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Biomedical subjects

B Martin

Publications and source records attributed to B Martin.

At least 37 records · Page 2Linked to original sources

NICE guidelines for central venous catheterization in children. Is the evidence base sufficient?

BACKGROUND: Recent guidelines from the National Institute for Clinical Excellence (NICE) recommend the use of ultrasound guidance for central venous catheterization in children. This study prospectively examined the use of ultrasound guidance for central venous catheterization in children undergoing heart surgery. METHODS: One hundred and twenty-four infants and children were randomized to either ultrasound-guided or traditional landmark-guided central venous catheterization. RESULTS: Success rates were significantly greater in the landmark group compared with the ultrasound group (89.3% vs 78%, P<0.002), and arterial puncture rates were significantly lower in the landmark group (6.2% vs 11.9%, P<0.03). There was no significant difference between the two groups in the time taken to perform the catheterization. CONCLUSIONS: These results are different from the published results on which the NICE guidelines were based; however, the evidence base in children is small. There is currently insufficient evidence to support the use of ultrasound guidance for central venous catheterization in children.

Carotid Artery Injuries↗

[Surgical management of rectovaginal septum endometriosis from a continuous series of 50 cases].

OBJECTIVES: To assess the value of MRI and ano-rectal endosonography (ARES) for the diagnosis and surgical prognosis of rectovaginal septum endometriosis and to analyse the surgical management in order to evaluate its functional results and complications. PATIENTS AND METHODS: Retrospective study of 50 consecutive patients operated for a clinical presumption of endometriosis nodule of the recto vaginal septum. Thirty-nine patients had a MRI, 31 an ARES and 28 both exams. All the patients had a complete dissection of the rectovaginal septum and all lesions were excised. RESULTS: For the diagnosis of rectovaginal septum endometriosis nodule, MRI results are: sensitivity 73%, specificity 50%, positive predictive value (PPV) 89%, negative predictive value (NPV) 25%; for uterosacral ligaments involvement: sensitivity 84%, specificity 95%, PPV 94%, NPV 86% and for rectal wall infiltration: sensitivity 53%, specificity 82%, PPV 69%, NPV 69%. The ARES results for diagnosis of rectovaginal septum endometriosis nodule are: sensitivity 93%, specificity 100%, PPV 100%, NPV 50% and for rectal wall infiltration: sensitivity 100%, specificity 71%, PPV 81%, NPV 100%. ARES appeared more sensitive than MRI for the detection of rectal wall infiltration (P = 0.002) and for rectovaginal septum endometriosis nodule diagnosis (P = 0.03). Eighty-nine percent of the patients had a coelioscopy in first intention and 15 laparoconversions were performed, 11 in order to perform a digestive resection: 45 nodules were found. In 43cases the nodule was excised, associated to 19 digestive resections, 30 colpectomys, and 22 uterosacral ligaments resections. Three patients required an additional surgical treatment by Hartman's procedure with Mickulicz's drainage for peritonitis. Forty-one nodules were endometriosis nodules: the two other cases were fibrosis nodules. Thirty-three patients were interviewed about the evolution of their pains over a mean history of 20 months: 90% of the patients were satisfied with the management results. DISCUSSION AND CONCLUSIONS: Our data support the efficiency of MRI for rectovaginal septum endometriosis nodule and uterosacral ligaments involvement diagnosis; accord ARES to rectovaginal septum endometriosis nodule diagnosis and its reliability in establishing a diagnosis of rectal wall involvement. The surgical cure of rectovaginal septum nodules without digestive infiltration is performed by coelioscopic or coelio-vaginal procedure, but in case of associated digestive affliction, laparotomy is actually the standard procedure in order to achieve a complete cure of the lesions. Complications, in particular peritonitis, are not frequent. Our data support the efficiency of radical surgical treatment for the improvement of pain symptoms. Results on fertility seem to be satisfactory, but complication risks suggest being careful in this indication. Clinical examination during a catamenial period is essential in order to evoke the diagnosis. MRI yields a complete map of the sub-peritoneal and peritoneal lesions and ARES allows for the diagnosis of an infiltration of the rectal wall. Pre-operative association of those two exams is actually indispensable for the surgical management of those patients, which consists of complete excision of endometriosical lesions and is efficient at treating pain symptoms and fertility. Complications are rare but severe, therefore, justifying a cure in specialised centres.

Adult↗

De novo germline mutation in the serine-threonine kinase STK11/LKB1 gene associated with Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disease, characterized phenotypically by mucocutaneous pigmentation and hamartomatous polyposis. Affected patients are at an increased risk of developing gastrointestinal and other malignancies. Mutations in the STK11/LKB1 (LKB1) gene, which encodes for a serine-threonine kinase, have been identified as a genetic cause of PJS. Molecular analysis of the LKB1 gene in a simplex case of PJS revealed a substitution of cytosine (C) for guanine (G) at codon 246 in exon 6, resulting in the Tyr246X mutation. The nucleotide substitution leads to a premature stop codon at the 246 residue, predicting a truncated protein and presumed loss of kinase activity. Analysis of DNA from both parents of the PJS patient did not show this mutation, which is therefore a de novo mutation. We isolated DNA from microdissected gastrointestinal hamartomatous polyps in the PJS patient and investigated the loss of heterozygosity (LOH) at the LKB1 locus by real-time fluorescence polymerase chain reaction genotyping using a fluorescent resonance energy transfer technique. The results suggest a different mechanism from LOH in the formation of hamartomatous polyps.

AMP-Activated Protein Kinase Kinases↗

Ki67 expression in bronchial preneoplastic lesions and carcinoma in situ defined according to the new 1999 WHO/IASLC criteria: a preliminary study.

AIMS: The World Health Organization classification of bronchial intraepithelial neoplastic lesions has been shown to be reproducible. However little is known about its biological value. The aim of this study was to assess the proliferative activity of mild (MiD), moderate (MoD), severe (SD) dysplasia and carcinoma in situ (CIS) by the expression of Ki67 on biopsy specimens obtained during fluorescence bronchoscopy. METHODS AND RESULTS: The percentage of Ki67+ lesional nuclei was calculated in each lesion. In addition, the presence of Ki67 clusters (defined as a group of at least two strongly Ki67+ nuclei located in the upper third of the epithelium) and a Ki67 score were evaluated. The Ki67 score depended on the proportion of the stained nuclei and on the intensity of staining. MiD, MoD, SD and CIS showed increased Ki67 staining (respectively, 10%, 20%, 30% and 40% median values of positive cells). Thirty-one percent MiD, 77% MoD, 91% SD and 100% CIS showed one or more positive clusters. When only multiple clusters were considered the difference between high- and low-grade lesions was accentuated. Ki67+ clusters were more frequent in SD (91%) and CIS (94%) compared with MiD (15%) and MoD (22%). This difference was statistically significant (P < 0.01). Evaluation of the Ki67 score was in line with the above results: high grade lesions (SD and CIS) more often showed scores >4 (P = 0.05 between MiD plus MoD versus SD plus CIS). CONCLUSIONS: Ki67 expression increases from MiD to CIS with a statistically significant difference between MiD plus MoD and SD plus CIS. These results suggest that, in terms of Ki67 positivity, SD behaves like CIS rather than like MiD or MoD.

Biopsy↗

Development of a community-based medical rehabilitation programme in the Kivalliq Region of Nunavut, Canada.

OBJECTIVE: In 2000, the University of Manitoba and the Department of Health and Social Services of Nunavut, Canada, jointly embarked upon the development of a community-based medical rehabilitation programme in the Kivalliq Region of Canada's central Arctic. Two main objectives were identified in moving forward with the implementation of a rehabilitation programme. Firstly, to conduct a region wide community needs assessment for rehabilitation services for all age groups of all residents of the Kivalliq Region of Nunavut. Secondly, to provide information from which a community-based rehabilitation therapy programme could be developed. METHODS: A community needs assessment of the Kivalliq Region was carried out to guide the implementation of physiotherapy, occupational therapy and speech language pathology services. RESULTS: There are now two physiotherapists, one occupational therapist, and one speech language pathologist providing rehabilitation services to the residents of the Kivalliq Region of Nunavut. The results of this needs assessment, the challenges and successes of this medical rehabilitation programme are discussed. CONCLUSION: The total population of the service area is approximately 8,000 people, the significant majority of whom self-report as Inuit, and are widely dispersed over eight communities. Despite the challenges in terms of culture, geography and recruitment of introducing a rehabilitation program in Canada's north, the residents of the Kivalliq Region now have a viable model of receiving rehabilitative intervention in their home communities.

Community Health Services↗

The role of HER-2/neu expression on the survival of patients with lung cancer: a systematic review of the literature.

C-erbB-2 prognostic value for survival in patients with lung cancer remains controversial. We performed a systematic review of the literature to clarify its impact. Studies were identified by an electronic search in order to aggregate the survival results, after a methodological assessment using the scale of the European Lung Cancer Working Party. To be eligible, a study had to deal with c-erbB-2 assessment in lung cancer patients and to analyse survival according to c-erbB-2 expression. In total, 30 studies were eligible: 24 studies dealt with non-small-cell lung carcinoma (NSCLC), five with adenocarcinoma and one study dealt with small-cell carcinoma. In all, 31% of the patients were positive for c-erbB-2. According to c-erbB-2 expression, 13 studies were 'negative' (significant detrimental effect on survival), one 'positive' (significant survival improvement) and 16 not significant. Significant studies had a better subscore relative to analysis and results report than nonsignificant studies. In total, 86% of the significant studies and only 56% of the nonsignificant studies were evaluable for the meta-analysis. This suggests a possible bias in our aggregated results. For NSCLC, the hazard ratio was 1.55 (95% CI: 1.29-1.86) in favour of tumours that do not express c-erbB-2. In conclusion, the overexpression of c-erbB-2 might be a factor of poor prognosis for survival in NSCLC, but there is a potential bias in favour of the significant studies with an overestimation risk of the magnitude of the true effect of c-erbB-2 overexpression.

Adenocarcinoma↗

Role of Bcl-2 as a prognostic factor for survival in lung cancer: a systematic review of the literature with meta-analysis.

The role of the anti-apoptotic protein Bcl-2 in lung cancer remains controversial. In order to clarify its impact on survival in small and non-small cell lung cancer (NSCLC), we performed a systematic review of the literature. Trials were selected for further analysis if they provided an independent assessment of Bcl-2 in lung cancer and reported analysis of survival data according to Bcl-2 status. To make it possible to aggregate survival results of the published studies, their methodology was assessed using a quality scale designed by the European Lung Cancer Working Party (including study design, laboratory methods and analysis). Of 28 studies, 11 identified Bcl-2 expression as a favourable prognostic factor and three linked it with poor prognosis; 14 trials were not significant. No differences in scoring measurement were detected between the studies, except that significantly higher scores were found in the trials with the largest sample sizes. Assessments of methodology and of laboratory technique were made independently of the conclusion of the trials. A total of 25 trials, comprising 3370 patients, provided sufficient information for the meta-analysis. The studies were categorised according to histology, disease stage and laboratory technique. The combined hazard ratio (HR) suggested that a positive Bcl-2 status has a favourable impact on survival: 0.70 (95% confidence interval 0.57-0.86) in seven studies on stages I-II NSCLC; 0.50 (0.39-0.65) in eight studies on surgically resected NSCLC; 0.91 (0.76-1.10) in six studies on any stage NSCLC; 0.57 (0.41-0.78) in five studies on squamous cell cancer; 0.75 (0.61-0.93) and 0.71 (0.61-0.83) respectively for five studies detecting Bcl-2 by immunohistochemistry with Ab clone 100 and for 13 studies assessing Bcl-2 with Ab clone 124; 0.92 (0.73-1.16) for four studies on small cell lung cancer; 1.26 (0.58-2.72) for three studies on neuroendocrine tumours. In NSCLC, Bcl-2 expression was associated with a better prognosis. The data on Bcl-2 expression in small cell lung cancer were insufficient to assess its prognostic value.

Clinical Trials as Topic↗

Complexed PSA performance for prostate cancer detection in an African-American population.

OBJECTIVES: Complexed prostate-specific antigen (cPSA) has been shown to improve the differentiation of benign and malignant disease compared with total PSA (tPSA) in studies evaluating predominantly white populations of men. We sought to evaluate the diagnostic performance of cPSA relative to tPSA in a population of African-American men. METHODS: Consecutive African-American men scheduled for prostate biopsy were enrolled prospectively at the Louisiana State University Medical Center, New Orleans. Serum was collected before the biopsy procedure and tested with the Immuno 1 tPSA and cPSA methods. Receiver operating characteristic curve analysis was performed and the area under the curve was calculated for tPSA and cPSA. RESULTS: A total of 156 patients were evaluated, 51 (32.7%) of whom were diagnosed with prostate cancer. The median PSA value for men with prostate cancer was 4.96 ng/mL and for those with benign disease was 3.93 ng/mL. The receiver operating characteristic analysis indicated that the area under the curve for cPSA (0.679) was statistically greater than that achieved for tPSA (0.642, P = 0.004). Using cutoff values for cPSA of 2.3 ng/mL and for tPSA of 2.85 ng/mL provided a specificity of 31.4% and 26.7%, respectively, at a sensitivity for prostate cancer detection of 95%. This was not statistically significant (P = 0.18). CONCLUSIONS: cPSA offers modest improvement in prostate cancer detection compared with tPSA in African-American men, but not at the clinically relevant 95% sensitivity level. Additional work is needed to improve prostate cancer detection in this high-risk cohort of patients.

Adenocarcinoma↗

Investigating the origin of AIDS: some ethical dimensions.

The theory that AIDS originated from contaminated polio vaccines raises a number of challenging issues with ethical dimensions. The Journal of Medical Ethics dealt with a submission about the theory a decade ago; subsequent developments have raised further issues. Four areas of contention are addressed: whether the theory should be investigated; whether anyone should be blamed; whether defamation actions are appropriate, and whether the scientific community has a responsibility to examine unorthodox theories.

Acquired Immunodeficiency Syndrome↗

Viral hepatitis in a Canadian First Nations community.

Serological markers for hepatitis A (HAV), B (HBV) and C (HCV) were documented in 315 inhabitants (27%) of a central Manitoba First Nations community. Serologic evidence of HAV infection (anti-HAV positive) was almost universal (92%) by the age of 20 years. HBV infection (antibody to hepatitis B core antigen positive) had occurred in only 2.3% of the study population and no chronic carriers were identified. Serological evidence of HCV infection (anti-HCV positive) was documented in 2.2% of the population but ongoing viremia (HCV-RNA positive by polymerase chain reaction) was absent. The results of this study highlight the importance of universal HAV vaccination; likely reflect the efficacy of existing prenatal screening and immunoprophylaxis programs for HBV; and raise the possibility that First Nations peoples have an enhanced ability to spontaneously clear HCV.

Adult↗

Epidermal growth factor receptor expression in pre-invasive and early invasive bronchial lesions.

The 1999 World Health Organization/International Association for the Study of Lung Cancer histological classification of preneoplastic bronchial lesions has been shown to be reproducible but little is known about its biological significance. The current study evaluated the correspondence between the morphological changes of the bronchial epithelium and epidermal growth factor receptor (EGF-R) expression. Thirteen normal bronchial epithelia, 19 hyperplasia, 16 metaplasia, 10 mild dysplasia, one moderate dysplasia, 10 severe dysplasia (SD), 14 carcinoma in situ (CIS) and 11 microinvasive tumours were assessed. A global EGF-R score obtained by the sum of the positivity score plus the EGF-R staining intensity score was calculated for each lesion. A global EGF-R score of >5 was reached only in one metaplasia, in six SD, in six CIS and in six microinvasive tumours. There was no difference in EGF-R expression between normal, hyperplastic and metaplastic epithelia versus mild dysplasia or between severe dysplasia versus CIS and microinvasive tumours but there was a statistically significant difference between mild versus severe dysplasia. This study demonstrates that epidermal growth factor receptor expression rate changes with the stage of the bronchial lesion, increasing from normal epithelium to carcinoma in situ and microinvasive tumours with a statistically significant difference between mild versus severe dysplasia.

Adult↗

Fragile histidine triad protein expression in nonsmall cell lung cancer and correlation with Ki-67 and with p53.

Fragile histidine triad (FHIT) is a tumour suppressor gene, which is altered in a variety of epithelial tumours, including lung cancer. Biochemical and functional pathways of its tumourigenicity are not yet understood. Its role in tumour proliferation is particularly controversial. The purpose of this study was to correlate the expression of FHIT protein in nonsmall cell lung cancer (NSCLC) with tumour proliferation as estimated by Ki-67 antigen and with p53, a suppressor gene. FHIT, Ki-67 and p53 expression were evaluated by immunohistochemistry in 119 resected NSCLC. Altogether, 58 tumours were negative (expression <10%) for FHIT. The median expression in tumours was 15% positive cells, in comparison with 100% in normal matched lung tissue. The expression was as strong as in normal tissue in only 19 cases. FHIT expression was significantly lower in squamous cell carcinoma (SCC) (5%) than in adenocarcinoma (ADC) (64%). The median expression of Ki-67 was 20% and 69% of tumours were positives (expression >10%). Ki-67 expression was significantly higher in SCC (33.3%) than in ADC (10%). The loss of FHIT protein was not correlated with the expression of p53 (median: 7.5%, 58% of positive tumours for a cut-off of 10% of positive cells) or Ki-67. But percentage of labelled cells for p53 and Ki-67 were significantly correlated. The results suggest that for fragile histidine triad, the pathway of tumourigenesis is independent of p53 and of tumoural proliferation, as reported previously in vitro.

Acid Anhydride Hydrolases↗

[EGF-R expression correlation between biopsy and surgical specimens of lung carcinoma].

INTRODUCTION: Most of the time, biological parameters are evaluated on tissues obtained on surgical samples of the primary tumour. New approaches in non small cell lung cancer (NSCLC) treatment consist to administer neoadjuvant chemotherapy or anti-EGF-R (epidermal growth factor receptor) drug. METHODS: We assessed the expression of EGF-R by immunohistochemistry on biopsy samples and on the paired resected tumours in 27 patients. RESULTS: The mean percentage of EGF-R positive neoplastic cells was 11% in surgical specimens compared to 28% in biopsy specimens (p=0.02) although a good correlation (R=0.67; p=0.0001) between biopsies and surgical specimens was observed. Furthermore, the positivity (cut-off > 1% cells) rate was not statistically different between biopsies (55%) and tumours (48%) (p=0.63). In term of positivity rate, we found 85% concordant results between biopsies and resected tumours, 4% false negative and 11% false positive on biopsies in comparison with the resected tumours. The positive and negative predictive value of the biopsies were respectively 80% and 92%. CONCLUSIONS: The evaluation of EGF-R by immunohistochemistry on biopsies may provide reliable information about non small cell lung cancer EGF-R status.

Adenocarcinoma↗

The role of microvessel density on the survival of patients with lung cancer: a systematic review of the literature with meta-analysis.

In order to determine whether angiogenesis is a prognostic marker in lung cancer, we performed a systematic review of the literature to assess the prognostic value on survival of microvessel count in patients with lung cancer. Published studies were identified by an electronic search in order to aggregate survival results, after a methodological assessment using a quality scale designed by the European Lung Cancer Working Party. To be eligible, a study had to deal with microvessel count assessment in lung cancer patients on the primary site and to provide survival analysis according to microvessel count expression. Microvessel count has been assessed on surgical samples by immunohistochemistry using factor VIII in 14 studies, CD34 in 10 and CD31 in eight. Respectively 1866, 1440 and 1093 non-small cell lung cancer patients were considered. The overall median quality scores were respectively 52, 59 and 59% for studies assessing microvessel count via factor VIII, CD34 and CD31, without significant difference between studies evaluable or not for meta-analysis nor between studies with significant or non significant results. Seven 'factor VIII' studies, nine 'CD34' and seven 'CD31' provided sufficient data allowing a meta-analysis on survival and were evaluable for results aggregation. This showed that a high microvessel count in the primitive lung tumour was a statistically significant poor prognostic factor for survival in non small cell lung cancer whatever it was assessed by factor VIII (HR: 1.81; 95% CI: 1.16-2.84), CD34 (HR: 1.99; 95% CI: 1.53-2.58) or CD31 (HR: 1.80; 95% CI: 1.10-2.96). Variations in survival among the individual studies can be explained in addition to patients selection criteria by the heterogeneous methodologies used to stain and count microvessels: different antibody clones, identification of 'hotspots', Weidner or Chalkey counting method, cut-off selection. Microvessel count, reflecting the angiogenesis, appears to be a poor prognostic factor for survival in surgically treated non small cell lung cancer but standardisation of angiogenesis assessment by the microvessel count is necessary.

Humans↗

Outcome of the first 3-years of a DNA-based neonatal screening program for glutaric acidemia type 1 in Manitoba and northwestern Ontario, Canada.

Glutaric acidemia type 1 (GA1) is overrepresented in the aboriginal population of Island Lake, Manitoba, and northwestern Ontario who speak the Ojibway-Cree (Oji-Cree) dialect. The carrier frequency in these communities has been predicted to be as high as 1 in 10 individuals. Prior to beginning newborn screening for GA1 in May 1998, 18 of 20 affected patients diagnosed at this center have been from these high-risk communities. Most have followed an acute encephalopathic course with permanent neurologic sequelae and high mortality. They excrete small amounts of glutaric acid and 3-hydroxyglutaric acid and have significant residual enzyme activity. A single homozygous mutation in glutaryl-CoA-dehydrogenase (GCDH IVS-1 + 5g right arrow t) has been identified in this population. DNA-based newborn screening targeted to our high-risk communities was begun in order to provide presymptomatic detection and treatment of affected patients. Of the first 1176 newborns screened, 4 affected infants were identified and treated with a low-protein diet, carnitine, and riboflavin. All 4 infants have required numerous hospitalizations for treatment of intercurrent illnesses. Eventually, 3 infants presented with acute dystonic encephalopathy and seizures along with permanent neurological sequelae. One of these infants died unexpectedly at home at 18 months of age. The fourth, now 9 months old, has had a gastrostomy tube placed to facilitate fluid replacement in addition to a standard treatment protocol and is doing well. The reasons for our initial disappointing outcomes in the first 3 of 4 affected babies are likely multiple. Based on our early experience and that of other centers screening newborns for GA1, current therapeutic strategies may be insufficient in preventing the occurrence of neurologic sequelae in some children. An incomplete understanding of the neurotoxic mechanisms underlying this devastating disorder hampers effective management.

Canada↗