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Biomedical subjects

V Jensen

Publications and source records attributed to V Jensen.

At least 19 recordsLinked to original sources
PubMed1997

MIB-1 expression in breast carcinomas with medullary features. An immunohistological study including correlations with p53 and bcl-2.

Typical medullary carcinoma (TMC) is usually considered to have a more favourable prognosis than other types of infiltrating breast carcinomas. This is a biological paradox, since its clinical behaviour is not in agreement with its anaplastic morphology and high mitotic rate. It should be remembered that neoplastic growth reflects cell production minus cell loss, the latter being achieved by apoptosis. At present, bcl-2 oncogene (apoptosis inhibitor) and p53 gene are assumed to be involved in the regulation of cell death and tumour proliferation. Sixty breast carcinomas, initially indexed as medullary carcinomas, were re-classified using the diagnostic criteria given by Ridolfi. This review yielded 13 typical (TMC), 24 atypical (AMC), and 23 non-medullary carcinomas (NMC). Following antigen retrieval by microwave treatment, immunohistochemical analyses, using MIB-1, p53 and bcl-2 monoclonal antibodies were performed on serial sections from formalin-fixed, paraffin-embedded specimens. TMC revealed the highest incidence of intense p53 positivity, and the highest mean MIB-1 index, and absence of the apoptosis-inhibitor protein bcl-2. These results suggest the presence of a higher overall cell turnover in TMC than in AMC and NMC. Increased apoptosis balancing the increased cell proliferation might be among the possible explanations for the more favourable prognosis in TMC.

Adult↗
PubMed1997

Prognostic comparison of three classifications for medullary carcinomas of the breast.

The aim of this study was to make prognostic comparisons between the modified scheme of Pedersen et al. the definitions of Tavassoli and the Ridolfi criteria for medullary carcinomas. Sixty breast carcinomas primarily diagnosed as medullary carcinomas were reclassified into typical medullary carcinoma (TMC), atypical medullary carcinoma (AMC) and non-medullary carcinoma (NMC) according to the three classifications. The Ridolfi classification proved to be superior to the two other schemes in discriminating survival differences between the three groups TMC, AMC and NMC. All 13 patients with TMC are still alive indicating an excellent prognosis, while 29% and 39% of the 47 patients in the AMC and NMC category, respectively, have died of their disease. In the simplified system of Pedersen et al. the survival at 10 years for TMC patients decreased to 75% and no significant survival difference between the three groups could be demonstrated. As the prognosis for AMC proved to be worse compared to TMC and in fact was similar to NMC with values of 43% at 10 years in the Ridolfi classification, we find no reasons to maintain this category. We conclude that as long as no alternative and more easily applicable diagnostic method exists, pathologists should still apply the Ridolfi criteria on these tumours with medullary features leaving two diagnostic possibilities: TMC or NMC (i.e. poorly differentiated ductal carcinoma). Only lesions that fulfil all six criteria without any doubt should be diagnosed as TMC, thus avoiding overdiagnosis and a resulting risk of undertreatment.

Adult↗
PubMed1997

Total number of cancer cell nuclei and mitoses in breast tumors estimated by the optical disector.

OBJECTIVE: The total number of cancer cell nuclei, N(nuc), and of mitoses, N(mit), in the primary lesion are potentially important indicators of tumor biology. In the present study, such estimates were obtained on breast cancers by an unbiased stereologic method. STUDY DESIGN: The total number estimates are the product of two variables: (1) the volume of tumor, V(T), estimated by the Cavalieri principle, and (2) the densities of cancer cell nuclei and of mitoses obtained in small, three-dimensional samples (i.e., optical disectors) of 40-micron-thick methacrylate sections, which were selected systematically at random from the whole specimen. RESULTS: In 93 prospectively collected tumors, N(nuc) ranged from 0.06 to 7.9 10(9) (median, 0.6 10(9)), and N(mit) ranged from 0.02 to 64 10(6) (median, 1.5 10(6)). Both N(nuc) and N(mit) correlated significantly with V(T) (r = .77 and .60, respectively); however, the steep slopes of the regression lines indicated that densities of nuclei and mitoses increased as a function of tumor size. On average, N(mit) and estimates of mitotic frequency tended to be larger in lymph node-positive patients as compared with lymph node-positive patients as compared with lymph node-negative ones (2P < or = .08), whereas no such relation was found for nuclear counts (2P > or = .40). By counting a median number of 195 nuclei and 28 mitoses per tumor, the average coefficients of error of N(nuc) and N(mit) were 17% and 32%, respectively; this gave seemingly sufficient precision as compared with the huge interpatient variation in estimates, 180% and 490%. Moreover, the intraobserver reproducibility of density estimates was excellent (r > or = .88). CONCLUSION: The present study showed the feasibility, efficiency and reproducibility of the unbiased optical disector principle applied to human breast cancer and provided data on new parameters of biologic relevance. The technique seems suitable for use in experimental oncology, but further studies are needed to investigate its clinical value.

Breast Neoplasms↗
PubMed1996

The anaesthetic management of a patient with Emery-Dreifuss muscular dystrophy.

PURPOSE: This case report presents a patient with Emery-Dreifuss Muscular Dystrophy and describes the anaesthetic considerations. CLINICAL FEATURES: The features of Emery-Dreifuss Muscular Dystrophy are contractures, humeroperoneal muscle weakness and cardiomyopathy. The anaesthetic considerations for this syndrome are difficult tracheal intubation, difficult spinal anaesthetic, heart block, gastric reflux, rhabdomyolysis, and unproved malignant hyperthermia susceptibility. CONCLUSION: The major anaesthetic problem for the patient with Emery-Dreifuss Muscular Dystrophy could be a life-threatening cardiomyopathy.

Adult↗
PubMed1996

MIB-1 expression and iododeoxyuridine labelling in soft tissue sarcomas: an immunohistochemical study including correlations with p53, bcl-2 and histological characteristics.

We investigated the relationship between immunohistochemical estimates of proliferative activity and expression of bcl-2 protein and mutant p53 protein in 23 cases of soft tissue sarcoma. Furthermore, the reproducibility of estimates of proliferative activity was analysed and correlations between the variables and with mitotic score were investigated. Proliferative activity was assessed by use of monoclonal antibody MIB-1 and staining for iododeoxyuridine (IdUrd), and evaluated in multiple, random, systematically sampled fields of vision. MIB-1 indices were higher than those of IdUrd but for each case the two values were positively correlated (r = 0.78). The MIB-1 index correlated positively with mitotic score (2P < 0.001) and malignancy grade (2P = 0.001). The intraobserver reproducibility of the MIB-1 and IdUrd indices were excellent (r = 0.98 and r = 0.90, respectively). p53 expression was detected in 43% and strong bcl-2 expression was present in 57% of the studied cases. Expression of p53 and bcl-2 were not significantly correlated to proliferative activity or the histological features. We conclude, that the MIB-1 index is a reliable and reproducible estimate of proliferative activity and might improve the accuracy of conventional malignancy grading of soft tissue sarcomas. Furthermore, the results indicate that neither mutant p53 protein nor bcl-2 oncogene alone are sufficient to induce increased proliferation in these sarcomas.

Antigens, Nuclear↗
PubMed1996

Stereologic estimation of breast tumor size.

OBJECTIVE: The largest tumor diameter, D(T), is a variable of great clinical value in breast cancer but a biased and imprecise estimator of real tumor size. Three-dimensional, shape-independent estimates would more realistically reflect the tumor bulk and provide more accurate clinical staging. For experimental oncology, the measurements may be useful for precise assessment of tumor burden. STUDY DESIGN: In 64 prospectively collected breast cancers, unbiased stereology was used for estimating the gross tumor volume, V(T), cutting specimens into parallel, equally thick sections with subsequent determination of total tumor sectional area. For comparison, the volume of invasive tumor epithelium, "V"(epi), was obtained by microscopic examination of systematically sampled tissue fractions of the same tumors, embedded in both methacrylate and paraffin. RESULTS: The median D(T) was 2.2 cm, and the median V(T) was 6.72 cm3. The correlation between these variables was not very close (r = .77), and the slope of the regression line was steeper than expected, presumably reflecting a change in tumor shape with growing size. The sampling scheme used for estimation of V(T) proved highly efficient, yielding a mean error coefficient of 9%. The median "V"(epi) in methacrylate was 1.19 cm3, 21% larger than in paraffin. Estimates of "V" (epi) were highly reproducible (r = .97) and correlated highly with point counting-based estimates of the feature (r = .96). "V"(epi) correlated with V(T) (r > or = .75), but the slopes of the regression lines were steeper than expected, corresponding with the correlation found between epithelial volume fraction and tumor size (r = .26). On average, about 25% of the gross tumor was composed of invasive epithelium, but with a wide range. CONCLUSION: In breast cancer, realistic estimates of tumor volume, volume of invasive epithelium and epithelial volume fraction can be obtained by efficient stereologic techniques, which seem useful for clinical and experimental oncology. In the present methodologic study, baseline data were generated. Further studies are needed to assess the clinical value of stereologic tumor size estimates as compared with traditional staging parameters.

Breast Neoplasms↗
PubMed1995

Impairment of synaptic vesicle clustering and of synaptic transmission, and increased seizure propensity, in synapsin I-deficient mice.

Synapsin I has been proposed to be involved in the modulation of neurotransmitter release by controlling the availability of synaptic vesicles for exocytosis. To further understand the role of synapsin I in the function of adult nerve terminals, we studied synapsin I-deficient mice generated by homologous recombination. The organization of synaptic vesicles at presynaptic terminals of synapsin I-deficient mice was markedly altered: densely packed vesicles were only present in a narrow rim at active zones, whereas the majority of vesicles were dispersed throughout the terminal area. This was in contrast to the organized vesicle clusters present in terminals of wild-type animals. Release of glutamate from nerve endings, induced by K+,4-aminopyridine, or a Ca2+ ionophore, was markedly decreased in synapsin I mutant mice. The recovery of synaptic transmission after depletion of neurotransmitter by high-frequency stimulation was greatly delayed. Finally, synapsin I-deficient mice exhibited a strikingly increased response to electrical stimulation, as measured by electrographic and behavioral seizures. These results provide strong support for the hypothesis that synapsin I plays a key role in the regulation of nerve terminal function in mature synapses.

Animals↗
PubMed1995

Analysis of dendritic spines in rat CA1 pyramidal cells intracellularly filled with a fluorescent dye.

The dendritic branching pattern and the distribution of dendritic spines were studied in hippocampal neurones with an improved technique. In slices taken from adult Wistar rats, CA1 pyramidal cells were filled with Lucifer yellow and examined under a laser-scanning confocal microscope. The basal dendrites were found evenly distributed inside a regular cupola-shaped volume. Their total length was about 4,500 microns. The branches divided between one and three times, with the initial segments comprising less than 2%, and the long terminal segments (mean length, 119 microns) including more than 80% of the total length of the basal dendrites. The apical dendritic branches emerged obliquely from the main shaft, ran for a distance of 50 to 250 microns, and made up a total length of about 5,100 microns in stratum radiatum and between 1,100 and 3,200 microns in stratum lacunosum-moleculare. The mean total length of the dendritic tree was 11,900 microns. All values were corrected for shrinkage. Shrinkage was measured in three dimensions and was 20.2% in the horizontal (x/y) plane and 40.9% in the vertical (z) plane. Both the basal and the apical dendritic branches were covered by regularly spaced spines. When corrected for dehydration-induced shrinkage and for hidden spines, the density was 1.80 and 2.00 spines/microns dendritic length for the basal and apical dendritic branches, respectively. Apart from the initial parts of the branches, which had few or no spines, the spines were remarkably evenly spaced. In particular, the distance between spine heads was significantly different from a random distribution, suggesting a regulatory process for the spacing of spines.

Animals↗
PubMed1995

The prognostic value of oncogenic antigen 519 (OA-519) expression and proliferative activity detected by antibody MIB-1 in node-negative breast cancer.

The prognostic value of oncogenic antigen 519 (OA-519) expression and tumour proliferative activity was evaluated in a retrospective series of 118 patients with low-risk breast cancer. Low risk was defined as negative axillary nodes, tumour diameter < or = 50 mm, and no histological evidence of invasion of skin or deep fascia (= T1N0M0 and T2N0M0). The median follow-up time was 104 months (range 5-143 months). Immunohistochemical analysis of OA-519 expression was performed on formalin-fixed, paraffin-embedded tissue. The proliferative activity was estimated using a Ki-67 equivalent monoclonal antibody (MIB-1), which is applicable on formalin-fixed, paraffin-embedded tissue after microwave pretreatment. OA-519 was expressed in about one-third of the tumours and the percentage of proliferating cells (the MIB-1 index) ranged between 1 and 72 per cent (median 17 per cent). Using multivariate Cox analysis, both the MIB-1 index and OA-519 expression were of independent prognostic value (2p < or = 0.01), and the combined immunohistological approach may therefore be useful in selecting patients with node-negative breast cancer who might benefit from adjuvant therapy.

Adult↗
PubMed1995

Quantitative histopathology in lymph node-negative breast cancer. Prognostic significance of mitotic counts.

Reliable prognostic factors are needed to improve the stratification of patients with lymph node-negative breast cancer to different therapy modalities. We investigated the prognostic value of quantitative histopathology in a retrospective study of 98 "low-risk" breast cancer patients (T1+2N0M0) with a median follow-up of 9 years. An interactive video system and stereological and morphometric techniques were used to obtain estimates of four nuclear features (mean volume, mean profile area, volume fraction, and profile density), and two mitotic counts [mitotic profile frequency (MF) and mitotic profile density (MD)]. All measurements were performed in fields of vision sampled systematically from the whole tumour area of a routine histological section. Histological grade, histological type, and oestrogen receptor (ER) status was reassessed, whereas tumour diameter and age at diagnosis were recorded from the files. We found that all quantitative histopathological variables and ER status were correlated with histological grade. Single-factor prognostic analyses showed a highly significant value of MF (2p = 0.001) and a marginally significant value of MD (2p = 0.09), whereas no other variable approached statistical significance (2p > or = 0.25). In a multivariate Cox analysis, MF was the only parameter of significant independent prognostic value (2p = 0.03). Thus, the prognostic value of nuclear features found in previous studies could not be reproduced, whereas the marked value of mitotic counts for prediction of the outcome in patients with breast cancer was confirmed. Mitotic counts are easily obtained and may be of clinical value for identification of high-risk cases among patients with lymph node-negative breast cancer.

Adult↗
PubMed1995

Immunohistochemical quantitation of oestrogen receptors and proliferative activity in oestrogen receptor positive breast cancer.

AIM: To evaluate the effect of the duration of formalin fixation and of tumour heterogeneity on quantitative estimates of oestrogen receptor content (oestrogen receptor index) and proliferative activity (MIB-1 index) in breast cancer. METHODS: Two monoclonal antibodies, MIB-1 and oestrogen receptor, were applied to formalin fixed, paraffin wax embedded tissue from 25 prospectively collected oestrogen receptor positive breast carcinomas, using a microwave antigen retrieval method. Tumour tissue was allocated systematically to different periods of fixation to ensure minimal intraspecimen variation. The percentages of MIB-1 positive and oestrogen receptor positive nuclei were estimated in fields of vision sampled systematically from the entire specimen and from the whole tumour area of one "representative" cross-section. RESULTS: No correlation was found between the oestrogen receptor and MIB-1 indices and the duration of formalin fixation. The estimated MIB-1 and oestrogen receptor indices in tissue sampled systematically from the entire tumour were closely correlated with estimates obtained in a "representative" section. The intra- and interobserver correlation of the MIB-1 index was good, although a slight systematical error at the second assessment of the intraobserver study was noted. CONCLUSION: Quantitative estimates of oestrogen receptor content and proliferative activity are not significantly influenced by the period of fixation in formalin, varying from less than four hours to more than 48 hours. The MIB-1 and the oestrogen receptor indices obtained in a "representative" section do not deviate significantly from average indices determined in tissue samples from the entire tumour. Finally, the estimation of MIB-1 index is reproducible, justifying its routine use.

Antibodies, Monoclonal↗
PubMed1994

Specificity of protein kinase inhibitor peptides and induction of long-term potentiation.

Previous studies have used synthetic peptide analogs, corresponding to sequences within the pseudosubstrate domain of protein kinase C (PKC) or the autoregulatory domain of Ca2+/calmodulin-dependent protein kinase II (CaMKII), in attempts to define the contribution of each of these protein kinases to induction of long-term potentiation (LTP). However, the specificity of these inhibitor peptides is not absolute. Using intracellular delivery to rat CA1 hippocampal neurons, we have determined the relative potency of two protein kinase inhibitor peptides, PKC-(19-36) and [Ala286]CaMKII-(281-302), as inhibitors of the induction of LTP. Both peptides blocked the induction of LTP; however, PKC-(19-36) was 30-fold more potent than [Ala286]CaMKII-(281-302). The relative specificity of PKC-(19-36), [Ala286]CaMKII-(281-302), and several other CaMKII peptide analogs for protein kinase inhibition in vitro was also determined. A comparison of the potencies of PKC-(19-36) and [Ala286]CaMKII-(281-302) in the physiological assay with their Ki values for protein kinase inhibition in vitro indicates that the blockade of induction of LTP observed for each peptide is attributable to inhibition of PKC.

Amino Acid Sequence↗
PubMed1991

The TURP syndrome.

This article discusses the presentation, aetiology, treatment and prevention of central nervous system disturbances after transurethral resection of the prostate. Nausea and vomiting, visual symptoms, and altered states of consciousness have been reported as complications due to intravascular absorption of irrigating fluid. Hypotonicity after absorption of the irrigating fluid causes cerebral oedema. Hyperglycinaemia may cause visual disturbances and hyperammonaemia may cause delayed coma.

Consciousness Disorders↗
PubMed1984

Tardy posterior interosseous nerve palsy as a result of an unreduced radial head dislocation in Monteggia fractures: a report of two cases.

Tardy palsy of the posterior interosseous nerve after a malunited Monteggia fracture with an unreduced dislocation of the radial head is considered to be extremely rare. Four earlier cases were treated by excision of the radial head or by tendon transfers. Another two cases have been reported, both treated successfully by decompression of the nerve in the radial tunnel between the two heads of the supinator. This simple operation should be given a trial before tendon transfers are considered, even if the palsy has been of long duration.

Adult↗
PubMed1983

Femoral-femoral cardiopulmonary bypass prior to induction of anaesthesia in the management of upper airway obstruction.

A case is presented of a female with respiratory distress who was initially treated as having asthma. Her chest x-ray was normal but tracheal tomograms revealed a tracheal tumour almost completely occluding the tracheal lumen. The impending tracheal occlusion was managed with femoral-femoral cardiopulmonary bypass instituted under local anaesthesia prior to induction of anaesthesia and diagnostic bronchoscopy and airway establishment with tracheal intubation. Other indications for the use of cardiopulmonary bypass prior to the induction of anaesthesia are reviewed.

Aged↗
PubMed1983

Influence of moderate alcohol intake on wakening plasma thiopental concentration.

In an earlier study, an inverse correlation between thiopental-induced sleeping time and alcohol intake in the preceding week was demonstrated in women undergoing termination of pregnancy. In order to investigate the mechanism behind the apparent cross-tolerance, the relationship between alcohol consumption in the week preceding thiopental/nitrous oxide/oxygen anesthesia and wakening plasma thiopental concentration on one hand and sleeping time on the other was examined in 68 women scheduled for termination of pregnancy and in 37 women scheduled for diagnostic uterine dilatation and curettage. In terms of pure alcohol, the weekly intake (mean +/- s.d.) was 1.17 +/- 2.07 ml . kg-1 in the former and 1.49 +/- 1.70 ml . kg-1 in the latter group. A positive correlation between alcohol consumption and wakening plasma thiopental concentration was found in both groups, reaching statistical significance (P less than 0.05) in the group undergoing termination of pregnancy, but not in the other. The inverse correlation found earlier between alcohol intake and sleeping time was not reproduced significantly in any of the groups. The results indicate that moderate alcohol intake may induce cerebral tolerance to thiopental.

Abortion, Induced↗
PubMed1982

Influence of moderate alcohol intake on thiopental anesthesia.

The relationship between alcohol intake over the week preceding anesthesia and various anesthetic parameters was examined in 119 women scheduled for termination of pregnancy under thiopental-nitrous oxide anesthesia. In terms of pure alcohol, the weekly intake was 1.03 +/- 1.09 ml.kg-1 (mean +/- s.d.), range 0-5.93, i.e. below average consumption in Denmark. Alcohol intake was negatively correlated with anesthetic sleeping time (P less than 0.01). Time and quality of anesthesia induction and frequency of anesthetic complications were not significantly correlated with the use of alcohol. Preanesthetic anxiety was not significantly correlated with any of the above data. Induction time and postoperative awareness were positively and sleeping time negatively correlated with age (P less than 0.05). The results indicate cross-tolerance between alcohol and thiopental, even when the regular intake of the former is low, and increasing thiopental requirements with increasing age.

Abortion, Induced↗