Biomedical subjects

J Guerra

Publications and source records attributed to J Guerra.

At least 19 recordsLinked to original sources

PubMed1999

Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group.

BACKGROUND: Oral leukotriene receptor antagonists have been shown to have efficacy in chronic asthma. OBJECTIVE: To compare the clinical benefit of montelukast, a once-daily oral leukotriene receptor antagonist; placebo; and inhaled beclomethasone. DESIGN: Randomized, double-blind, double-dummy, placebo-controlled, parallel-group, 12-week study. SETTING: 36 sites worldwide. PATIENTS: 895 patients 15 to 85 years of age with chronic asthma and an FEV1 50% to 85% of predicted. INTERVENTIONS: Montelukast, 10 mg once daily at bedtime; inhaled beclomethasone, 200 microg twice daily, administered with a spacer device; or placebo. MEASUREMENTS: Primary end points were daytime asthma symptom score and FEV1. Secondary end points were peak expiratory flow rates in the morning and evening, as-needed beta-agonist use, nocturnal awakenings, asthma-specific quality of life, and worsening asthma episodes. RESULTS: Over the 12-week treatment period, the average percentage change from baseline in FEV1 was 13.1% with beclomethasone, 7.4% with montelukast, and 0.7% with placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). The average change from baseline in daytime symptom score was -0.62 for beclomethasone, -0.41 for montelukast, and -0.17 for placebo (P < 0.001 for each active treatment compared with placebo; P < 0.01 for beclomethasone compared with montelukast). Each agent improved peak expiratory flow rates and quality of life, reduced nocturnal awakenings and asthma attacks, increased the number of asthma-control days, and decreased the number of days with asthma exacerbations (P < 0.001 for each active treatment compared with placebo for each end point; P < 0.01 for beclomethasone compared with montelukast for each end point). Although beclomethasone had a greater mean clinical benefit than montelukast, montelukast had a faster onset of action and a greater initial effect. The two agents caused similar decreases in peripheral blood eosinophil counts (P < 0.05 for each agent compared with placebo). Both agents had tolerability profiles similar to that of placebo over the 12-week study. CONCLUSIONS: Although beclomethasone had a larger mean effect than montelukast, both drugs provided clinical benefit to patients with chronic asthma. This finding is consistent with the use of these agents as controller medications for chronic asthma.

Acetates↗

PubMed1999

[Radioimmunoscintigraphy of colorectal cancer using the anti-CEA monoclonal antibody BW 431/26. Final results].

The anti-carcinoembryonic antigen (CEA) antibody, BW 431/26 (Scintimun CEA, Behringwerke, Marburg, Germany ) labeled with technetium pertechnectate (99mTc), is an intact immunoglobulin G1, monoclonal antibody that has been used to image colorectal cancer. Planar and SPECT images of chest, abdomen and pelvis were performed at 10 minutes, 4-6 and 18-24 hours after the intravenous antibody injection. 44 patients were studied and the pathological antibody concentration localization by radioimmunoimaging (RI) were correlated with surgical, clinical and other imaging modality findings to validate the RI. The RI was positive in 29 patients and negative in the other 15 patients. The CEA and CA 19.9 were elevated in the serum of some patients with primary tumors or recurrence. The HAMA were determined in all the patients before and after the RI.

Adult↗

PubMed1998

Expression of inducible nitric oxide synthase after endothelial denudation of the rat carotid artery: role of platelets.

There is functional evidence suggesting that endothelial denudation stimulates inducible nitric oxide synthase (iNOS) activity in the vascular wall. In vitro studies have shown that iNOS expression in smooth muscle cells is reduced by endothelial cells. In the present study we have analyzed the time course of iNOS protein expression in the arterial wall after in vivo deendothelialization. Endothelial denudation was performed in the left carotid artery of Wistar rats, and the right carotid artery was used as control. Whereas iNOS protein was weakly expressed 6, 24, and 48 hours after endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after vascular damage. Because platelet adhesion and aggregation occur early after endothelial damage, we studied the role of activated platelets in the negative modulation of iNOS protein expression during the first 2 days after endothelial denudation. Early after in vivo endothelial injury, platelet-depleted rats showed a marked iNOS protein expression in the vascular wall. Similar results were obtained by blocking the platelet glycoprotein (GP) IIb/IIIa. Although iNOS protein is present in the arterial wall several days after endothelial denudation, early after arterial wall injury iNOS protein is weakly expressed. Platelets play a crucial role in preventing iNOS protein expression early after endothelial damage, an effect that can be avoided with GP IIb/IIIa blockers. Although iNOS protein was weakly expressed in vivo in the rat carotid artery wall 6, 24, and 48 hours after balloon endothelial denudation, a marked iNOS expression was found 7, 14, and 30 days after arterial damage. iNOS expression could be increased early after endothelial injury by removing circulating platelets and by an antibody against the GP IIb/IIIa. In conclusion, platelets prevent iNOS protein expression early after endothelial balloon damage, an effect that can be avoided with GP IIb/IIIa blocking agents.

Animals↗

PubMed1998

Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats.

Two NO synthase (NOS) isoforms have been described in vessels, an endothelial constitutive NOS (eNOS) and an inducible NOS (iNOS). The purpose of the present study was to examine the endothelium-dependent and endothelium-independent hypotensive response in aging rats, analyzing the ability of their vessels to produce NO. The studies were performed in 2 groups of euvolemic, conscious, male Wistar rats: aging rats (n=20, 18 months old) and young rats (n=20, 5 months old). The hypotensive responses to acetylcholine, bradykinin, and sodium nitroprusside were determined. Furthermore, the expression of the NOS isoforms by Western blot and the eNOS and iNOS activities, defined as Ca2+-dependent and Ca2+-independent conversion of [14C]L-arginine into [14C]L-citrulline, respectively, were also determined. In the aging rats, we found an impaired hypotensive response to acetylcholine and bradykinin (2 NO- and endothelium-dependent hypotensive agents) that was accompanied by a preserved hypotensive response to sodium nitroprusside. Aging rats also demonstrated an enhanced sensitivity response to the pressor effect of the L-arginine antagonist L-Nomega-nitro-L-arginine and a reduced vasoconstrictor response to angiotensin II. The inhibition of NO synthesis normalized the pressor effect of angiotensin II in the aging animals. Nitrite plus nitrate plasma levels were increased in aging rats. Furthermore, cGMP content was also higher in the aging vessels. In the aging aortas, the expression of both eNOS and iNOS isoforms was enhanced. However, in aging rats, the activity of the eNOS isoform was markedly reduced, a finding that was accompanied by the presence of iNOS activity. The vessel wall of aging rats showed an enhanced expression of eNOS and iNOS isoforms. However, eNOS activity was reduced in the aging animals. These findings could explain the impaired endothelium-dependent hypotensive response associated with aging.

Acetylcholine↗

PubMed1998

Percutaneous dilatation of biliary strictures through the afferent limb of a modified Roux-en-Y choledochojejunostomy or hepaticojejunostomy.

BACKGROUND: This report is a 13-year prospective evaluation of percutaneous balloon dilatation of benign biliary strictures through the subcutaneous or subfascially positioned afferent limb of a choledocho or hepaticojejunostomy in 30 patients. DATA SOURCE: Twenty-seven strictures developed after a common duct injury sustained at the time of cholecystectomy, two after hepatectomy reconstruction for trauma and one following a gastrectomy. Twelve injuries (40%) were recognized at operation. Of the 18 patients where the injury was unrecognized at the time of operation, 8 had not been reoperated at the time of referral, 7 had late repairs by the referring physician, and 3 had late repairs at our institution. The follow-up is 1 to 13 years. RESULTS: There has been 1 late death and 6 patients are lost alive. The jejunal-limb was accessed 50 times with two minor and no major complications. There have been two parajejunal hernia repairs, but there have not been any reoperations for recurrent biliary strictures. CONCLUSIONS: Benign biliary strictures can be effectively managed by repeat balloon dilatations thru the afferent limb of a choledocho or hepaticojejunostomy, thus eliminating the need for repeat surgical interventions.

Adult↗

PubMed1997

Identification of the major positive regulators of c-myb expression in hematopoietic cells of different lineages.

The c-myb gene is primarily expressed in hematopoietic cells, and it is overexpressed in many leukemias. The regulation of its expression is of critical importance in hematopoietic cells. We identified the major positive regulatory sites in the 5'-flanking sequence of the human c-myb gene, and we found that the positive regulators differed in cells of different lineages. In the Molt-4 T-cell line, two Ets-like binding sites were required for the expression of c-myb. The 5' site played a minor role in the regulation of c-myb expression, and we demonstrated that a protein of 67 kDa bound to this site. Antibodies against Ets proteins showed no cross-reactivity with this protein. We showed that Ets-1 bound to the 3'-regulatory site in the c-myb promoter by electrophoretic mobility shift assay and antibody studies. Both of these Ets-like binding sites were nonfunctional in the DHL-9 B-cell line and the K562 myeloid cell line. We identified a novel transcription factor of 50.5 kDa that was required for expression of c-myb in these cell lines.

Binding Sites↗

PubMed1997

Effect of doxazosin on endothelial dysfunction in hypercholesterolemic/antioxidant-deficient rats.

Hypertension, hypercholesterolemia, atherosclerosis, and coronary heart disease are associated with abnormal endothelium-dependent, nitric oxide-mediated vasorelaxation. In rats, hypercholesterolemia in combination with deficiencies of vitamin E and selenium results in increased endogenous lipid oxidation and endothelial dysfunction. Two hydroxymetabolites of doxazosin, an alpha 1-adrenergic blocking antihypertensive agent, inhibit human lipid oxidation in vitro in a dose-dependent fashion. The present studies were performed to determine the effect of in vivo treatment with doxazosin on endothelial dysfunction in hypercholesterolemic/ antioxidant-deficient rats. Dahl rats were fed 1) a standard diet, 2) a high cholesterol (4%) diet, or 3) a high cholesterol, vitamin E- and selenium-deficient diet. A subgroup of animals in each group were administered doxazosin (3.5 mg/100 g/day) for 16 weeks. In the aortas, vascular relaxations induced by acetylcholine were significantly decreased (P < .05) in high cholesterol/antioxidant-deficient rats compared with normal and high cholesterol animals. Doxazosin treatment prevented the impairment in endothelium-dependent vascular relaxation in the high cholesterol/antioxidant-deficient group. Vasorelaxation in response to the exogenous nitric oxide donor diethylamine nanoate, which was significantly impaired (P < .05) in aortas from high cholesterol/antioxidant-deficient animals compared with normal and high cholesterol animals, was normalized in aortas from high cholesterol/ antioxidant-deficient animals that had received doxazosin. The antioxidant effect of doxazosin may have therapeutic implications in diseases associated with endothelial dysfunction linked to products of lipid oxidation.

Adrenergic alpha-Antagonists↗

PubMed1996

Pathophysiology of the vascular wall: the role of nitric oxide in renal disease.

Nitric oxide (NO) is formed in the endothelium by the constitutive enzyme NO synthase from the substrate amino acid L-arginine. As an endogenous vasodilator it contributes to renal arteriolar tone and modulates relaxation of the mesangium, thus contributing to regulation of glomerular microcirculation. NO also plays a role in regulating renal sodium excretion and renin release. It has antiplatelet and antithrombogenic effects and thus helps prevent thrombosis within the glomerular capillaries. In sepsis and sepsis-related syndromes, NO has a renoprotective role in that it aids in maintaining renal vasodilation and inhibiting platelet adhesion and aggregation. More knowledge of these effects may lead to the design of therapeutic interventions for preventing glomerular injury.

Animals↗

PubMed1995

Repression of the c-myb gene by WT1 protein in T and B cell lines.

The c-myb gene is primarily expressed in immature hematopoietic cells, and it is overexpressed in many leukemias. We have investigated the role of negative regulatory sites in the c-myb promoter in the Molt-4 T cell line and in the DHL-9 B cell line. A potential binding site for either the EGR-1 or WT1 protein was identified by in vivo footprinting in the 5'-flanking region of c-myb in a region of negative regulatory activity in T cells. We showed by electrophoretic mobility shift assay and electrophoretic mobility shift assay Western that WT1, EGR-1, and Sp1 bound to this site. A mutation of this site which prevented protein binding increased the activity of the c-myb promoter by 2.5-fold. In the DHL-9 B cell line, this site was nonfunctional; however, we found a potential EGF-1/WT1 site located more 3' in a region of negative regulatory activity. We showed that WT1, EGR-1, and Sp1 bound to this site, and that mutation of this site increased the activity of the c-myb promoter by 3.2-fold. Cotransfection of a WT1 expression vector repressed the activity of the c-myb promoter in both cell lines, and this repression was relieved when the EGR-1/WT1 sites were removed. Cotransfection of either an EGR-1 or Sp1 expression vector had no significant effect on the activity of the c-myb promoter. We conclude that WT1 is a negative regulator of c-myb expression in both T and B cell lines.

Animals↗

PubMed1995

Myb binding sites mediate negative regulation of c-myb expression in T-cell lines.

In hematopoietic cell development, the c-myb transcription factor plays an important role. c-myb mRNA is expressed at high levels in immature proliferating cells and in leukemic cells. We have investigated the regulatory role of Myb protein binding to the human c-myb promoter. Three Myb binding sites have been described at approximately 600 bp upstream of the cap site. By transient transfection assays in hematopoietic cell lines, we found that deletion of the previously defined most 5' Myb binding site had no effect on activity, whereas deletion of the region containing the remaining two Myb binding sites resulted in an increase in activity in both a T-cell line and a myeloid cell line. To specifically test the importance of these two Myb binding sites, the activity of three-point mutation constructs was measured. Mutation of either Myb binding site resulted in an increase in activity compared with the wild-type promoter in T cells. Mutation of both sites produced even higher activity. Transfection of the Myb site mutants into the myeloid cell line resulted in no change in activity compared with the wild type construct. Results from gel shift analysis, UV cross-linking, and Western blots showed that both c-Myb and B-Myb bound to the Myb I and II sites. We conclude that the Myb family proteins negatively regulate c-myb expression in T-cell lines in contrast to the positive regulation via these sites, which has been shown in fibroblasts. In addition, in a myeloid cell line, the Myb binding sites are nonfunctional.

Base Sequence↗

PubMed1995

Pulmonary scar carcinoma: report of three cases and review of the literature.

Pulmonary scar carcinoma was described as a distinct clinicopathological entity over 50 years ago. There are many theories on the formation of this entity. We present three cases of pulmonary scar carcinoma with a high ratio of adenocarcinoma. One patient had a favorable postoperative course despite a 14-month delay in treatment. Necropsy specimen of another patient showed two primary scar carcinomas unrelated to each other. Literature review and discussion of etiology, diagnosis, and treatment modalities of pulmonary scar carcinoma were done. Pathogenesis and prognosis of the neoplasms associated with apical scars are not clearly understood.

Adenocarcinoma↗

PubMed1995

Balloon dilatation through the subcutaneously placed afferent limb of a hepaticojejunostomy in patients with resected Klatskin tumors.

It is generally conceded that palliation for proximal bile duct tumors (Klatskin) is exceptional if obstruction and the resultant infections can be prevented. Our experience with balloon dilatations thru the subcutaneously placed afferent limb of a choledocho or hepatico jejunostomy in patients with benign strictures suggests that this approach will be effective in patients with malignancies and thus provide long-term control of the obstruction without the need for external tubes. This is a report on one patient who, following a resected Klatskin tumor with positive margins, was treated with transhepatic internal external stents and was converted to a subcutaneous limb following numerous bouts of cholangitis. A schedule for repeat dilatations thru the jejunal limb was established. The patient has remained afebrile with a normal bilirubin and a moderately elevated alkaline phosphatase. Recurrent tumors or postirradiation strictures in patients with resected Klatskin tumors can be effectively controlled by repeated balloon dilatation without the need for external stents.

Aged↗

PubMed1994

Axillofemoral bypass graft in a spinal cord injured patient with impending gangrene.

The axillofemoral bypass graft, an extra-anatomic graft, connects the axillary artery to the femoral artery and is used in the treatment of significant aortoiliac occlusive disease in poor-risk patients. A common indication for axillofemoral bypass is a "hostile abdomen" (postoperative adhesions, neoplasms or radiation). Less frequent indications are aortic mycotic aneurysm, infected aortobifemoral bypass graft, aortoduodenal fistula, inflammatory aneurysm and extensive retroperitoneal fibrosis. Spinal cord injured patients with peripheral arterial disease have two problems: 1) lack of premonitory symptoms (absence of claudication, paresthesias or rest pain) and 2) difficulty preventing pressure sores in the already poorly perfused limb. Indications for arterial reconstructive surgery are more drastic in this set of patients (impending gangrene and/or ischemic ulcers). Many spinal cord injured patients have sources of possible contamination (cystostomy and/or colostomy) which make intra-abdominal clean surgery impossible. We present a spinal cord injured patient with a permanent cystostomy and impending gangrene of the left foot. He underwent a left axillofemoral bypass graft and had a good postoperative course. We conclude that axillofemoral bypass graft is a good alternative for limb salvage in the spinal cord injured patient, especially when there is a source of possible contamination (colostomy and/or cystostomy) that would interfere with more common bypass grafting. The role of the noninvasive vascular laboratory for early detection of vascular disease is emphasized.

Aortic Diseases↗

PubMed1993

Accelerated fractionation in inoperable non-small cell lung cancer. A phase I/II study.

BACKGROUND: A prospective, single-treatment-arm, Phase I/II trial was performed to determine the tumor response to an accelerated regimen and assess the feasibility and toxic effects of this approach in patients with inoperable non-small cell lung cancer (NSCLC). METHODS: Thirty-seven previously untreated patients with inoperable NSCLC who had no evidence of metastatic disease entered the study. All patients were able to walk and had disease that was measurable or assessable. Patients with palpable supraclavicular disease and weight loss were also eligible. Radiation therapy consisted of an altered fractionation regimen with a concomitant boost technique. The original lung volume received a dose of 40 Gy in 20 daily fractions to the computerized axial tomography (CT)-defined primary tumor and mediastinal nodes. The boost dose (10 Gy) was administered concomitantly with the last five fractions of the original volume treatments, with an interfraction interval of 6-8 hours. The maximal allowed dose to the cord was 46 Gy. RESULTS: At a median follow-up of 36 months, complete response was achieved in 29% (9 of 31) of the patients and a partial response in 42% (13 of 31). The overall survival rate at 36 months was 10% (median survival time, 8 months). Survival rates were 25%, 8%, and 0% for the complete responders, partial responders, and nonresponders, respectively. Local failure alone was observed in 35.5% of all patients, local and distant failure in 42%, and distant failure only in 13%. Treatments were well tolerated, and all patients were able to complete the planned regimen. Grade 1 and 2 esophagitis occurred in 65% and 26% of the patients, respectively. The clinical condition of two patients (6%) was compatible with radiation pneumonitis. Moist desquamation of the skin occurred in two patients, but most had either mild (55%) or moderate (19%) skin erythema. Late complications have been limited to radiologically detected lung fibrosis. CONCLUSIONS: The accelerated fractionation schedule used in this trial was well tolerated with shortening of overall treatment time. Local tumor control and overall survival are similar to those resulting from conventional fractionation without an increase in normal tissue effects. These results are encouraging, and additional studies testing higher tumor doses are warranted.

Aged↗

PubMed1993

Clinical experience with electron pseudoarc therapy.

Between November 1986 and June 1990, 24 patients were treated with electron pseudoarc therapy at McGill University. There were 21 females and three males aged 27 to 81 years (median 62 years). 17 patients, nine of whom had received previous conventional locoregional irradiation, were treated palliatively for locally extensive breast carcinoma. Eight of these 17 patients achieved a complete, and six a partial, response to treatment; nine subsequently developed evidence of progressive disease within the treatment field after intervals of one to 27 months (median 5 months) following therapy. Eight patients developed moist desquamation of the treated chest wall, which was extensive in four; one of these patients developed chronic ulceration of the skin. The latter and one additional patient developed radiation pneumonitis. Seven patients were treated with radical intent, two following mastectomy for breast carcinoma, and one each for chest wall lymphoma, chest wall sarcoma, scalp angiosarcoma, scalp lymphoma and posterior cervical soft tissue sarcoma. Local control was achieved in six of these seven patients with minimal toxicity. Electron pseudoarc therapy is a treatment option for selected breast carcinoma patients for palliation of extensive chest wall disease, although morbidity may be considerable. The technique may, however, play a more useful role in other situations where the superficial portion of large curved surfaces is to be treated with curative intent.

Adult↗

PubMed1993

Schistosomiasis and vascular alterations of the colonic mucosa.

The diagnosis of schistosomiasis is made by identification of Schistosoma in stool and urine, or by colonic or hepatic biopsies. The authors demonstrate in this paper, however, that it is also possible to suspect this disease by colonoscopy, i.e., by macroscopic observation of the vascular alterations in the mucous membrane of parasite infected patients. Out of 33 patients -21 with schistosomiasis and 12 with other intestinal parasitoses--the endoscopist correctly diagnosed Schistosomiasis in 18 (85.7%) patients, although he had no previous experience of the diagnosis. Since this infection is widespread throughout the world, these endoscopic findings are important; they may help the physician correctly diagnosis schistosomiasis in non-endemic areas where the diagnosis may not be suspected.

Adult↗

PubMed1991

Detection of clinically suspected deep vein thrombosis using light reflection rheography.

Venography is the current standard for the diagnosis of deep vein thrombosis (DVT). Noninvasive tests have differing sensitivity and specificity, are technically demanding, and may be subject to variability in interpretation. Light reflection rheography (LRR) is a noninvasive method utilizing light-emitting diodes and a sensor to measure light reflected from the skin surface. The intensity of reflected light establishes a graphic pattern that indirectly quantifies parameters of venous function by measuring changes in the microcirculation. Seventy-two patients who underwent contrast venography at our institution were also evaluated with LRR. Twenty-four patients were found to have DVT as demonstrated by venography. Of these, 23 also had DVT detected by LRR. No evidence of thrombus was seen in 45 patients studied by venography; in this group, 35 had normal venous emptying indicated by LRR. Using LRR, a sensitivity of 96% was achieved in the evaluation of clinically suspected DVT. This sensitivity is comparable with other noninvasive tests. In addition, LRR is easy to operate, portable, inexpensive, and not technically demanding. Further investigation is needed to confirm these data and further define the role of LRR in the evaluation of clinically suspected DVT.

Adult↗

PubMed1991

Physical aspects of the angle-beta concept in electron arc therapy.

A technique for the determination of treatment parameters that are required to achieve a desired depth dose distribution in electron arc therapy is discussed and a method for calculating isodose distributions is presented. Both the treatment technique and the dose calculation method rely on the angle beta concept, which uniquely describes the dependence of the radial percentage depth doses in electron arc therapy on the nominal field width, isocenter depth, and virtual source-axis distance. The angle beta concept is discussed in detail and the electron pseudo-arc therapy technique used at McGill is described. Also presented is the method used to achieve dose homogeneity in target volumes treated with the pseudo-arc technique.

Electrons↗