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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 127 records · Page 7Linked to original sources

Hypocalcemia and parathyroid hormone secretion in critically ill patients.

OBJECTIVE: To investigate possible causes of hypocalcemia and to assess parathyroid hormone (PTH) secretion in intensive care unit (ICU) patients. DESIGN: Combined cross-sectional and prospective study. SETTING: ICU in a university hospital. PATIENTS: Thirteen patients with sepsis and 13 patients who underwent major surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Calcium metabolic indices were investigated during the first 24 hrs in the ICU and after 2 days. Eight of the surgical patients and five of the septic patients were subjected to a citrate/calcium infusion on day 1 in the ICU, to study the dynamics of PTH secretion. The blood ionized calcium (Ca2+) concentration was generally low in the septic patients (mean +/- SD, 1.03+/-0.08 mmol/L; reference value, 1.10-1.30) and increased, but not normalized, after 2 days. Hypocalcemia was only occasionally seen in the surgical patients. In the septic patients, urinary excretion of calcium was low; and, in both patient groups, elevated concentrations of two markers of bone resorption, deoxypyridinoline and ICTP (serum carboxy-terminal cross-linked telopeptide of type I collagen), were found. In cases of sepsis, the concentrations of proinflammatory cytokines were high (394+/-536 pg/mL for tumor necrosis factor-alpha and 5676+/-5190 pg/mL for interleukin-6, both normally <10-20). The Ca2+ concentration was inversely related to tumor necrosis factor-alpha and interleukin-6 (r2 = .35-.42; p<.01), as well as to procalcitonin (r2 = .71; p<.01). Despite normocalcemia in the surgical patients, serum PTH concentrations were elevated in both patient groups (97 and 109 ng/L) (reference value, <55 ng/L), both on day 1 and day 3 in the ICU. The citrate/calcium infusion revealed an increased secretory response of PTH to lowered Ca2+ concentrations in both groups of patients (p<.05), when compared with matched healthy controls. CONCLUSION: Hypocalcemia was common in septic ICU patients and was not the result of an increased urinary excretion of calcium or of an attenuated bone resorption, but seemed related to the inflammatory response. An increased PTH secretion was found in both patient groups.

APACHE↗

Hypocalcemia during porcine endotoxemic shock: effects of calcium administration.

OBJECTIVE: To evaluate the pathophysiology involved in hypocalcemia in septic shock and to investigate the value of calcium administration. DESIGN: Prospective, randomized placebo-controlled trial with parallel groups. SETTING: Animal research laboratory at the University Hospital of Uppsala. SUBJECTS: Twenty-four pigs aged 12-14 wks receiving general anesthesia. INTERVENTIONS: Twenty pigs received endotoxin infusion (10 microg/kg/hr) for 6 hrs. Ten of these pigs also received a calcium infusion (20 mmol total) in parallel. Four control pigs received only saline. MEASUREMENTS AND MAIN RESULTS: At the end of the study, blood ionized calcium (Ca2+) had declined from 1.32+/-0.04 mmol/L (mean +/- SD) to 1.09+/-0.06 mmol/L in pigs receiving endotoxin (p < .05 vs. controls) compared with 1.38+/-0.04 mmol/L to 1.25+/-0.07 mmol/L in controls and 1.39+/-0.03 mmol/L to 1.24+/-0.07 mmol/L in endotoxemic pigs receiving calcium. In both endotoxemic groups, total calcium levels in ascites were increased by 56% (p < .005 vs. controls), and an accumulation of calcium in the liver was mainly seen in the endotoxemic group receiving calcium (p < .008 vs. controls). Total Ca2+ levels in adiposal tissue and skeletal muscle were similar in all groups. Calcium administration did not significantly alter systemic hemodynamics or survival in this model of septic shock (four survivors in the endotoxemic group and five in the calcium administration group). CONCLUSIONS: Endotoxemia in the pig rapidly induced hypocalcemia. Calcium accumulation was found in ascites and in the liver, but not in other examined tissues. Calcium administration, restoring the Ca2+ concentration, did not improve hemodynamics or survival in this model of hypodynamic sepsis. Porcine endotoxemic shock, which replicates human septic shock, seems to be suitable for evaluating calcium turnover.

Animals↗

Matched-field processing using measured replica fields

An approach for avoiding the problem of environmental uncertainty is tested using data from the TESPEX experiments. Acoustic data basing is an alternative to the difficult task of characterizing the environment by performing direct measurements and solving inverse problems. A source is towed throughout the region of interest to obtain a database of the acoustic field on an array of receivers. With this approach, there is no need to determine environmental parameters or solve the wave equation. Replica fields from an acoustic database are used to perform environmental source tracking [J. Acoust. Soc. Am. 94, 3335-3341 (1993)], which exploits environmental complexity and source motion.

Journal Article↗

Lower frequency of focal lip sialadenitis (focus score) in smoking patients. Can tobacco diminish the salivary gland involvement as judged by histological examination and anti-SSA/Ro and anti-SSB/La antibodies in Sjögren's syndrome?

OBJECTIVES: Prospectively collected computer database information was previously assessed on a cohort of 300 patients who fulfilled the Copenhagen classification criteria for primary Sjögren's syndrome. Analysis of the clinical data showed that patients who smoked had a decreased lower lip salivary gland focus score (p<0.05). The aim of this original report is to describe the tobacco habits in patients with primary Sjögren's syndrome or stomatitis sicca only and to determine if there is a correlation between smoking habits and focus score in lower lip biopsies as well as ciculating autoantibodies and IgG. METHODS: All living patients with primary Sjögren's syndrome or stomatitis sicca only, who were still in contact with the Sjögren's Syndrome Research Centre were asked to fill in a detailed questionnaire concerning present and past smoking habits, which was compared with smoking habits in a sex and age matched control group (n=3700) from the general population. In addition, the patients previous lower lip biopsies were blindly re-evaluated and divided by the presence of focus score (focus score = number of lymphocyte foci per 4 mm(2) glandular tissue) into those being normal (focus score </= 1) or abnormal (focus score > 1). Furthermore the cohort was divided into three groups; 10-45, 46-60 and >/= 61 years of age. Finally the focus score was related to the smoking habits. Seroimmunological (ANA; anti-SSA/Ro antibodies; anti-SSB/La antibodies; IgM-RF and IgG) samples were analysed routinely. RESULTS: The questionnaire was answered by 98% (n=355) of the cohort and the percentage of current smokers, former smokers and historical non-smokers at the time of lower lip biopsy was not statistically different from that of the control group. Cigarette smoking at the time of lower lip biopsy is associated with lower risk of abnormal focus score (p<0.001; odds ratio 0.29, 95%CI 0.16 to 0.50). The odds ratio for having focal sialadenitis (focus score > 1) compared with having a non-focal sialadenitis or normal biopsy (focus score </= 1) was decreased in all three age groups (10-45: odds ratio 0.27, 95%CI 0.11 to 0.71; 46-60: odds ratio 0.22, 95%CI 0. 08 to 0.59; and >/= 61: odds ratio 0.36, 95%CI 0.10 to 1.43) although there was only statistical significance in the two younger age groups. Moreover, among current smokers at the time of the lower lip biopsy there was a decreasing odds ratio for an abnormal lip focus score with increasing number of cigarettes smoked per week (p trend 0.00). In the group of former smokers, which included patients that had stopped smoking up to 30 years ago, the results were in between those of the smokers and the historical non-smokers (odds ratio 0.57, 95%CI 0.34 to 0.97, compared with never smokers). Present or past smoking did not correlate with the function of the salivary glands as judged by unstimulated whole sialometry, stimulated whole sialometry or salivary gland scintigraphy. Among former smokers, the median time lapse between the first symptom of primary Sjögren's syndrome and the performance of the lower lip biopsy was approximately half as long as the median time lapse between smoking cessation and biopsy (8 versus 15 years). Hence, symptoms of Sjögren's syndrome are unlikely to have had a significant influence on smoking habits at the time of the biopsy. Among the seroimmunological results only anti-SSA/Ro and anti-SSB/La antibodies reached statistical significance in a manner similar to the way smoking influenced the focus score in lower lip biopsies. On the other hand the level of significance was consistently more pronounced for the influence of smoking on the focus score than for the influence on anti-SSA/Ro and anti-SSB/La autoantibodies. CONCLUSION: This is believed to be the first report showing that cigarette smoking is negatively associated with focal sialadenitis-focus score >1-in lower lip biopsy in patients with primary Sjögren's syndrome. Furthermore, tobacco seems to decrea

Adult↗

Lung and chest wall mechanics in anesthetized children. Influence of body position.

The mechanical behavior of the lung and chest wall has not been determined in preschool children. We therefore obtained static expiratory pressure-volume (P-V) curves of the respiratory system, partitioned into lung and chest wall components using esophageal (Pes) and airway pressure (Paw) registration in 17 anesthetized children (0.2 to 15.5 yr) in the supine and lateral position. From the P-V curves the inspiratory capacity (IC), the chest wall elastance (Ecw), and the maximal compliance of the respiratory system (Crs) and lungs (C(lung)) were calculated and related to growth. At IC (Paw = 30 cm H(2)O), Pes was the same in the two positions: 11 +/- 3 cm H(2)O. In contrast, at end-expiration (Paw = 0), Pes was close to zero in the lateral position, but markedly positive in the supine position (7 +/- 2 cm H(2)O). C(lung) was similar in both positions and increased with growth. Thus, C(lung) in the lateral position (ml/cm H(2)O) = 0.0017 x length(2.26) (cm), r(2) = 0.90. Crs and IC were approximately 20% greater (p </= 0.001) in the supine position than in the lateral, and correlated strongly (r(2) >/= 0.93) with power functions of length in both positions. Ecw expressed as a fraction of total respiratory system elastance (Ecw/Ers) was 33 +/- 12% in the lateral position and 12 +/- 16% supine (p < 0.001). We conclude that the respiratory mechanics in children correlated closely with body size and showed important differences between the supine and lateral positions.

Adolescent↗

Peroral immunotherapy with yolk antibodies for the prevention and treatment of enteric infections.

Oral administration of specific antibodies is an attractive approach to establish protective immunity against gastrointestinal pathogens in humans and animals. The increasing number of antibiotic-resistant bacteria emphasize the need to find alternatives to antibiotics. Immunotherapy can also be used against pathogens that are difficult to treat with traditional antibiotics. Laying hens are very good producers of specific antibodies. After immunization, the specific antibodies are transported to the egg yolk from which the antibodies then can be purified. A laying hen produces more than 20 g of yolk antibodies (IgY) per year. These antibodies also have biochemical properties that make them attractive for peroral immunotherapy: They neither activate mammalian complement nor interact with mammalian Fc receptors that could mediate inflammatory response in the gastrointestinal tract. Eggs are also normal dietary components and thus there is practically no risk of toxic side effects of IgY. Yolk antibodies have been shown in several studies to prevent bacterial and viral infections.

Animals↗

Large differences in laboratory utilisation between hospitals in Sweden.

There are large differences in the use of laboratory tests between hospitals in Sweden. These differences are not only due to differences between the patients treated but also to differences in practice. Use of laboratory test seems to reflect local traditions to a large extent. These large variations in practice are not compatible with the objective of providing care on equal terms and reduce the cost-effectiveness of clinical chemistry. Recently, several intervention studies have been performed in Sweden with the aim to optimise the use of clinical chemistry tests in primary care. The results show that it is possible to reduce the cost in primary care by SEK 100 million per year while increasing the clinical usefulness. This constitutes approximately 10% of the total cost for clinical chemistry tests in primary care. It should also be possible to reduce the cost for clinical chemistry tests in secondary and tertiary care. Hospitals order more tests than primary care and the potential savings are thus greater. We have studied the ordering habits for eleven Swedish hospitals. The comparison was made in the form of ratios between related laboratory tests to reduce the effects of differences in size between the studied laboratories. The large variation between hospitals indicates that a continuous discussion between the clinicians and the laboratories could reduce the cost. We have used the figures from the comparison and calculated the potential savings for seven frequently used tests. The potential yearly saving in Sweden for these tests is approximately SEK 150 million.

Clinical Chemistry Tests↗

Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock.

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin's cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.

Animals↗

A clinical study of root surface conditioning with an EDTA gel. I. Nonsurgical periodontal treatment.

The present study was undertaken to investigate if subgingival administration of an EDTA gel has any adjunctive effect to subgingival and supragingival root debridement. The investigation was performed in one study center involving 6 clinical investigators and 91 patients. The patients were selected from 2 patient populations: 41 were included from a consecutive referral material on a voluntary basis, and 50 were included from a maintenance care material at the clinic. No significant differences were found between the EDTA-treated and control groups with respect to clinical attachment gain or probing pocket depth reduction. The referral patients showed a significant improvement of pocket depth and attachment gain compared to maintenance care patients at the clinic. In multiple regression analyses, it was found that patients with small attachment losses at baseline responded better to treatment than patients with severe periodontitis. Also, in multivariate analyses, referral patients responded better than maintenance patients when controlling for other predictors.

Adult↗

Identification of dipeptidyl peptidase IV as the antigen of a monoclonal anti-prostasome antibody.

BACKGROUND: Our purpose was to elucidate the identity of an antigen of a monoclonal antibody against prostasomes, which are prostate-derived organelles occurring freely in human semen. METHODS: Monoclonal antibodies against prostasomes were generated by intrasplenic immunization to allow better characterization of the prostasomes. One third of the resulting antibodies bound to a 110-kDa prostasomal protein on Western blots. RESULTS: The antigen was purified from seminal prostasomes by anion exchange chromatography and gel electrophoresis. After in-gel digestion and amino-acid sequence analysis of selected peptides, it was identified as dipeptidyl peptidase IV (DPP IV), EC 3.4.14.5, also known as T-cell-activating antigen CD26. No DPP IV could be detected in the supernatant obtained after preparative ultracentrifugation of the prostasomes. CONCLUSIONS: DPP IV/CD26 is structurally bound to prostasomes rather than being free in seminal fluid. This enzyme may play a critical role in the promoting effect of prostasomes on forward motility of spermatozoa.

Amino Acid Sequence↗

Characterisation of endothelin-1-related protein in human adrenal cortex and in cortical lesions.

Endothelin (ET)-1 is a 21-amino acid peptide with potent vasopressor and vasoconstrictive properties. Biochemical studies suggest that this peptide occurs in the adrenal cortex, where it appears to influence steroid hormone production and catecholamine release. Concomitant with our previous immunohistological study, we found ET-1 immunoreactive (IR) cells in human adrenal cortex and cortical neoplasms, but not in the medulla. These ET-1 IR cells were numerous in adenomas, but were seen only occasionally in some of the carcinomas. In the present study, the ET-1 IR protein was extracted from normal (n = 5) and hyperplastic (n=3) human cortex as well as from cortical adenomas (n = 10) and carcinomas (n = 5). Its molecular weight, determined by SDS-polyacrylamide gel electrophoresis and immunoblotting, was 9 kD, which is lower than that of prepro-ET-1 (21 kD), but larger than that of pre-ET-1 (4.3 kD) and ET-1 (2.5 kD). The normal cortical specimens, hyperplasias, adenomas and three of the five carcinomas all contained this distinct band. The two carcinomas lacking it were associated with Conn's syndrome. The protein may constitute a protein not previously described, but further studies are needed to determine its complete structure.

Adrenal Cortex↗

A single computer-controlled mechanical insufflation allows determination of the pressure-volume relationship of the respiratory system.

OBJECTIVE: To evaluate and further develop a method for determination and mathematical characterisation of the elastic pressure-volume (Pel-V) relationship in mechanically ventilated human subjects during one single modified insufflation with simultaneous determination of resistance of the respiratory system. SUBJECTS: Eight adult non-smoking human subjects without heart, lung, or thoracic cage disease scheduled for non-thoracic surgery. The study was performed in anaesthetised and muscle-relaxed subjects. MEASUREMENTS AND MAIN RESULTS: The Pel-V curve was determined with a computer-controlled Servo Ventilator 900C during a modified insufflation with either constant or sinusoidally varying flow. Pressure and flow were measured with the built-in sensors of the ventilator. Tracheal pressure (Ptr) was calculated by subtracting the pressure drop over the tracheal tube. The elastic recoil pressure in the peripheral lung, Pel, was obtained from the calculated Ptr by subtracting the pressure drop over the airways. Ptr was also directly measured through a catheter. The calculated Ptr gave similar results as the directly measured Ptr, thus indicating the reliability of the signal originating from the ventilator sensor for computation of downstream pressures. The inflection points of the sigmoidal Pel-V curve and the compliance of the linear segment were determined with high reproducibility. CONCLUSIONS: Using one single modified insufflation allows a fast and accurate determination of respiratory mechanics. The Pel-V curves were determined with high reproducibility and were adequately described by a three-segment model of the curve incorporating a linear segment between two asymmetrical non-linear segments.

Adult↗