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Biomedical subjects

D Black

Publications and source records attributed to D Black.

At least 19 recordsLinked to original sources
PubMed2006

A systematic review on the efficacy of cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for diffuse malignancy peritoneal mesothelioma.

BACKGROUND: In the past, diffuse malignant peritoneal mesothelioma (DMPM) was regarded as a preterminal condition. The length of survival was dependent upon the aggressive versus indolent biologic behavior of the neoplasm. The overall median survival was approximately 1 year after systemic chemotherapy. Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established. PATIENTS AND METHODS: Searches for relevant studies published in peer-reviewed medical journals on CRS and PIC for DMPM before May 2006 were carried out on six databases. The reference lists of all retrieved articles were reviewed for further identification of potentially relevant studies. Expert academic surgeons in Washington, DC, USA were asked whether they knew about any important unpublished data. Two investigators independently evaluated each study according to predefined criteria. The quality of each study was assessed. Clinical effectiveness was synthesized through a narrative review with full tabulation of results of all included studies. RESULTS: Seven prospective observational studies from six tertiary institutions were available, allowing 240 DMPM patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. The perioperative morbidity varied from 25% to 40% and mortality ranged from 0% to 8%. CONCLUSIONS: This systematic review evaluated the current evidence for CRS and PIC for DMPM. Seven observational studies were available for assessment, which demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.

Antibiotics, Antineoplastic↗
PubMed2005

Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation.

BACKGROUND: Cathepsin K (catK), a lysosomal cysteine protease, was identified in a gene-profiling experiment that compared human early plaques, advanced stable plaques, and advanced atherosclerotic plaques containing a thrombus, where it was highly upregulated in advanced stable plaques. METHODS AND RESULTS: To assess the function of catK in atherosclerosis, catK(-/-)/apolipoprotein (apo) E(-/-) mice were generated. At 26 weeks of age, plaque area in the catK(-/-)/apoE(-/-) mice was reduced (41.8%) owing to a decrease in the number of advanced lesions as well as a decrease in individual advanced plaque area. This suggests an important role for catK in atherosclerosis progression. Advanced plaques of catK(-/-)/apoE(-/-) mice showed an increase in collagen content. Medial elastin fibers were less prone to rupture than those of apoE(-/-) mice. Although the relative macrophage content did not differ, individual macrophage size increased. In vitro studies of bone marrow derived-macrophages confirmed this observation. Scavenger receptor-mediated uptake (particularly by CD36) of modified LDL increased in the absence of catK, resulting in an increased macrophage size because of increased cellular storage of cholesterol esters, thereby enlarging the lysosomes. CONCLUSIONS: A deficiency of catK reduces plaque progression and induces plaque fibrosis but aggravates macrophage foam cell formation in atherosclerosis.

Animals↗
PubMed2005

Topography and anisotropy of the skin surface with ageing.

BACKGROUND/PURPOSE: Most studies of how the relief of the skin surface changes on ageing are based solely on topography, and a few have taken into account anisotropy parameters. However, the calculation of these parameters is often carried out manually and as the techniques of data acquisition have progressed rapidly, a certain degree of obsolescence has been reached. It is for this reason that we have undertaken a similar study but with more advanced equipment. MATERIALS AND METHODS: The Dermatop system analyses the relief of Silflo negative prints of the skin surface. It is based on the projection of interference fringes and phase shift and provides surface parameters and not profiles. In addition, the Toposurf software enables image processing and the precise and automatic calculation of the topography parameters (roughness, developed surface area and peak-trough amplitude) and anisotropy (level of anisotropy and furrow density). These parameters were studied on the forearm and temple of 40 men and 40 women evenly distributed into two groups: the first including subjects aged 25-35 years and the second 50-65 years. RESULTS: Roughness of both sites increases with age, independent of sex, but to a lesser extent in women than in men. The developed surface area and the peak-trough amplitude increase significantly with age irrespective of the site and the sex. The level of anisotropy increases with age, in both men and women, on the forearm and the temple, the site more exposed to light being more affected. The density of the furrows decreases with age in both sexes and both sites but with a greater increase for the temple, which is more exposed to solar ageing. CONCLUSION: The study of these new parameters will allow objective evaluation of the action of topical dermatological and cosmetic treatment, and new techniques in plastic surgery (e.g. laser resurfacing), and will enable the accurate follow-up of certain pathologies.

Adult↗
PubMed2004

Randomized clinical trial of distal anastomotic interposition vein cuff in infrainguinal polytetrafluoroethylene bypass grafting.

BACKGROUND: The aim was to examine the effect of a Miller vein cuff at the distal anastomosis on the medium- to long-term patency and limb salvage rates of femoral to above-knee and femoral to below-knee popliteal artery polytetrafluoroethylene (PTFE) bypasses. METHODS: This study involved extended follow-up of the original cohort of patients included in a previously reported multicentre randomized clinical study. Outcome measures were bypass graft patency and limb salvage. RESULTS: Two hundred and sixty-one bypass operations were originally randomized. For this study, full data were available on 235 (120 with a Miller cuff, 115 without). The cumulative 5-year patency rate for above-knee bypasses with a Miller cuff was 40 per cent, compared with 42 per cent for non-cuffed bypasses (P = 0.702). The cumulative 3-year patency rate for below-knee bypasses with a Miller cuff was 45 per cent, compared with 19 per cent for non-cuffed bypasses (P = 0.018). A Miller cuff had no significant effect on limb salvage for above-knee or below-knee bypasses. CONCLUSION: Three-year patency rates of femoral to below-knee popliteal PTFE bypasses were improved by a Miller cuff. Miller cuffs had no effect on patency rates for femoral to above-knee popliteal bypasses at 5 years and did not improve limb salvage in either group.

Aged↗
PubMed2003

Genomics in target and drug discovery.

Genomics-based discovery of novel therapeutic drug targets requires the design of well-controlled biological or pharmacological experiments with experimental questions and hypotheses that relate to the therapeutic area of interest. This will aid the validation level of differentially expressed genes and hence facilitate the de-selection of the genes that are identified in microarray experiments. We here provide an example of how this approach is followed in the manipulation of human macrophage foam cells towards the discovery of novel drug targets for treatment of atherosclerosis.

Arteriosclerosis↗
PubMed2003

Avian cryptococcosis.

Clinical and laboratory findings in 15 unreported cases of avian cryptococcosis from Australia were collated and contrasted with 11 cases recorded in the literature. Cryptococcus species produced localized invasive disease of the upper respiratory tract of captive parrots living in Australia. This resulted in signs referable to mycotic rhinitis or to involvement of structures contiguous with the nasal cavity, such as the beak, sinuses, choana, retrobulbar space and palate. Parrots of widely differing ages were affected and of the seven birds for which sex was determinable, six were male. Cryptococcus bacillisporus (formerly C. neoformans var. gattii) accounted for four of five infections in which the species or variety was determinable, suggesting that exposure to eucalyptus material may be a predisposing factor. In these cases, Cryptococcus appeared to behave as a primary pathogen of immunocompetent hosts. One tissue specimen was available from an Australian racing pigeon with minimally invasive subcutaneous disease; immunohistology demonstrated a C. neoformans var. grubii (formerly C. neoformans var. neoformans serotype A) infection, presumably subsequent to traumatic inoculation of yeast cells into the subcutis. Two similar cases had been reported previously in pigeons domiciled in America. Data for parrots, one pigeon and other birds studied principally in America and Europe (and likely infected with C. neoformans) suggested a different pattern of disease, more suggestive of opportunistic infection of immunodeficient hosts. In this cohort of patients, the organism was not restricted to cool superficial sites such as the upper respiratory tract or subcutis. Instead, infections typically penetrated the lower respiratory tract or disseminated widely to a variety of internal organs. Finally, three captive North Island brown kiwis, one residing in Australia, the other two in New Zealand, died as a result of severe diffuse cryptococcal pneumonia (two cases) or widely disseminated disease (one case). C. bacillisporus strains were isolated from all three cases, as reported previously for another kiwi with disseminated disease in New Zealand.

Animals↗
PubMed2002

Quantitative ultrasound and mortality: a prospective study.

Previous studies suggest that low bone mineral density (BMD) is associated with increased mortality, but the relationship between quantitative ultrasound (QUS) and mortality is unknown. We studied 5816 women over age 70 years enrolled in the Study of Osteoporotic Fractures. QUS of the calcaneus, and BMD of the calcaneus and hip, were measured at baseline, and women were contacted every 4 months to determine vital status. All reported deaths were confirmed by review of the death certificate or hospital records, and classified by ICD-9 code. During 5.0 years of follow-up, 677 women died. Women in the lowest quintile of QUS had the highest mortality during follow-up. After adjustment for age, grip strength, weight, height, health status, estrogen use, smoking, physical activity, and history of hypertension, diabetes, cardiovascular disease, cancer and stroke, each 1 SD reduction in broadband ultrasonic attenuation (BUA) was associated with a 16% increase in mortality (RH = 1.16; 95% CI: 1.07, 1.26). Mortality from cardiovascular disease, cancer and other causes were all increased among women with low QUS, but the association with cancer deaths was not statistically significant after multiple adjustments (RH = 1.09; CI: 0.93, 1.27). Low BMD was also associated with an increased risk of total and cause-specific mortality, but we found little evidence that BUA and BMD were independent predictors of mortality. Results were similar among women who did not fracture during follow-up. In this large population-based study of older women, low QUS is associated with both total and cause-specific mortality. This relationship was independent of other factors associated with mortality, such as age and health status, and suggests QUS and BMD may reflect some aspect of aging not captured by these traditional factors.

Absorptiometry, Photon↗
PubMed2002

Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gut: analysis by gene array and in situ hybridisation.

BACKGROUND AND AIM: Matrix metalloproteinases (MMPs) have been implicated in tissue remodelling and ulceration in inflammatory bowel disease and coeliac disease. Studies to date have concluded that stromelysin 1 is functionally involved in mucosal degradation. However, there are many other MMPs whose function in the gut is currently unknown. This work had two aims: firstly, to use gene array technology to measure changes in MMP and tissue inhibitor of metalloproteinase (TIMP) expression in a model of T cell mediated injury in the gut, and secondly, to correlate data from gene arrays with that generated by in situ hybridisation. METHODS: T cells in explants of human fetal gut were activated with pokeweed mitogen or anti-CD3 plus interleukin 12. Gene array analysis and in situ hybridisation were performed to investigate changes in MMP gene expression. RESULTS: Both gene array analysis and in situ hybridisation indicated marked upregulation of stromelysin 2 and macrophage metalloelastase expression in the explants associated with mucosal destruction. The arrays also confirmed our previous observation that interstitial collagenase (MMP-1), stromelysin 1 (MMP-3), and gelatinase B (MMP-9) are upregulated but there was no change in MMP-2, -7, -8, -9, -11, -13, -14-17, or -19. Following T cell activation, transcripts for TIMPs were reduced. CONCLUSIONS: These results show that there is differential upregulation of MMPs during T cell responses in the gut and suggest that further studies on the role of stromelysin 2 and macrophage metalloelastase may show that they have a functional role. In addition, the increase in MMPs and reduction in TIMPs suggest that the protease/antiprotease balance in the mucosa may determine the extent of mucosal degradation.

Collagenases↗
PubMed2001

Fluvoxamine in the treatment of panic disorder: a multi-center, double-blind, placebo-controlled study in outpatients.

Serotonergic mechanisms have been implicated in panic disorder, and several preliminary studies suggest that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), is helpful in its treatment. This 8-week double-blind parallel-group study compared fluvoxamine with a placebo in 188 patients with DSM-III-R defined panic disorder with or without agoraphobia. Efficacy assessments included a Daily Panic Attack Inventory, the Sheehan Disability Scale, the Clinical Anxiety Scale and the Clinical Global Impression Scale. When compared with the placebo, fluvoxamine produced highly significant improvements in most measures of the frequency and severity of panic disorder and in the more global aspects of disability and distress. Significant improvement was evident as early as week 1 for some panic variables. Fluvoxamine is a potent anti-panic agent with a relatively rapid onset of action.

Adolescent↗
PubMed2001

Use of thigh pressure cuffs to modulate simulated microgravity-induced changes in the skin measured with high-resolution B-scan ultrasound.

OBJECTIVE: The aim of the present study was to evaluate the fluid shift in a simulated microgravity experiment and to test the use of thigh cuffs to help alleviate the problem. METHODS: The change in skin thickness was assessed by a 20 MHz B-scan ultrasound device. This was performed on eight volunteers who underwent two successive 7-day periods of -6 degrees anti-orthostatic bed-rest, with or without the daytime use of thigh cuffs. The thigh cuffs were used to counteract the development of facial oedema. RESULTS: In the control group (without thigh cuffs), the results showed a steady increase in skin thickness of the combined dermis and hypodermis of the forehead and a reduction of the thickness of this tissue on the tibia. For the countermeasure group, although thigh cuffs were only employed during the daytime - being removed at night - their use reduced the amplitude and kinetics of the fluid shift, resulting in greater beneficial effects at the end of the day than early in the morning. CONCLUSION: These results of objective measurements of skin made using a non-invasive high frequency ultrasonography method confirm reports by cosmonauts of a reduction in facial oedema and a more 'comfortable' adaptation to microgravity by the use of thigh cuffs during space flight. This system is potentially promising for investigating fluid shifts in the skin and may prove useful in the evaluation of some oedematous skin diseases, as well as their therapy.

Adult↗
PubMed2001

Skin topography measurement by interference fringe projection: a technical validation.

BACKGROUND/AIMS: The quantitative analysis of skin topography is frequently used in cosmetology to evaluate the efficacy of hydrating or anti-wrinkle creams (micro-topography studies) or creams for slimming or to alleviate stretch marks (macro-topography studies). Numerous methods involving the three-dimensional (3-D) reconstruction of the topography from silicone replicas have been developed. Some of the main techniques applied include optical profilometry based on the reflection of oblique lighting or on transparency, and profilometry by laser focusing or triangulation. METHODS: We chose to test the Dermatop system developed by Eotech Co., which is based on interference fringe projection profilometry associated with the Toposurf surface processing software. Owing to the system's principle of operation, we first ran three experiments to evaluate the influence of ambient lighting on the 3-D reconstruction and the surface roughness parameters, the influence of the calibration device built into the acquisition system and the influence of calibration in terms of ambient lighting correction. We then evaluated the accuracy, the repeatability and the reproducibility of the measurements provided by the system from known metal topographic standards and skin replicas. RESULTS: It was seen that external lighting can cause variations in the calculation of parameters SPa, SPt and SPtm which can reach error levels of about 5% if the operator does not almost systematically calibrate the apparatus between each measurement. These three experiments enabled us to standardise the protocol for the acquisition of 3-D information, in order to minimise the lighting problems and yet respect the requirements for routine studies. The correlation coefficient between the theoretical values and the mean of experimental values was 0.9955 for parameter SPa and 0.9983 for parameter SPtm. Repeatability presented variations of under 4%, irrespective of the parameters, and reproducibility of under 6%. CONCLUSIONS: The technique provides very satisfactory results from the point of view of accuracy, repeatability and reproducibility. It is an excellent compromise between cost, accuracy and the time required.

Dermatology↗
PubMed2001

A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial.

Vitamin D deficiency leads to secondary hyperparathyroidism, increased bone turnover, and bone loss and, when severe, to osteomalacia. Vitamin D deficiency is common in elderly people, especially the institutionalized. The definition of vitamin D deficiency is hampered by the fact that large interlaboratory differences exist in assays for serum 25-hydroxyvitamin D (25OHD), the main circulating metabolite. The international Multiple Outcomes of Raloxifene Evaluation study, a large prospective intervention trial in postmenopausal women with osteoporosis, offered the opportunity to compare vitamin D status and parathyroid function throughout many countries over the world. For this study, baseline data were available from 7564 postmenopausal women from 25 countries on 5 continents. All women had osteoporosis, i.e. bone mineral density (BMD) at femoral neck or lumbar spine was lower than t-score -2.5, or they had 2 vertebral fractures. Serum 25OHD was measured by RIA, and serum PTH was measured by immunoradiometric assay. BMD was measured by dual x-ray absorptiometry. The mean (+/-SD) serum 25OHD was 70.8 +/- 30.9 nmol/L. A low serum 25OHD (<25 nmol/L) was observed in 4.1% of all women in the Multiple Outcomes of Raloxifene Evaluation study, ranging from 0% in south east Asia (very few patients) to 8.3% in southern Europe. Serum 25OHD was between 25-50 nmol/L in 24.3% of the women. Serum 25OHD showed a significant seasonal relationship, with lower values in all regions in winter. Serum PTH correlated negatively with serum 25OHD (r = -0.25; P < 0.001). This significant negative correlation was observed in all regions. When serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, mean serum PTH levels were 4.8, 4.1, and 3.5 pmol/L, respectively (by ANOVA, P < 0.001). Similarly, mean alkaline phosphatase levels were 83.7, 79.1, and 75.7 U/L (P < 0.001), respectively, with increasing serum 25OHD. The effect of serum 25OHD on BMD was only significant for the BMD of the trochanter where a serum 25OHD level less than 25 nmol/L was associated with a 4% lower BMD. After 6 months of treatment with vitamin D(3) (400-600 IU/day) and calcium (500 mg/day), serum 25OHD increased from 70.8 +/- 29.8 to 92.3 +/- 28.6 nmol/L. Serum PTH decreased significantly after 6 months of treatment, and this decrease depended on baseline serum 25OHD. When baseline serum 25OHD was less than 25, 25-50, or more than 50 nmol/L, respectively, serum PTH decreased by 0.8, 0.5, or 0.2 pmol/L, respectively (P < 0.001). In conclusion, serum 25OHD was less than 25 nmol/L in 4% of the women, and this was associated with a 30% higher serum PTH. In 24% of the women serum 25OHD was between 25-50 nmol/L, associated with a 15% higher level of serum PTH compared with women with a serum 25OHD greater than 50 nmol/L. A low serum 25OHD level was also associated with higher serum alkaline phosphatase and lower BMD of the trochanter. Treatment with vitamin D(3) and calcium increased serum 25OHD and decreased serum PTH significantly; the effect was greater for lower baseline serum 25OHD.

Absorptiometry, Photon↗