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Biomedical subjects

M Martin

Publications and source records attributed to M Martin.

At least 343 records · Page 19Linked to original sources
PubMed1996

Expression of fibronectin ED-A+ and ED-B+ isoforms by human and experimental colorectal cancer. Contribution of cancer cells and tumor-associated myofibroblasts.

Alternative splicing of primary fibronectin (FN) mRNA results in the synthesis of different isoforms. ED-A+ and ED-B+ FN isoforms are absent from plasma FN and are representative of cellular FN. Their expression was studied in human and rat normal colon, in human colorectal carcinomas, and in transplanted tumors derived from a chemically-induced rat colon cancer. In normal colon, only the ED-A+ FN isoform was expressed as a thin deposit between crypt colonocytes and pericryptal myofibroblasts. Conversely, heavy ED-A+ FN deposits and lighter ED-B+ FN expression were found in the stroma of colorectal tumors in association with myofibroblasts surrounding tumor glands. Some colonic cancer cells also contained intracellular FN isoform granules and expressed FN mRNA. Tumor-associated myofibroblasts and some cancer cell lines were able to synthesize and deposit extracellular ED-A+ and ED-B+ FN in vitro. FN isoform deposition by tumor-associated myofibroblasts was not modulated by colon cancer cell-conditioned medium, but was strongly enhanced when myofibroblasts were cultured on colon cancer cell extracellular matrix or on laminin. These results show that the ED-A+ and ED-B+ FN isoforms were overexpressed in colorectal cancer. Cancer cells can deposit these FN isoforms directly and also stimulate their deposition by tumor-associated myofibroblasts.

Actins↗
PubMed1996

Nephelometric determination of carbohydrate deficient transferrin.

We describe a technique for measuring carbohydrate-deficient transferrin (CDT) in serum. Serum transferrin fractions are separated by anion-exchange chromatography on microcolumns. Sialic acid-deficient transferrin fractions are collected in the eluate, and transferrin is then quantified by a rate-nephelometric technique. Imprecision (CV) was 4-5% within-run and 7-9% between runs (n = 15). Comparison with an isoelectric focusing-immunofixation method for transferrin index (x) yielded y = 761x + 7, Sy/x = 39 mg/L. Assay of sera from 90 abstainers or moderate consumers of alcohol showed that 81 (90%) had CDT concentrations between 30 and 70 mg/L. Among 74 alcoholics admitted to an alcohol treatment center, 54 (73%) had CDT > 70 mg/L, i.e., the diagnostic sensitivity was 73% at a specificity of 90% (area under receiver-operator characteristic curve = 0.891).

Adolescent↗
PubMed1996

Characterization of the cloned HEL cell thromboxane A2 receptor: evidence that the affinity state can be altered by G alpha 13 and G alpha q.

Thromboxane A2 (TXA2) induces activation of platelets and vascular smooth muscle contraction via cell surface receptors. A platelet type TXA2 receptor from the megakaryocyte-like HEL cell was cloned with a deduced amino acid sequenced identical to that previously reported for the human placental TXA2 receptor. Transient expression of the HEL cell TXA2 receptor cDNA and radioligand binding studies with the agonist 125I-BOP showed a single class of binding sites with an affinity comparable to a low affinity platelet TXA2 receptor. Using a series of 13-azapinane TXA2 analogs, which discriminate between TXA2 receptor subtypes in platelets and vascular smooth muscle, we found that the cloned HEL cell TXA2 receptor is characteristic of a platelet type TXA2 receptor and that its binding characteristics are different from those of vascular smooth muscle cells. The affinity of the HEL cell TXA2 receptor for 125I-BOP was significantly (P < .05) increased upon co-transfection with G alpha 13 alone, or with G alpha q alone and with G alpha 13 and G alpha 12 together (n = 4-6). GTP gamma S significantly (P < .05) decreased the affinity of the receptor for 125I-BOP in COS-7 cell membranes coexpressing HEL-TXR and G alpha 13 to a value comparable to HEL-TXA2 receptor alone. We conclude that 1) the cloned HEL cell TXA2 receptor has pharmacological characteristics of a low affinity platelet type receptor and 2) that the affinity state of this receptor may be influenced by interaction with G alpha 13 and G alpha q.

Base Sequence↗
PubMed1996

Inflammatory cells infiltrating human colorectal carcinomas express HLA class II but not B7-1 and B7-2 costimulatory molecules of the T-cell activation.

Colon cancer cells express potentially immunogenic proteins but are not rejected by the immune system. To induce an effective immune response, antigenic peptides have to be presented to T lymphocytes by professional antigen-presenting cells in association with HLA class II molecules. Antigen-presenting cells also have to express B7 family molecules, B7-1 and B7-2, which deliver the costimulatory signals that are required to prevent T cell anergy. We studied B7-1 and B7-2 expression by the antigen-presenting cells that infiltrate colorectal cancer stroma. In 25 samples of colorectal carcinomas, a panel of monoclonal antibodies was used to label macrophages, dendritic cells, and T lymphocytes that infiltrate the tumor stroma and the morphologically normal distant mucosa. The expression of HLA class II and B7 molecules involved in T-cell activation was studied using specific monoclonal antibodies. Biopsy pieces from two patients with active Crohn's disease were used as controls. All of the samples were heavily infiltrated by macrophages and/or dendritic cells that strongly expressed HLA class II molecules. In contrast, antibodies to B7-1 and/or B7-2 stained no cells in 16 of the 25 samples of colorectal tumors and less than 1% of the inflammatory cells that infiltrated tumor stroma of the other nine tumor samples. B7 molecules were also poorly expressed by rare cells in the lamina propria of the morphologically normal colorectal mucosa. In contrast, many inflammatory cells that infiltrated the two Crohn's disease samples strongly expressed B7-1 and B7-2, especially in the granulomas. We conclude that most HLA class II+ inflammatory cells that infiltrate colorectal cancers do not express the B7-1 and B7-2 costimulatory molecules. This defect may contribute to the failure of the immune system to recognize tumor cells as antigenic.

Adenocarcinoma↗
PubMed1996

[Place of iridium 192 implantation in irradiation of T1-T2 squamous cell carcinoma of the velopharyngeal arch].

We have reviewed the results of 165 T1 and T2 squamous cell carcinomas of the faucial arch treated by definitive irradiation including or not iridium 192 brachytherapy to ascertain whether a significant relationship exists between iridium implantation, local control, complications and survival. From March 1971 to November 1990, 58 T1 and 107 T2 (NO: 107/165; N1: 30/165; N2: 9/165; N3: 19/165) biopsy proven squamous cell carcinomas of the tonsillar region (104/165) and the soft palate and uvula (61/165) were treated in the Henri Mondor Hospital by definitive irradiation with curative intent. From 1971 to 1981 (period 1), only guide gutter technique was available, so that implants were reserved for small tumors: patients were either managed by definitive telecobaltherapy to tumor site and neck node areas (group I; n = 48; mean dose: 70 Gy; confidence interval: +/- 5.5, 5 fractions of 1.8 Gy per week) or by exclusive iridium implant (group 2; n = 11; all T1NO; 64 Gy +/- 4.8) or by a combination of external beam radiation therapy to tumor site and neck nodes areas and iridium implant (group 3; n = 40). In 1981 (period 2), a new plastic tube technique, which enables implantation of larger areas, was introduced and all patients (group 4; n = 66) were then managed by external radiation therapy (group 3 + 4: 47 Gy +/- 4.3) followed by an iridium implant (31 Gy +/- 10.5). Clinically positive neck nodes either received additional external dose with electrons or were excised. Overall 5-year survival (Kaplan Meier) was 23%, 50.5%, and 60% in groups 1, 2 and 3 + 4, respectively (p < 0.001, log rank). Five-year local control was 58%, 100%, and 91%, respectively (p < 0.001). Five-year necrosis rate was 10%, 25% and 30%, respectively (NS). Comparison of results between the two periods of the study (group 1 + 2 + 3 vs group 4) shows that these two groups are statistically comparable according to site and size of tumor and N status and that both local control (77% vs 94% at 5 years; p < 0.01) and disease free survival (56% vs 71%; p = 0.03) were improved after 1980, while there was a trend to an increase in overall survival (42% vs 53% at 5 years; p = 0.08); nodal control (86% vs 95% at 5 years) and necrosis rate (11% vs 20% at 5 years) were not modified. Multivariate analysis showed that both local control (p < 0.0001) and overall survival (p < 0.0001) were improved when tumor was implanted. We recommend then to treat T1 and T2 squamous cell carcinomas of the faucial arch by external radiation therapy to tumor site and neck areas (45 Gy/25 fractions/5 weeks) followed by a 30 Gy iridium implant and, for patients with clinically positive nodes, either a further 25-30 Gy electron beam irradiation to the nodes or neck node dissection.

Adult↗
PubMed1996

[Comparison of concomitant radiotherapy and chemotherapy with radiotherapy alone in advanced cancers of the head and neck: results of a randomized trial].

From April 1987 to October 1992, 67 patients with inoperable squamous cell carcinoma of the head and neck region were included in a randomized trial. All patients had induction chemotherapy with cisplatin (100 mg/m2, D1) and fluorouracil (1 g/m2, from D1 to D5) every three weeks for a total of three cycles. Patients were randomized to concurrent external radiation therapy (70 Gy/39 fractions/8 weeks) and chemotherapy with cisplatin (50 mg/m2 in short infusion, D1, D15, D29, D43) and fluorouracil (5 mg/kg, intra-muscular, every Monday, Wednesday and Friday) (experimental group) versus radiotherapy alone with the same modalities (control group). The followup for living patients was 14 to 60 months with a median of 42 months. Analysis of preliminary results has shown that: 1) early and late side effects are similar in both groups; 2) after completion of treatment, the percentage of patients in complete remission was 71% (20/28) in the experimental group and 43% (12/28) in the control group; this difference was statistically significant among non responders to induction chemotherapy (1/15 versus 13/20, P = 0.001), but non significant among responders (11/13 versus 7/8) and 3) there were no differences between both randomized groups in term of 3-year overall survival and of 3-year loco-regional control. Results are discussed taking into account a review of literature.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Intrahepatic arterial chemoembolization for hepatocellular carcinoma and metastatic neuroendocrine tumors in the era of liver transplantation.

Surgical resection has been the standard approach for primary and metastatic liver tumors. Long-term survival, however, is limited because of recurrence or hepatic decompensation. Failure of chemotherapeutic regimens or liver transplantation (OLT) to prevent recurrence has resulted in the need for multimodality therapies. We report our experience with preoperative hepatic arterial chemoembolization (CET) followed by OLT in highly select patients. Over a 33-month period, 23 of 41 patients (56%) referred with primary (n = 16) or metastatic neuroendocrine (n = 7) liver tumors met eligibility requirements. Despite mild, self-limited chemical hepatitis, CET was well tolerated in all but three elderly patients who succumbed to liver failure. Four of five patients ultimately received OLT. Three are alive and free of disease at a mean followup of 17 months, one died of recurrent hepatocellular carcinoma, and one (NET) remains well at 33 months with elevated glucagon levels but no measurable disease. All NET patients are alive with resolution of hormonal symptoms. Four of five noncirrhotic patients died of disease, and one has progressive tumor growth. Although OLT following CET achieves superior survival, its application is limited to a minority of patients with such tumors. Careful pretreatment staging and patient selection combined with caution in the use of CET in elderly cirrhotic patients is critical to the success of such therapies.

Adult↗
PubMed1996

Fibrinolytic treatment with ultra-high streptokinase infusion via the dorsalis pedis vein offers no advantage over systemic infusion via the brachial vein in patients with deep vein thrombosis of the leg.

The present study into the fibrinolytic therapy of deep vein thrombosis (DVT) considers whether streptokinase infusion into the dorsalis pedis vein of the affected leg (ipsipedal infusion) yields higher lysis rates than systemic infusion via the brachial vein (systemic infusion). In both cases the dosage regimen selected was a short-term ultra-high streptokinase (UHSK) infusion of 1.5 million IUSK/hour over a period of 6 hours (total SK dose: 9 million IU). A series of one to three UHSK infusions was given on one to three consecutive days. Forty patients were randomised to either systemic (Group S) or ipsipedal (Group IP) treatment. The distribution of important parameters determining a fibrinolytic response (e.g. the age, site and extent of DVT, and number of UHSK infusion series) was virtually identical in the two treatment groups. The rates for total and partial thrombolysis in the systemic infusion group were 50% and 10% respectively compared with 30% and 20% respectively in the ipsipedal group. The distribution of side-effects was approximately identical in the two groups. The results show that ipsipedal UHSK lysis via the dorsalis pedis vein confers no advantage over systemic infusion via the brachial vein.

Adult↗
PubMed1996

Determinants of prolonged oral cecal transit time during late phase pregnancy.

We examined the course of delayed oral cecal transit time (OCTT) and the impact of different variables in late pregnancy. Thirty-three women in late trimester were evaluated and 29 were re-tested post partum. Results were compared with 17 controls. A breath hydrogen test was used to measure OCTT. The impact of 3 demographic and 5 biochemical parameters was evaluated. Oral cecal transit time (99.2 +/- 7.8 min) during pregnancy was significantly prolonged compared both with controls (63.5 +/- 8.7 min) (p = 0.0042) and post partum (68.5 +/- 6.4 min) (p < 0.002). However, 40% during pregnancy had a normal OCTT. Post partum, 8 (29.6%) continued to have delayed OCTT. Serum free T4 levels were significantly lower than in controls (p < 0.0001) and post partum (p < 0.001), but did not correlate with OCTT. Gravidity rank correlated with OCTT (p = 0.022). By multivariate analysis, only 17% of the observed variability during pregnancy could be explained by these parameters. In controls, a formula including progesterone and gastrin levels was significant in explaining 54.7% of variability. Application of both formulae to post-partum returnees overpredicted OCTT; however, the one from pregnancy was more accurate. We conclude that in pregnancy multiple factors account for delayed OCTT and these may be different from controls and post partum. Pregnancy may still influence OCTT post partum.

Adult↗
PubMed1996

Lactose handling by women with lactose malabsorption is improved during pregnancy.

OBJECTIVE: To evaluate lactose handling among women in late pregnancy and post partum to determine whether lactose handling is altered in pregnancy. DESIGN: Prospective study of lactose intolerance among pregnant women with and without lactose malabsorption. SETTING: Gastroenterology service of the Sir Mortimer B. Davis-Jewish General Hospital, Montreal. PATIENTS: Thirty-three pregnant women, of whom 18 had lactose malabsorption, 12 did not and 3 were excluded. OUTCOME MEASURES: Lactose breath hydrogen (BH2) concentration after ingestion of lactose or lactulose; comparison before and after delivery of area under the curve (AUC) for lactose, oral-cecal transit time (OCTT) for lactulose, lactose-BH2-derived transit time and estimated dietary lactose consumption. RESULTS: After weaning (at a median time of 9 months after delivery), 28 of the women returned for follow-up. Of the 12 who could absorb lactose before delivery, 4 could no longer absorb lactose. Of the other 16 women, lactose intolerance worsened in 12, remained the same in 2 and improved in 2. The AUC was greater (p < 0.005), the maximal BH2 concentration was higher (p = 0.004) and the number of women whose BH2 concentration peaked was fewer (p < 0.025) post partum than before delivery. The women's symptoms during and after lactose BH2 tests were also greater post partum. The OCTT (based on the lactulose BH2 test) was shorter post partum (p = 0.001). Transit time derived from lactose BH2 tests was also shorter, but not significantly so. The OCTT was not inversely correlated with the change in AUC before and after delivery, but the lactose-BH2-derived transit time was inversely correlated. Pregnant women consumed more lactose before delivery than afterward (p < 0.004). CONCLUSIONS: Women with lactose malabsorption handle lactose better than usual in late pregnancy. Slow intestinal transit and bacterial adaptation to increased lactose intake may be primarily responsible.

Breath Tests↗
PubMed1996

Combination protocols for prevention of CMV disease in the high risk transplant patient.

Overall, the results seen in this study are encouraging. In this high-risk group of patients where the expected disease rate would normally be at least 55% to 60% without prophylaxis, a combination protocol of GCV, ACV, and CMVIG limited the rate of disease to 19%. When disease occurred, it was generally mild and easily treatable. While stratification of patients according to organ transplant group and donor/recipient serology may help to better define future protocol designs, the combination strategy used in this study has clearly demonstrated its usefulness in the high-risk transplantation population.

Cytomegalovirus Infections↗
PubMed1996

A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.

This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.

Adult↗
PubMed1995

Occupational injuries, illness affect 1 in 13 Canadians.

One in every 13 Canadian workers has experienced a work-related illness or injury, federal data indicate. Occupational-health clinics in Ontario report a growing number of cases of sick-building syndrome, repetitive-strain injury, asthma and chemical exposure, as well as injuries related to the use of construction equipment. In the past the medical profession assumed that men incurred most work-related injuries, but today, says an occupational-health specialist, "work-related illness and injuries are just as likely to happen to women or to white-collar professionals."

Canada↗
PubMed1995

Lineage switch of a mouse pre-B cell line (SPGM-1) to macrophage-like cells after incubation with phorbol ester and calcium ionophore.

The mouse CD5 positive pre-B cell line SPGM-1 can be induced to switch its lineage commitment towards macrophage differentiation by treatment with a combination of phorbol ester and a calcium ionophore. When cultured with these reagents the pre-B cells ceased to proliferate and rapidly became adherent to plastic surfaces. This morphological change was accompanied by the loss of pre-B cell-specific surface markers, such as PB76 and most prominently the mu heavy chain of the immunoglobulin receptor complex. In addition, the mRNA of the surrogate light chain lambda 5 disappeared while the induction of lysozyme mRNA could be detected. Differentiated SPGM-1 cells phagocytosed latex beads and showed nonspecific esterase activity. The high efficiency and speed of differentiation in this cellular system makes SPGM-1 a highly suitable model for studying the phenomenon of lineage switching during hemopoesis.

Animals↗