; 74% of hysterectomies were performed abdominally, 24% vaginally and 2% were laparoscopically assisted. In 80% of the patients uterine leiomyomas, adenomyosis, dysfunctional uterine bleeding or uterine prolapse were the indications for hysterectomy The overall complication rate was 44% for abdominal hysterectomy (AH) and 27.3% for vaginal hysterectomy (VH). An unintended major surgical procedure was required in 3% and 1% of women undergoing AH and VH respectively The rate of return to the operating room for haemostasis was 0.6% for AH and 0.2% for VH. The AH group was four times more likely than the VH group to require surgical intervention (36% versus 9%) at readmission. Vaginal hysterectomy was associated with a lower febrile morbidity and minor complication rate. Prophylactic antibiotics reduced the febrile morbidity for VH and AH by 50% (Student's t-test, p = 0.02) and 40% (Student's t-test, p < 0.001) respectively The overall mortality rate was 1.5 per 1000.

Aged↗

Survey of computed tomography scanning and endoscopic sinus surgery in a group of district general hospitals in south Essex.

The management of chronic sino-nasal disease has changed significantly in the last 15 years with the advent of topical nasal steroids and minimally invasive endoscopic surgery, but survey data from district hospitals in the UK have not been published to date. We examined the current management of 383 consecutively scanned patients with sino-nasal symptoms in three district hospitals. Survey standards were set, and were attained in 56 per cent for symptom recording, 60 per cent for pre-scan diagnosis, 62 per cent for endoscopic examination in out-patients, and 73 per cent for topical steroid use before scanning. The variability of sinus disease makes it difficult to be dogmatic about proper indications for surgery, but subsequent surgical management, as ascertained from the notes, showed large differences between consultants in the three hospitals. The rate of minor complications was 2.2 per cent, there were no major complications, and the vast majority of patients stated that their nasal symptoms were improved by surgery. The survey showed that endoscopic sinus surgery is safe and effective when practised in a district hospital setting.

Adolescent↗

A practical approach to nutritional support for patients with advanced cancer.

Palliative care can last from a few days to months and, in some cases, years. Consequently the nutritional needs of palliative care patients also vary, as does the extent to which nutrition intervention is pursued. Anorexia and cachexia are common side-effects of advanced cancer. They are characterized by physical depletion of the patients and an emotional drain on them, their families and carers. Pulling together the practical aspects of nutrition support and the emotional and social significance of food requires a skillful practitioner; an experienced dietitian can be a valued member of the palliative care team. This article examines the role of nutrition support in the palliative care setting, focusing upon practical advice including food modification, the use of oral supplements and enteral feeding.

Adult↗

Utilization of oriented peptide libraries to identify substrate motifs selected by ATM.

The ataxia telangiectasia mutated (ATM) gene encodes a serine/threonine protein kinase that plays a critical role in genomic surveillance and development. Here, we use a peptide library approach to define the in vitro substrate specificity of ATM kinase activity. The peptide library analysis identified an optimal sequence with a central core motif of LSQE that is preferentially phosphorylated by ATM. The contributions of the amino acids surrounding serine in the LSQE motif were assessed by utilizing specific peptide libraries or individual peptide substrates. All amino acids comprising the LSQE sequence were critical for maximum peptide substrate suitability for ATM. The DNA-dependent protein kinase (DNA-PK), a Ser/Thr kinase related to ATM and important in DNA repair, was compared with ATM in terms of peptide substrate selectivity. DNA-PK was found to be unique in its preference of neighboring amino acids to the phosphorylated serine. Peptide library analyses defined a preferred amino acid motif for ATM that permits clear distinctions between ATM and DNA-PK kinase activity. Data base searches using the library-derived ATM sequence identified previously characterized substrates of ATM, as well as novel candidate substrate targets that may function downstream in ATM-directed signaling pathways.

Amino Acid Motifs↗

Five French (5 Fr) guiding catheters for percutaneous coronary angioplasty and stent placement: An initial feasibility study.

Thirty patients were treated with percutaneous coronary intervention (PCI) using a 5 Fr guiding catheter. A recently developed, mechanically advantaged hand injector was used to deliver contrast and achieved excellent visualization through the 5 Fr system. Stent sizes ranged from 2.25 to 4.00 mm in diameter and from 8 to 24 mm in length. All primary lesions were successfully treated. The average contrast use was 70 cc per case. There were no major complications and only one minor femoral hematoma. In selected patients, a balloon angioplasty and stent placement can be performed safely and successfully with 5 Fr guiding catheters using currently available products. This technique creates a smaller arterial puncture site, which may obviate the need for a closure device and allow early and safe ambulation. With 5 Fr systems, it appears that contrast usage is reduced, thereby potentially decreasing cost and morbidity. Cathet. Cardiovasc. Intervent. 51:352-357, 2000.

Angioplasty, Balloon, Coronary↗

Cluster of cases of Mycobacterium chelonae bacteraemia.

Mycobacterium chelonae was isolated from the blood of four immunosuppressed patients over a period of 10 weeks. Three patients had intravascular catheters in situ and the other had a biliary stent. All presented with recurrent fever despite treatment with broad-spectrum antibiotics. Blood cultures using standard bacteriological medium yielded a gram-positive bacillus from each patient. Ziehl-Neelsen staining of these cultures demonstrated a branching acid-fast bacillus that was subsequently identified as Mycobacterium chelonae in each case. The isolates were sensitive to clarithromycin and, although success of treatment with clarithromycin monotherapy has been variable, this antibiotic combined with removal of the intravascular catheters was used to treat those three patients. The treatment was successful with no recurrence of symptoms after 12 months of follow-up. The patient with the biliary stent died soon after Mycobacterium chelonae was isolated. Pyrolysis mass spectrometry analysis indicated the isolates were of two distinct strains. Radiological insertion of the Hickman lines and biliary stent was implicated epidemiologically as the source of infection.

Adult↗

Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae.

Haemophilus influenzae (Hi), a commensal of the human respiratory mucosa, is an important cause of localized and systemic infections. We show that distinct strains belonging to typable (THi) and non-typable (NTHi) H. influenzae target human carcinoembryonic antigens (the membrane associated CEA family of cell adhesion molecules, are now termed CEACAMs). All strains of H. influenzae biogroup aegyptius (Hi-aeg) and more than 70% of THi and NTHi strains tested specifically recognize CEACAMI-Fc soluble constructs. Furthermore, transfection of Chinese hamster ovary cells with human CEACAM1 cDNA alone was sufficient for promoting Hi interactions with the transfected cells. The majority of the Hi-aeg strains tested interacted with soluble constructs containing only the N-terminal domain. In contrast, several THi and NTHi strains reacted with soluble constructs only when additional extracellular A and B domains of the receptor were present. The use of monoclonal antibodies confirmed that THi and NTHi strains also interact primarily at the N-domain. We used site-directed mutants of CEACAM1 that contained substitutions at surface exposed amino acids and a molecular model of the N-domain to identify the residues involved in interactions with Hi ligands. The studies show that a common region exposed at the CFG face of the molecule is targeted by diverse Hi strains. However, mutation at distinct sites within this area affected the interactions of distinct strains signifying the potential for tissue tropism via this receptor. Analyses of the molecular basis of interaction with human cell lines and purified CEA show that Hi strains, especially those belonging to Hi-aeg, interact with multiple CEACAMs. Because Neisseria meningitidis (Nm) strains are also known to bind at the CFG face of the receptor, we used Nm and Hi strains in co-infection experiments and demonstrate competition between these mucosal pathogens in colonization of target cells via CEACAMs.

Amino Acid Sequence↗

Interferential therapy machines as possible vehicles for cross-infection.

Interferential therapy machines are used to apply alternating electric currents to patients for the treatment of various musculo-skeletal complaints. The potential for such machines to transfer skin microflora from one patient to another during treatment was investigated. The efficacy of the current disinfection procedure of the machines was also evaluated. In both the laboratory and clinical situation, interferential treatment, (which involves the direct application of electrodes to the skin surface) resulted in the transfer of micro-organisms from the skin of one subject to another. To decrease the likelihood of transmission of micro-organisms via interferential therapy machines, it is recommended that both the suction cups and sponges are disinfected with 70% isopropyl alcohol after the treatment of each patient. The use of disposable electrodes could also be considered.

Cross Infection↗