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Biomedical subjects

R Jacob

Publications and source records attributed to R Jacob.

299 records · Page 17Linked to original sources
PubMedDate not supplied

Calcium oscillations in endothelial cells.

Several different types of endothelial cells are now known to respond to agonist stimulation with oscillations of cytosolic free [Ca2+] ([Ca2+]i). The oscillations can be repetitive [Ca2+]i spikes or sinusoidal-like oscillations according to the type of endothelial cell. Several properties of these oscillations are described including the effect of removal of extracellular Ca2+ and of changes in membrane potential, and the spatial heterogeneity of the oscillations. Results obtained with human umbilical vein endothelial cells are assessed in relation to a model for [Ca2+]i oscillations that involves Ca(2+)-induced Ca2+ release. In some preparations the oscillations are synchronized in neighbouring cells, whereas in other preparations they are not. The degree of synchrony may have functional implications and this is discussed with respect to control of blood flow and transmural permeability. A third functional implication of oscillations, their possible effect on desensitization, is also discussed.

Animals↗
PubMedDate not supplied

Health care technology in Canada (with special reference to Quebec).

In Canada, all citizens are insured for health services. Health care is a provincial responsibility. The federal role is limited to health care financing, health protection including regulation of pharmaceuticals, and environmental health. The health care system represents a balance among government direction, consumer choice, and provider autonomy. Canada has largely controlled the costs of health care by funding and management mechanisms, the most important of which is the global budget formula used to fund hospitals. This paper discusses the Canadian health care system, with particular emphasis on the province of Quebec. In 1988, the provincial government of Quebec established the first Canadian body dedicated to technology assessment. Since then, a national coordinating office and several other provincial bodies have developed. The work of these and other evaluation efforts has had a growing influence on technology management decisions, particularly those dealing with procurement of capital-intensive technologies. Expanding this influence into the realm of technology use, especially for low-cost, high-volume technologies, remains a challenge.

Canada↗
PubMedDate not supplied

[Fluorine-18]fluorodeoxyglucose positron emission tomography, DNA ploidy and growth fraction in squamous-cell carcinomas of the head and neck.

BACKGROUND: Positron emission tomography (PET) offers an opportunity to examine noninvasively cellular functions with different tracers. [(18)F]Fluorodeoxyglucose (FDG) is most commonly used in identifying malignant tumors. Several tumor biologic characteristics (tumor cell viability, growth faction, treatment response to radiation, cell membrane dysfunction, recurrence rate) are suggested to be characterized by [(18)F]FDG PET. The aim of this study was to assess which other tumor biologic characteristics of squamous-cell carcinoma of the head and neck are correlated with [(18)F]FDG PET. METHODS: [(18)F]FDG PET was performed in 14 patients with squamous-cell carcinomas of the upper digestive tract (TNM classification T(2)-T(4), N(1)-N(3)). After attenuation correction, predefined areas of the tumor were semiquantitatively analyzed by the technique of the region of interest and calculated as standard uptake values (SUV). Afterwards, 5 biopsies of different tumor regions were obtained during endoscopy in each patient under general anesthesia, and a correlation between SUV of [(18)F]FDG PET and tumor biologic parameters was attempted. These parameters included: quantitative DNA measurements (i.e. 2c deviation index, 5c exceeding rate), immunohistochemical assessment of growth fraction (i.e. Ki67-MIB-1, PCNA) along with morphological tumor front grading. RESULTS: The results revealed a marked variation of proliferation and cellular differentiation in various regions of the tumor for all parameters examined. There was a close correlation between [(18)F]FDG uptake and growth fraction (r = 0.83 for Ki67-MIB-1 and r = 0.8 for PCNA). A poor correlation was found between DNA aneuploidy (r = 0.4) or tumor front grading (r = 0.12) and [(18)F]FDG uptake. CONCLUSIONS: Our results confirm previous clinical and histologic observations that squamous-cell carcinomas of the upper digestive tract are heterogeneous tumors. Ki67 antigen, which has been shown to be of predictive value for proliferation and individual prognosis, correlated with [(18)F]FDG uptake. Using [(18)F]FDG PET, the main proliferation centers of inhomogeneous squamous-cell carcinomas could be identified with possible clinical implications for patient management.

Adult↗
PubMedDate not supplied

Histological grading, growth fraction and DNA-ploidy as criteria for the treatment of pharyngeal and supraglottic squamous cell carcinomas: a preliminary, prospective study.

BACKGROUND: Individualized treatment for patients with squamous cell carcinomas is most desirable. Biologic parameters of tumors may provide relevant criteria to achieve this goal. The aim of this study was: (1) to avoid elective neck dissection in patients with squamous cell carcinomas of the pharynx and supraglottis staged N0 by ultrasonography; (2) to administer postoperative radiotherapy only in patients staged 'highly aggressive' by biologic tumor parameters, in order to reduce patient morbidity and to improve quality of life. STUDY DESIGN AND METHODS: This prospective trial was performed in 35 patients (any T stage, N0 or N1 by ultrasonographic examination). Tumor biopsies were taken for histological examination and for evaluation of some biological tumor markers. These parameters comprised DNA cytometric examinations, histological grading of the tumor front and immunohistochemical staining for proliferation markers (MIB1, PCNA). Based on these parameters, tumors were classified into 'low aggressive' (group 1) and highly aggressive (group 2) behavior. In all patients, second primaries were excluded by endoscopy, and the presenting tumor was resected with clear margins. In cases of ultrasonographically enlarged lymph nodes, functional neck dissection was performed. When biologic tumor profile showed low aggressive behavior (group 1), no postoperative radiotherapy was advised. In cases of highly aggressive tumors, radiotherapy was recommended postoperatively independent of all other parameters (group 2a and 2b). RESULTS: The average follow-up was 36 months (range 16-65 months). Fifteen patients were included in group 1, 20 patients in group 2. Three patients with highly aggressive tumors who refused RTx were regarded independently (group 2b). In this pilot study of 35 patients, there was no difference in disease-free survival between group 1 and group 2a. Twenty-five of 35 patients were alive with no evidence of disease 29-65 months after treatment (3 died of disease; 5 died of second primary carcinomas; 2 died independent of disease). Eleven of 15 patients survived disease free in group 1, 13/17 in group 2a. In group 2b, 2 out of 3 patients, who were advised but refused postoperative radiotherapy, had recurrences. CONCLUSIONS: The results of this preliminary study point towards usefulness of some tumor biologic parameters in decision making for individualized treatment in patients with squamous cell carcinomas.

Adult↗
PubMedDate not supplied

Intracellular membranes as boundaries for ionic distribution. In situ elemental distribution in guinea pig heart muscle in different defined electro-mechanical coupling states.

Using x-ray microanalysis and cryoultramicrotomy, calcium and other diffusible elements were localized in heart muscle strips which had been shock frozen under different, defined conditions of electromechanical coupling. Guniea pig papillary muscles were shock frozen: 1) 1/2 seconds after paired stimulation, 2) 5 minutes after rest in normal bath medium and 3) 5 minutes after rest in bath medium to which noradrenaline was added. In 1) high calcium concentrations of 11.5 mmol/kg d.w. were regularly detected in sites at the level of Z-lines, which probably correspond to the Z rete of SR. In 2) in which the mechanogram of the fist contraction after rest normally showed a small and retarded peak, the cell stores seemed to be nearly empty, with exception of a few regions between the mitochondria which revealed calcium accumulations of 77 mmol/kg d.w. These regions included JSR and/or T-tubuli. In 3) in which the mechanogram of the first contraction after rest normally showed a retarded peak with high tension, calcium was found in several cell structures. The highest amount, 25 mmol/kg d.w., was detected over the cell membrane. Measurable amounts were also detected over Z-lines and sarcomeres. In the present experiments, the respective rate of rise of tension, and time to peak tension, were extremely different. Possible correlations between different contraction patterns and different calcium stores involved in the various experiments have been discussed.

Animals↗
PubMedDate not supplied

Biologic characteristics of paragangliomas of the nasal cavity and paranasal sinuses.

Paragangliomas of the nasal cavity and paranasal sinuses are extremely rare. This study was conducted to investigate the biologic characteristics of these lesions on different molecular levels and to estimate their biologic behavior. Operative specimens of three patients who underwent surgery for a paraganglioma of the nasal cavity (one case) or paranasal sinuses (two cases) were investigated by routine histology, quantitative DNA analysis, and immunohistochemical assessment of proliferation markers (i.e., Proliferating Cell Nuclear Antigen, PCNA; Ki67-MIB-1), the expression of cell-surface antigens, which reflect the tumor-stroma interaction (i.e., CD 44 v0.4/5 and 6, CD 54, CD 106), oncogene products (nm-23; p53), and bcl-2 as a marker of apoptosis. Histologically, two tumors were paragangliomas of the adenomatous subtype, one lesion was classified as angiomatous. According to DNA analysis, aneuploid cells were detected in all tumors. Two of three paragangliomas were classified as a DNA type III pattern, implying a high percentage of aneuploid cells and an aggressive behavior. Immunohistochemically, paragangliomas of the nasal cavity showed increased scores for both proliferation markers tested, indicating a rapid growth pattern. According to the expression of cell-surface markers and oncogene products, these tumors displayed an aggressive behavior and an infiltrating growth pattern. The highest value for the parameters of quantitative DNA analysis and highest proliferation scores were found in a tumor of a patient who developed multiple tumor recurrences after radical excision of the lesion with clear margins, and finally died of disease. In conclusion, paragangliomas of the nasal cavity and paranasal sinuses examined in this study should be regarded as suspicious concerning their biologic and clinical behavior. Radical excision, and in cases with highly aggressive biology, postoperative radiation therapy are recommended. Tumor biologic examinations can help to recognize high-risk patients for developing recurrences and possibly lesions with a malignant behavior and to enhance our understanding of the biology of these extremely rare tumors of the nasal cavity and paranasal sinuses.

Aneuploidy↗
PubMedDate not supplied

Proliferative activity and cytometric characteristics in polyps of the nasal cavity and paranasal sinuses.

Although several investigations have revealed the influence of cytokines, allergy, and environmental factors in polyp development, the etiology of nasal polyps is still unknown. To estimate the biology of this common disease the operative specimens of 50 patients who underwent surgery for polyps of the nasal cavity and the paranasal sinuses were examined; of these, 10 patients had recurrent disease and 23 patients had an allergy. The investigations included routine histology and quantitative DNA measurements, along with immunohistochemical identification of proliferation markers (i.e., MIB-1; proliferating cell nuclear antigen, PCNA). Histologically, most polyps revealed an infiltration with lymphocytes, eosinophilic granulocytes, and plasma cells. Twenty-five percent had a squamous metaplasia of the respiratory epithelium. Quantitative DNA analysis demonstrated diploid stemlines and lack of aneuploid cells with a DNA content exceeding 5c in most cases. Immunohistochemical detection of proliferation markers showed low proliferation rates in all cases. In 27 polyps no MIB-1 expression was detected, and in 7 polyps no PCNA expression was detected. The polyps of the 23 patients with proven allergic diathesis did not reveal higher scores for the parameters of DNA analysis (i.e., ploidy status and percentage of aneuploid cells) and proliferation scores. Nasal polyps of 10 patients with recurrent disease displayed higher scores for proliferation markers, and in five cases aneuploid cells with 5c exceeding rate (5cER) of 1.5-11.7% were detected. According to these results, polyps of the nasal cavity and paranasal sinuses showed low proliferation scores and were diploid. The data demonstrated that there was no increase of proliferation activity or ploidy shift toward aneuploidy in patients with allergy. Nevertheless, in recurrent disease some increase in proliferation activity and some changes in the parameters of the DNA analysis occurred, indicating more aggressive behavior of recurrent polyps in single cases.

Adolescent↗
PubMedDate not supplied

Effects of re-use on the physical characteristics of angiographic catheters.

Five types of angiographic catheters used in current radiological and haemodynamic clinical practice at Sacré-Coeur Hospital in Montreal were studied for their mechanical sturdiness, and also with respect to the possibility that re-use could be associated with blood contamination by loose particles. Samples were taken both from new catheters and from catheters re-used up to 10 times. Routine cleaning and sterilization procedures showed no adverse effects on the maximum tensile strength and elongation at break of catheters. While some biological debris were occasionally present in re-used catheters, they appeared to be firmly fixed to the lumen surface, and they seemed unlikely to be carried into the blood stream during catheterization. On the other hand, new catheters exhibited a substantially higher loose particicle count than catheters which had been properly cleaned and sterilized. It is concluded that properly handled re-used angiographic catheters are just as safe for the patient as new catheters. The limit on the number of re-uses may depend on the care taken to avoid damage to the lumen surface during cleaning, on ageing on the catheter material and on economic considerations.

Angiography↗
PubMedDate not supplied

Mania associated with interferon alpha2b treatment.

Neuropsychiatric side effects are common with Interferon a 2b. Psychosis and depression have been reported. Several cases of mania have been reported but only few have been associated with treatment for hepatitis B. We report a case of mania with psychotic symptoms in a 21-year-old female diagnosed to have hepatitis-B infection, who was receiving interferon. The report supports the view that dose reductions or pauses during interferon treatment can cause mania. Family history of mood disorder could be a risk factor. Atypical presentations are common in interferon-induced mania. Mania induced by interferon responds well to antimanic drugs. Since the use of interferon is increasing in developing countries, the need for awareness of side effects and management issues are important and these are highlighted.

Adult↗
PubMedDate not supplied

Surgical management of coarctation of aorta.

Between 1961 and 1988, 68 patients underwent operation for coarctation of the aorta. The average age of presentation of these subjects was higher than in other series. 7.1 percent were asymptomatic, a finding which is not seen in reports from the west. Operative procedures included resection and end to end anastomosis, resection and graft interposition, bypass grafting, patch aortoplasty and subclavian flap aortoplasty. However, the technique of patch aortoplasty, routinely performed in the last 24 years of this series seemed by far the most satisfactory procedure. Subclavian flap aortoplasty was carried out in a selected group of younger children. Associated cardiac anomalies influenced the results adversely. The overall operative mortality was 5.8 percent. Hypertension did not regress in 11.7 per cent of patients inspite of a successful operation as judged by the return of peripheral pulses in the lower limbs. Re-coarctation was not seen in this series. The overall results of operation for coarctation of the aorta have been very satisfactory and comparable with those in other published series.

Adolescent↗