Search PubMed⌕ Search

Biomedical subjects

L Martin

Publications and source records attributed to L Martin.

At least 55 records · Page 3Linked to original sources
PubMed2003

Angiogenesis and invasive recurrence in ductal carcinoma in situ of the breast.

The development of an invasive recurrence following treatment for ductal carcinoma in situ (DCIS) converts a non-fatal disease to one associated with mortality. To date, no pathological or molecular features have been found to predict for the type of recurrence. Previous studies have suggested that in DCIS angiogenesis may be an important factor in determining the transformation from in situ to invasive carcinoma. We looked at 355 cases of DCIS and found that 32 had subsequently developed recurrent disease. In these 32 cases and in matched controls, periductal vascular density was determined using morphometry and anti-endothelial antibodies, von Willebrand factor (vWF) and CD34. Vascular density was related to the risk of both invasive and in situ recurrence. Normal lobules at least 2 mm away were used as controls. Differences in the phenotype of individual blood vessels was detected by performing dual staining immunofluorescence on selected cases. The microvessel density (MVD), as detected with the CD34 antibody, was higher around foci of DCIS than around normal breast lobules (P=0.001). Furthermore, it was significantly higher in cases of DCIS that recurred (P<0.0001). The findings with the vWF antibody were less clear cut and suggested a trend in decreasing MVD with increasingly aggressive disease. Dual immunofluorescence staining shows that the increase in MVD seen around DCIS is due to an increase in CD34+/vWF-blood vessels. An increase in CD34+/vWF-of blood vessels may be able to predict cases of DCIS that are at a high risk of developing a recurrence.

Aged↗
PubMed2003

Cerebrospinal fluid pseudocyst of the breast.

A 39 year old lady presented with a lump in her right breast. She was known to have had a ventriculo-peritoneal shunt inserted for childhood hydrocephalus. Mammography revealed a calcified, fractured shunt with an associated soft tissue swelling which resolved following shunt removal. Shunt fracture secondary to calcification is extremely rare, and presentation as a breast lump has not been previously described. This case identifies a rare cause of breast lumps and highlights the importance of complete triple assessment in all patients presenting with a breast lump.

Adult↗
PubMed2003

Mechanical effect of additional supports in a rocking on heels movement.

This study examined the influence of the addition of handles on postural adjustments associated to a rocking on heels movement. Upper and lower limb muscle EMG activities were recorded and the forces applied to the handles and beneath the feet were measured. Without handles, the anticipatory activation of the Gastrocnemius Medialis displaced the COP forwards, enabling the backward shift of the CG required to rock back on heels. This anticipatory postural activity disappeared with handles and was substituted by an EMG activity on the upper limbs. This activity engendered a forward and downward push on the handles, which largely contributed to create the dynamic conditions required to perform the movement.

Adult↗
PubMed2003

Hypoxia-mediated tumour targeting.

Hypoxia is a common physiological feature of tumours. It activates a signalling cascade that culminates in the stabilization of the HIF-1 transcription factor and activation of genes that possess a hypoxia response element (HRE). We have used an optimized hypoxia responsive promoter (OBHRE) to investigate hypoxia-targeted gene expression in vivo in the context of an adenovirus vector. The OBHRE promoter showed limited activity in the liver or spleen such that expression was 1000-fold lower than that driven by the strong CMV/IE promoter. However, in the context of the tumour microenvironment, the OBHRE promoter achieved expression levels comparable to that of the CMV/IE promoter. Next, we showed that an adenovirus expressing the human cytochrome P450 (CYP2B6) regulated by the OBHRE promoter delays tumour growth in response to the prodrug cyclophosphamide (CPA). Finally, we exploited the hepatotropism of adenovirus to investigate whether the OBHRE promoter could mitigate the hepatotoxicity of a recombinant adenovirus expressing thymidine kinase (TK) in the context of the prodrug ganciclovir (GCV). High-dose Ad.CMVTK/GCV treatment caused significant liver necrosis whereas the same dose of Ad.HRETK was well tolerated. These in vivo data demonstrate that hypoxia-targeted gene expression via the OBHRE promoter can be used to increase the therapeutic window of cytotoxic cancer gene therapy.

Adenoviridae↗
PubMed2003

Sporadic colorectal cancers with defective mismatch repair display a number of specific morphological characteristics: relationship between the expression of hMLH1 and hMSH2 proteins and clinicopathological features of 273 adenocarcinomas.

AIMS: The aim of this study was to assess the independent value of pathological criteria in the diagnosis of mismatch repair (MMR)-defective sporadic colorectal cancers. METHODS AND RESULTS: Resected colorectal adenocarcinomas (n = 273) were reviewed in order to identify a number of specific morphological features of MMR-defective carcinomas. Of the 273 cases, 35.2% were right-sided and 5.9% were poorly differentiated. Focal extracellular mucin secretion was seen in 5.1% of cases and a stromal follicular reaction in 4.6%. The expression of the two major MMR proteins hMLH1 and hMSH2 was studied by immunohistochemistry. Carcinomas were considered deficient in the MMR system when a loss of nuclear signal in neoplastic cells was observed for one of the proteins. Such an extinction was seen in 37 of the cases (13.6%). The hMLH1 protein was the one most frequently altered (86.5%). After multivariate analysis, three independent factors were significantly associated with MMR deficiency: proximal location [odds ratio (OR) = 9.30; 95% confidence interval (CI) 2.79, 30.98], the presence of a true stromal follicular reaction (OR = 13.60; 95% CI 2.98, 62.00) and poor differentiation (OR = 8.33; 95% CI 1.63, 40.32). CONCLUSIONS: These results confirm that sporadic colorectal MMR-defective adenocarcinomas display certain specific morphological characteristics. However, these pathological features are not sufficiently predictive and immunohistochemistry is needed to identify such tumours accurately.

Adaptor Proteins, Signal Transducing↗
PubMed2003

A 5-year follow-up study of disease incidence in men with an abnormal hormone pattern.

OBJECTIVES: Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases. To test this hypothesis, we conducted a 5-year follow-up study in middle-aged men. METHODS: A population-based cohort study conducted in 1995 amongst 141 Swedish men born in 1944, in whom a clinical examination supplemented by medical history aimed to disclose the presence of cardiovascular disease (CVD) (myocardial infarction, angina pectoris, stroke), type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000. In addition, salivary cortisol levels were measured repeatedly over the day. Serum testosterone concentrations were also determined. Using the baseline data, an algorithm was constructed, which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal. RESULTS: By the end of follow-up, men with an abnormal hormone secretion pattern (n = 73) had elevated mean arterial pressure (P = 0.003), fasting insulin (P = 0.009) and insulin : glucose ratio (P = 0.005) compared with men with a normal secretion pattern (n = 68). Body mass index, waist circumference, and waist : hip ratio were significantly elevated in both groups. However, the 5-year incidence of CVD, type 2 diabetes, and hypertension were significantly higher (P < 0.001) in men with an abnormal neuroendocrine secretory pattern compared to men with a normal pattern. CONCLUSIONS: These data suggest that an abnormal neuroendocrine secretory pattern is prospectively associated with an increased incidence of cardiovascular-related events and type 2 diabetes.

Angina Pectoris↗
PubMed2003

Influence of age and body size on the digestibility of a dry expanded diet in dogs.

The objectives of the study were (i) to evaluate the effects of age and body size on the apparent digestibility of a dry expanded diet and (ii) to determine whether poor faecal quality could be related to lower nutrient utilization. Four breeds of dogs were used: six Miniature Poodles (MP), six Medium Schnauzers (MS), six Giant Schnauzers (GS) and six Great Danes (GD). Digestive trials were performed at 11, 21, 35 and 60 weeks of age. Faecal moisture and scoring were recorded at the same periods. Digestibility coefficients of all macronutrients increased significantly (p < 0.05) with age in all four breeds. Organic matter digestibility increased from 80.2 +/- 1.5 to 85.5 +/- 1.5% in MP; from 80.2 +/- 0.9 to 86.3 +/- 0.5% in MS; from 79.6 +/- 4.2 to 88.9 +/- 0.5% in GS and from 85.7 +/- 1.5 to 88.4 +/- 0.8% in GD. Crude protein digestibility increased from 74.5 +/- 4.0 to 81.5 +/- 1.9% in MP; from 74.3 +/- 3.9 to 82.6 +/- 0.9% in MS; from 71.8 +/- 6.0 to 85.9 +/- 0.9% in GS and from 80.8 +/- 4.6 to 84.8 +/- 1.3% in GD between 11 and 60 weeks of age, respectively. Mean faecal moisture also increased over the growth, except in GS. Nutrient digestibility was significantly higher in large dogs at all age periods. However, larger dogs showed lower faecal scores and increased faecal moisture. In conclusion, these results show (i) an effect of age and body size on nutrients digestibility and (ii) that the lower faecal quality observed in healthy large breed dogs does not appear related to lower nutrient utilization.

Aging↗
PubMed2003

Finger flexors fatigue in trained rock climbers and untrained sedentary subjects.

The present series of experiments were conducted to access the surface EMG frequency parameters during repeated fingertip isometric contractions to determine if they can be used as a fatigue index under specific grip used in rock climbing. Electromyograms of the finger flexors and extensors were characterised in ten elite climbers and ten non-climbers. The exercise consisted in reaching 80 % of maximal isometric finger force as quickly as possible intermittently with a 5-s contraction followed by 5-s of rest until exhaustion (i. e. when the subject was unable to maintain 80 - 70 % MVC force range for the 5 s). The results clearly indicate that expert climbers performed significantly greater fingertip force than sedentary subjects (420 +/- 46 N vs. 342 +/- 56 N). This force was maintained during twelve repetitions (12.88 +/- 4.96) in sedentary subjects, whereas the climbers maintained the force during nineteen repetitions (19.33 +/- 4.84). The median frequency of both the flexor and extensor EMG power spectra decreased during fatiguing isometric contractions, but at different rates in climbers and non-climbers. In non-climbers, the results replicated previous findings, whereas in climbers the results were novel.

Adult↗
PubMed2003

Intramural neovascularization and haemorrhages are major long-term effects of intravascular gamma-radiation after stenting.

Structural changes that might influence the structural integrity of the vessel in response to intravascular brachytherapy (IVB) and stenting were examined, focus being on the importance of neovascularization in rabbit stented arteries. Stents were implanted in the infrarenal aortas of rabbits, immediately followed by gamma IVB or a sham radiation procedure, and the arteries harvested at 6 months. Labelling for von Willebrand factor showed an increase in adventitial and medial neovascularization in irradiated versus control arteries group (5.04+/-0.89 versus 1.51+/-0.23 mm(-2), respectively; p=0.004). Moreover, intramedial haemorrhages (free hemosiderin deposition) and inflammation (macrophages) were only observed in irradiated arteries. No significant change in expression of matrix metalloproteinase 1, 2 or 3 was observed between the irradiated and control group while collagen content decreased in the irradiated versus the control group (10.05%+/-1.48% versus 31.92%+/-3.12%, respectively; p<0.001). The study supports the hypothesis that IVB associated with stenting induces late deleterious effects on the medial layer, characterized by formation of intramural neovessels, haemorrhages and a decrease in collagen content.

Animals↗
PubMed2003

Inflammatory markers in cystic fibrosis patients with transmissible Pseudomonas aeruginosa.

Chronic Pseudomonas aeruginosa infection in cystic fibrosis (CF) leads to a damaging host inflammatory response. There are an increasing number of reports of P. aeruginosa cross-infection at CF centres. The clinical significance of acquisition of a transmissible strain for patients who already harbour P. aeruginosa is unclear. In this study, levels of inflammatory markers in clinically stable adult CF patients who harbour transmissible and sporadic strains of P. aeruginosa have been compared. Patients with CF and chronic P. aeruginosa infection were grouped into those who harbour a transmissible P. aeruginosa and those who harbour their own sporadic strains. Total white cell and differential counts, sputum neutrophil elastase (NE), interleukin (IL)-8, tumour necrosis factor (TNF)-alpha, plasma IL-6 and NE/alpha1-antitrypsin complexes, serum C-reactive protein, and urine TNF receptor 1 were all measured in clinically stable patients 4-6 weeks following completion of intravenous antibiotic therapy. The two groups (both n=20) were well matched for per cent predicted forced expiratory volume in one second, per cent predicted forced vital capacity and body mass index. There were no significant differences in levels of white cell counts or inflammatory markers between the two groups. At times of clinical stability, cystic fibrosis patients infected with transmissible Pseudomonas aeruginosa do not have a heightened inflammatory response above that of those harbouring sporadic strains.

Adult↗
PubMed2003

["Sunshine at school": a network for training on sun exposure. Assessment of knowledge among 683 children].

INTRODUCTION: The protection of children from sun exposure appears inadequate. We assessed the knowledge of pre-teenagers, before and after they attended a training session on sun exposure. This investigation was carried out in Orléans and in 5 surrounding cities, from September 2000 to April 2002. MATERIAL AND METHODS: A didactic slide show on sun exposure and photoprotection was presented to 683 children in grade 4 and 5 by a nurse and a dermatologist during 30 informative sessions. The children filled in questionnaires at each training session and then one month later. The questionnaires contained 10 closed questions involving 32 cognitive and behavioral items. RESULTS: Forty-five percent of the children claimed that they were exposed to the sun more than one hour a day during holidays, 14 p. 100 more than 3 hours a day; 26 p. 100 declared they had never been sunburnt; 46 p. 100 said they had been less than 5 times, 15 p. 100 from 5 to 10 times and 12 p. 100 more than 10 times; 74 p. 100 of the children claimed they enjoyed getting sun-tanned; 80 p. 100 knew that sun exposure could lead to serious diseases, while 73 p. 100 realized that contracting sunburns during childhood increases the risk of subsequent skin cancers; 89 p. 100 knew of the necessity of sun-screen use prior to exposure, 94 p. 100 knew that they help to protect the skin whereas 78 p. 100 knew it must be applied on a regular basis; 77 p. 100 of the children had been informed of the importance of sun protection factor; 92 p. 100 of them were aware of the relevance of a cap and sunglasses for protection from the sun, whereas only 45 p. 100 knew of the need for a tee-shirt. DISCUSSION: Our study showed that children are generally aware of the dangers of sun exposure. This might be the result of previously initiated information and prevention campaigns on skin cancers. This study suggests the efficiency of such projects, and the lasting effects of the information received within one month. However, large numbers of children are still overexposed and subsequently suffer from traumas. The appeal of sun embellishment appears to go back to childhood, and should be taken into account from the early stages of childhood in future preventive actions. An efficient policy of education on sun exposure - including teaching tools relevant to each age--still has to be developed.

Child↗
PubMed2002

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas.

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Vascular density and phenotype around ductal carcinoma in situ (DCIS) of the breast.

Up to 50% of recurrences of ductal carcinoma in situ of the breast are associated with invasive carcinoma but no pathological or molecular features have yet been found to predict for the development of invasive disease. For a tumour to invade, it requires the formation of new blood vessels. Previous studies have described a vascular rim around ducts involved by ductal carcinoma in situ, raising the possibility that the characteristics of periductal vascularisation may be important in determining transformation from in situ to invasive disease. Periductal vascular density and phenotype were determined using morphometry and a panel of anti-endothelial antibodies (von Willebrand factor, CD31, CD141 and CD34) and related to the presence of invasive carcinoma and other histological features. Compared to normal lobules, pure ductal carcinoma in situ exhibited a greater density of CD34+ and CD31+ vessels but a decrease in those that were immunopositive for vWF, indicating a difference in phenotype and in density. Ductal carcinoma in situ associated with invasive carcinoma showed a profile of vascular immunostaining similar to that of pure ductal carcinoma in situ but there were significantly greater numbers of CD34+ and CD141+ vessels and fewer staining for vWF. There was a significant negative correlation between vascular density and both the cross-sectional areas of the ducts involved and the extent of the necrosis of the tumour they contained. A correlation between vascular density and nuclear grade was also noted, being highest in the intermediate grade. The greater density of CD34+ and CD141+ vessels around ductal carcinoma in situ associated with invasive carcinoma could reflect a greater predisposition to invade but a direct effect of co-existent invasive carcinoma cannot entirely be ruled out in the present study. The relationship between vascular density, grade, duct size and nuclear grade suggests that periductal angiogenesis increases with tumour growth rate but is unable to keep pace with the most rapidly growing lesions.

Antigens, CD34↗
PubMed2002

Diversity in antimicrobial resistance and other characteristics among Salmonella typhimurium DT104 isolates.

Multiresistant Salmonella enterica subspecies enterica serovar Typhimurium definitive type 104 (S. Typhimurium DT104 or DT104) bacteria are important pathogens in animals and humans. DT104 isolates are often called pentaresistant strains that spread clonally. The purpose of this study was to determine phenotypic, genotypic, and epidemiologic characteristics of 175 S. Typhimurium DT104 strains isolated from food-producing animals in Canada. More than 90% of the isolates were resistant to ampicillin (Amp), chloramphenicol (Chl), florfenicol (Flo), sulfisoxazole (Sul), and tetracycline (Tet), 53% of the isolates were additionally resistant to spectinomycin (Spc) and streptomycin (Str), and 28% to kanamycin (Kan) and neomycin (Neo). Sixty-one percent of the strains harbored a single 60-MDa plasmid, 21% contained 60- and 2.0-MDa plasmids, and 4% had 60, 4.6- and 2.0-MDa plasmids. Resistance to Kan and Neo was encoded by the aminoglycoside aphA-1 gene on 2.0-MDa plasmids, whereas resistance to trimethoprim (Tmp) and Sul was encoded by the dhfrIb gene on 4.6-MDa plasmids. Polymerase chain reactions (PCR) showed the presence of integrons with the ant (3")-Ia aminoglycoside adenyltransferase and the bla(PSE-1) beta-lactamase gene cassettes, and the presence of the flost gene in all but one strain resistant to Spc and Str, Amp, and Chl and Flo, respectively. DT104 isolates from cattle at six feedlots represented a separate clone; they were sensitive to Str and Spc and lacked the ant (3")-Ia gene. Pulsed-field gel electrophoresis (PFGE) using Bln I, Spe I, and Xba I resulted in 15, 12, and 8 PFGE patterns, respectively. In summary, we observed considerable diversity in phenotypic, genotypic, and epidemiological characteristics among the DT104 isolates.

Animals↗