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Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 37 records · Page 2Linked to original sources

Colonic fermentation of inulin increases whole-body acetate turnover in dogs.

Metabolism of acetate from colonic fermentation was investigated in dogs. Beagle dogs (n = 9) were fed a control diet for 17 d followed by a 3% inulin-enriched diet (from chicory) for 4 and 21 d. On 3 occasions, the dogs were administered simultaneously infusions of [1-(13)C]acetate i.v. and [1,2-(13)C(2)]acetate intrarectally. Peripheral acetate concentration and turnover did not change over time after consumption of an inulin-enriched diet for 4 d. After 21 d of consuming the inulin-enriched diet, the whole-body acetate turnover increased significantly by 31% from (mean +/- SEM) 15.6 +/- 2.2 to 20.4 +/- 2.9 micromol/(kg . min) without a change in concentration. The rate of colonic acetate production that reached the peripheral circulation was 4.8 +/- 1.8 micromol/(kg . min). However, no [1,2-(13)C(2)]acetate tracer was recovered in the peripheral circulation. The fraction of oxidized tracer was higher in the gut (64 +/- 3%) than in peripheral circulation (46 +/- 3%) in dogs fed an inulin-enriched diet for 21 d. In conclusion, colonic fermentation of inulin occurred and indirectly stimulated whole-body acetate turnover in dogs fed an inulin-enriched diet for 21 d.

Acetates↗

Clinical variants of the preprotuberant stage of dermatofibrosarcoma protuberans.

BACKGROUND: Some cases of dermatofibrosarcoma protuberans (DFSP) do not protrude above the skin. OBJECTIVES: To assess the prevalence of these DFSPs and further to describe their presentation and course. METHODS: One hundred and forty-three patients were retrospectively collected. They were asked to complete a standardized questionnaire indicating the history and appearance of the DFSP from the first skin changes identified to the time of diagnosis. RESULTS: Eighty-one DFSPs were described as protuberant ab initio, and 62 as initially nonprotuberant (npDFSP). The latter remained at this stage for a mean period of 7.6 years. Twenty-nine per cent of npDFSPs were 'morphoea-like', 19% were 'atrophoderma-like' and 42% were 'angioma-like'. Age at diagnosis was similar for both initial presentations. npDFSPs were most often misdiagnosed by physicians. CONCLUSIONS: Nearly half the patients first identified their early DFSP-related skin changes as patches. Both this frequency and the long duration at this preprotuberant stage should prompt dermatologists to consider the diagnosis of DFSP earlier, in order to make surgical treatment easier.

Adolescent↗

Warfarin-induced small bowel obstruction.

We present a rare case of small bowel obstruction in a patient on long-term anticoagulation. A 53-year woman presented with abdominal pain and vomiting. She was on warfarin following aortic and mitral valve surgery. A small bowel follow through revealed jejunal narrowing consistent with a stricture. This probably was the result of submucosal bleeding because of over warfarinazation. The warfarin was stopped and she started on heparin with complete resolution of symptoms. This rare complication of anticoagulation should be considered in patients on warfarin. Early diagnosis is crucial as most patients are treated conservatively with very few patients requiring surgery.

Female↗

Lactate is mainly fermented to butyrate by human intestinal microfloras but inter-individual variation is evident.

AIM: To assess the role of lactate as a precursor for butyrate biosynthesis in human colonic microflora. METHODS AND RESULTS: Three human faecal microfloras were incubated in vitro with media supplemented with 30 mmol l(-1) unenriched or 13C-enriched lactate. Lactate metabolism and short-chain fatty acid (SCFA) production were quantified. Lactate conversion to butyrate was investigated by gas chromatography-mass spectrometry and the pathways involved were identified by 13C nuclear magnetic resonance spectroscopy. All human faecal microfloras rapidly and completely fermented lactate, yielding approx. 19 mmol l(-1) total SCFAs. However, the SCFA composition varied markedly between microfloras. Butyrate was the main end-product for two microfloras but not for the third (60 and 61%vs 27% of the net concentration of SCFA produced respectively). The latter was typified by its ability to produce propionate as a major product (37%), and valerate (3%). 13C-Labelling showed that butyrate was produced through the acetyl-CoA pathway and that the three microfloras possessed significant differences in their metabolic pathways for lactate consumption. CONCLUSIONS: In contrast to the ruminal microflora, the human intestinal microflora can utilize both d- and l-lactate as precursors for butyrate synthesis. Inter-individual variation is found. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests that the butyrogenic capability of colonic prebiotics could be related to lactate availability. These findings will direct the development of selection strategies for the isolation of new butyrate-producing bacteria among the lactate-utilizing bacteria present in the human intestinal microfloras.

Adult↗

Microdot test of foveal function. A comparison with visual acuity at high and low contrast.

PURPOSE: To define normal values across age from novel computerized tests of foveal vision and to compare the findings with visual acuity (VA) at high and low contrast. SUBJECTS AND METHODS: Sixty-one healthy volunteers, aged 22-87, with subjectively normal vision participated in the study. The right eye from each subject was tested with Snellen letter VA at high contrast, at 10% contrast using the Tri-VA test and with the Rarebit Microdot Fovea Test (RMFT), in addition to biomicroscopy and fundus examination. RESULTS: The median letter VA was 0.77 minimum angle of resolution (MAR; range 0.63-1.54) with a significant decline in letter VA with increasing age (r = 0.7, p < 0.001). The median Tri-VA resolution threshold at 10% contrast was 1.8 MAR (range 0.9-4.1) and a significant age effect (r = 0.7) was observed, most pronounced above 65 years. The median RMFT hit rate was 100% (range 97-100) in the age group below 65 years and 87.5% (range 34-98) in subjects older than 65 years. CONCLUSION: The study shows a decline in foveal function with age with all three methods, reflecting the loss of neural detectors with increasing age. The hit rate to microdot stimuli appears to be a sensitive measure, which can be used for fine-graded evaluation of foveal function.

Adult↗

The role of anticipatory postural adjustments in a rocking on heels movement.

We studied the anticipatory postural adjustments (APAs) associated with a voluntary rocking on heels movement performed in a self-paced manner. Ground reaction forces and the EMG activity of the leg muscles were recorded. Such a movement shifted the centre of gravity (CG) backwards, due to APAs on the lower limbs. It is generally assumed that APAs only generate corrections in the opposite direction to the perturbation due to the focal movement. However, our study shows that APAs, by creating the initial backward oriented impulse, displace the CG backwards and generate the dynamic conditions required to move.

Adolescent↗

[Lung separation after reintubation with airway exchange catheter in multiple trauma patient with massive haemoptysis].

A 24-year-old man fell from the third floor. He developed an unilateral pulmonary parenchymal injury and a significant haemoptysis following blunt thoracic trauma. Because of its abundance, it was not possible to obtain adequat oxygenation. To protect controlateral lung from inhalation and to achieve adequat oxygenation, we used double lumen endotracheal tube, lung separation and one lung ventilation. To solve potential airway management difficulties (haemorrhage, trauma, cervical immobilization), we used airway exchange catheter (Cook) to place the double lumen endotracheal tube. Haemoptysis has been controlled by embolization of the right bronchial artery.

Accidental Falls↗

[Pneumatic anti-shock garment use leading to non-visualization of pelvic arterial bleeding on angiography].

Initial reports of pneumatic anti-shock garment (PASG) in severely hypotensive patients appeared promising. Nevertheless, large-scale studies in prehospital settings have shown no overall reduction in mortality rates among hypotensive patients with application of the PASG. However, in a subsample of patients with blood pressure < or =50 mmHg, PASG seems to be useful to reduce bleeding and improve survival. To our knowledge, our case report is the first which directly showns on angiography the hemostatic effect of PASG on pelvic trauma bleeding. In spite of its possible complications, PASG remains one of the tools of trained trauma teams who regularly treated severe haemorrhagic shock.

Adult↗

Development and performance of the vehicle-mounted radiation monitoring equipment used in the Maralinga rehabilitation project.

The rehabilitation of the former nuclear test site at Maralinga involved (among other processes) the removal of contaminated soil from an area of approximately 2.5 km2. The two most stringent rehabilitation criteria required measurements to ensure that no radioactive particle exceeding 100 kBq of 241Am activity, and no area of 1 ha exceeding 3 kBq/m2 of 241Am activity, remained in the rehabilitated area. The project timetable required that the area be scanned at the rate of approximately 3 ha/day. Two vehicle-mounted detection systems were developed and constructed to obtain the necessary measurements in the available timeframe. The scientific basis for the designs are presented, together with details of the selected equipment and technical solutions found. The performance of this equipment in the field is discussed in terms of both its scientific and technical operation. Based on the experience gained at Maralinga, improved versions of this equipment were produced under contract for the People's Republic of China.

Americium↗

Early detection of prostate cancer in African-American men through use of multiple biomarkers: human kallikrein 2 (hK2), prostate-specific antigen (PSA), and free PSA (fPSA).

Recent studies have reported enhanced prostate cancer detection in Caucasians with serum human glandular kallikrein 2 (hK2) in combination with total- (tPSA) and free-prostate-specific antigen (fPSA). The purpose of this study is to validate these findings in an African-American patient cohort. A total of 137 African-American men were found by routine screening to have tPSA levels above 2.5 ng/ml or an abnormal digital rectal examination. Sera were drawn prior to biopsy of the prostate and Hybritech PSA, FPSA and hK2 (for research use only, not for use in diagnostic procedures) concentrations were determined on Beckman Coulter's Access immunoanalyzer. These independent variables and the ratios of percent fPSA (%fPSA), hK2/tPSA, hK2/fPSA, and hK2*tPSA/fPSA were compared between cancer and non-cancer groups. In all, 49 of 137 men had prostate cancer. hK2 and its calculated ratios outperformed tPSA on receiver operator characteristic (ROC) analysis, but %fPSA had statistically the highest area under the curve (AUC) at 0.801. When restricting the analysis to only the tPSA range of 4.0-10 ng/ml, hK2/fPSA yielded the highest AUC (0.721). The ratio of hK2/fPSA was also found to increase the positive predictive value (PPV) of the %fPSA ranges less than 10 and 10-25%. %fPSA offered the best performance and highest specificity in prostate cancer detection in African-American males over the entire range of tPSA. hK2/fPSA may offer modest improvement in the tPSA range of 4.0-10 ng/ml. Furthermore, hK2/fPSA can enhance the PPV of low %fPSA values. Therefore, the use of multiple biomarkers may ultimately increase the specificity of prostate cancer screening in African-American men.

Black or African American↗

What is the best way to assess microsatellite instability status in colorectal cancer? Study on a population base of 462 colorectal cancers.

The assessment of the microsatellite instability (MSI) status in colorectal cancers is presently warranted for three reasons: 1) as a screening tool for hereditary nonpolyposis colorectal cancer, 2) as a prognostic marker, and 3) as a potential predictive factor of chemotherapy response. The aim of this study was to evaluate, on a large scale with tissue samples coming from a number of different sources, the difficulties met with routine use of immunohistochemistry (IHC) and to determine if it really does offer an accurate alternative to PCR genotyping. Colorectal carcinomas from 462 consecutive patients resected in public or private hospitals were assessed for MSI status by two methods: MSI testing (with BAT-26 microsatellite) and IHC detection of hMLH1, hMSH2, and hMSH6 proteins. Of the 398 cancers tested, immunohistochemistry was noncontributory in 42 (10.5%), focal in 9 (2.3%), and discordant with the PCR results in 36 (9%). For these 87 cases, complementary analyses were performed to explain discrepancy. After additional IHC assay with modified processing protocols, 8 cases remained noncontributory, 2 focal, and 28 discordant: 18 microsatellite stability IHC/MSI PCR and 10 MSI IHC/microsatellite stability PCR. For these discordant cases, we performed a multiplex PCR assay on DNA extracted from the frozen sample and BAT-26 was amplified from DNA extracted from the paraffin blocks used for IHC. Four discordant cases were reclassified after PCR multiplex assay (3 as MSI and 1 as microsatellite stability). Five other cases displayed intratumoral heterogeneity and 19 remained discordant. The discrepancy could be partly explained by variable technical protocols of fixation in the different laboratories, leading to variations in staining quality and difficulties in IHC interpretation. This population-based study is the first one to show that IHC is not sensitive and specific enough to be used routinely. Immunohistochemistry analysis of MMR proteins must be performed in standardized conditions and interpreted by confirmed pathologists. It cannot replace PCR as long as protocols are not optimized and harmonized.

Aged↗

Use of checkerboard DNA-DNA hybridization to study complex microbial ecosystems.

It has been difficult to conduct large scale studies of microbiologically complex ecosystems using conventional microbiological techniques. Molecular identification techniques in new probe-target formats, such as checkerboard DNA-DNA hybridization, permit enumeration of large numbers of species in very large numbers of samples. Digoxigenin-labeled whole genomic probes to 40 common subgingival species were tested in a checkerboard hydridization format. Chemifluorescent signals resulting from the hybridization reactions were quantified using a Fluorimager and used to evaluate sensitivity and specificity of the probes. Sensitivity of the DNA probes was adjusted to detect 10(4) cells. In all, 93.5% of potential cross-reactions to 80 cultivable species exhibited signals <5% of that detected for the homologous probe signal. Competitive hybridization and probes prepared by subtraction hybridization and polymerase chain reaction were effective in minimizing cross-reactions for closely related taxa. To demonstrate utility, the technique was used to evaluate 8887 subgingival plaque samples from 79 periodontally healthy and 272 chronic periodontitis subjects and 8126 samples from 166 subjects taken prior to and after periodontal therapy. Significant differences were detected for many taxa for mean counts, proportion of total sample, and percentage of sites colonized between samples from periodontally healthy and periodontitis subjects. Further, significant reductions were observed post therapy for many subgingival species including periodontal pathogens. DNA probes used in the checkerboard DNA-DNA format provide a useful tool for the enumeration of bacterial species in microbiologically complex systems.

Bacterial Typing Techniques↗

Insulin resistance and changes in plasma concentration of TNFalpha, IGF1, and NEFA in dogs during weight gain and obesity.

Obesity-induced insulin resistance (IR) is a common problem in humans as well as domestic dogs. It is well-known that this syndrome is associated with many modifications but it is still unclear if the changes are alterations or adaptations. The purpose of this study was to develop obesity-induced IR in dogs, through a long-term overfeeding period, and to explore hormonal and metabolic disturbances associated with the development of this syndrome. Dogs were overfed for 7 months. Body weight increased by 43 +/- 5%, and insulin sensitivity decreased by 44 +/- 5%. Plasma insulin-like growth factor 1 (IGF1), tumour necrosis factor alpha (TNFalpha), and non-esterified fatty acids (NEFA) concentrations progressively increased during the overfeeding period (IGF1: 111 +/- 13 to 266 +/- 32 ng/ml, p < 0.001; TNFalpha: 5 +/- 5 to 134 +/- 41 pg/ml; NEFA: 0.974 +/- 0.094 to 1.590 +/- 0.127 mmol/l, p < 0.05). These metabolic and hormonal impairments are associated with IR, in obese dogs, and could explain, at least in part, the outbreak of this syndrome.

Animals↗

Reported versus confirmed wheeze and lung function in early life.

AIMS: To investigate the relation between parentally reported wheeze (unconfirmed), physician confirmed wheeze, and subsequent lung function. METHODS: Children at risk of allergic disease (one parent atopic) were recruited antenatally and followed prospectively from birth. During the first three years of life parents were asked to contact the study team if their child was wheezy. The presence of wheeze was confirmed or not by the primary care or study physician. Respiratory questionnaire and specific airway resistance measurement (sR(aw), body plethysmograph) were completed at age 3 years. RESULTS: A total of 454 children were followed from birth to 3 years of age. One hundred and eighty six (40.9%) of the parents reported their child wheezing in the first three years of life, and in 130 (28.6%) the wheeze was confirmed. A total of 428 children attended the three year clinic review, of whom 274 (64%) successfully carried out lung function tests. There was no significant difference in sR(aw) (kPa.s; geometric mean, 95% CI) between children who had never wheezed (n = 152; 1.03, 1.00 to 1.06) and those with a parentally reported but unconfirmed wheeze (n = 36; 1.02, 0.96 to 1.07, p = 1.00). sR(aw) was significantly higher in children with a physician confirmed wheeze (n = 86; 1.17, 1.11 to 1.22, p < 0.001) compared to those with no history of wheeze or with unconfirmed wheeze. CONCLUSIONS: Children with physician confirmed wheeze have significantly poorer lung function compared to those with parentally reported but unconfirmed and those who have never wheezed. A proportion of parents may have little understanding of what medical professionals mean by the term "wheeze".

Analysis of Variance↗

Inflammatory related changes in bone mineral content in adults with cystic fibrosis.

BACKGROUND: Proinflammatory cytokines stimulate osteoclast activity and this could lead to increased bone resorption in patients with cystic fibrosis. The aim of this study was to determine whether markers of systemic inflammation are related to changes in bone mineral content (BMC) in adults with cystic fibrosis. METHODS: Total body BMC was assessed by dual energy x ray absorptiometry in 100 patients (54 male) of mean (SD) age 25.6 (7.1) years and forced expiratory volume in 1 second (FEV(1)) 61.8 (24.1)% predicted on recruitment to the study and 1 year later. Blood was also taken at these time points to measure markers of systemic inflammation. RESULTS: After 1 year BMC had reduced by 16.1 (62.1) g, p = 0.01; (0.6 (2.8)%). The change in BMC was related to mean levels of interleukin (IL)-6 (r(s) = -0.39, p<0.001) and C reactive protein (r(s) = -0.34, p = 0.002), intravenous antibiotic use (r(s) = -0.27, p = 0.006) and oral corticosteroid use (r(s) = -0.20, p = 0.045). Urinary markers of osteoclast activity were also related to IL-6 (r(s) = 0.27, p = 0.02). Multiple linear regression revealed that IL-6 (coefficient -2.2 (95% CI -3.4 to -1.0) per pg/ml, p = 0.001), colonisation with Burkholderia cepacia (coefficient -46.8 (95% CI -75.5 to -18.1), p = 0.002), and annual change in BMI (coefficient 15.4 (95% CI 3.6 to 27.2) per kg/m(2), p = 0.011) were independently significant predictors of annual change in BMC. CONCLUSIONS: These data suggest a pathophysiological mechanism by which chronic pulmonary infection results in bone loss in patients with cystic fibrosis.

Absorptiometry, Photon↗

3D analysis of posturo-kinetic coordination associated with a climbing task in children and teenagers.

The aim of this study was to characterize the modifications of the posturo-kinetic coordination during a climbing task as a function of postural and/or movement constraints in children (8-10 years) and adolescents (10-15 years). A 3D-analysis of forces was recorded for different movement amplitudes and types of holds. The results show the involvement of horizontal and vertical forces to maintain equilibrium during the steady state changes for different experimental groups. The contribution of horizontal and vertical forces changes in the course of movement realization. The vertical momentum (Iz) is mainly involved in the movement initiation: this role is mostly meaning for children. The horizontal momentum (Ih) is mainly involved in controlling equilibrium: this role is mostly meaning for adolescents.

Adolescent↗

Relaxant effects of parathyroid hormone and parathyroid hormone-related peptides on oviduct motility in birds and mammals: possible role of nitric oxide.

Parathyroid hormone (PTH) and PTH-related peptides (PTHrP) have previously been shown to modulate the contractile state of numerous types of smooth muscle. The effects of N-terminal PTH and PTHrP on spontaneous in vitro contractility of oviducal smooth muscle using tissues from egg-laying Japanese quail (10-15 h post ovulation), 4 and 9 days pregnant mouse uterus were investigated. Myometrial tissues from both species contracted vigorously for several hours, when incubated in organ baths in De Jalon's solution gassed with 5%CO2/95%O2. Contractions were enhanced in high (1.2-2.5 mM) compared with low (0.1-0.5 mM) calcium (Ca) containing media. Bovine PTH(1-34) (bPTH(1-34)), human PTH(1-34 amide) (hPTHrP(1-34) amide), and hPTHrP(1-40) caused similar concentration-related inhibition of contractions in media containing 1.2mM Ca over a range of 10(-9) to 10(-7)M, whereas C-terminal hPTHrP(107-139) was devoid of such activity. Responses to bPTH(1-34) in 4 and 9-day pregnant mouse tissues were similar but hPTHrP(1-40) showed substantial loss of activity in 9-day, compared with 4-day pregnant mouse tissues. Repeated exposure of mouse uterine tissue to the peptides resulted in desensitisation of responses. The EC50 responses of mouse tissues were inhibited by the PTH/PTHrP receptor antagonist, hPTHrP(7-34) amide. Responses to bPTH(1-34) were also inhibited by both non-selective and selective neuronal nitric oxide synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (0.01-1mM) and 7-nitroindazole (0.01-10 microM), respectively. Both NOS inhibitors were more effective in inhibiting bPTH(1-34)-induced relaxation in the absence of L-arginine compared with in the presence of 1mM L-arginine (a NOS substrate) in the incubation media. It is concluded that relaxant responses to N-terminal PTH and PTHrP peptides are well conserved in oviducal and uterine tissues from avian and mammalian species. The results also suggest that NO may be responsible for mediating relaxant activities of these peptides in pregnant mouse uterine tissue.

Animals↗