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Biomedical subjects

G Larsson

Publications and source records attributed to G Larsson.

At least 73 records · Page 4Linked to original sources

In situ detection of myocardial infarction in pig by measurements of aspartate aminotransferase (ASAT) activity in the interstitial fluid.

Microdialysis probes permeable to large molecules (m.w. cut-off > 200 kD) were introduced into the myocardium of anaesthetized pigs in order to evaluate their potential for early detection of myocardial ischaemia and enzyme markers for infarction. The left anterior descending coronary artery was occluded for 30 min and the myocardium was reperfused for 3 h. The concentrations of aspartate aminotransferase (ASAT), lactate, glucose and selected free amino acids were measured. The levels in the interstitium of ischaemic and non-ischaemic myocardium were compared with those in plasma from the coronary sinus as well as from a peripheral vein. Twelve probes were inserted in six pigs and withdrawn after 8-72 hours of sampling. No complications occurred. Simultaneous 100% increase of ASAT and lactate was found in myocardial dialysates after 30 min of ischaemia. ASAT activity remained at that level until the end of reperfusion. The plasma peak ASAT level was not attained until after 3 h. Glutamate was the only amino acid which increased significantly in the myocardial interstitium during ischaemia, peaking after 30 min of reperfusion. Dialysates from the unaffected myocardium showed no effects on lactate, ASAT or glutamate. The use of myocardial microdialysis for pre- and postoperative recordings in man is discussed.

Amino Acids↗

Frequency/volume chart: the basic tool for investigating urinary symptoms.

BACKGROUND: This article reviews the literature on the frequency/volume chart. The frequency/volume chart is the systematic registration of point of time of voiding and voided volume done by the patient in her own environment for a specified period of time, usually 24 or 48 hours. The chart can be supplemented with the registration of incontinence episodes. Measurements obtained from the frequency/volume chart include total voided volume/24 hours, frequency of micturition, mean voided volume, largest single voided volume and range of voided volumes. RESULTS: Normal values for these measurements as well as values for patients with stress incontinence and detrusor instability are presented. CONCLUSIONS: The frequency/volume chart is a simple and inexpensive way of recording basic data, some of which can be obtained in no other way, e.g. total voided volume. The frequency/ volume chart has acceptable reproducibility but limited diagnostic capacity. It provides a basis for instituting treatment in many patients and provides the best tool for following the result of treatment in patients with the urge syndrome.

Adult↗

Pad weighing tests: the best way to quantify urine loss in patients with incontinence.

This article reviews the literature on pad weighing tests composed to measure urinary incontinence. The tests can be divided into short-term tests (one to two hours) performed in a clinic or laboratory, or long-term tests (12 to 48 hours) performed by the patient at home. The short-term tests, apart from practical disadvantages, have low negative predictive value and require retrograde filling of the bladder to reach acceptable reproducibility. The long-term tests have practical advantages, better sensitivity and acceptable reproducibility. Pad weighing tests have no value for the purpose of differential diagnosis. The validity of the long-term test as a measure of the symptom of urinary incontinence is obvious whereas it is unclear what the short-term test measures.

Female↗

Kinetic characterization of dUTPase from Escherichia coli.

The enzyme dUTPase catalyzes the hydrolysis of dUTP to dUMP and pyrophosphate, thereby preventing a deleterious incorporation of uracil into DNA. The best known dUTPase is that from Escherichia coli, which, like the human enzyme, consists of three identical subunits. In the present work, the catalytic properties of the E. coli dUTPase were investigated in the pH range 5-11. The enzyme was found to be highly specific for dUTP and discriminated both base and sugar as well as the phosphate moiety (bound dUDP was not hydrolyzed). The second best substrate among the nucleotides serving as building blocks for DNA was dCTP, which was hydrolyzed an astonishing 10(5) times less efficiently than dUTP, a decline largely accounted for by a higher Km for dCTP. With dUTP.Mg as substrate, kcat was found to vary little with pH and to range from 6 to 9 s-1. Km passed through a broad minimum in the neutral pH range with values approaching 10(-7) M. It increased with deprotonation of the uracil moiety of dUTP and showed dependence on two ionizations in the enzyme, exhibiting pKa values of 5.8 and 10.3. When excess dUTPase was reacted with dUTP middle dotMg at pH 8, the two protons transferred to the reaction medium were released in a concerted mode after the rate-limiting step. The Mg2+ ion enhances binding to dUTPase of dUTP by a factor of 100 and dUDP by a factor of 10. Only one enantiomer of the substrate analog 2'-deoxyuridine-5'-(alpha-thio)-triphosphate was hydrolyzed by the enzyme. These results are interpreted to favor a catalytic mechanism involving magnesium binding to the alpha-phosphate, rate-limiting hydrolysis by a shielded and activated water molecule and a fast ordered desorption of the products. The results are discussed with reference to recent data on the structure of the E. coli dUTPase.UDP complex.

Deoxyuracil Nucleotides↗

Crystallization and preliminary X-ray analysis of human dUTPase.

Human dUTPase, expressed in Escherichia coli, has been crystallized. Single crystals were obtained by the vapour-diffusion technique using 2-propanol and PEG 4000 as precipitants. The enzyme was co-crystallized with the substrate dUTP and a metal chelator EDTA to prevent hydrolysis of the substrate. The crystals belong to the orthorombic space group P2(1)2(1)2(1) with cell dimensions a = 67.51, b = 68.26 and c = 91.00 A. The crystallographic asymmetric unit contains one trimer of identical subunits.

Journal Article↗

Rapid sampling, cell inactivation and evaluation of low extracellular glucose concentrations during fed-batch cultivation.

A method for rapid extracellular sampling, cell inactivation and handling of a large number samples has been developed and evaluated. This method might be used during experiments, where concentrations of extracellular components in the range of some milligrams per litre has to be evaluated. The analysis should be performed by enzymatic or colorimetric analysis and is shown to be suitable for measuring low nutrient concentrations present in fed-batch cultivation. The test organisms were Escherichia coli and Saccharomyces cerevisiae and the model substance was glucose. Using this technique, the sample can be taken in less than 0.15 s, a time during which negligible glucose is shown to be consumed from the sample. The glucose consumption is stopped by a rapid pH decrease using perchloric acid in a defined concentration that depended on the organism studied. This concentration was chosen in order to avoid cell lysis that could affect the glucose concentration by the intracellular release of glucose containing compounds and thereby expose them to the acid. It was seen that the sample mixed rapidly with the acid and that no hydrolysis of glucose related compounds interfered with the analysis. The samples were neutralised and the precipitation centrifuged to minimise the effect on the chosen enzymatic analysis. This analysis was modified and the accuracy determined in order to analyse concentrations in the milligram range. A method to increase the handling of a large number of samples was also devised which is based on measurements on microtiter plates and allows samples to be evaluated with a high statistical accuracy with minimum sample waste in a short time. The ability of the method is shown by a study of the metabolic response of a shift in glucose feed, as followed by glucose analysis.

Cell Division↗

Reproducibility of a new method to determine cough-induced leak-point pressure in women with stress urinary incontinence.

The aim of the study was to test the reproducibility of a new method of determining cough-induced leak-point pressure (CILPP). A cough-induced increased in intra-abdominal pressure was recorded vaginally in 26 women with stress incontinence and urinary leakage was detected electronically. CILPP determinations and short-term pad tests were carried out on two different occasions. Reproducibility is expressed by a coefficient of repeatability as limits of agreement. These indicate that, for 95% of the cases, a repeat measurement of CILPP will be between 0.72 and 1.28 times the first measurement. The coefficient of variation was 11.2%. There was a moderate inverse correlation between pad-test data and CILPP. It was concluded that the new method allows for an accurate determination of CILPP, which represents a quantitative and dynamic assessment of urethral function. The reproducibility of the method appears to be better than that of pad tests and standard urodynamic parameters. The correlation with pad-test data gives support to the validity of the method.

Adult↗

Synthesis of 2'-deoxyuridine 5'-(alpha,beta-imido) triphosphate: a substrate analogue and potent inhibitor of dUTPase.

The dUDP analogue, 2'-deoxyuridine 5'-(alpha,beta-imido)diphosphate (dUPNP) was synthesized. The corresponding triphosphate analogue (dUPNPP) was prepared by enzymic phosphorylation of dUPNP using the enzyme pyruvate kinase and phosphoenolpyruvate as the phosphate donor. This method was successful in phosphorylating the imidodiphosphate analogue of 2'-deoxythymidine (dTPNP) to 2'-deoxythymidine 5'-(alpha, beta-imido)triphosphate (dTPNPP), in contradiction to a previous report. The properties of dUPNPP have been tested using the enzyme dUTPase from Escherichia coli. This enzyme, having a crucial role in nucleotide metabolism, is strictly specific for its substrate (dUTP) and catalyzes the hydrolysis of the alpha, beta-bridge, resulting in dUMP and pyrophosphate. Replacement of the alpha, beta-bridging oxygen in dUTP with an imido group resulted in a nonhydrolyzable substrate analogue and a potent competitive inhibitor of dUTPase (Ki = 5 microM). The analogue prepared (dUPNPP) may be utilized in crystallographic studies of the active site of dUTPase to provide knowledge about specific interactions involved in substrate binding and as a parental compound in design of dUTPase inhibition for medical purposes.

Creatine Kinase↗

A comparison of contraceptive habits and pregnancy outcome at 19 years of age in two cohorts of Swedish women born 1962 and 1972.

The prevalence of contraception and pregnancy outcome in two representative samples of 19-year-old women resident in the city of Göteborg, born in 1962 (n = 596) and 1972 (n = 641), respectively, was assessed and compared using a postal questionnaire technique. The prevalence of different contraceptive techniques was as follows (62/72): Oral contraception (OC) alone 44%/35%, (p < 0.001); OC + condom 1%/12%, p < 0.001; intrauterine device 4%/1%, p < 0.001; condom only 11%/14%; depot gestagen 0%/0.3%; no contraception 40%/38%. The median duration of OC use was 15 and 14 months, respectively. Fear of OCs was the commonest reason given for cessation of OC in the 62 cohort and that contraception was no longer required in the 72 cohort. The proportion of women who gave the latter explanation for cessation of OC had increased (p < 0.001) from 10% in 1981 to 57% in 1991, indicating that young women in Sweden now tend not to continue with OCs when a relationship ends. Although the prevalence of cigarette smoking was reduced (p < 0.05 in the 72 cohort compared to the 62 cohort), there was still an over-representation of smokers in both cohorts among contraceptive users (p < 0.001) and in women who had been pregnant (p < 0.001) or undergone an abortion (p < 0.001). Pregnancies were reported by 11% of the women from the 62 cohort and by 13% from the 72 cohort. A greater proportion (p < 0.001) of pregnancies terminated in legal abortion in the 72 cohort (61%) compared to the 62 cohort (50%). The medical complication rate following legal abortion was lower (p < 0.05) in the 72 cohort compared to the 62 cohort.

Abortion, Legal↗

Crystal structure of the Escherichia coli dUTPase in complex with a substrate analogue (dUDP).

We have determined the structure of the homotrimeric dUTPase from Escherichia coli, completed with an inhibitor and substrate analogue, dUDP. Three molecules of dUDP are found symmetrically bound per trimer, each in a shallow cleft between adjacent subunits, interacting with evolutionary conserved residues. The interactions of the uracil ring and the deoxypentose with the protein are consistent with the high specificity of the enzyme with respect to these groups. The positions of the two phosphate groups and adjacent water molecules are discussed in relation to the mechanism and kinetics of catalysis. The role that dUTPase plays in DNA metabolism makes the enzyme a potential target for chemotherapeutic drugs: the results presented here will aid in the design and development of inhibitory compounds.

Amino Acid Sequence↗

Anxiety and depression in hospitalized patients with cancer: agreement in patient-staff dyads.

Patient and staff perceptions of patient anxiety and depression were determined in 53 dyads of hospitalized cancer patients and their nursing staff. Patient anxiety and depression were assessed with the Hospital Anxiety and Depression Scale. In addition, anxiety was measured by a numerical (0-10) scale. A staff person who had been caring for a certain patient the previous 3 days assessed that patient's anxiety and depression with staff versions of the same instruments. For one subsample (n = 18), staff were also asked to estimate their own hypothetical anxiety were they to have the same disease as the patient. Results indicate that staff overestimated patient anxiety systematically and showed limited ability to adequately assess patient anxiety and depression in terms of rank. Patients and staff agreed about individual patients' levels of anxiety and depression only to a limited degree. Discrepancies between patient and staff ratings of patient anxiety predominantly concerned patients reporting low anxiety levels. Several explanations for these findings are discussed. One possible explanation, the "requirement of mourning" hypothesis, is supported by our findings that staff estimation of patient anxiety was strongly associated with their estimation of their own hypothetical anxiety if they were to be in the patient's situation.

Adult↗

Response of guanosine tetraphosphate to glucose fluctuations in fed-batch cultivations of Escherichia coli.

A rapid transient increase of guanosine 3'-diphosphate 5'-diphosphate (ppGpp) in Escherichia coli was found in response to short-term glucose fluctuations that may occur in large-scale fed-batch cultivations. The concentration of ppGpp was measured in laboratory-scale glucose limited fed-batch cultivations. Starvation zones were imitated by using an intermittent feeding scheme or a two-compartment reactor system. The cellular concentration of ppGpp per biomass increased from 80 nmol to 300-600 nmol per g cell dry weight within only 1 min after consumption of the residual glucose in dependence on the test system, which is much faster than earlier described in literature. Readdition of glucose caused immediate reduction of the ppGpp to the basic level which did not differ in cultivations with simulated starvation zones from control cultivations. Possible physiological consequences by an enhanced stringent response in cultivations with limited mass transfer have to be considered.

Biotechnology↗

Quality of care from the elderly person's perspective: subjective importance and perceived reality.

The aim of this study was to carry out a theoretically-based survey of elderly persons' perceptions of quality of care, in terms of their evaluations of actual care conditions, as well as the subjective importance they ascribe to these. The sample consisted of 428 elderly (> or = 60 years) persons, in four different care environments: a geriatric department (N = 51); persons receiving home nursing (N = 111); nursing homes (N = 111); and service homes (N = 154) in two Swedish cities. Data were collected by way of personal interviews, structured from the questionnaire, Quality from the Patients' Perspective (QPP). The QPP is theory-based and consists of 40 items covering 17 factors. Each item was evaluated in two ways by the respondent: assessment of perceived reality, and evaluation of subjective importance (Likert scales). The results show that personal characteristics, such as age, sex, and self-rated health, had a limited effect on reports of what were regarded as highly important care characteristics, as well as on ratings of actual care conditions. Psychological well-being was strongly related to perceived reality ratings: a favorable well-being covaried with favorable ratings and vice versa. Considerable differences were noted in both types of ratings when the four types of care environments were compared. On the subjective importance scales, persons living in service homes reported lower scores, particularly on the scales designed to measure the medical-technical competence of the caregivers. On the perceived reality scales, the participants in service homes and the geriatric department scored lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Distribution↗

New kinetic data on estradiol in light of the vaginal ring concept.

The principal estrogen produced by the functioning premenopausal ovary is 17 beta-estradiol. At the point of irreversible ovarian failure, at menopause, the production of estradiol decreases dramatically, which results in circulating serum levels less than 120 pmol/l. It is important to recognise the pharmacokinetic and metabolic outcomes associated with dosage and route of delivery of estrogen. One of the most promising methods of administering estrogen replacement therapy (ERT) for local effects is the estradiol vaginal ring designed for a controlled continuous low release (7.5 micrograms estradiol/24 h) over a period of 90 days. The present study was undertaken to characterise the basal endogenous turnover of estradiol in postmenopausal women. Information on the disposition of estradiol after an intravenous dose formed the base of the kinetic model. The rate of extent of absorption of estradiol was assessed after ring application. Individual serum concentrations of estradiol were analysed without subtraction of the basal estradiol levels. The results indicate a rapidly eliminated compound (plasma clearance 2 l/min) with a distribution of approximately 50 l, resulting in an efficient half-life of about 20 min. The endogenous production was highly variable (< 1-44 micrograms/24 h). The steady-state estradiol levels following ring application did not increase and were well within the normal basal estradiol range seen in untreated women. In light of the present findings, the low daily dose, the low availability of estradiol across the vaginal wall and the controlled local delivery, favour the use of the estradiol vaginal ring.

Administration, Intravaginal↗

Sense of coherence among elderly somatic patients: predictive power regarding future needs of care.

The main aim was to study the predictive power of sense of coherence regarding future needs of care among elderly patients evaluated as medically ready for discharge from somatic emergency care. A secondary aim was to study the consistency of sense of coherence over time among patients with this kind of experience. The sample consisted of 53 Swedish patients (mean age 82.8 years, SD = 6.6 years) who had completed their medical treatment at surgical or orthopaedic departments. The predominant diagnosis was lower limb fractures. Sense of coherence was assessed twice, on the day the patient was evaluated as medically ready for discharge and 1 month later. On the second assessment occasion, 28 patients had returned to their homes, 17 were staying at institutions, and eight had died. Patients who returned to their homes reported the strongest sense of coherence while still in hospital. Patients who were staying at institutions scored lowest on the overall sense of coherence scale and on the comprehensibility subscale. Patients who died before the second measurement occasion scored lowest on the meaningfulness subscale. A correlation of 0.51 was noted between the two assessments of sense of coherence, indicating a moderate temporal consistency.

Aged↗