Biomedical subjects
A Gabriel
Publications and source records attributed to A Gabriel.
[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.
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.
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.
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.
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).
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.
[Postoperative delirium following vascular surgery. Comparative results in a prospective study].
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[Assessment of usefulness of PCNA and protein p53 in subjects with laryngeal cancer with local recurrence].
The authors estimated PCNA and P53 in subjects with laryngeal cancer in whom local or nodal recurrences were observed. The study included 54 patients from Upper Silesia in age 37-79 years (mean 57 +/- 8.8). The mean value of the PCNA index in subjects with local recurrence (LR) was 24.2% +/- 12.1 while in subjects without LR 22.1% +/- 9.4 (p > 0.05). Additionally, 21 subjects were separated from the investigated group in whom no lymph node metastases were found during laryngectomy. Among these subjects in 16 LR was observed (PCNA index was 30.9% +/- 12.5) while in remaining 5 subjects, in whom LR did not develop, PCNA index was 21.7% +/- 11.2. Analysis of the P53 index in subjects with LR revealed significantly higher values (19.2% +/- 9.1) in comparison to cases without LR (13.2% +/- 6.3). Our study revealed usefulness of the P53 and PCNA as markers which could support the histological diagnostic process describing biology of the cancer cells. The demonstrated increase of PCNA and P53 index in patients with LR might be useful in prediction of LR.
[Precancerous states of the larynx: analysis of mono- and polyclonality of the cells with high proliferative index (p53, PCNA)].
The aim of the study was analysis of relationship between proliferation index (PCNA) and protein p53 content in dysplastic laryngeal epithelium and the degree of dysplasia, age of patients and smoking. The study population consisted of 45 patients (mean age 57.7 +/- 6.2) with chronic laryngitis. It was revealed epithelial dysplasia varying in intensity in 36 patients and epithelial hyperplasia without dysplasia (acanthosis) in 9 patients--control group. Mean value of p53 protein index was 8.91 +/- 7.43% in dysplastic epithelium and 3.67 +/- 3.4 in hyperplastic epithelium without dysplasia. The difference was statistically significant (p = 0.007). P53 content significantly differed between groups with grade I and grade II dysplasia (p = 0.03) and between groups with grade I and grade III dysplasia (p = 0.03). The difference was found between groups with grade II and III dysplasia and group with hyperplasia without dysplasia. The analysis of the correlation between degree of dysplasia and value of PCNA index showed absence of differences. There was no relationship between smoking, age of patients and Value of p53 and PCNA index.
[The prospective analysis of laryngeal cancer growth dynamics in compliance with evaluation of DNA content and ploidy in cytologic material].
The aim of this study was evaluation of DNA ploidy in the cytological samples from patients with laryngeal cancer and comparison a type of DNA ploidy with histological grading (G) and staging of neoplasmatic process. The examinations were performed on 47 patients operated due to laryngeal cancer (3 women, 44 men, mean age 58). Cytological material was collected from squamous carcinoma tissue by imprinting method. Slides were staining by Feulgen method in order to quantitative analysis of DNA by static cytophotometry. In studied material, aneuploid, polyploid and hypoploid tumors were found in 22 patients and diploid tumors were found in 25 cases. Analysis of DNA ploidy type distribution in correlation to G feature showed:--diploid type were dominated in G1 and G2 tumors,--aneuploid and polyploid type were dominated in G3 tumors. Hypoploid and polyploid tumors were appeared in patients with metastases to cervical lymph nodes more frequently than in patients without metastases. Analysis of DNA ploidy complete traditional histopathological diagnosis of laryngeal cancer and may be useful in predicting metastases to cervical lymph nodes.
[Assessment of utility of nm 23 antigen as a metastatic potential marker in laryngeal cancers: preliminary study].
The aim of the study was the analysis of the utility of nm 23 protein in prediction of cervical lymph node metastases in patients with laryngeal cancer. A preliminary study was performed in 35 patients with laryngeal cancer with cervical lymph node metastases, which were confirmed by histopathologist. The control group consisted of 30 patients with laryngeal cancer without cervical lymph node metastases. In statistical analysis T and N were taken into account. In the investigated group with metastases the presence of positive immunostaining was found in 11% of cases while in the control group in 20%. The analysis of the presence of nm 23 protein revealed a weak usefulness of this marker as a factor which predicts the presence of the cervical metastases.
[Assessment of usefulness of PCNA and oncoprotein p53 staining in prediction of the recurrences in subjects operated on for laryngeal carcinoma].
The authors estimated PCNA and P53 in subjects with laryngeal cancer with local or nodal recurrences. The study concerned 54 patients from Upper Silesia aged 37-79 (mean 57 +/- 8.8). The mean value of the PCNA index in subjects with local recurrence (LR) was 24.2% +/- 12.1 while in subjects without LR 22.1% +/- 9.4 (p > 0.05). Additionally, 21 subjects in whom no lymph node metastases were found during laryngectomy were separated from the investigated group. In 16 of them local recurrences were observed and the mean value of PCNA index was 30.9% +/- 12.5. In remaining 5 subjects in whom local recurrences were not developed the mean value of PCNA index was 21.7% +/- 11.2. The analysis of the P53 index in subjects with LR revealed significantly higher values (19.2% +/- 9.1) in comparison with cases without LR (13.2% +/- 6.3). The assessment of the mean values of PCNA and P53 index depending on T, N or stage as well as nodal recurrence did not reveal any statistical significance. Our study revealed usefulness of the P53 and PCNA as markers which could support the histological diagnostic process describing biology of the cancer cells. The demonstrated increase of PCNA and P53 index in patients with LR might be useful in prediction of LR.
Absence of Brca2 causes genome instability by chromosome breakage and loss associated with centrosome amplification.
Women heterozygous for mutations in the breast-cancer susceptibility genes BRCA1 and BRCA2 have a highly elevated risk of developing breast cancer [1]. BRCA1 and BRCA2 encode large proteins with no sequence similarity to one another. Although involvement in DNA repair and transcription has been suggested, it is still not understood how loss of function of these genes leads to breast cancer [2]. Embryonic fibroblasts (MEFs) derived from mice homozygous for a hypomorphic mutation (Brca2(Tr2014)) within the 3' region of exon 11 in Brca2 [3], or a similar mutation (Brca2(Tr)) [4], proliferate poorly in culture and overexpress the tumour suppressor p53 and the cyclin-dependent kinase inhibitor p21(Waf1/Cip1). These MEFs have intact p53-dependent DNA damage G(1)-S [3] [4] and G(2)-M checkpoints [4], but are impaired in DNA double-strand break repair [3] and develop chromosome aberrations [4]. Here, we report that Brca2(Tr2014/Tr2014) MEFs frequently develop micronuclei. These abnormal DNA-containing bodies were formed through both loss of acentric chromosome fragments and by chromosome missegregation, which resulted in aneuploidy. Absence of Brca2 also led to centrosome amplification, which we found associated with the formation of micronuclei. These data suggest a potential mechanism whereby loss of BRCA2 may, within subclones, drive the loss of cell-cycle regulation genes, enabling proliferation and tumourigenesis.
Fidelity of retrotransposon replication.
Ty1, the genetically tractable retrotransposable element found in the yeast Saccharomyces cerevisiae, closely resembles vertebrate retroviruses both in structure and in mechanism of replication. By direct sequence analysis, we examined the rate and spectrum of new mutations appearing during a single cycle of Ty1 replication. The rate of new mutations was comparable to those seen for replicating retroviruses. All observed changes were base substitutions, and their location suggested that template ends may be hot spots for generating these mutations. To test this, we developed methods to examine, at the nucleotide level, the end structure of the expected Ty1 replication intermediates. Our results demonstrate that Ty1 reverse transcriptase can add terminal non-templated bases in vivo during each step in replication. Furthermore, Ty1 RNAse H creates multiple template ends by imprecisely cleaving RNA. This expands the range of sites of subsequent non-templated base addition. Finally, on reaching template ends, Ty1 reverse transcriptase can strand transfer to inappropriate templates. Taken together, these mutagenic mechanisms may influence the evolution of particular regions of the Ty1 genome and serve as a mechanism to regulate the overall level of Ty1 transposition in its host cell.
Recurrent DNA copy number losses associated with metastasis of larynx carcinoma.
Squamous cell carcinomas of the head and neck show frequent and complex chromosome aberrations, but little is known about the changes that occur during the metastatic process. To compare the accumulation of changes in primary and metastatic tumors we analyzed 19 pairs of primary larynx cancer tumors and their metastases. The most frequent changes were found at 3p, 3q, 5p, 9, and 13. Losses at 13, 8p, and 9q were more frequent in metastases than in primary tumors.
Upper posterior mediastinal tumor supplied by an atrial branch of the left circumflex artery.
We report a case of a 39-year-old woman with an upper posterior mediastinal tumor. The tumor was demonstrated by echocardiography and further defined by computerized tomography and magnetic resonance imaging. The tumor was fed by a large atrial branch of the left circumflex artery. Because of its location (adjacent to large vessels), it could not be resected by surgery.
Clinical application of proliferating cell nuclear antigen, oncoprotein p53 and tumor front grading analysis in patients operated on for laryngeal cancer.
The authors assessed proliferating cell nuclear antigen (PCNA), p-53 oncoprotein and morphologic tumor front grading (TFG) in patients with advanced squamous cell carcinoma (SCC), of the larynx and a poor prognosis and tried to find a correlation with tumor stage, the Broders grading system, local and neck lymph node metastases, as well as nodal and local recurrences. In addition, utility of the parameters investigated was evaluated in developing a prognostic factor model, using uni- and multivariate Cox regression analysis. Included in this study were 54 patients (mean age 57 years +/- 8.6). PCNA-positive staining was found in all but one patient with advanced disease, while p-53 stained positively in only 24 subjects (44.4%). The PCNA index ranged from 4.6 to 59.0% (mean, 23.4 +/- 11. 0) and the p-53 index varied from 4.0 to 42.0% (mean, 17.2 +/- 8.6). The TFG score ranged from 9 to 23 points (mean, 15.1 +/- 3.2). PCNA, p-53 and TFG were found to be the markers that provided significant additional information about the biological behavior of tumor cells. The high variability of the results (PCNA, p-53) and high percentage of negatively stained cells (p-53) reduced their application in clinical use. PCNA correlated with tumor grade, G (r = 0.38; P < 0. 01), but negatively with nodal (N) disease(r = -0.37; P < 0.01). The mean values of PCNA and p-53 index were higher in the subgroup with local recurrences. Our present attempt to develop a useful prognostic factor model failed.