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Biomedical subjects

K Jacobsen

Publications and source records attributed to K Jacobsen.

At least 37 records · Page 2Linked to original sources
PubMed1994

[Pneumonia among patients admitted to intensive care units. An epidemiological multicenter study of APACHE II score, incidence and course].

Pneumonia in patients in intensive care units (ICU) is associated with several diagnostic difficulties and high mortality. This study was conducted to describe the diagnostic procedures and clinical characteristics of the pneumonic and critically ill patient in relation to APACHE II score. The material consisted of 193 patients admitted to seven Danish ICUs and is also included in a European epidemiologic survey (EURO.NIS). Twenty-eight (14.5%) developed pneumonia and 18 (9.3%) of these were nosocomial (> 48h after admission). Patients with pneumonia had a significantly higher APACHE II score, duration of stay and mortality. The techniques used to diagnose pneumonia were mainly conventional and did not or only seldom include protected brush, bronchoalveolar lavage or pulmonary biosy. The predominant pathogens isolated in tracheal aspirate were Gram-negative bacilli (50%). The APACHE II scoring system was found to stratify patients with respect to mortality, duration of stay and pneumonia diagnosed in ICU.

Adult↗
PubMed1994

Immunohistochemical detection of metallothionein in primary breast carcinomas and their axillary lymph node metastases.

Metallothioneins (MTs) are low-molecular-weight proteins with specific binding for group II metal ions. MTs are involved in the detoxification of metals, but can also play a role in protection of the cell against certain anticancer agents and from damage of irradiation. High expression of MTs in primary breast carcinomas has been found to be associated with poorer prognosis. Expression of MT (MT) was examined immunohistochemically in 160 breast carcinomas and their concomitant lymph node metastases. The immunoreactivity appeared to be independent of the length of fixation when the section was microwaved before incubation with the primary antibody, a monoclonal antibody E-9. The findings were correlated with various histopathological factors, disease-free survival and over-all survival. Patients were divided into two groups, those with MT over-expression (above 10% of positive tumour cells), and those with low MT expression (below 10% positive). MT over-expression was found to be correlated with postmenopausal status and inversely with positive progesterone receptor status (PgR). MT over-expression showed statistically significant correlation with poor over-all survival. No differences in survival were seen between pre- and postmenopausal patients. PgR was in univariate analysis a poor prognostic parameter. In one fourth of the patients, the lymph node metastases showed increased MT expression compared with the primary tumour. These patients had a poorer, but not statistically significant different survival. MT expression was not correlated to chemo- or radiation therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1994

Apoptosis and macrophage-mediated cell deletion in the regulation of B lymphopoiesis in mouse bone marrow.

Studies of cell population dynamics and microenvironmental organization of B lymphopoiesis in the bone marrow of normal mice and in various genetically modified states have shown that cell loss, involving processes of apoptosis and macrophage-mediated cell deletion, is a prominent feature of the primary genesis of B lymphocytes. Balanced against the influence of proliferative stimulants, the programmed death of precursor B cells provides a quantitative control, determining the magnitude of the final output of functional B lymphocytes to the peripheral immune system. The cell loss mechanisms can be readily set in motion by external or systemic influences, making the B-cell output particularly vulnerable to suppression by ionizing irradiation, stress or other systemic mediators. In addition, however, cell loss exerts an important quality control in the formation of the primary B-cell repertoire. The combination of apoptosis and macrophage-mediated deletion, acting at successive stages of B-cell differentiation, efficiently eliminates many precursors having non-productive Ig gene rearrangements, cell cycle dysregulations, and certain autoreactive Ig specificities. Outstanding areas of further work abound. Important questions concern the nature of mechanisms which underlie the processes of B-cell apoptosis and macrophage deletion in bone marrow, the microenvironmental signals involved in B-cell life or death decisions and genetic factors which may override these B-cell culling mechanisms. The answers will be relevant to problems of autoimmune disease, humoral immunodeficiency and B-cell neoplasia.

Animals↗
PubMed1993

Electroacupuncture in anaesthesia for hysterectomy.

We have studied the effects of electroacupuncture at classical acupuncture points, applied before and during surgery in patients undergoing hysterectomy, on postoperative pain and metabolic stress responses in a prospective, randomized and patient-blinded manner. Fifty otherwise healthy women were allocated randomly to receive or not receive electroacupuncture. Electroacupuncture was begun 20 min before skin incision and continued to the end of surgery. All patients received similar general anaesthesia and all received patient-controlled analgesia (PCA) after operation. Postoperative pain in the two groups was evaluated by recording analgesic requirements by PCA and by pain-rating performed by patients and nursing staff. There were no significant differences between the two groups in postoperative analgesic requirements, pain-rating or metabolic stress responses.

Adult↗
PubMed1993

Cell populations during tumorigenesis in Eu-myc transgenic mice.

Transgenic mice bearing a c-myc oncogene under control of the immunoglobulin heavy chain (Igh) enhancer (Eu-myc mice) (1, reviewed in 2) undergo a reproducible series of developmental stages and die from malignancies of the B lymphocyte lineage. To investigate the cellular events underlying tumorigenesis in this model, we quantified B lymphoid subpopulations and turnover at various stages of this process. An early stage was characterized by the presence in the blood of many large proliferating B lineage cells marked by surface antigen phenotype IgM+l-, B220low, CD5-, Mac-1low. During a prolonged intermediate 'remission' phase of different duration in each mouse, B lymphocytes in the periphery were non-proliferative, few, and of conventional phenotype (IgM+, B220+, CD5-, Mac-1-), while subsets of precursor B cells were both numerous and highly proliferative in the bone marrow. In the final stage of tumorigenesis, large proliferating cells similar in phenotype to those of the early period reappeared and increased rapidly in numbers. This B cell tumorigenic progression occurred independently of interactions with T lymphocytes. Evidence of massive cell death in the bone marrow during the intermediate phase, plus molecular characterization of the final tumors, suggested that the end of the peripheral 'remission' period and entry into the terminal stage of tumorigenesis may be due to a clone of cells acquiring the ability to circumvent normal processes of cell death and elimination that usually regulate the egress of B cells from the bone marrow to the periphery.

Age Factors↗
PubMed1992

Highly restricted expression of a stromal cell determinant in mouse bone marrow in vivo.

B lymphocyte precursor cells in mouse bone marrow develop in close association with stromal cells which provide essential growth signals. To identify molecules that may normally play a role in this interaction we have examined the in vivo binding of a new monoclonal antibody (mAb) (KMI6) that recognizes a determinant on a bone marrow stromal cell line (BMS2) in vitro. Flow cytometric and radioautographic evaluations revealed that the antigen recognized by KMI6 is represented on the surface of an extremely small number of cells in bone marrow cell suspensions from adult mice. An apparent molecular mass of 110 kD was obtained by surface labeling of a stromal cell clone and immunoprecipitation. Purified mAb KMI6 labeled with 125I was then given intravenously to young C3H/HeJ mice. Unbound mAb was washed out by cardiac perfusion and femoral bone marrow was examined by light and electron microscope radioautography. KMI6 labeling was heavy on the plasma membrane of many stromal cells, especially those located towards the outer subosteal region. The KMI6-labeled stromal cells were usually associated with cells of lymphoid morphology which they often completely surrounded. The labeling was restricted to areas of stromal cell plasma membranes in contact with lymphoid cells. The lymphoid cells themselves, as well as macrophages and other hemopoietic cells, failed to bind mAb KMI6 significantly. Stromal cells in bone marrow depleted of hemopoietic cells by gamma-irradiation (9,5 Gy) bound mAb KMI6 at reduced intensity. The results demonstrate that the KMI6 determinant, a 110-kD protein, is expressed on bone marrow stromal cells in vivo. Its restriction to areas of interaction with lymphoid cells suggests a role in forming microenvironmental niches of B lymphopoiesis. The surface membrane of individual stromal cells may thus be functionally polarized towards interacting B cell precursors and other hemopoietic cells.

Animals↗
PubMed1992

Dynamics and localization of early B-lymphocyte precursor cells (pro-B cells) in the bone marrow of scid mice.

Mice homozygous for the scid (severe combined immunodeficiency) mutation are generally unable to produce B lymphocytes, a condition attributed to defective rearrangement of immunoglobulin genes in precursor B cells. Some early B-lineage cells are present in the bone marrow (BM), however. In scid mice, we defined three subsets of early progenitor B cells lacking mu heavy chains (pro-B cells) based on the expression of terminal deoxynucleotidyl transferase (TdT) and B220 glycoprotein: (a) early pro-B cells (TdT+B220-), (b) intermediate pro-B cells (TdT+B220+), and (c) late pro-B cells (TdT-B220+). Double immunofluorescence labeling of BM cell suspensions has shown normal numbers of early and intermediate pro-B cells, substantially reduced numbers of late pro-B cells, and an absence of pre-B cells and B cells. Early and intermediate pro-B cells accumulated in metaphase in near-normal numbers after intraperitoneal (IP) vincristine administration. B220+ pro-B cells have been localized in BM sections by the binding of intravenously (IV) administered 125I monoclonal antibody (MoAb) 14.8, detected by light and electron microscope radioautography. Many B220+ cells were located peripherally in the bone-lining cell layers associated with stromal reticular cells. More centrally located B220+ cells were frequently associated with macrophages containing prominent cytoplasmic inclusions. Occasional B220+ cells were present in venous sinusoids. These results demonstrate that many pro-B cells in scid mice occupy microenvironments in the BM near the surrounding bone. The pro-B cells maintain normal rates of production during stages of presumptive mu heavy-chain gene rearrangement, apparently unaffected by the absence of a mature B cell pool. Nearly all defective cells then abort at the late pro-B cell stage and are deleted, apparently by macrophages. The findings contribute to models of in vivo differentiation, regulation, localization, and selection of early B-lineage cells in the BM.

Animals↗
PubMed1992

Acute and habitual caffeine ingestion and metabolic responses to steady-state exercise.

This study compared the exercise catecholamine and metabolic responses to a caffeine challenge in trained subjects before and after a 6-wk period of increased caffeine ingestion. Trained subjects (n = 6) were challenged with 500 mg of caffeine followed by prolonged exercise before and after 6 wk of increased caffeine ingestion (500 mg ingested before each daily run). A control group (n = 6) of trained subjects followed the same protocol except for caffeine ingestion. Acute caffeine ingestion resulted in increased plasma epinephrine and decreased respiratory exchange ratio (RER) during exercise. After 6 wk of caffeine supplementation, the epinephrine response to exercise or caffeine plus exercise was decreased, although the latter still resulted in a lower RER value compared with exercise without caffeine ingestion. Activity of key metabolic enzymes (hexokinase, citrate synthase, phosphorylase, and 3-hydroxyacyl-coenzyme A dehydrogenase) from biopsies of the gastrocnemius showed no response to 6 wk of this increased adrenergic receptor stimulation and, on the basis of the lower RER, enhanced fat metabolism. This study suggests that caffeine ingestion by trained subjects causes increases in plasma epinephrine and reduces the RER during exercise. However, habitual stimulation results in a general dampening of the epinephrine response to caffeine or exercise. There was no indication that increased adrenergic stimulation and fat oxidation caused any adaptation in the activity of metabolic enzymes.

Adult↗
PubMed1991

[Vision tests for the severely handicapped].

The methods available for acuity assessment of multi-handicapped persons are limited by lack of verbal, manual and locomotor response indicators. However, eye activity itself, can provide a clue to what is seen. The results in the present study suggest that the preferential looking technique, using gratings as stimuli and eye movements as response indicators, is a useful tool for assessing the acuity of multi-handicapped people. However, acuity testing of multi-handicapped people was very time consuming, and called for many individual adaptations.

Blindness↗
PubMed1990

[Selective screening for hypercholesterolemia. Results from a screening model in general practice].

At present, it appears to be probable that both dietary changes and medicinal treatment can reduce the risk of development of coronary disease in middle-aged men with moderately to severely raised blood cholesterol values. Internationally, the limits for cholesterol intervention are considerably lower than in Denmark. Extensive cholesterol screening is, however, very expensive and the identified persons with high cholesterol values will frequently be found in sex and age groups where the beneficial effect of intervention is probably limited. A model for selective cholesterol screening in high risk groups in general practice is described here. In 20 general practices, all of the men aged 45-59 years belonging to the practice were invited to examination of cholesterol and blood pressure. Plasma cholesterol was measured by means of a Reflotron (results are available within three minutes) and the blood pressure and tobacco consumption were registered. After this, the patient's own general practitioner calculated with each of the persons the risk for development of myocardial infarction within the next ten years and intervention could be commenced immediately. 41% of those invited came for examination. Out of these, 29% had cholesterol values greater than or equal to 7.0 mmol/l (Danish limiting value), 44% greater than or equal to 6.5 mmol/l (limiting value in the remainder of Western Europe), and 5% greater than or equal to 9.0 mmol/l (severe hypercholesterolaemia) while only 18% had completely normal cholesterol less than 5.2 mmol/l. In every practice, two patients on an average were found with severe hypercholesterolaemia greater than or equal to 9.0 mmol/l. 28% of the participants had at least two of the three risk factors investigated. (ABSTRACT TRUNCATED AT 250 WORDS)

Denmark↗
PubMed1990

[Formalized dietary advice in hypercholesterolemia. Results in 110 men diagnosed by selective screening in general practice].

In connection with a screening investigation for high blood cholesterol in middle-aged men in general practice in the Municipality of Copenhagen, all participants with cholesterol values greater than or equal to 7.5 mmol/l were given brief advice by their own general practitioner and were invited to come for fasting blood lipid tests approximately ten days later. In cases with continued cholesterol greater than or equal to 6.8 mmol/l, the participants together with wives or partners were invited to formalized dietary advice in small groups. Already before the formalized dietary advice, an average decrease in serum cholesterol of 10% was observed. This was attributed to biological variation, absence of fasting, the degree of error between the measuring methods and also a genuine decrease on the basis of the brief dietary advice by the general practitioner. On control after dietary advice, a further decrease in cholesterol of 15% was observed while low density lipoprotein cholesterol fell by 20% and triglycerides by 23%. These decreases must be considered to result mainly from the dietary advice. It is concluded that a single but professional session of dietary advice in small groups and with involvement of the wives or partners is an effective method of treatment in hypercholesterolaemia. If the decrease in cholesterol obtained can be maintained, the literature suggests that the risk of development of ischaemic heart disease during the subsequent 5-7 years is reduced by 20-30%.

Denmark↗
PubMed1990

[Measurement of blood cholesterol, decentralized, using a Reflotron, or centralized in a laboratory. A comparison].

In connection with an extensive screening programme for blood cholesterol, the cholesterol values in 105 participants were measured on a sample of capillary blood employing a Reflotron and, simultaneously, samples of venous blood were examined by conventional enzymatic analysis in a laboratory. Whereas the day-to-day variation and the scatter involved were quite limited in the laboratory, the variation scatter between the two methods of measurement was 0.65 mmol/l. This figure was, however, no greater than that described between different laboratories in USA. Nevertheless, it is an important problem with the Reflotron method that even slight deviations from the recommended procedure of withdrawing blood involve a systematic risk for erroneously low cholesterol results.

Blood Chemical Analysis↗
PubMed1990

[Screening for cardiovascular risk factors in a large workplace].

A screening investigation was carried out in a large industry in the Copenhagen region and 1,472 of the employees were offered examination of blood cholesterol and measurement of blood pressure. At this examination the employees completed a one-page questionnaire about other cardiovascular risk factors. 45% of those invited participated in the investigation, the poorest participation was among women and the greatest among the male officials. On account of the limited number of female employees, the majority of results were only calculated for men. Over 1/3 of these had hypercholesteremia (greater than or equal to 7.0 mmol/l) and nearly 1/3 had, simultaneously, at least two cardiovascular risk factors in addition to age and male sex. Extensive occupational investigations under the auspices of WHO have demonstrated that energetic intervention at the place of work aimed at the cardiovascular risk factors can reduce the risk of development of coronary heart disease and death within a six-year follow-up period. It is therefore emphasized that similar interventions are very necessary also in Denmark.

Adult↗
PubMed1990

Microenvironmental organization and stromal cell associations of B lymphocyte precursor cells in mouse bone marrow.

B lymphocyte precursor cells expressing B220 glycoprotein have been examined in mouse bone marrow (BM) by the in vivo binding of monoclonal antibody (mAb) 14.8 visualized by light and electron microscope radio autography. Young mice were injected intravenously with 125I-labeled mAb 14.8 and then perfused to remove unbound antibody. Quantitative analysis of radioauto graphic sections of femoral BM revealed many labeled mAb 14.8-binding cells which were situated both singly and in groups throughout the extravascular BM parenchyma. Groups of large 14.8+ cells were located in patchy areas in the peripheral regions of the BM near the endosteum. These cells were shown to include proliferating precursor B cells by using mice given vincristine sulfate to stop cells in metaphase and mice treated from birth with anti-IgM antibodies to delete mature B lymphocytes. Electron microscopy revealed clusters of 14.8+ cells intimately associated with the processes of stromal reticular cells. Other 14.8+ cells were in close contact with macrophages; in some instances the intervening cell membranes were indistinct and the macrophages contained 14.8+ material in their cytoplasm. In addition, 14.8+ small lymphocytes were highly concentrated within the lumen of some sinusoids. The present method of detecting B lineage precursor cells in situ has led to a working model of the microenvironmental organization of primary B cell genesis in vivo. The model proposes (a) a centrally directed sequence of differentiation initiated by early precursor cells situated peripherally near the surrounding bone; (b) close associations between precursor B cells and stromal reticular cells; (c) deletion of ineffective B cells by macrophages, and (d) an intravascular maturation phase before B lymphocytes are finally delivered into the blood stream.

Animals↗