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Biomedical subjects

J Guerra

Publications and source records attributed to J Guerra.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Inhibition of alveolar macrophages by pentoxifylline.

BACKGROUND AND METHODS: Pentoxifylline can inhibit blood leukocyte functions in vitro, and some inflammatory processes in the lung in vivo. Therefore, we examined the effects of pentoxifylline on alveolar macrophage functions in vitro. Alveolar macrophages were harvested from normal rat lungs by airway lavage. The dose-response relationship of varying concentrations of pentoxifylline and in vitro cell functions were examined. Macrophage functions studied included adherence to nylon wool, random (unstimulated) and zymosan-activated serum-stimulated migration through 5 microns millipore filters, and superoxide generation induced by zymosan-activated serum as assayed by cytochrome c reduction. RESULTS: Pentoxifylline inhibited superoxide generation and stimulated migration (but not random migration or adherence) in a dose-dependent fashion. Statistically significant inhibition was demonstrated at 0.5 mM and 5.0 mM concentrations of pentoxifylline, respectively, for stimulated migration and superoxide generation. CONCLUSIONS: Pentoxifylline can inhibit some alveolar macrophage functions in vitro. These effects may inhibit some forms of inflammatory lung injury, particularly when iv infusion of high doses of pentoxifylline are utilized. However, potentially adverse effects on inflammatory defense mechanisms must be considered as well.

Animals↗

A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.

BACKGROUND: For patients with locally or regionally advanced non-small-cell lung cancer radiation is the standard treatment, but survival remains poor. We therefore conducted a randomized trial to determine whether induction chemotherapy before irradiation improves survival. METHODS: All the patients had documented non-small-cell cancer of the lung with Stage III disease established by clinical or surgical staging. Eligibility requirements included excellent performance status, minimal weight loss, and visible disease on radiography. Patients randomly assigned to group 1 received cisplatin (100 mg per square meter of body-surface area given intravenously on days 1 and 29) and vinblastine (5 mg per square meter given intravenously on days 1, 8, 15, 22, and 29) and then began radiation therapy on day 50 (60 Gy over a 6-week period). Patients assigned to group 2 received the same radiation therapy but began it immediately and received no chemotherapy. RESULTS: The eligible patients in group 1 (n = 78) and group 2 (n = 77) were comparable in terms of age (median, 60 years), sex, performance status, histologic features, stage of disease, and completeness of radiation therapy. The median survival was greater for those in group 1-13.8 versus 9.7 months (P = 0.0066 by log-rank test). Rates of survival in group 1 were 55 percent after one year, 26 percent after two years, and 23 percent after three years, as compared with 40, 13, and 11 percent, respectively, in group 2. Those in group 1 had a higher incidence of serious infections requiring hospitalization (7 percent, vs. 3 percent in group 2) and severe weight loss (14 percent vs. 6 percent), but there were no treatment-related deaths. CONCLUSIONS: In patients with Stage III non-small-cell lung cancer, induction chemotherapy with cisplatin and vinblastine before radiation significantly improves median survival (by about four months) and doubles the number of long-term survivors, as compared with radiation therapy alone. Since three quarters of the patients still die within three years, however, further improvements in systemic and local therapy are needed.

Antineoplastic Combined Chemotherapy Protocols↗

Hepatic cirrhosis and hepatitis: MR imaging enhanced with superparamagnetic iron oxide.

Superparamagnetic iron oxide was applied as a reticuloendothelial contrast agent in the diagnosis of cirrhosis and hepatitis in seven patients. Three patients had compensated cirrhosis, and four had active hepatitis. T1- and T2-weighted spin-echo magnetic resonance images were obtained before and 1 hour after the administration of iron oxide. Eight patients without diffuse liver disease served as a control group. Normal liver tissue showed a 75% +/- 9% reduction in signal intensity after the administration of iron oxide, and the liver appeared homogeneously hypointense. Cirrhotic liver tissue showed a smaller response (P less than .05) to iron oxide, with a 52% +/- 13% reduction in liver signal intensity. Inhomogeneous structures could be observed in enhanced images and are thought to represent fibrous bands or regenerating nodules. Liver tissue with active hepatitis showed a markedly reduced response to iron oxide (11% +/- 2%) (P less than .05), and the parenchyma appeared homogeneous. The authors conclude that the uptake of iron oxide particles is inhomogeneously altered in cirrhosis because of structural changes and homogeneously decreased in hepatitis because of functional changes of hepatic parenchyma.

Contrast Media↗

[Famotidine in the treatment of duodenal peptic ulcer].

A multicenter, open study was designed to evaluate the efficacy and tolerability of a novel and potent H2 receptor antagonist, Famotidine, in the treatment of duodenal ulcer. Thirty-four patients with endoscopically proven active duodenal ulcer were treated with Famotidine, 40 mg, one tablet, at bedtime, for six weeks. Follow-up endoscopic exams were done every two weeks until ulcer healing was obtained. One patient was excluded from further analysis as he failed to follow the protocol. Healing rates achieved were 48.5%, 91% and 97% by the second, fourth and sixth week of treatment respectively. After 72 hours 52% of the patients were asymptomatic and 79% at the end of the first week of treatment. Famotidine was well tolerated, no clinical neither laboratory adverse events were observed during the study. Famotidine, a novel H2 receptor antagonist appears to be effective and well tolerated in the treatment of most patients with duodenal ulcer.

Adult↗

Rapid serial enzyme measurements in evaluation of patients with suspected myocardial infarction.

Because clinical and laboratory criteria cannot accurately establish the presence or absence of acute myocardial infarction (AMI) at the time of initial presentation, this diagnosis is not confirmed in the majority of patients admitted to coronary care units. To study the effectiveness of serial changes in enzyme activity in specimens taken at presentation and 8 hours later in establishing the likelihood of AMI, the results in 1,214 patients with acute cardiac symptoms of less than 24 hours' duration were retrospectively evaluated. In 1,007 patients with initially normal creatine kinase (CK), an increase in CK (positive delta-CK) occurred in 98% of patients with AMI and 16% of patients without AMI. In 196 patients with elevated total CK, a low ratio of CK to aspartate aminotransferase was found in 98% of patients with AMI and 33% of patients without AMI. These 2 enzyme ratios had a sensitivity greater than 90% in patients with typical and atypical histories. The overall predictive value of serial enzyme measurements for AMI was 53%, compared with 18% in patients selected for admission. These results suggest that serial enzyme measurements could be used in the initial evaluation of patients with suspected AMI, and have the potential to reduce the number of patients admitted to coronary care units who do not have AMI.

Aspartate Aminotransferases↗

Results of surgery for obstructing carcinomatosis of gastrointestinal, pancreatic, or biliary origin.

Results of operation for obstructing carcinomatosis of gastrointestinal (GI), pancreatic, or biliary origin were reviewed to assess relief of symptoms, management of re-obstruction, and duration of hospitalization. A retrospective review (1977 to 1986) identified 89 patients, 59 (66%) of whom had tumors originating in the colon, and 19 (21%) in the stomach. Normal bowel function was restored for a median of 102 days in 66 patients (74%) and all but four (94%) were discharged. Forty-one (46%) patients remained unobstructed until death. Twenty-three (26%) were not relieved by operation and died a median of 33 days later (P less than .005). Forty-eight (81.4%) of the 59 colon cancer patients and ten (52.6%) of 19 with gastric cancer (P less than .05) were benefited by the operation, although comparison of duration of function was less striking (P less than .1). In-hospital mortality was 13% and complications occurred in 44%. Obstruction recurred in 38% of those relieved by the initial operation. Normal bowel function was restored in six (46%) of 13 patients undergoing a second laparotomy (median, 158 days) and in six of 13 (46%) treated with nasogastric suction. Obstruction recurred again in four of the latter six patients (median, 39 days). Hospitalization averaged 31 days (median, 25 days) for the first procedure and 41 days (median, 39 days) for patients operated for recurrent obstruction. These results justify laparotomy for intestinal obstruction in known or suspected carcinomatosis, particularly of colonic origin, if performance status is compatible with a reasonable quality of life.

Adenocarcinoma↗

[Epidemiological and clinical features of brucellosis in 39 family groups].

Clinical epidemiological evaluations on brucellosis, done during the last five years in endemic areas in Lima (Peru), in 39 families with 232 members, have let us observe a high rate of symptomatic infection 118/232 (50.9%) and has also let us identify, as risk factors to contract the disease; age older than 10 years 97/190 (56.3%) versus 11/42 (26.1%); in younger than 10 years of age (p less than 0.05) and families with 5 or less members 40/54 (74.0%) versus 78/175 (44.5%) of more numerous families (p less than 0.001), and also to be exposed to a common source as a form to contract the disease. We observed the importance of an adequate treatment in early stages of the disease. We detected major clinical gravity in women 23/55 than in men 5/38 (p less than 0.01), specially in brucellar arthritis (p less than 0.05). Period of time between the appearance of index case and secondary cases was of 33.8 days, but range was of 1-115 days. The heterogeneous aspects of the disease between members of the same family, suggest that response of host, more than bacterial virulence, is so important in the clinical course of the disease.

Adolescent↗