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Biomedical subjects

J Couture

Publications and source records attributed to J Couture.

At least 19 recordsLinked to original sources

Post-operative radiochemotherapy for gastric cancer: adoption and adaptation.

AIMS: Intergroup study 0116 (INT-0116) showed an 11% absolute improvement in 3-year survival with post-operative radiochemotherapy for gastric cancer, but reported 33% severe acute GI toxicity using conventional simulation with large fields. We adapted the treatment using conformal radiotherapy techniques and assessed toxicity and outcome in 20 consecutive patients. METHODS: A conformal radiotherapy technique previously developed for gastric lymphoma was adapted to treat the target volume defined in INT-0116. The five-field plan used a large anterior field, plus asymmetrically matched upper AP:PA fields and lower lateral fields. Consecutive patients with ECOG PS 0-2 and stage IB-IV non-metastatic gastric cancer were treated with 5-FU (425 mg/m2 daily x 5 days) and leucovorin (20 mg/m2 daily x 5 days) for one cycle prior to and two cycles following concurrent radiation (45 Gy/25 fractions) with identical drug dosages on the first 4 and last 3 days of radiation. Acute toxicity was prospectively recorded weekly using RTOG and NCI common toxicity criteria. Patient charts were reviewed in November 2003 and late toxicity and outcome were recorded. RESULTS: Nineteen of 20 patients completed radiotherapy and 14 completed all chemotherapy cycles. One patient died of neutropenic sepsis. Maximum acute toxicity [grade (number)] was: 5(1), 4(0), 3(4), 2(10), 1(4), 0(1). There were two grade 1 late toxicities. Two-year overall survival is 70% (95% confidence interval: 50-90). CONCLUSIONS: Conformal radiotherapy may improve acute toxicity (25% grade 3 or greater toxicity as compared with 41% reported in INT-0116). Survival is comparable to that achieved in the INT-0116 treatment arm (approximately 60% at 2 years). INT-0116 results can be achieved outside a study setting; however, further efforts to improve treatment efficacy and minimize toxicity are warranted.

Adult↗

Guidelines 2000 for colon and rectal cancer surgery.

BACKGROUND: Oncologic resection techniques affect outcome for colon cancer and rectal cancer, but standardized guidelines have not been adopted. The National Cancer Institute sponsored a panel of experts to systematically review current literature and to draft guidelines that provide uniform definitions, principles, and practices. METHODS: Methods were similar to those described by the American Society of Clinical Oncology in developing practice guidelines. Experts representing oncology and surgery met to review current literature on oncologic resection techniques for level of evidence (I-V, where I is the best evidence and V is the least compelling) and grade of recommendation (A-D, where A is based on the best evidence and D is based on the weakest evidence). Initial guidelines were drafted, reviewed, and accepted by consensus. RESULTS: For the following seven factors, the level of evidence was II, III, or IV, and the findings were generally consistent (grade B): anatomic definition of colon versus rectum, tumor-node-metastasis staging, radial margins, adjuvant R0 stage, inadvertent rectal perforation, distal and proximal rectal margins, and en bloc resection of adherent tumors. For another seven factors, the level of evidence was II, III, or IV, but findings were inconsistent (grade C): laparoscopic colectomy; colon lymphadenectomy; level of proximal vessel ligation, mesorectal excision, and extended lateral pelvic lymph node dissection (all three for rectal cancer); no-touch technique; and bowel washout. For the other four factors, there was little or no systematic empirical evidence (grade D): abdominal exploration, oophorectomy, extent of colon resection, and total length of rectum resected. CONCLUSIONS: The panel reports surgical guidelines and definitions based on the best available evidence. The availability of more standardized information in the future should allow for more grade A recommendations.

Colonic Neoplasms↗

Soft tissue sarcomas involving the pelvis.

BACKGROUND AND OBJECTIVES: Soft tissue sarcomas (STS) of the true pelvis are rare tumors and there is little information in the literature related to pelvic STS. The purposes of this review were to understand the anatomic extension of these tumors to better plan surgical treatment and to determine the outcome of these patients. METHODS: Eighteen consecutive patients presenting between 1987 and 1995 with soft tissue sarcomas involving the true pelvis were retrospectively reviewed at minimum follow-up of 18 months. Cross-sectional imaging was reviewed for each patient to determine the anatomical location of the lesions. RESULTS: The tumors were confined to the true pelvis in 4 patients, extended to the retroperitoneum in three cases, and extended to the thigh in 11 patients. Adjuvant radiation was administered to all but 2 patients who had received radiation to the region in the past and all patients underwent surgical resection (local resection in 13 patients and hindquarter amputation in 5 patients). Surgical resection had a high rate of morbidity and complications including positive resection margins in nine individuals. Of the 18 patients, 11 died at a mean time of 15.5 (2-58) months from surgery, 4 were alive with evidence of disease at a mean time of 44.3 (18-68) months, and 3 were alive with no evidence of disease at a mean time of 57 (43-71) months. CONCLUSIONS: Soft tissue sarcoma of the pelvis is fortunately a rare disease with a high risk of local and systemic disease progression despite treatment with irradiation and surgical resection.

Adult↗

Impact of a cost-sharing drug insurance plan on drug utilization among older people.

OBJECTIVES: In August 1996, the Régie de l'assurance-maladie du QuEbec (RAMQ), the government body responsible for medical insurance in the Canadian province of Quebec, introduced a cost-sharing drug insurance plan. Before this plan, individuals age 65 years and older had to pay Canadian (CDN)$2 per prescription, with the remaining cost paid by the RAMQ. With the new plan, beneficiaries may have to pay an amount between CDN$200 and CDN$925 per year, depending on their income. Concerned that this financial constraint imposed on older people might have an impact on the use of medications, we investigated whether the consumption of four classes of medications, antihypertensive agents, anticoagulants, nitrates, and benzodiazepines, was affected by the drug plan implementation. DESIGN: Time series models with pre/post comparison group. SETTING: Administrative computerized databases of the RAMQ. PARTICIPANTS: Random sample of Quebec residents age 65 years and older registered in the provincial drug plan between August 1992 and June 1997: 54,771 users of nitrates, 133,146 users of antihypertensive agents, 45,534 users of anti-coagulants, and 26,165 users of benzodiazepines. MEASUREMENTS: We modeled the monthly consumption of the medications under study between August 1992 and June 1996. Monthly drug consumptions predicted from the models were compared with those observed for the 13 months (August 1996 to August 1997) following the implementation of the new drug plan using 95% confidence intervals. The number of prescriptions dispensed served as an indicator for drug consumption. RESULTS: During the study period we observed a nonstatistically significant decrease in number of prescriptions of 5.1% for nitrates, 1.1% for antihypertensive agents, and 0.8% for benzodiazepines, and a nonstatistically significant increase of 1.6% for anticoagulants. CONCLUSION: Residents of Quebec age 65 years and older were not found to have reduced significantly their consumption of nitrates, antihypertensive agents, anticoagulants, and benzodiazepines during the 13 months that followed the implementation of a cost-sharing drug insurance plan.

Aged↗

Anatomic landmarks to estimate the length of the diaphragm from chest radiographs: effects of emphysema and lung volume reduction surgery.

STUDY OBJECTIVES: To define anatomic landmarks that can be used to predict insertions of the diaphragm on chest radiographs and to estimate diaphragm length. DESIGN: Prospective clinical trial with a parallel group design. SETTING: Laboratory investigations in normal volunteers recruited by advertisement and in emphysema outpatients being evaluated for elective bilateral lung volume reduction surgery (LVRS). PATIENTS: Twenty-six normal subjects classified into young and older age groups, with a third group of 13 emphysema patients matched for age and sex with the older group. MEASUREMENTS: Identification and between-group comparisons were made of anatomic landmarks on anteroposterior and lateral chest radiographs obtained at total lung capacity. Predicted landmarks were generated from normal subjects. Within-subject and between-group comparisons were made of diaphragm length index (DLI) based on observed anatomic landmarks (DLIobs) and diaphragm length index based on predicted anatomic landmarks (DLIpred) at functional residual capacity. RESULTS: Anatomic landmarks were not different between the three groups or between male and female subjects, and were not different before and after LVRS in emphysema patients. No difference was found between DLIobs and DLIpred in normal subjects and emphysema patients, but both were smaller in emphysema patients than in normal subjects and increased after LVRS in emphysema patients. CONCLUSION: This study validates the use of anatomic landmarks to estimate DLI. Using these landmarks simplifies the determination of diaphragmatic lengths and could be a useful tool for the evaluation of the functional capacity of the diaphragm, and possibly as a prognostic indicator of patients who are candidates for LVRS.

Adult↗

Proliferation parameters in epidermoid carcinomas of the anal canal.

PURPOSE: In a prospective study, we assessed the proliferation parameters in primary epidermoid carcinomas of the anal canal, and results were compared with those in cervical carcinomas. METHODS: Between January 1992 and December 1996, 32 patients with primary epidermoid carcinoma of the anal canal were studied prospectively. Patients were given i.v. bromodeoxyuridine and proliferation parameters were obtained using flow cytometry. The treatment protocol consisted of radiation therapy (XRT) (24 Gy/12-3.5 week split-28 Gy/14) and concurrent 5-fluorouracil and mitomycin C. Proliferation parameters were not obtained in six patients, leaving 26 patients in the analysis. There were 16 females and ten males, with two T1, 16 T2, five T3 and three T4 lesions. Median follow-up was 3.6 years. There were 22 squamous cell and four basaloid carcinomas. Six tumors were aneuploid. RESULTS: Median values for T(s) and S-phase fraction were 7.7 h and 8.2%, respectively. The median LI was 6.8% (0.9-35.7%), and the median T(pot) was 4.1 days (0.9-30 days). There was no correlation of LI or T(pot) with gender, age, tumor stage, size or histology. Local failure was observed in five patients (T(pot)>4.1 days, n=3; LI>6.8%, n=4). Isolated regional failure or distant disease in the absence of local failure was not observed. The small number of outcome events precluded a definitive analysis of the prognostic role of LI and T(pot). Values for the proliferation parameters were similar to those in our updated study of patients with carcinoma of the uterine cervix (n=107), median LI of 6.7% and median T(pot) of 5.5 days. CONCLUSIONS: We conclude that proliferation parameters in anal carcinomas are similar to those in cervical carcinomas. Rapid tumor proliferation does not have an apparent adverse impact on outcome in anal carcinomas managed by split-course XRT with concurrent 5-florouracil and mitomycin C.

Adult↗

A germline mutation at the extreme 3' end of the APC gene results in a severe desmoid phenotype and is associated with overexpression of beta-catenin in the desmoid tumor.

Desmoid tumors arise sporadically or as part of the extraintestinal manifestations of familial adenomatous polyposis (FAP). In FAP, two distinct clinical presentations of the desmoid phenotype are seen: 1) one or a few desmoid tumors present predominantly in the abdominal wall or the abdomen; 2) a florid proliferation of tumors early in life, mostly near the axial skeleton or extremities. These different phenotypes have been associated with different sites of germline mutations in the adenomatous polyposis coli gene (APC gene). We present a large, French-Canadian kindred with a florid desmoid tumor phenotype caused by a germline mutation at codon 2643-2644 of the APC gene. The phenotype was characterized by the early onset of multiple tumors, arising near the axial skeleton and in proximal extremities. The penetrance of desmoid tumors was near 100% in this kindred. However, the expression of the disease was variable amongst the different affected relatives. Many gene carriers had cutaneous cysts. Polyposis of the colon was rarely observed in the affected individuals and we did not document upper gastro-intestinal polyps. The mutant APC allele did not express a stable truncated protein in vivo. Molecular analysis of the proband's tumor DNA revealed a somatic inactivating mutation of the wild-type allele. Immunohistochemistry on the tumor also demonstrated elevated levels of beta-catenin. The present study demonstrates that this extreme 3' APC mutation is associated with a severely penetrant desmoid phenotype and attenuated polyposis coli. It also suggests the involvement of the beta-catenin pathway in the development of desmoid tumors in FAP. The natural history of the disease is variable between individuals, and surgical interventions have to be timed appropriately due to the frequent recurrences.

3' Untranslated Regions↗

Temporal relation between acoustic and force responses at the adductor pollicis during nondepolarizing neuromuscular block.

BACKGROUND: Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography. METHODS: Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery. RESULTS: Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force. CONCLUSION: Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.

Adult↗

Determination of neostigmine in human plasma and cerebrospinal fluid by high-performance liquid chromatography with ultraviolet detection.

A high-performance liquid chromatographic assay coupled with ultraviolet detection has been developed for the determination of neostigmine in human plasma and cerebrospinal fluid. A novel solid-phase extraction procedure was first used for this analyte and allowed good recovery (89+/-4.5%) together with ease and speed of execution. The method was sensitive, reproducible (C.V.<4.5%) and accurate (100+/-6.6%) over the range 2.6-167.0 ng/ml neostigmine concentrations in plasma or cerebrospinal fluid, and was applied successfully to study the pharmacokinetics of neostigmine in patients suffering from chronic postoperative abdominal pain.

Cholinesterase Inhibitors↗

In normal subjects bracing impairs the function of the inspiratory muscles.

Normal subjects can increase their capacity to sustain hyperpnoea by bracing their arms on fixed objects, a procedure which is also known to reduce dyspnoea in patients with chronic obstructive pulmonary disease (COPD). In the present study, it was tested whether bracing per se could improve the function of the diaphragm. The effect of bracing on diaphragm function was studied in six normal subjects by recording changes in oesophageal (delta Poes) and transdiaphragmatic (delta Pdi) pressure during inspiratory capacity (IC) manoeuvres in the seated and upright postures, and in the seated posture, also during bilateral phrenic nerve stimulation (BPNS) at functional residual capacity (FRC). The pattern of ribcage motion and deformation associated with bracing and with diaphragm contraction was also evaluated using inductance plethysmography and magnetometers. Bracing increased FRC by >300 mL and reduced IC by approximately 200 mL, in both postures. Delta Pdi during BPNS decreased on average by 15% indicating an impaired diaphragmatic function. The ribcage was deformed with bracing and was more distortable during BPNS. In conclusion, in normal subjects, bracing impairs the function of the inspiratory muscles and reduces ribcage stability. These negative effects cannot explain the improved capacity to sustain hyperpnoea when the arms are braced.

Adult↗

Preferential allelic expression can lead to reduced expression of BRCA1 in sporadic breast cancers.

BRCA1 is considered to be a tumor-suppressor gene, yet mutations in this gene are uncommon in sporadic breast tumors. We investigated whether mechanisms other than DNA mutations that affect the coding region might be involved in breast carcinogenesis. Since loss of expression of the BRCA1 gene would lead to lack of protein, we evaluated the level of BRCA1 mRNA in 21 normal epithelial specimens and in 74 breast carcinomas using quantitative reverse-transcription-polymerase-chain-reaction (RT-PCR). All normal breast epithelial samples expressed BRCA1 mRNA. On the other hand, the tumor specimens exhibited approximately 10-fold range of levels of BRCA1, with some specimens expressing barely detectable amounts of BRCA1 mRNA. The distribution in levels was significantly higher in normal breast epithelial cells than in tumor specimens (p = 0.004). Examination of the BRCA1 locus indicated that deletion of the BRCA1 gene may account for low levels of BRCA1 in a number of specimens. In addition, analysis of samples with relatively reduced levels of BRCA1 expression revealed preferential allele-specific expression in a number of cases, suggesting the presence of regulatory mutations. Our data suggest that the BRCA1 gene may be involved in sporadic breast carcinogenesis through a reduction in gene expression.

Alleles↗

Can we treat respiratory failure in Friedreich ataxia?

BACKGROUND: Neurochemical disorders associated with spinocerebellar ataxias are multiple. OBJECTIVE: To use replacement and neuroprotective therapy in a case of severe respiratory failure in Friedreich ataxia. PATIENT AND TREATMENT: A 44-year-old man with severe Friedreich ataxia displayed arduous periodic breathing associated with minor desaturation as well as obstructive or mixed apneas associated with severe desaturation during the night. He was given oxitriptan (5-hydroxy-L-tryptophan) (1500 mg/d), thiamine hydrochloride (100 mg/d), and amantadine hydrochloride (100 mg/d). The first sleep study was conducted during the night before treatment, whereas the second was performed during the night after 9 months of treatment. RESULTS: After treatment, striking clinical improvement of spastic dysphonia was accompanied by significant diminution in the time spent in periodic breathing and in the number of obstructive and mixed apneas during the night. Controlled studies are needed.

5-Hydroxytryptophan↗

Pre-operative assessment of axillary lymph node status in patients with breast adenocarcinoma using intravenous 99mtechnetium mAb-170H.82 (Tru-Scint AD).

Immunoscintigraphy of the axilla has potential utility for the diagnostic and prognostic assessment of patients with breast adenocarcinoma. mAb-170H.82 is a murine monoclonal antibody (mAb) derived against synthetic Thomsen-Friedenreich (TF) antigen. Tru-Scint AD, a 99mTc-mAb-170H.82 immunoconjugate, has previously been shown to localize in various human adenocarcinomas. The purpose of this study was to evaluate the accuracy of this immunoconjugate in the pre-operative assessment of axillary lymph nodes in patients with known breast adenocarcinoma. Sixteen patients with documented primary breast cancer were injected intravenously with 1 mg of immunoconjugate (radioactivity 1.8 GBq) and imaged 22-24 hrs post-injection. Both planar and single photon emission computed tomographic (SPECT) images were obtained and reviewed in a blinded fashion. Imaging results were compared with surgical and pathological findings. Seven of 16 patients were found to have histologically positive axillary nodes: 5 of these sites were detected by immunoscintigraphy (sensitivity = 71%). Nine patients had pathologically disease-free axillary nodes: only 1 of these was misidentified as positive by immunoscintigraphy (specificity = 89%). These results suggest that immunoscintigraphy with 99mTc-mAb-170H.82 has promise in the detection of axillary lymph node involvement in patients with breast cancer. Further studies are warranted to define the role of immunoscintigraphy in axillary staging.

Adenocarcinoma↗

Diaphragmatic fatigue investigated by phonomyography.

Diaphragmatic phonomyogram (PMG) evoked by maximal bilateral phrenic nerve stimulation has previously been described as a good index of contractility of fresh and fatigued diaphragm. In the present study we hypothesized that diaphragmatic contractility changes could be even more simply evaluated by recording the relationship between the PMG and the compound motor action potential (CMAP) amplitudes during graded submaximal unilateral phrenic nerve stimulation at various intensities. Relationships between CMAPs and PMGs from left and right hemidiaphragms were recorded by means of surface electrodes and miniature microphones placed over the lower rib cage (eighth intercostal space) in five healthy subjects before and after a diaphragmatic fatigue task. These relationships in each subject were linear. The slope of these relationships decreased by 61.1 +/- 20.7% and by 70.4 +/- 14.6% on the right and left side respectively, but the intercepts did not change significantly. By comparison, transdiaphragmatic twitch pressure during maximal bilateral stimulation (PdiT) declined by 49.4 +/- 15%. We conclude that PMG during submaximal unilateral phrenic nerve stimulation is a reliable index of diaphragm contractility changes caused by fatigue. Using this method we have shown that all diaphragmatic motor units can be affected by fatigue.

Action Potentials↗

Effects of lung volume and fatigue on evoked diaphragmatic phonomyogram in normal subjects.

BACKGROUND: A diaphragmatic phonomyogram (PMG) evoked by maximal phrenic nerve stimulation at end expiratory lung volume (FRC) has been previously described as a good index of changes in diaphragmatic contractility with fatigue. A study was undertaken to assess whether this conclusion could be extended to different lung volumes. METHODS: Diaphragmatic compound motor action potentials (CMAPs) were recorded on each side of the chest by the means of surface electrodes placed over the eight intercostal spaces in five healthy subjects. Diaphragmatic PMGs from both sides were recorded with condenser microphones fixed to the skin close to the CMAP recording electrodes. Oesophageal and gastric balloon tipped catheters were employed to measure transdiaphragmatic pressure twitches (TwPDI) which served as the standard measure of changes in diaphragmatic contractility. PMG and TwPDI responses were compared at different lung volumes over inspiratory capacity both before and after fatiguing inspiratory resistive loading. RESULTS: No consistent relationship was found in different subjects or on different days in the same subject between PMG and lung volume or between PMG and TwPDI. However, the PMG:CMAP ratio from both sides at any given lung volume decreased after fatigue in roughly the same proportion as the TwPDI. CONCLUSIONS: These results show that, although PMG can detect changes in diaphragmatic contractility caused by fatigue in normal subjects, lung volume changes need to be controlled and each subject should serve as his or her own control.

Action Potentials↗

A preventive registry for hereditary nonpolyposis colorectal cancer.

Hereditary nonpolyposis colorectal cancer (HNPCC) is a genetic disorder characterized by a strong family history of colorectal and extracolonic cancers, usually at a young age. This article presents a new provincial service for families with HNPCC. The Steve Atanas Stavro Familial Gastrointestinal Cancer Registry at Mount Sinai Hospital is accruing patients that meet a set of criteria establishing a putative diagnosis of HNPCC. The objectives of the Registry are to develop and assess patient pedigrees, to coordinate screening procedures for at-risk persons, to maintain a prospective database of patient information, to provide education and support for families and to contribute to research. To date, surgeons and patients are the most common referral sources, while oncologists and geneticists are the least common. The ultimate goal of the HNPCC service is the secondary prevention of cancer and a corresponding decrease in mortality for HNPCC family members.

Colorectal Neoplasms↗

Influence of agents affecting monooxygenase activity on taurolithocholic acid-induced cholestasis.

In rats, pretreatment with certain ketones results in enhanced taurolithocholic acid (TLCA)-induced reduction in bile flow, whereas pretreatment with inhibitors of protein synthesis diminishes the effect on bile flow of cholestatic regimens. In the present study, the possible role of cytochrome P-450 in the ketone potentiation phenomenon was investigated. Male rats were pretreated with inducers or inhibitors of hepatic cytochrome P-450 and the impact of these pretreatments on TLCA-induced cholestasis assessed. Phenobarbital, 3-methylcholanthrene, chlordecone or mirex were used as inducers, and SKF 525-A, piperonyl butoxide, or cobaltous chloride as inhibitors of monooxygenase activity. Phenobarbital and 3-methylcholanthrene pretreatment enhanced TLCA-induced reduction of bile flow, while mirex and chlordecone were without effect. The three inhibitors of monooxygenase activity did not diminish TLCA-induced cholestasis. Instead, piperonyl butoxide and cobaltous chloride appeared to enhance the action of TLCA. Consequently, an increase in cytochrome P-450 (or specific isozymes) as a common denominator in the potentiation phenomenon appears unlikely. While hepatic proteins may play an important role in the potentiation of TLCA-induced cholestasis following pretreatment with ketones, the pattern of potentiation after pretreatment of rats with different inducers or inhibitors of cytochrome P-450 does not appear to implicate this family of proteins.

Animals↗