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Biomedical subjects

J Bax

Publications and source records attributed to J Bax.

At least 19 recordsLinked to original sources

The regulatory background of nuclear cardiology in Europe: a survey by the European Council of Nuclear Cardiology.

PURPOSE: Nuclear cardiology is a well-validated, non-invasive imaging modality that is highly cost-effective as a diagnostic and prognostic tool in the evaluation of patients with known or suspected coronary artery disease. However, the number of procedures in Europe is very far from that which would be expected on the basis of epidemiological data, particularly when comparison is made with the USA. As a preliminary step for future action aimed at improving and increasing nuclear cardiology practice in Europe, the European Council of Nuclear Cardiology performed a survey to identify the regulatory issues and the training components pertaining to the practice of nuclear cardiology. METHODS: a questionnaire was sent to 31 national nuclear medicine societies and to 40 national cardiology societies. The main areas covered by the survey were: (1) the license requirements, (2) the theoretical and practical aspects of training and (3) supervision of the stress test during a nuclear cardiology study. RESULTS: The results show that, in a setting of wide heterogeneity of national regulations, education and professional practice, nuclear medicine is a restricted and closely regulated specialty. This situation guarantees the quality and safe use of radionuclides; at the same time, however, it limits integration of nuclear medicine into the clinical arena. CONCLUSION: Cardiologists should become more involved in nuclear cardiology, to further stimulate the use of this powerful diagnostic and prognostic imaging modality.

Cardiology↗

EANM/ESC procedural guidelines for myocardial perfusion imaging in nuclear cardiology.

The European procedural guidelines for radionuclide imaging of myocardial perfusion and viability are presented in 13 sections covering patient information, radiopharmaceuticals, injected activities and dosimetry, stress tests, imaging protocols and acquisition, quality control and reconstruction methods, gated studies and attenuation-scatter compensation, data analysis, reports and image display, and positron emission tomography. If the specific recommendations given could not be based on evidence from original, scientific studies, we tried to express this state-of-art. The guidelines are designed to assist in the practice of performing, interpreting and reporting myocardial perfusion SPET. The guidelines do not discuss clinical indications, benefits or drawbacks of radionuclide myocardial imaging compared to non-nuclear techniques, nor do they cover cost benefit or cost effectiveness.

Cardiology↗

Pre-discharge stress echocardiography and exercise ECG for risk stratification after uncomplicated acute myocardial infarction: results of the COSTAMI-II (cost of strategies after myocardial infarction) trial.

OBJECTIVE: To compare in a prospective, randomised, multicentre trial the relative merits of pre-discharge exercise ECG and early pharmacological stress echocardiography concerning risk stratification and costs of treating patients with uncomplicated acute myocardial infarction. DESIGN: 262 patients from six participating centres with a recent uncomplicated myocardial infarction were randomly assigned to early (day 3-5) pharmacological stress echocardiography (n = 132) or conventional pre-discharge (day 7-9) maximum symptom limited exercise ECG (n = 130). RESULTS: No complication occurred during either stress echocardiography or exercise ECG. At one year follow up there were 26 events (1 death, 5 non-fatal reinfarctions, 20 patients with unstable angina requiring hospitalisation) in patients randomly assigned to early stress echocardiography and 18 events (2 reinfarctions, 16 unstable angina requiring hospitalisation) in the group randomly assigned to exercise ECG (not significant). The negative predictive value was 92% for stress echocardiography and 88% for exercise ECG (not significant). Total costs of the two strategies were similar (not significant). CONCLUSION: Early pharmacological stress echocardiography and conventional pre-discharge symptom limited exercise ECG have similar clinical outcome and costs after uncomplicated infarction. Early pharmacological stress echocardiography should be considered a valid alternative even for patients with interpretable baseline ECG who can exercise.

Adult↗

High prevalence of hyperhomocysteinemia and asymptomatic vascular disease in siblings of young patients with vascular disease and hyperhomocysteinemia.

Hyperhomocysteinemia (HHC) is associated with an increased risk of atherosclerotic vascular disease and may be inherited. Fasting and postmethionine HHC are independent risk factors that overlap to a limited extent. To study the familial occurrence of HHC, we investigated the prevalence of HHC (both fasting and after methionine) among 450 siblings of 167 consecutive young patients with vascular disease and postmethionine HHC. Furthermore, all subjects with postmethionine HHC (n = 125) were invited for noninvasive vascular testing; 101 (80.8%) agreed. Of those with a normal postmethionine plasma level (n = 325), we randomly selected 73 subjects for further studies; 53 agreed (72.6%). Thus, a total of 154 siblings underwent ultrasonography of the carotid arteries, measurement of ankle-brachial pressure indices at rest and after a treadmill exercise test, and exercise electrocardiographic stress testing. We observed HHC after methionine, fasting, or both, in 27.8% (95% CI, 23.7 to 31.9), 11.1% (CI, 8.2 to 14.0) and 8.7% (CI, 6.1 to 11.3) of the siblings. Abnormal peripheral, coronary, or carotid artery tests were observed in 35.7% (CI, 28.1 to 43.3), 7.1% (CI, 3.0 to 11.2), and 7.1% (CI, 3.0 to 11.2). Univariate and multivariate analyses revealed weak evidence of a relationship with homocysteine levels. In conclusion, we found a high prevalence of HHC and asymptomatic vascular disease in siblings of young patients with vascular (mainly peripheral arterial) disease and HHC. Our data raise the possibility that homocysteine does not play a major role in the early, asymptomatic phases of vascular disease, at least among siblings of young patients with vascular disease.

Adult↗

Variability of the main sequence.

PURPOSE: This study investigated the relationship between amplitude and peak velocity of saccadic eye movements (the so-called main sequence) and the intra-individual variability of the main sequence. METHODS: Saccadic amplitudes and peak velocities were measured twice in 58 healthy subjects with an infrared reflection technique. RESULTS: Considerable intra-individual variability was found between the first and second recordings. CONCLUSIONS: Intra-individual variability of saccadic peak velocity affects the interpretation of changes in repeated recordings of peak velocities, such as before and after medication is administered. Furthermore, considerable intra-individual variability decreases the probability that statistically significant differences between patients and control subjects can be detected, especially when groups are small. Calculating the intraclass correlation coefficient allows the number of subjects in comparative studies to be determined.

Adult↗

Cell specific DNA alkylation in target and non-target organs of N-nitrosobis(2-oxopropyl)amine-induced carcinogenesis in hamster and rat.

Tissue-specific formation and short-term persistence of alkylated DNA bases have been studied immunocytochemically in Syrian hamsters and rats killed 3-48 h after a single s.c. or oral dose of N-nitrosobis(2-oxopropyl)amine (BOP). Antisera specific for O6-(m)ethylguanine and for 7-(m)ethylguanine were used. Strong nuclear staining, indicative of a high level of DNA alkylation, was observed at all time points in the intra- and interlobular duct cells and in the centroacinar cells of the hamster pancreas, the main target organ of BOP-induced carcinogenesis. Acinar cells were weakly stained for up to 24 h. In the liver, nuclear staining was strong in all cell types, and more pronounced in the periportal than in the central venous area. Both O6-alkylguanine and 7-alkylguanine preferentially disappeared from the centrilobular area of the liver which is in agreement with the high O6-methyltransferase activity of liver and the unusually high levels of 7-methylguanine DNA glycosylase activity in hamster tissues. Strong staining was observed throughout the experiment in the tubular cells of the renal cortex and in bronchiolar Clara and alveolar type II cells of the lung. The staining intensity of the cells of the thyroid follicles and of the columnar epithelial cells of the colon was moderate. In the rat, nuclear staining was strong in the nasal cavity (Bowman glands), the epithelium lining the thyroid follicles, the lung, liver and in the fibroblasts of the ureter intima and adventitia. The epithelial cell nuclei of the colon and ureter were moderately stained. In the pancreas, staining was weak in acinar, duct and islet cells; no acinar staining remained at 48 h. In the liver, nuclear staining was strong all over the lobule. O6-Alkylguanine was preferentially removed from the centrilobular area. The renal tubular cells were only weakly stained. From the present study we can conclude that--with the exception of hamster kidney and rat liver--high levels of DNA alkylation and stability of the alkylated products were related to a high tumor incidence.

Alkylation↗

Activation of c-K-ras is frequent in pancreatic carcinomas of Syrian hamsters, but is absent in pancreatic tumors of rats.

We have investigated the presence of mutations in ras genes at codons 12, 13 and 61 in chemically induced pancreatic tumors of rats and Syrian hamsters. Mutations were detected by means of allele-specific oligonucleotide hybridization to ras sequences amplified in vitro by the polymerase chain reaction. No mutations were observed in the c-K-ras gene or the c-H-ras gene of nine azaserine-induced adenomas and 15 carcinomas of the rat pancreas. This indicates that activated ras genes are not commonly involved in rat pancreatic cancer evolving from acinar cells. However, in 19 out of 20 ductular adenocarcinomas of hamster pancreas (95%), either codon 12 or 13 of the c-K-ras gene was mutated. This indicates that the activation of c-K-ras is a frequent event in the multistep process of pancreatic carcinogenesis induced by the alkylating carcinogen N-nitrosobis(2-oxopropyl)amine (BOP). The mutations of both codons were G----A transitions of the second base which is consistent with the type of mutation to be expected from DNA alkylation. Activation of the c-K-ras gene, therefore, may not only be a frequent but also an early event in hamster pancreas carcinogenesis. The frequent activation of the c-K-ras gene in both human and hamster pancreatic cancer emphasizes the relevance of BOP-induced pancreatic adenocarcinomas in Syrian hamsters as an experimental model system for studying human pancreatic cancer.

Adenocarcinoma↗

Long-term persistence of DNA alkylation in hamster tissues after N-nitrosobis(2-oxopropyl)amine.

The persistence of 7- and O6-alkylation of guanine in DNA of cell nuclei of male Syrian hamster pancreas, liver, kidneys, lungs [target tissues of N-nitrosobis(2-oxopropyl)amine (BOP)] and salivary glands (nontarget tissue) was studied immunocytochemically 6 h, 1, 3, 7, 14, 28, and 56 days after a single s.c. injection of 20 mg BOP/kg. Conventional antisera raised against O6-methylguanine and imidazole-ring-opened 7-methyl-guanine were used. Persistent alkyl-specific staining was observed for up to 7 days (7-alkylguanine) or 56 days (O6-alkylguanine) in inter- and intralobular duct cells and centro-acinar cells of the pancreas, periportal hepatocytes and bile duct cells of the liver, cells of the proximal convoluted tubules of the renal cortex, and bronchiolar Clara and alveolar cells in the lungs. Both adducts disappeared from centrilobular liver cells within 1 day, from pancreatic acinar cells within 3 days, and from ducts and acini of the submandibular salivary glands within 14 days after BOP treatment. A high level of persistent O6-alkylation of guanine was related with a high tumor incidence only in case of the ductal/ductular system of the pancreas, the main target tissue of BOP-induced carcinogenesis. The relatively weak carcinogenicity of BOP in other tissues with long-term persistence of O6-alkylguanine in DNA indicates that the formation and persistence of DNA alkylation are not sufficient to account for the carcinogenic organotropism of BOP. Additional factors, such as cell proliferation, appropriate promoting stimuli and the (onco)genes critically involved, may be as important as the modification of DNA.

Alkylation↗

Kinetics of induction and growth of putative precancerous acinar cell foci in azaserine-induced rat pancreas carcinogenesis.

The kinetics of induction and growth of acinar cell lesions has been investigated in rat pancreas after a single dose of the carcinogen azaserine. The time--response relationship was studied in male Wistar-related rats given a single i.p. injection of 30 mg L-azaserine/kg body weight at 18 days of age. Rats were killed between 4 and 78 weeks after treatment and ATPase-stained pancreas sections were quantitatively evaluated for the number and size of acidophilic, ATPase-positive and basophilic, ATPase-deficient foci. The number of acidophilic foci remained constant from 8 weeks onwards, while the number of basophilic foci slightly increased with time. The size of both acidophilic and basophilic foci increased throughout the experimental period. Due to two times higher number/cm3 and faster growth of the acidophilic foci, four times more acidophilic than basophilic focus tissue was present at the end of the experiment. Progression of acidophilic foci to adenomas and carcinomas was occasionally seen at later time points (greater than 34 weeks) in this rat strain. The dose--response relationship was studied in male and female Sprague--Dawley rats given a single i.p. injection of 0-45 mg azaserine/kg body weight at 19 days of age. Rats were autopsied at 17 weeks after treatment, and pancreas sections were quantitatively evaluated after ATPase histochemistry. The relationship between dose and number of foci was linear up to 30 mg/kg azaserine for both acidophilic and basophilic foci in males and females. For each individual dose, the number of foci induced was the same in males and females, and there were two to three times more acidophilic than basophilic foci. The percentage of pancreatic tissue occupied by focus tissue was 1.75 times higher in males, pointing to a higher growth-potential of acidophilic foci in males than in females. The first-order dose--response kinetics indicate that the conversion of a normal acinar cell into a focus-forming cell occurs by one specific azaserine-mediated rare event, occurring probably at the genetic level of the target cell.

Adenosine Triphosphatases↗

Adherence of human helper/memory T-cell subsets to psoriatic dermal endothelium.

Dermal lymphocytic infiltrates are characteristic features of psoriasis and may be involved in the pathogenesis of the disease. We have previously shown that specialized endothelial cells are present in the dermis of psoriatic skin and are capable of supporting lymphocyte adherence and promoting lymphocyte extravasation. In this study, we investigated the dermal endothelial binding properties of human lymphocyte subsets and the role of LFA-1 molecules in the adhesion process. It was found that both human T cells and B cells adhered to frozen sections of psoriatic plaques, but with different cell dose-response relationships. In addition, quantitative assessment of lymphocyte adhesion demonstrated that human CD4+T cells and the CDw29+ (helper-inducer) subset adhered preferentially to the papillary dermis as compared with CD8+ T cells or the CD45R+ (suppressor-inducer) subset. Moreover, human lymphocytes adhered to untreated psoriatic plaques, but not to uninvolved skin or to steroid-treated, clinically and histologically resolved lesions. Preincubation of T lymphocytes with saturating amounts of monoclonal antibody 60.3 against the surface membrane CD18 glycoprotein complex inhibited partially their capacity to bind to untreated psoriatic plaques. These observations suggest that the emigration of human CD4+ T cell and the CDw29+ helper-inducer subset is promoted by selective adherence to psoriatic dermal endothelia, with LFA-1 molecules playing an accessory role in the binding process.

Administration, Topical↗

Modulation of putative preneoplastic foci in exocrine pancreas of rats and hamsters. Interaction of dietary fat and coffee.

The effects of coffee and dietary fat (alone and in combination) on the development of preneoplastic lesions in exocrine pancreas were investigated in rats and hamsters, treated with azaserine or N-nitrosobis(2-oxopropyl)amine, respectively. The animals were given the respective diets (5% or 25% corn oil) and coffee (instead of drinking water) within one week after the treatment with carcinogen. At four months postinitiation, the pancreata were quantitatively examined for the number and size of preneoplastic foci. In rats, coffee alone inhibited growth of acidophilic foci and, moreover, slightly inhibited the positive modulating effect of fat on growth of these foci, pointing to a negative rather than a positive interaction between these two life-style factors. In hamsters, coffee alone enhanced growth of cystic foci, whereas fat alone enhanced growth of ductular foci. An interaction between fat and coffee on pancreatic carcinogenesis in hamsters could not be demonstrated.

Animals↗

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic coffee ingestion.

The effect of chronic coffee ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body weight at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body weight at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either in combination with coffee or not. Coffee was provided instead of drinking water. A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and coffee after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. In rat pancreas, the numbers of adenomas and carcinomas were significantly lower in the group maintained on the combination of a high-fat diet and coffee than in the high-fat group without coffee, while in the latter group the number of adenomas and carcinomas had significantly increased as compared to the low-fat controls. In hamsters, the number of ductal/ductular adenocarcinomas had significantly increased in the high-fat group as compared to the low-fat controls. The inhibitory effect of coffee on dietary fat-promoted pancreatic carcinogenesis was also noticed in this species but was less pronounced than in rats. It was concluded that chronic coffee consumption has an inhibitory effect on dietary fat-promoted pancreatic carcinogenesis in rats and hamsters. More research is needed to elucidate the mechanism by which coffee (constituents) modulates carcinogenesis.

Adenocarcinoma↗

Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic ethanol ingestion.

The effect of chronic ethanol ingestion on dietary fat-promoted pancreatic carcinogenesis was investigated in rats and hamsters. Rats were given a single i.p. injection of 30 mg azaserine per kg body wt at 19 days of age. Hamsters were injected s.c. with 20 mg N-nitrosobis(2-oxopropyl)amine (BOP) per kg body wt at 6 and 7 weeks of age. The animals were fed a semi-purified diet high in unsaturated fat (25% corn oil) either separately or in combination with ethanol. Ethanol was provided in drinking water at a concentration of 10% (w/v). A separate group maintained on a diet low in unsaturated fat (5% corn oil) was included as extra controls. The rats and hamsters were given their diets and received ethanol via their drinking water after treatment with carcinogen. Terminal autopsy of rats was 15 months after azaserine treatment and of hamsters 12 months after the last injection with BOP. Dietary fat was found to enhance pancreatic carcinogenesis in both rats and hamsters. In rats, ethanol slightly enhanced the multiplicity but not the incidence of malignant tumours, while in hamsters ethanol did not show any modulating effect on dietary fat-promoted carcinogenesis. It was concluded that dietary fat-promoted pancreatic carcinogenesis as observed in the animal models applied is not significantly modulated by chronic ethanol ingestion.

Animals↗

Single cell analysis of DNA modifications induced by chemical carcinogens and cytostatic drugs.

Antibodies recognizing specific DNA modifications allow the immunocytochemical visualization and quantification of these modifications at the level of the individual cell. Thus, the formation and repair of DNA adducts induced by chemical mutagens and carcinogens and by cytostatic drugs can be studied in very small samples in relation to e.g. cell type and tissue localization. A number of existing and potential applications in the fields of chemical carcinogenesis, chemical mutagenesis, experimental chemotherapy and molecular epidemiology are illustrated.

Animals↗

Adenosine triphosphatase, a new marker for the differentiation of putative precancerous foci induced in rat pancreas by azaserine.

Enzyme-histochemical investigation of pancreatic carcinogenesis in male Wistar rats treated at the age of 19 days by a single dose of 30 mg azaserine/kg body wt led to the detection of a new 'marker' for the recognition of foci of atypical acinar cells: the Mg2+-dependent ATPase. The two well-known populations of pancreatic atypical acinar cell foci, classified histologically as basophilic and acidophilic foci, showed a decreased and strongly increased ATPase reaction, respectively. The enhanced enzyme activity of the acidophilic foci has been characterized as unspecific nucleoside polyphosphatase. To validate the new marker, comparative quantitative evaluation was performed on haematoxylin and eosin-stained paraffin sections and ATPase-stained cryostat sections of the same pancreata of 25 azaserine-treated rats. Evaluation of basophilic ATPase-deficient foci of small diameter was more reproducible in haematoxylin and eosin-stained sections, while small acidophilic strongly ATPase-positive foci could be detected more reliably by the ATPase staining technique. The number of foci/cm3 pancreas was similar for both staining techniques above a focus diameter of about 100 microns for basophilic foci and 200 micronfor acidophilic foci. There were more acidophilic than basophilic foci/cm3 pancreas, and the acidophilic foci had significantly larger mean focal diameters than the basophilic foci. Together with the strong acidophilic staining of the latter emerging adenoma, this suggests that the acidophilic foci represent a neoplastic cell population progressing eventually to pancreatic carcinoma. The new 'marker' enzyme ATPase may greatly facilitate further investigations into the role of these putative preneoplastic lesions in pancreatic carcinogenesis.

Adenosine Triphosphatases↗