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Biomedical subjects

A Gabriel

Publications and source records attributed to A Gabriel.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Adrenergic beta-Antagonists↗
PubMed2001

Comparative pathogenesis of acute and latent infections of calves with bovine herpesvirus types 1 and 5.

This study was conducted to compare the pathogenesis of acute and latent infections with closely related bovine herpesvirus types 1 (BHV-1) and 5 (BHV-5) in their natural host. Two groups of eight calves were inoculated intranasally with BHV-1 or BHV-5. Although BHV-1 and BHV-5 similarly replicate in the nasal mucosa after inoculation, both viruses differ markedly in their ability to cause disease, BHV-5 being responsible of some fatal encephalitis while BHV-1 inducing rhinotracheitis. Virus isolation and immunohistochemistry demonstrated that BHV-5 replicates extensively in neurons of the central nervous system (CNS) and in respiratory cells of lungs, tracheal and nasal mucosae. Invasion of the CNS likely occurs through the trigeminal and olfactory pathways. Both groups developed cross-neutralising antibodies during this experiment suggesting partial clinical cross-protection afforded by the two infections. Three months after primary infection, experimental reactivation showed that BHV-5 was able to establish latency in the trigeminal ganglia but also the CNS of surviving calves. Moreover, laboratory findings suggested that BHV-5 could also persist in the tracheal and nasal mucosae. These results indicate that, after primary infection, BHV-1 and BHV-5 displayed similar biological features and consequently need to be considered together for the control of BHV-1 infection.

Acute Disease↗
PubMed2001

Bi-directional modulation of 5-hydroxytryptamine-induced plasma extravasation in the rat knee joint by nociceptin.

The role of nociceptin, the endogenous ligand for the opioid receptor-like (ORL1) receptor, in nociceptive processing is controversial. Most studies demonstrate hyperalgesia following supraspinal administration, analgesia following intrathecal and peripheral administration at higher doses, and hyperalgesia following intrathecal and peripheral application at lower doses. The present study investigates the effect of nociceptin on synovial plasma extravasation and its ability to modulate 5-hydroxytryptamine-induced synovial plasma extravasation using the rat knee joint model of inflammation. Nociceptin alone does not alter synovial plasma extravasation from baseline. Nociceptin at concentrations up to 1 nM enhances 5-hydroxytryptamine-induced synovial plasma extravasation (up to 50%) and nociceptin at concentrations above 100 nM inhibits 5-hydroxytryptamine-induced synovial plasma extravasation (down to 45%). The novel, selective ORL1 receptor antagonist J-113397 potently inhibits the pro-inflammatory effect of nociceptin, but only partly inhibits, at higher concentrations, the anti-inflammatory effects of nociceptin.These findings demonstrate a dose-dependent bi-directional effect of nociceptin on inflammatory processes and may indicate a target for novel therapeutics.

Animals↗
PubMed2001

[Treatment for acute renal failure--concepts and controversies. 1. Pharmacologic treatment and experimental strategies].

Acute renal failure is the common result of various damaging mechanisms. Prophylaxis and differentiated therapy of acute renal failure are of outmost importance in anaesthesiology and intensive care medicine. The efficiency of pharmacotherapy is narrowly limited. Diuretics increase the urine output, but they do neither ameliorate the clinical course of the patient nor the prognosis of established acute renal failure. Dopamine and natriuretic peptides have no use in prevention and treatment of acute renal failure. Calcium-channel-blockers are valuable in cadaveric kidney transplantation. Osmodiuretics prevent intratubular precipitation of hemoglobin and myoglobin crystals; they also have some value in cadaveric kidney transplantation. Experimental studies investigated the possibility to enhance the regeneration of the tubular epithelial cell. Whereas in vitro studies and studies in animal models using various growth factors yielded promising results, these could not be reproduced in patients with acute renal failure. The physiology of NO in the kidney is incompletely understood. Actual progress is made in the understanding of lipid peroxidation and potential pharmacological implications. The mainstay for the assurance of high-quality patient care remain a vigilant identification of the patient at risk and an arduous search to avoid nephrotoxic substances and situations implicating potential renal damage.

Acute Kidney Injury↗
PubMed2001

[Treatment of acute renal failure--concepts and controversies. 2. Extracorporeal renal replacement and peritoneal dialysis].

Therapy of prolonged acute renal failure regularly requires a renal replacement therapy. This can be achieved by different extracorporal renal replacement therapies (ERRT) or by peritoneal dialysis. ERRT are classified according to the physical principle underlying toxin elimination as hemodialysis (diffusion) and hemofiltration (convection). Another classification refers to intermittent or continuous application modes. Biocompatibility of membranes is judged according to their activation of the complement system. Prospective randomized studies did not consolidate the assumptions about the benefit of particular modalities proposed on theoretical foundations. Mortality, duration and complication rates of acute renal failure are not significantly decreased by use of biocompatible membranes. Continuous modalities are not generally preferable but optimize treatment in hemodynamically unstable patients, in whom they endorse fluid balancing and maintenance of sufficient arterial blood pressure. The use of demanding hemofiltration techniques for cytokine removal should be limited to clinical studies. The effects of ERRT-"intensity" and the best timing for initiation of ERRT have not been evaluated sufficiently. The choice of the ERRT modality is subject to clinical judgement (criterion: hemodynamic situation), practical aspects (criteria: availability of equipment and handling experience), and costs. Prior to their general use new and expensive technical modalities and membrane types should be thoroughly evaluated in studies with regard to outcome-related aspects such as patient survival and preservation of renal function.

Acute Kidney Injury↗
PubMed2001

Effect of total venous occlusion on capillary flow and necrosis in skeletal muscle.

Limb replantation and microvascular transfer of flaps are sometimes complicated by postoperative venous thrombosis. Total venous occlusion can lead to complete shutdown of microvascular perfusion, resulting in failure of the transfer or replantation. Once venous return stops, it must be restored within a critical period of time for tissue survival. The purpose of this experiment was to delineate this critical period of time at which no reflow and irreversible muscle necrosis occurs by the use of a rat gracilis flap microcirculation model. The gracilis muscle of 40 male Wistar rats (135.3 +/- 37.2 g) was elevated on its vascular pedicle and mounted on a raised platform for videomicroscopic analysis. Animals were randomly assigned to one of four groups: (1) sham (no total venous occlusion), (2) 10 minutes of total venous occlusion, (3) 30 minutes of total venous occlusion, and (4) 60 minutes of total venous occlusion. Total venous occlusion was established by placing a microvascular clamp across the femoral vein at the junction of the gracilis pedicle. The number of flowing capillaries in five consecutive high-power fields (832x) were counted at baseline and at 5, 15, 30, 60, 120, 180 minutes, and 24 hours after reperfusion. At 24 hours after reperfusion, the gracilis muscles were harvested and stained with nitroblue tetrazolium. Percentage of muscle necrosis was measured by using computer planimetry. The data were reported as mean +/- standard error of mean and were compared between groups by analysis of variance and appropriate post hoc comparisons. Total venous occlusion for 10, 30, and 60 minutes showed a significant decrease in the number of flowing capillaries through 24-hour postreversal. There was a significant drop (p < 0.01) in the number of flowing capillaries from 30 minutes of total venous occlusion to 60 minutes of total venous occlusion at all times. Muscle necrosis was significantly increased in all three groups of total venous occlusion compared with the sham group (36.1 +/- 1.7 percent, 45.5 +/- 3.4 percent, 74.1 +/- 4.7 percent versus 14.3 +/- 1.7 percent, and p < 0.01). These results indicate that irreversible tissue damage occurs in a very short time interval (60 minutes) in this model, making the early detection of venous occlusion critical to the successful correction of this complication.

Animals↗
PubMed2001

A short pseudoautosomal region in laboratory mice.

The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis. During female meiosis, X chromosomes can pair and recombine along their entire length; recombination in the PAR is therefore approximately 10x greater in male meiosis compared with female meiosis. A consequence of the presence of the PAR in two copies in males and females is that genes in the region escape the process of X-inactivation. Although the structure and gene content of the human PAR at Xq/Yq is well understood, the mouse PAR, which appears to be of independent evolutionary origin, is poorly characterized. Here we describe a yeast artificial chromosome (YAC) contig covering the distal part of the mouse X chromosome, which we have used to define the pseudoautosomal boundary, that is, the point of divergence of X-specific and X-Y-identical sequences. In addition, we have investigated the size of the mouse PAR by integrating a unique restriction endonuclease recognition site just proximal to the pseudoautosomal boundary by homologous recombination. Restriction digestion of this modified DNA and pulsed field gel electrophoresis reveal that the PAR in these cells is approximately 700 kb. Thus, the mouse PAR, although small in size, has retained essential sex chromosome pairing functions despite its rapid rate of evolution.

Animals↗
PubMed2001

A Ty1 reverse transcriptase active-site aspartate mutation blocks transposition but not polymerization.

Reverse transcriptases (RTs) are found in a wide variety of mobile genetic elements including viruses, retrotransposons, and infectious organellar introns. An invariant triad of aspartates is thought to be required for the catalytic function of RTs. We generated RT mutants in the yeast retrotransposon Ty1, changing each of these active-site aspartates to asparagine or glutamate. All but one of the mutants lacked detectable polymerase activity. The novel exception, D(211)N, retained near wild-type in vitro polymerase activity within virus-like particles but failed to carry out in vivo transposition. For this mutant, minus-strand synthesis is impaired and formation of the plus-strand strong-stop intermediate is eliminated. Intragenic second-site suppressor mutations of the transposition defect map to the RNase H domain of the enzyme. Our results demonstrate that one of the three active-site aspartates in a retrotransposon RT is not catalytically critical. This implies a basic difference in the polymerase active-site geometry of Ty1 and human immunodeficiency virus RT and shows that subtle mutations in one domain can cause dramatic functional effects on a distant domain of the same enzyme.

Amino Acid Substitution↗
PubMed2001

Bcl-2 antigen expression in patients with chronic hepatitis C and advanced fibrosis.

Bcl-2 antigen is a proto-oncogene responsible for the inhibition of the death of cells in the mechanism of apoptosis. The expression of bcl-2 antigen was analysed in liver bioptates obtained from patients with chronic hepatitis C. Thirty-five patients with advanced fibrosis (bridging fibrosis or cirrhosis) and various inflammatory activity were investigated. Control group was formed of the subjects with minimum or non-existent fibrosis. Histological and immunohistochemical assessments were performed with the use of widely-acceptable methods. The expression of bcl-2 antigen within portal spaces and lobules was evaluated. The values of lobular index declined as the fibrosis increased. As far as portal space index is concerned, no significant changes in correlation with fibrosis advancement were noticed. Additionally, the expression of bcl-2 antigen was recorded within lymphocyte infiltrations in lobules and portal spaces, in the epithelium of bile ducts in portal spaces and proliferating bile ductules in lobules as well as in perisinusoid cells. In hepatocytes, bcl-2 expression was detected more often among controls than in the analysed patients. The expression of bcl-2 antigen is directly proportional to the degree of inflammatory activity and it is inversely proportional to the degree of fibrosis. It seems that positive colour reaction with bcl-2 antigen in lobules may be of prognostic value for the prediction of collagen fibroplasia development. Bcl-2 expression in portal spaces has a limited diagnostic value for the prediction of the scope of fibrosis in patients with chronic hepatitis C.

Antigens↗
PubMed2000

[Delirium after vascular surgery interventions. Intermediate-term results of a prospective study].

INTRODUCTION: Postoperative delirium is a common psychic disturbance occurring acutely after various surgical procedures and typically presenting with a fluctuating course. These patients' recovery takes longer. In this study we analyze the incidence of postoperative delirium in patients undergoing vascular surgery and try to identify risk factors for its development. METHODS: Patients undergoing elective arterial operations were included. Their medical history, the specific vascular diagnosis and operation performed, the medication and laboratory data were monitored. Additionally the patients were preoperatively interviewed by a psychiatrist. Intraoperatively the drugs, infusions, possible transfusions, blood gases and pressures were monitored, as were the times of surgery and anesthesia. Postoperatively patients were seen daily by the psychiatrist and the surgeon for at least 7 days. Postoperative delirium was diagnosed according to DSM IV criteria, and mild, moderate and severe delirium were distinguished. RESULTS: Fifty-four patients entered the study. Twenty-one (38.9%) developed postoperative delirium (11 mild, 2 moderate, 8 severe). Patients with aortic operations developed delirium more frequently than those with non-aortic procedures(55.5 vs 22.2%, n = 27 each). Some preexisting diseases (hearing disturbance) increased the probability of postoperative delirium, while age was not identified as a risk factor. General psychopathological and depressive disturbances increased the likelihood of postoperative delirium. Patients who had a severe intraoperative course developed postoperative delirium more frequently. This was not seen in the absolute time of surgery or anesthesia nor in the intraoperative development of blood pressure or intraarterial gases, which did not differ between patients with and without postoperative delirium. More reliable parameters were an increased intraoperative need for crystalloid volume, intra- or postoperatively decreased hemoglobin values (Hb < 10 g/dl) and the development of acidosis that had to be treated. Patients with delirium had serious complications more often (8/21 = 38.1% vs 6/33 = 18.2%) and needed Intensive Care treatment longer (2.7 vs 2.1 days, only aortic surgery 3.2 vs 2.4 days). CONCLUSIONS: Postoperative delirium after vascular surgery is frequent. Patients undergoing aortic surgery, with specific concomitant medical disease, psychopathological disturbances and a severe intraoperative course, are at risk of developing postoperative delirium.

Aged↗
PubMed2000

Fast oscillations display sharper orientation tuning than slower components of the same recordings in striate cortex of the awake monkey.

We wanted to know whether fast oscillations ( approximately 30-80 Hz) in striate cortex of awake monkeys show sharper orientation selectivity than (i) slower components, including spike rate modulations, and (ii) broad-band signals of the same recordings. As fast oscillations are probably of cortical origin this may further clarify whether cortical network mechanisms are substantially involved in generating orientation selectivity. We recorded multi unit activity (MUA) and local field potentials (LFP, 1-140 Hz) by the same microelectrodes from upper layers of macaque striate cortex during visual stimulation with grating textures of different orientations. An orientation index (OI) was derived from the cortical responses in three frequency ranges (low, 0-11.7 Hz; medium, 11.7-31.3 Hz; and fast oscillations, 31.3-62.5 Hz) and for the broad-band LFP and MUA power. (i) Both LFP and MUA fast oscillations reveal a higher orientation index than signal components in the low and medium frequency ranges. (ii) For MUA the orientation index was significantly higher with fast oscillations than for the lower frequency ranges and the initial broad-band transient responses. (iii) LFPs show a significantly higher orientation index only for the fast oscillations during sustained activation compared with their broad-band power during the transient responses. Thus, our main result is the sharper orientation tuning of fast oscillations in spike activities of local populations compared with slower components of the same broad-band recordings. As fast oscillations occur synchronized in the awake monkey's striate cortex we assume that they have enhanced probability of activating successive stages of visual processing and hence contribute to the perception of orientation.

Animals↗
PubMed2000

Thymoma--the usefulness of some prognostic factors for diagnosis and surgical treatment.

AIMS: The aim of the study was to identify prognostic factors which could help evaluate both the treatment offered to patients with thymoma and late results. METHODS: Forty patients were treated for mediastinal thymoma. The patients were staged clinico-pathologically (according to Masaoka) on the basis of the retrospective analysis of their operation protocols as follows: seven (17.5%)-stage I, 19 (22. 5%)-stage II, 17 (42.5%)-stage III, seven (17.5%)-stage IV. Analysis of DNA contents in cell nuclei of 23 thymomas was performed by the flow cytofluorometric method. RESULTS: From the whole group of patients, 65% survived for 5 years, 55% survived for 10 years and 43% survived for 15 years. We noted significant differences in survival time between stage I and stage IV (P<0.0012); stage II and stage IV (P<0.0006), as well as between stage III and stage IV (P<0. 005). Significantly worse prognosis was observed in the case of cortical thymomas as compared with medullary or mixed types (P<0. 0001 P<0.002). Analysis of DNA content showed signficantly higher probability of survival for the patients who had DI=1.0 (diploid), as compared with DNA >1.0 (aneuploid) (P<0.006). Of the 11 patients with diploid tumours, 91% survived for 5 years, but of the 12 aneuploid, only 23% survived. CONCLUSION: The most important positive prognostic factors influencing survival rate in patients with thymoma are: lower stage, medullary type (according to Muller-Hermelink classification), possibility of performing complete resection, diploidal nature of the tumour. Multivariate analysis of survival revealed clinico-pathological stage (according to Masaoka) and histological type (according to Salyer) as significantly independent prognostic factors.

Adolescent↗
PubMed2000

Breast cancer progression and expression of blood group-related tumor-associated antigens.

There is sufficient evidence that blood group related Lewis antigens are tumor-associated molecules. We have conducted immunohistochemical analysis of the expression of Lewis antigens in breast cancer tissue as an indicator of the degree of malignancy and as a prognostic factor. The studies were performed by examining 43 female patients diagnosed with invasive ductal carcinoma of the breast. Postoperative specimens were stained immunohistochemically using a panel of monoclonal antibodies (MAbs) specific for tumor-associated antigens: sialosyl LewisA, LewisA, LewisB, Lewisx, and LewisY. The aims of the study were to compare the appearance of metastases, degree of cancer stage (pTNM), and its histologic differentiation with the expression of Lewis phenotype. The evaluation of antigen expression was performed quantitatively and independently by two pathologists. Statistical significance was defined by Mann-Whitney test. The presented analysis of Lewis antigens showed higher expression of LeB and LeA (p = 0.03) in patients in stage N2 than in stage N1. The expression of LeB and LeY was higher in patients in stage T4 than in stage T1 (p = 0.02). No differences were observed for histologic differentiation. These data suggest that the expression of sialosyl-LeA and LeB antigens in breast cancer may predict metastases to lymph nodes.

Antigens, Neoplasm↗
PubMed2000

Traumatic avulsion of kidney into the chest through a ruptured diaphragm in a boy.

This report presents a case of a teenage patient who survived following severe blunt trauma with complete avulsion of the right kidney into the chest through a ruptured diaphragm. The combination of kidney avulsion into the chest is extremely rare. Only three similar cases have been reported in the English literature to date (1-3).

Abdominal Injuries↗
PubMed2000

Nasal continuous positive airway pressure: A method to avoid endotracheal reintubation in postoperative high-risk patients with severe nonhypercapnic oxygenation failure.

OBJECTIVES: To study whether nasal continuous positive airway pressure (nCPAP) improves pulmonary oxygen transfer and avoids reintubation in patients with severe nonhypercapnic oxygenation failure after major cardiac, vascular, or abdominal surgery. DESIGN: Prospective interventional study. SETTING: Surgical ICU of a university hospital. PATIENTS: Twenty consecutive patients after thoracic, abdominal, or combined thoracoabdominal operations, in whom pulmonary oxygen transfer deteriorated continuously following elective extubation after initial mechanical ventilation. Respiratory failure was due to atelectasis and/or left heart failure, and all patients met predefined criteria for reintubation. INTERVENTIONS: nCPAP therapy (8 to 10 cm H(2)O) was initiated if PaO(2) had decreased to < 80 mm Hg despite application of 100% oxygen (flow, 25 L/min), intermittent mask continuous positive airway pressure, and maximum conventional therapy. MEASUREMENTS AND RESULTS: nCPAP treatment was started 24.1 +/- 3.4 h after elective extubation. PaO(2) was < 80 mm Hg in all patients, in 13 patients it was < 60 mm Hg, and in 3 patients it was < 50 mm Hg. Mean PaO(2)/fraction of inspired oxygen (FIO(2)) ratio had decreased to 60 +/- 2.6, and increased within the first hour of nCPAP to 136 +/- 12 (p < 0.001). The clinical condition in all patients improved further, and after 35.2 +/- 6.3 h, all patients were well oxygenated by face mask at ambient pressure (PaO(2)/FIO(2) ratio, 146 +/- 14). Two patients were reintubated for reasons unrelated to oxygenation or ventilation (data are presented as mean +/- SEM). CONCLUSIONS: nCPAP is safe, easy to apply, and effective to improve arterial blood oxygenation in < 1 h in postoperative patients with severe nonhypercapnic oxygenation failure. In these patients, who otherwise would have been reintubated, nCPAP can avoid endotracheal reintubation and mechanical ventilation.

Blood Gas Analysis↗