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Biomedical subjects

S J Hodges

Publications and source records attributed to S J Hodges.

At least 19 recordsLinked to original sources

Tumour necrosis factor alpha is an important mediator of portal and systemic haemodynamic derangements in alcoholic hepatitis.

BACKGROUND: The role of proinflammatory cytokines in the pathogenesis of portal hypertension is unclear. AIMS AND METHODS: This study tests the hypothesis that tumour necrosis factor alpha (TNF-alpha) is an important mediator of the circulatory disturbances in alcoholic hepatitis (AH) and evaluates the acute and short term effect of a single infusion of the monoclonal chimeric anti-TNF-alpha antibody (Infliximab) on portal and systemic haemodynamics in 10 patients with severe biopsy proven AH. Cardiovascular haemodynamics, hepatic venous pressure gradient (HVPG), and hepatic and renal blood flow were measured before, 24 hours after Infliximab, and prior to hospital discharge. RESULTS: Serum bilirubin (p<0.05), C reactive protein (p<0.001), and white cell count (p<0.01) were reduced significantly, as were plasma levels of interleukin (IL)-6 and IL-8 after treatment. Of the 10 patients, nine were alive at 28 days. Mean HVPG decreased significantly at 24 hours (23.4 (2.8) to 14.3 (1.9) mm Hg; p<0.001) with a sustained reduction prior to discharge (12.8 (1.9) mm Hg; p<0.001). Mean arterial pressure and systemic vascular resistance increased significantly (p<0.001and p<0.01, respectively), mirrored by a reduction in cardiac index (5.9 (0.5) to 4.7 (0.5) l/min/m(2); p<0.05) prior to discharge. Hepatic and renal blood flow also increased significantly (506.2 (42.9) to 646.3 (49.2) ml/min (p=0.001) and 424.3 (65.12) to 506.3 (85.7) ml/min (p=0.001), respectively) prior to discharge. CONCLUSION: The results of this study illustrate that anti-TNF-alpha treatment in AH patients produces a highly significant, early, and sustained reduction in HVPG, possibly through a combination of a reduction in cardiac output and intrahepatic resistance. In addition, there was a reduction in hepatic inflammation and improved organ blood flow, suggesting an important role for TNF-alpha in mediating the circulatory disturbances in AH.

Adult↗

Reduced bone formation in UK Gulf War veterans: a bone histomorphometric study.

AIMS: Gulf War veterans report a high prevalence of musculoskeletal symptoms. The aim of this study was to establish whether there were abnormalities in bone turnover and remodelling in a group of symptomatic subjects who had served in the Gulf War. METHODS: Iliac crest bone biopsies were obtained from 17 Gulf War veterans who were seeking litigation and compared with those of 13 age and sex matched healthy controls. Bone histomorphometry was performed using image analysis. RESULTS: Cancellous bone area was significantly lower in Gulf War veterans than in control subjects (p = 0.027) and this was associated with a significantly reduced mineral apposition rate (p = 0.002), mean wall width (p < 0.0001), and bone formation rate at the tissue level (p < 0.0001). CONCLUSIONS: These results demonstrate that in this group of Gulf War veterans there was a significant reduction in bone formation at both the cellular and tissue level and this was associated with a reduction in cancellous bone area. The cause of these abnormalities is unknown but might be related to potentially harmful exposures during service in the Gulf War or to changes in life style as a result of chronic ill health. The clinical relevance of the observed reduction in bone formation remains to be established.

Adult↗

Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk.

Increasing evidence indicates a significant role for vitamin K in bone metabolism and osteoporosis. In this study, we found a large geographic difference in serum vitamin K2 (menaquinone-7; MK-7) levels in postmenopausal women. Serum MK-7 concentrations were 5.26 +/- 6.13 ng/mL (mean +/- SD) in Japanese women in Tokyo, 1.22 +/- 1.85 in Japanese women in Hiroshima, and 0.37 +/- 0.20 in British women. We investigated the effect of Japanese fermented soybean food, natto, on serum vitamin K levels. Natto contains a large amount of MK-7 and is eaten frequently in eastern (Tokyo) but seldom in western (Hiroshima) Japan. Serum concentrations of MK-7 were significantly higher in frequent natto eaters, and natto intake resulted in a marked, sustained increase in serum MK-7 concentration. We analyzed the relation between the regional difference in natto intake and fracture incidence. A statistically significant inverse correlation was found between incidence of hip fractures in women and natto consumption in each prefecture throughout Japan. These findings indicate that the large geographic difference in MK-7 levels may be ascribed, at least in part, to natto intake and suggest the possibility that higher MK-7 level resulting from natto consumption may contribute to the relatively lower fracture risk in Japanese women.

Aged↗

The effect of micro-etching on the retention of orthodontic molar bands: a clinical trial.

Failure of orthodontic bands occurs most frequently at the band-cement interface, when conventional glass ionomer cements are used. Modification of the band surface may improve clinical performance by increasing the mechanical interlock at this junction. The aim of this prospective study was to compare the retention of micro-etched and untreated first molar orthodontic bands in a randomized, half-mouth trial. Seventy-nine patients had 304 bands cemented as part of routine fixed appliance therapy. The effect of micro-etching, patient age and gender, operator, molar crossbite, treatment mechanics, and arch on band failure was investigated. Failure rates and survival times were compared for each variable assessed. Micro-etched molar bands showed a significant reduction in clinical failure rate over untreated molar bands and an increase in mean survival time (P < 0.001). Of the other variables examined, only the presence of a molar crossbite had any significant effect on band failure (P = 0.004).

Acid Etching, Dental↗

Unusual indelible enamel staining following fixed appliance treatment.

Two cases are described of indelible enamel staining following fixed appliance therapy. The acquired pigmentation occurred in patients with an identifiable enamel defect prior to treatment. The interaction of factors to cause the staining is discussed and it's prevention in future cases highlighted. Subsequent restoration of the affected teeth is shown.

Amelogenesis Imperfecta↗

Gingival crevicular fluid osteocalcin in adult periodontitis.

This study aimed to detect the levels of osteocalcin in gingival crevicular fluid (GCF) from healthy (< or =3 mm sulcus depth and non-bleeding) and diseased sites (> or =6 mm probing depth and bleeding) in subjects with adult periodontitis, in order to further investigate its potential as a possible marker of the disease process. Periodontal probing depths, attachment levels and gingival indices were recorded from one healthy and one diseased site in each of 20 subjects with adult periodontitis. Both GCF accumulated in the periodontal pocket or sulci and GCF flowing into the periodontal pocket or sulci over a three-minute interval were sampled. The amounts of osteocalcin in each GCF sample was determined using immunoassays. A mean of 2.34 ng/site (2.7 microg/ml) osteocalcin was found at diseased sites and a mean of 2.47 ng/site (5.47 microg/ml) was found at healthy sites for the accumulated GCF collection method. A mean of 0.17 ng/ site (2.17 microg/ml) osteocalcin was found at diseased sites and a mean of 0.14 ng/ site (1.85 microg/ml) at healthy sites for the flow method of GCF collection. There were no statistically significant differences between osteocalcin levels in diseased and healthy sites in subjects with adult periodontitis.

Adult↗

Witkop tooth and nail syndrome: report of two cases in a family.

Tooth and nail syndrome, an autosomal dominant condition, is characterized by hypodontia and nail dysplasia. Mandibular incisors, second molars and maxillary canines are the most frequently missing teeth. Tooth shape may vary and conical and narrow crowns are common. Nail dysplasia affects fingernails and toenails and is often more severe in childhood. Nails may be spoon-shaped, ridged, slow growing and easily broken. The clinical and radiographic features of a father and son presenting with this rare condition are described.

Adult↗

Phylloquinone in gingival crevicular fluid in adult periodontitis.

Phylloquinone is a lipid soluble vitamin which is an absolute growth requirement for black-pigmented anaerobes, many of which are implicated in the aetiology of periodontal diseases. This cross-sectional study aimed to detect the levels of phylloquinone in GCF from healthy and diseased sites in subjects with adult periodontitis, in order to investigate further its potential role in the disease process. The sample consisted of eighteen patients with adult periodontitis. Periodontal probing depths, attachment levels and gingival indices were recorded from one healthy and one diseased site in each subject. GCF was sampled and the amount of phylloquinone in each sample was determined using reverse-phase high performance liquid chromatography coupled to electrochemical detection. The mean amount of phylloquinone in accumulated GCF from diseased sites was 406 pg/site and 80 pg/site from healthy sites (p=0.013). When the amounts of phylloquinone in GCF were expressed as concentrations the values were 228 ng/ml and 3350 ng/ml for diseased and healthy sites respectively (p=0.084). These findings suggest the levels of phylloquinone in GCF differs in periodontal health and disease in subjects with adult periodontitis. The total phylloquinone at diseased sites may provide the nutritional requirements favouring the growth of black-pigmented anaerobes.

Adult↗

The role of oxygen free radicals in idiopathic facial pain.

Patients with chronic facial pain including those with facial arthromyalgia (TMJ dysfunction syndrome) were investigated for evidence of abnormal systemic and intra-articular free radical activity. Chronic facial pain patients showed significantly raised serum 2,3-dihydroxybenzoic acid after an oral dose of 1.2 g of aspirin which indicates increased systemic free radical activity. This was reflected in the TMJ aspirates of the facial arthromyalgia patients which contained thiobarbituric acid-reactive substance (TBA-RS) which is also a product of free radical activity. The synovial aspirates also contained high levels of the hyperalgesic eicosanoid 15-HETE. However, there was no difference between the painful and symptom-free joints, which suggested that in part the clinical features are probably determined by asymmetrical masticatory function or as yet unknown algesic factors such as local cytokine production.

Administration, Oral↗

Supernumerary premolar teeth in siblings.

The familial nature of supernumerary teeth is discussed in this paper and illustrated with a report showing the development of supernumeraries in siblings. The orthodontic treatment and possible sequelae to the development of supernumerary teeth in the premolar region is highlighted.

Adolescent↗

Interleukin 6 production by lipopolysaccharide-stimulated human fibroblasts is potently inhibited by naphthoquinone (vitamin K) compounds.

Naphthoquinone vitamins (vitamins K) are widely recognized for their role in the gamma-carboxylation of specific glutamyl residues in coagulation, anti-coagulation and extra-hepatic proteins. Recently, however, there have been reports that these compounds can exert actions other than those normally associated with protein gamma-carboxylation. These observations suggest that naphthoquinones may have effects on the production of inflammatory mediators including cytokines. Fibroblasts are now recognized as a rich source of cytokines and we have examined the effect of various naphthoquinones on the production of interleukin 6 (IL-6) by lipopolysaccharide-stimulated human gingival fibroblasts. Compounds examined in this study include: phylloquinone (K1), menaquinone-4 (K2), menadione (K3), 2,3-dimethoxy-1,4-naphthoquinone (DMK) and a synthetic product of vitamin K catabolism, 2-methyl, 3-(2'methyl)-hexanoic acid-1,4-naphthoquinone (KCAT). All of these compounds are capable of inhibiting IL-6 production with a rank order of potency: KCAT > K3 > DMK > K2 > K1. The most potent compound, KCAT, inhibited IL-6 production with an IC50 of 3 x 10(-7)M. The mechanism of action of these naphthoquinones on fibroblast IL-6 production is unknown. Given that K3 and KCAT are inactive in the gamma-carboxylation reaction, we suggest that this activity is not essential for the inhibition of IL-6 production and that activity may be related to the redox capacity of these naphthoquinones.

Cells, Cultured↗

Detection and measurement of vitamins K1 and K2 in human cortical and trabecular bone.

Vitamin K plays an essential role in the gamma carboxylation of the gla-containing proteins of bone matrix, such as osteocalcin. We have measured the concentration of vitamin K1 (VK) and of the menaquinones MK-6, MK-7, and MK-8, the three major vitamin K2 moieties, in trabecular and cortical bone taken from the femoral neck of patients undergoing hip replacement. Both bone compartments were found to contain large amounts of VK, MK-6, MK-7, and MK-8. Concentrations were as high as those reported for the liver, the major storage organ for vitamin K. Further research is required to examine the association between vitamin K in bone and the gamma carboxylation of vitamin K-dependent bone proteins.

Aged↗

Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture.

We measured the serum levels of phylloquinone (vitamin K1) and of the menaquinones, MK-7 and MK-8, in a group of 51 women with a mean age of 81 years who were studied within a few hours after a hip fracture. A group of 38 healthy age-matched women randomly chosen from the same population served as controls. Patients with hip fracture had a marked reduction in serum vitamin K1 (336 +/- 302 versus 585 +/- 490 pg/ml, p < 0.01), MK-7 (120 +/- 84 versus 226 +/- 178 pg/ml, p < 0.001), and MK-8 (89 +/- 113 versus 161 +/- 145 pg/ml, p < 0.01), and a large number had undetectable levels, especially of MK-8. Vitamin K levels were not correlated with the time elapsed after fracture or with serum cortisol or other biochemical variables. These data suggest that patients with hip fracture have vitamin K deficiency, an abnormality that could affect bone metabolism through an impairment of the gamma carboxylation of the gla-containing proteins of bone.

Aged↗

Depressed levels of circulating menaquinones in patients with osteoporotic fractures of the spine and femoral neck.

Vitamin K1 functions in the conversion of glutamate residues, present in certain bone peptides, into the putatively active gamma-carboxyglutamate form. We have shown previously that the circulating levels of vitamin K1 are depressed in osteoporotic patients. However, it is known that menaquinones (vitamin K2:MK) may be more effective than vitamin K1 in this conversion of the inactive to active form of glutamate residues. A procedure for measuring such menaquinones has now demonstrated a marked deficiency of MK-7 and MK-8 in patients with osteoporotic fractures. It is suggested that estimates of circulating levels of K1, MK-7, and MK-8 might provide a biochemical risk marker of osteoporotic fractures.

Aged↗

Age-related changes in the circulating levels of congeners of vitamin K2, menaquinone-7 and menaquinone-8.

1. Through the vitamin K1 cycle, phylloquinone is now known to play an active role, not only in relation to prothrombin, but also in the synthesis of bone peptides. 2. The recent development of a sensitive method allowed the demonstration of a deficit of vitamin K1 in the circulation of osteoporotic subjects. 3. Vitamin K2, namely the menaquinones of various chain-lengths, has been shown by others to be more effective than vitamin K1 in the curative rat bioassay. 4. Earlier reports had shown that the concentration of menaquinones in human liver may exceed that of vitamin K1. But previous methods were too insensitive for testing the normal circulating levels of menaquinones in the human. 5. The new sensitive method has now been applied to measuring the circulating levels of vitamin K1 and of two of the menaquinones, namely menaquinone-7 and menaquinone-8. 6. In normal individuals, the circulating levels of vitamin K1 were the same, irrespective of age. 7. In young normal subjects, the combined levels of menaquinone-7 and menaquinone-8 were at least the same as the level of vitamin K1. In elderly normal subjects, there was a marked deficit of menaquinone-8.

Adult↗