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K Metze

Publications and source records attributed to K Metze.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effect of Ca2+ channel blockers on arterial hypertension and heart ischaemic lesions induced by chronic blockade of nitric oxide in the rat.

The effects of the Ca2+ channel blockers diltiazem, nifedipine and amlodipine were investigated on both arterial hypertension and myocardial changes induced by chronic blockade of nitric oxide synthesis. Control male Wistar rats received Nomega-nitro-L-arginine methyl ester (L-NAME; 20 mg rat(-1) day(-1)) in the drinking water for 8 weeks; blood pressure and body weight were monitored weekly. The Ca2+ channel blockers were given concomitantly to L-NAME, as follows: diltiazem (13.5 mg rat(-1) day(-1)) and amlodipine (6.25 mg rat(-1) day(-1)) were administered in the drinking water whereas nifedipine (6.25 mg rat(-1) day(-1)) was given in the chow. Nomega-nitro-L-arginine methyl ester induced a time-dependent increase in blood pressure which was significantly attenuated by diltiazem (154+/-1.6 vs. 139+/-1.6 mm Hg, p < 0.05), nifedipine (166+/-2.7 vs. 150+/-2.1 mm Hg, p < 0.05) and amlodipine (208+/-5.8 vs. 158+/-1.8 mm Hg, p < 0.05) at the last week of the treatment. Rats treated with the L-NAME also developed myocardial ischaemia, as indicated by the increased percentage of fibrous tissue found in the left ventricles of these animals (10.9+/-0.1%, p < 0.01) when compared to control ones (6.3+/-0.1%). Neither diltiazem (14.9+/-1.2%) nor nifedipine (11.1+/-1.5%) prevented this effect whereas amlodipine (6.9+/-1.1%, p < 0.01) virtually abolished the increase in fibrous tissue induced by L-NAME. The plasma concentration of the Ca2+ channel blockers was measured by liquid chromatography coupled to mass spectrometry at two different time points (morning and afternoon). Only amlodipine treatment was able to maintain constant levels (186+/-46 ng ml(-1) in the morning and 110+/-19 ng ml(-1) in the evening) compared to nifedipine (3003+/-578 ng ml(-1) in the morning and 436+/-100 ng ml(-1) in the evening) and diltiazem (77+/-51 ng ml(-1) in the morning and not detectable in the evening). In conclusion, our results indicate that amlodipine (but not diltiazem and nifedipine) can efficiently control myocardial ischaemia in nitric oxide deficient rats, probably due to its intrinsically long half-life.

Animals↗
PubMed1999

Changes in AgNOR configurations during the evolution and treatment of chronic lymphocytic leukemia.

The evolution of the pattern of nucleolar organiser regions (AgNORs) in circulating lymphocytes during the stable phase and after chemotherapy in CLL was analysed. Peripheral blood smears were stained by the AgNOR technique at diagnosis, during observation follow-up in stable phase, or at the beginning and at the end of chemotherapy in patients with progressive disease. The changes in the AgNOR pattern were compared with those of TTM used as a tumour burden parameter. Among 52 cases that entered the study, 29 were in stable phase and 23 had progressive disease and received chemotherapy. During stable phase, the AgNORs as well as TTM remained constant. In treated patients, the relative reduction of tumour mass was correlated with a decrease in the percentage of lymphocytes containing one AgNOR cluster. The percentage of cells with one compact nucleolus before chemotherapy was inversely correlated with the relative amount of tumor reduction after treatment. We conclude that the AgNOR pattern in CLL describes the cell kinetic changes during the evolution of the disease and is a prognostic factor for tumor reduction after treatment.

Aged↗
PubMed1999

Argyrophilic nucleolar organizer region (AgNOR) technique: a helpful tool for differential diagnosis in urinary cytology.

The aim of this study was to investigate whether the AgNOR technique could be helpful for the cytologic diagnosis of neoplastic and non-neoplastic urinary tract lesions. We analysed the AgNOR pattern in urinary cytology in samples from 70 patients. In every case the average number of silver precipitations per nucleus was counted and the range between the minimum and maximum AgNOR value calculated. Furthermore we noted whether the AgNOR precipitations had a homogeneous or heterogeneous distribution. The diseases were classified in three groups: non-neoplastic lesions, low grade and high grade carcinoma. Linear discriminant analysis (with jack-knife procedure) was performed with the AgNOR parameters as independent variables. The final diagnosis of each patient had been established by histological analysis of bladder biopsies. We obtained a correct classification in 84.3% of the cases. All patients with normal or reactive lesions were correctly classified and only two cases of low grade malignancy were erroneously diagnosed as non-malignant. Five high grade neoplasms had been classified as low grade and four low grade carcinomas had been over-diagnosed as high grade neoplasms. We conclude that a combined qualitative and quantitative AgNOR analysis can be useful in the differential diagnosis of urinary cytology.

Cytodiagnosis↗
PubMed1999

Quantitative analysis of modes of invasion and lymph node metastases in oral squamous cell carcinoma.

The mode of tumor invasion has been suggested to have a relationship to the occurrence of cervical metastasis and to prognosis in oral squamous cell carcinoma (OSCC). However, a tumor usually does not have a single mode of invasion, and the importance, if any, of the relative proportions of different modes for metastatic potential has not been studied. Forty two cases of OSCC resected with cervical lymph nodes were selected, 20 of which had nodal metastases and 22 which had not. The mode of invasion in the tumor-host interface was classified as: I - pushing borders, II - bands, III - thin cords, IV - single cells and analyzed in 20 consecutive medium power fields. Also studied were other morphological parameters: perineural and angiolymphatic invasion, tissue eosinophilia, mitosis and intensity of inflammatory infiltrate at the tumor-host interface. The majority of the cases (95.2%) showed two or more modes of invasion. Modes I, II and III occurred with similar frequency in cases with and without metastases. Mode II was the commonest and most extensive in both groups. No mode of invasion was significantly associated with metastases, independent of its extension. The other morphological parameters were neither significantly associated with cervical metastasis. In conclusion, OSCC usually shows two or more modes of tumor invasion if a large extension of tumor-host interface is analyzed. However, the relative proportions of the modes have no correlation with the metastatic potential.

Adult↗
PubMed1998

Relationship between morphometric analysis of nucleolar organizer regions and cell proliferation in acute leukemias.

Silver-stained nucleolar organizer regions in interphase cells have been widely studied as a cell kinetic parameter in different tissues. Many different approaches have been used for this evaluation, often leading to conflicting results. The aim of our study was to analyze several commonly used AgNOR parameters in bone marrow smears of 32 newly diagnosed cases of acute leukemia: number of clusters and dots, percentage of cells with one cluster (cells in a long G1 phase), total and percentage of silver-stained area per nucleus, mean size of AgNORs, and the Rüschoff index. These parameters were compared with the in vitro incorporation of bromodeoxyuridine (BrdU). A significant correlation was found between the BrdU index and the mean number of clusters (r = 0.60), dots (r = 0.60), percentage of cells with one cluster (r = -0.63), as well as with the mean size of AgNORs (r = -0.63) and the Rüschoff index (r = 0.72). In a factor analysis, total AgNOR area, its percentage of nuclear area, the mean AgNOR size, and the nuclear area formed one factor (factor of area parameters), and clusters, dots, the percentage of cells with one cluster, and BrdU index made another factor (factor of proliferation parameters). The Rüschoff index participated equally in both factors. Based on these data, we postulate that the number of clusters and dots are related to the percentage of cells in S-phase and the AgNOR area may be related to the cell duplication time, as has been reported in the literature. Mean size of AgNORs is smaller in highly proliferating cells. Probably the Rüschoff index is related to the percentage of cells in S-phase as well as to the cell duplication time, and seems to be the best AgNOR parameter for the global evaluation of cell kinetics in acute leukemias.

Adolescent↗
PubMed1998

The value of PCNA and AgNOR staining in endoscopic biopsies of gastric mucosa.

The aim of the present study was to examine the usefulness of the quantification of PC10-positive-cells and of Argyrophilic Nucleolar Organizer Regions (AgNORs) in gastric biopsies for the identification of gastric mucosal proliferative lesions. Fifty seven paraffin-embedded endoscopic biopsies were classified into four histologic groups: normal, inflammatory, dysplastic and neoplastic mucosa. The percentage of PC10-positive cells was determined by immunohistochemistry. The AgNOR parameters determined included the total number of all identifiable silver precipitations in the nucleus, the mean number of silver precipitations per cluster, and the presence of morphologically heterogenous silver precipitations. Group comparisons were performed using the Kruskall Wallis and Dunn non-parametric tests with a significance level of 5%. A discriminant analysis (followed by the jack-knife procedure) was performed using the three AgNOR parameters plus the percentage of PCNA-positive cells as the independent variables and histological groups as the dependent variable. All three AgNOR parameters, as well as the percentage of PCNA-stained nuclei, showed their highest values in the carcinoma group. However, no good differentiation among the four histologic groups was obtained using only one of these parameters, since there was always considerable overlap among them. By combining all the parameters in a linear discriminant analysis, we obtained a correct classification in 48 out of 57 cases. Within the classification errors there was only one false positive carcinoma, which was in fact a dysplasia and only one false negative carcinoma erroneously classified as dysplasia. The number of cells with heterogenous AgNORs was the most important parameter for the discriminant analysis. No correlation between PCNA values and the AgNOR parameters could be found, thus indicating that they do not represent the same phenomenon in the cell cycle. We concluded that the use of a combination of various proliferation parameters in a linear discriminant analysis may be helpful for differentiating gastric mucosal lesions. The peculiar AgNOR morphology is an important variable which should be taken in consideration in quantitative studies. PCNA and AgNORs seem to represent different physiological phenomena in the cell cycle.

Adenocarcinoma↗
PubMed1997

Non-specific inhibitors of nitric oxide synthase cause myocardial necrosis in the rat.

1. To study the effect of acute nitric oxide (NO) inhibition on the rat heart both in vitro and in vivo, male Wistar rats received a single bolus injection of saline, N omega-nitro-L-arginine methyl ester (L-NAME; 0.5, 1.5, 5.0, 15.0 and 45.0 mg/kg) and D-NAME (45.0 mg/kg). 2. Animals were killed 72 h after the bolus injection of L-NAME and the hearts were removed and studied under light microscopy. In other groups of animals; saline, L-NAME and D-NAME were administered as above and the mean arterial blood pressure (MABP/carotid) was recorded. Furthermore, L-NAME was also administered in the drinking water (20 mg/kg per day) for 72 h and animals were then killed and their hearts evaluated as described above. Hearts of control animals were perfused in vitro and coronary flow was measured following saline, L-NAME (45 micrograms/heart) and D-NAME (45 micrograms/heart). 3. Areas of necrosis were observed in the left ventricle of animals that had received L-NAME at 5.0, 15.0 and 45.0 mg/kg. Also, only doses higher than 1.5 mg/kg caused an important increase in MABP. The frequency and extent of the lesions paralleled the dose of L-NAME administered and no lesions were observed in D-NAME- and saline-treated animals. 4. The oral administration of L-NAME also caused myocardial lesions similar to those described above, but the frequency and extent of these lesions were more discrete compared with those observed following 5.0 mg/kg, i.v., L-NAME. 5. Bolus injection of L-NAME into control rat hearts in vitro resulted in a small and transient fall in coronary flow (17.2 +/- 1.4 and 12.2 +/- 1.2 mL/min before and after L-NAME administration, respectively) within 30 s and this was followed 4.5 min later by a further (11.5 +/- 1.6 mL/min) decrease. The administration of D-NAME to control hearts caused no change in coronary flow. 6. In conclusion, the acute inhibition of NO biosynthesis by L-NAME causes myocardial necrosis. Both high levels of MABP and a small but significant reduction in coronary flow (associated or not) can be responsible for the lesions we found.

Animals↗
PubMed1997

Attitudes of medical students to necropsy.

AIM: To compare the attitudes of students towards the necropsy at different stages of their undergraduate career. METHOD: Students in the first, fourth and sixth academic years (n = 283) were asked to respond anonymously to a questionnaire comprised of 26 attitude statements. These statements dealt with the importance of the necropsy in medicine, rapport with the bereaved family and emotional reactions to the necropsy. RESULTS: Of the students, 226 (80%) completed the questionnaire. Overall, the students agreed on/the importance of the necropsy. The three groups differed in 10 statements on the approach to the bereaved family and emotional reactions to the necropsy. First year students showed more personal involvement and would have more difficulties in approaching the family of the deceased as well as in attending a necropsy. These reactions were increasingly less noticeable with fourth and sixth year students. The latter group was also more inclined to accept cremation, organ donation and necropsy of their own corpses. CONCLUSION: The changes in attitudes towards the necropsy throughout undergraduate study may reflect both the influence of psychological defense mechanisms and the viewing of necropsy as a relevant tool in medical practice. Necropsy should be carefully and sensitively incorporated into programmes designed to teach students about death and dying. This might reduce both their reluctance to seek permission for necropsy and their difficulty in looking after the dying patient.

Adult↗
PubMed1996

Effects of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs.

The authors studied the effect of vitamin E on endothelium-dependent coronary flow in hypercholesterolemic dogs. Adult mongrel dogs weighing 7.4 +/- 1.0 kg were divided into control, hypercholesterolemic and vitamin E groups. The animals in the hypercholesterolemic group were fed a diet enriched with cholesterol (5% w/w) and coconut oil (10% w/w) for 40 days. The vitamin E group received the same diet plus 400 IU of vitamin E during the last 15 days of the experiment. Total serum cholesterol levels were evaluated at the beginning and at the end of the experiment using a commercial enzyme kit and a Beckman analyzer. The coronary flow was determined by electromagnetic flowmetry using a probe positioned in the left anterior descending coronary artery, near the ostium. A needle connected to a perfusion pump was introduced into the coronary artery for the administration of acetylcholine and sodium nitroprusside at a rate of 5 micrograms/kg per min. The aorta was cannulated for the measurement of arterial blood pressure via a pressure transducer coupled to a Siemens multi-channel recorder. The tissue cholesterol content and malonic dialdehyde (MDA) were also measured in isolated coronary vessel specimens. At the end of 40 days, the serum cholesterol levels had increased by 226% and 190% in the hypercholesterolemic and vitamin E groups, respectively. However, the difference in the levels of these two groups was not significant (P > 0.05). The aortic blood pressure and heart rate remained unchanged during acetylcholine administration. In contrast, systolic and diastolic pressure fell and the heart rate increased during the infusion of sodium nitroprusside. The tissue cholesterol content and MDA were significantly (P < 0.05) increased in coronary artery specimens from the hypercholesterolemic compared to control animals. Vitamin E was able to reduce these increases in cholesterol treated animals (P < 0.05). The percent change in coronary flow during acetylcholine administration was significantly lower in the hypercholesterolemic group when compared with control animals (P < 0.05) but was unaltered in the vitamin E group (P > 0.05). During sodium nitroprusside administration, the coronary flow increased in the vitamin E group (P < 0.05). The authors conclude that hypercholesterolemia reduces endothelium-dependent coronary flow and increases the tissue cholesterol content and MDA of coronary arteries. Vitamin E decreases the MDA and the tissue cholesterol content without significantly affecting the total serum cholesterol level. Vitamin E may thus restore coronary flow by reverting endothelial dysfunction.

Acetylcholine↗
PubMed1996

AgNOR clusters as a parameter of cell kinetics in chronic lymphocytic leukaemia.

Aims-To study correlations between the pattern of silver stained nucleolar organiser regions (AgNORs) in chronic lymphocytic leukaemia (CLL) and parameters of tumour kinetics. To investigate whether quantitation of the AgNOR pattern can be used to discriminate between patients with stable and progressive disease.Methods-Peripheral blood smears from 48 patients with CLL, classified as having either stable or progressive disease (Rai stage III or IV; bulky lymph nodes or massive splenomegaly; or peripheral lymphocytes >100 x 10(9)/1), were studied. For each patient, total tumour mass (TTM) and for patients undergoing a period of observation without treatment, the TTM duplication time (DT) and the lymphocyte doubling time (LDT) were calculated.Results-Four cell types could be distinguished according to their AgNOR pattern: (1) cells with a single cluster; (2) cells with a single compact nucleolus; (3) cells with two compact nucleoli; and (4) cells with several scattered dots. The percentage of cells with clusters was the AgNOR parameter which correlated best with TTM and LDT. Correlations were also seen between the proportion of cells with clusters and age and haemoglobin concentration. A significant correlation with DT could be detected only when age was kept constant. Linear discriminant analysis revealed that the percentage of cells with clusters was the most important prognostic factor. This alone classified 94% of the patients correctly (jackknive procedure) as either stable or progressive CLL.Conclusions-The percentage of circulating lymphocytes with clusters of AgNORs can be used as a parameter of tumour kinetics in CLL and helps to discriminate between patients with stable and progressive disease. For practical purposes, a value of more than 13% of cells with clusters is suggestive of progressive disease.

Journal Article↗
PubMed1995

Enalapril does not prevent the myocardial ischemia caused by the chronic inhibition of nitric oxide synthesis.

In rats, chronic administration of the nitric oxide (NO) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) causes arterial hypertension, cardiac hypertrophy and myocardial ischemic alterations such as necrosis and fibrosis. In this study, we evaluated the effect of 8 weeks of treatment with enalapril maleate on cardiac weight and on the development of the histological alterations induced by L-NAME. Enalapril significantly inhibited the development of both arterial hypertension (117.2 +/- 5.8, 161.8 +/- 8.8 and 122.0 +/- 10.6 mm Hg, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively) and left ventricular hypertrophy (1.36 +/- 0.13, 1.60 +/- 0.04 and 1.48 +/- 0.05 mg/g, for control, L-NAME- and L-NAME + enalapril-treated animals, respectively), but had no effect on the myocardial lesions. These findings demonstrate that although the renin-angiotensin system plays a major role in the development of arterial hypertension and cardiac hypertrophy, it does not modulate the ischemia-induced myocardial alterations observed in this model.

Angiotensin-Converting Enzyme Inhibitors↗