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Biomedical subjects

D Lundberg

Publications and source records attributed to D Lundberg.

At least 19 recordsLinked to original sources
PubMed2004

Studies on dodecyl betainate in combination with its degradation products or with phosphatidyl choline-phase behavior and hemolytic activity.

Surface active betaine esters contain a hydrolysable bond and give naturally occurring products (fatty alcohol and the amino acid betaine) on degradation. They are therefore interesting candidates for use as cationic surfactants in pharmaceutical applications. In this work the phase behavior of two systems of relevance for the utilization of dodecyl betainate as a pharmaceutical excipient is studied, namely dodecyl betainate/dodecanol/betaine hydrochloride/D2O and dodecyl betainate/phosphatidyl choline (PC)/ethanol/D2O. The techniques used for phase characterisation were 2H NMR measured on the solvent, small angle X-ray spectroscopy and optical microscopy. Dilute dodecyl betainate/PC dispersions were characterized using laser diffraction. It is shown that introduction of relatively small amounts of the hydrolysis products of dodecyl betainate, i.e., dodecanol and betaine (used in the form of betaine hydrochloride), has a strong effect on the phase behavior of the binary dodecyl betainate/D2O system. The degradation products change the average curvature of the surfactant film so that, instead of a hexagonal phase at concentrations above the micellar phase, a probably defective, lamellar phase seems to form. The dodecyl betainate/PC/ethanol/D2O system shows a large region of a highly swelling lamellar phase. Dispersions of dodecyl betainate/PC/ethanol in water can be prepared with low energy input; i.e., the preconcentrate can be regarded as a self-dispersing solution. Introduction of dodecyl betainate and its degradation products does not impair the ability of PC to form vesicles. Experiments for evaluating the toxicity of surface active betaine esters to erythrocytes were also performed. There are indications that the hemolytic activity of dodecyl betainate is lower than that of the stable surfactant tetradecyltrimethylammonium chloride, which has similar critical micelle concentration. A combination of dodecyl betainate and PC gives very low hemolytic activity.

Animals↗
PubMed2004

Abolished circadian rhythm of melatonin secretion in sedated and artificially ventilated intensive care patients.

BACKGROUND: Sleep disturbance is common in intensive care patients. Aside from its unpleasantness, there is a correlation with intensive care unit (ICU) syndrome/delirium. Reasons for sleep deprivation appear to be multifactorial, including the underlying illness, an acute superimposed disturbance, medications, and the ICU environment itself. There are reasons to believe that alterations of the 'biological clock' might contribute. Melatonin secretion is one reflection of this internal sleep/wake mechanism. Melatonin levels are normally high during the night and low during daytime, being suppressed by bright light. METHODS: Melatonin levels in blood and urine were studied over 3 consecutive days in eight critically ill patients during deep sedation and mechanical ventilation. Sedation was assessed with the sedation-agitation (SAS) scale and bispectral index (BIS) monitor. RESULTS: The circadian rhythm of melatonin release was abolished in all but one patient, who recovered much more quickly than the others. There was no correlation between melatonin levels and levels of sedation. CONCLUSIONS: This study indicates that dyssynchronization of the melatonin secretion rhythm is common in critically ill and mechanically ventilated patients. It could be hypothesized that an impairment of the melatonin rhythm may play a role in the development of sleep disturbances and delirium in intensive care patients, and that melatonin supply could reduce the incidence of these phenomena.

Aged↗
PubMed2004

Cancer patients' experiences of care related to pain management before and after palliative care referral.

Pain is the main problem for patients with cancer referred to palliative care (PC). Pain management in PC requires a multidimensional approach. A questionnaire was used to determine cancer patients' experiences of care related to pain management, before and after being referred to PC, and to also discover possible correlations between pain control and other aspects of care. Seventy-five consecutive patients from two PC teams were included in the study. The patients had experienced a statistically significant (P < 0.01) improvement in care after being referred to PC, despite the fact that pain control had not been optimized. Patients' description of 'pain control' after being referred to PC had a statistically significant correlation with their 'feeling of security' and 'continuity of care' throughout the same period. The conclusion is that care provided in PC is vital to successful pain management. Pain control depends not only on analgesics but also on many other aspects of care provided by the nurse. Continuity of care and the opportunity to talk increases the patients' feeling of security, which is also of utmost importance to successful pain management.

Adult↗
PubMed2003

The effect of heat and moisture exchanger on humidity and body temperature in a low-flow anaesthesia system.

BACKGROUND: Artificial humidification of dry inspired gases seems to reduce the drop in body temperature during surgery. The aim of this study was to evaluate the humidity and temperature of anaesthetic gases with heat and moisture exchangers (HMEs). The secondary aim was to evaluate if HMEs in combination with low-flow anaesthesia could prevent a decrease in the body temperature during general anaesthesia. METHODS: Ninety patients scheduled for general surgery were randomised to receive a fresh gas flow of 1.0, 3.0 or 6.0 l min-1 with or without HMEs in a circle anaesthesia system. Relative humidity, absolute humidity, temperature of inspired gases and body temperatures were measured during 120 min of anaesthesia. RESULTS: The inspiratory absolute humidity levels with HMEs were 32.7 +/- 3.1, 32.1 +/- 1.1 and 29.2 +/- 1.9 mg H2O l(-1) and 26.6 +/- 2.3, 22.6 +/- 3.0 and 13.0 +/- 2.6 mg H2O l(-1) without HMEs after 120 min of anaesthesia with 1.0, 3.0, or 6.0 l min(-1) fresh gas flows (P < 0.05, between with and without HME). The relative humidity levels with HMEs were 93.8 +/- 3.3, 92.7 +/- 2.2 and 90.7 +/- 3.5%, and without the HMEs 95.2 +/- 4.5, 86.8 +/- 8.0 and 52.8 +/- 9.8% (P < 0.05, between with and without HMEs in the 3.0 and 6.0 l min(-1) groups). The inspiratory gas temperatures with HMEs were 32.5 +/- 2.0, 32.4 +/- 0.5 and 31.0 +/- 1.9 degrees C, and 28.4 +/- 1.5, 27.1 +/- 0.8 and 26.1 +/- 0.6 degrees C without HMEs after 120 min of anaesthesia (P < 0.05, between with and without HME). The tympanic membrane temperatures at 120 min of anaesthesia were 35.8 +/- 0.6, 35.5 +/- 0.6 and 35.4 +/- 0.8 degrees C in the groups with HMEs, and 35.8 +/- 0.6, 35.3 +/- 0.7 and 35.3 +/- 0.9 degrees C in the groups without the HMEs (NS). CONCLUSIONS: The HMEs improved the inspiratory absolute humidity, relative humidity and temperature of the anaesthetic gases during different fresh gas flows. However, the HMEs were not able to prevent a body temperature drop during low-flow anaesthesia.

Adult↗
PubMed2001

Low-flow anaesthesia with desflurane: kinetics during clinical procedures.

BACKGROUND AND OBJECTIVE: Low-flow anaesthesia is economical and less polluting. The purpose of this study was to determine the inspired and end-tidal desflurane concentrations during anaesthesia with a vaporizer setting maintained at 5%, during low-flow anaesthesia after 120 min with fresh gas inflows of 1.0 and 2.0 L min-1. METHODS: The study was both prospective and randomized, including 56 patients (28 patients in each group) scheduled for elective surgery of an expected anaesthesia time of at least 120 min. Inspired and end-tidal concentrations of desflurane were measured during low-flow anaesthesia with fresh gas inflows of 1.0 and 2.0 L min-1. The vaporizer setting was fixed at 5% desflurane. RESULTS: The inspired and end-tidal concentrations of desflurane in the 1.0 L min-1 group after 120 min were 4.54% vs. 4.37% (P < 0.001). In the 2.0 L min-1 group, the inspired and end-tidal concentrations of desflurane were 4.76% vs. 4.58% (P < 0.001). The estimated end-tidal/inspired ratios at 120 min of anaesthesia were 0.96 in both groups. At a fresh gas flow of 1.0 L min-1, the end-tidal concentration was 0.87 of the vaporizer setting. Increasing the fresh gas flow to 2.0 L min-1 increased the end-tidal value by 0.05. CONCLUSION: There is a significant difference between the inspired and end-tidal concentrations of desflurane when fresh gas inflows were 1.0 and 2.0 L min-1, but not for the ratio of inspired/end-tidal.

Adult↗
PubMed2001

Clinical signs of ICU syndrome/delirium: an observational study.

Some clinical signs of the intensive care unit (ICU) syndrome/delirium are probably known, but there may be additional signs that can be observed during the care of ICU patients. The aim of this study was to investigate and describe the clinical signs of the ICU syndrome in relation to patients' reactions and behaviour following the second day of their stay in an ICU. A total of 31 patients were observed during the weaning process and in the days following extubation. Informal dialogues between the patient and the observer, using parts of the questionnaire 'Organic Brain Syndrome Scale' were also carried out. The data was structured in a chronological order and consists of descriptions of patients' behaviour and reactions, together with events, occurrences and environmental circumstances. It was found that the patients showed a great variety of clinical signs that could be related to the ICU syndrome. Such signs were the quality, ability and divergence of speech; talking, movements, bodily position and facial expressions. Several patients also related unreal experiences only occasionally, while others experienced them during longer periods. The clinical signs did not seem to be separate phenomena but were inter-connected and part of a progression, and, therefore must be seen in the overall context and situation. Longer periods of observation and repeated interaction with patients are necessary in order to be aware of onset and clinical signs of the ICU syndrome.

Delirium↗
PubMed2000

Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist.

The pharmacological and pharmacokinetic profile of SB-222200 [(S)-(-)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car boxami de], a human NK-3 receptor (hNK-3R) antagonist, was determined. SB-222200 inhibited (125)I-[MePhe(7)]neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K(i) = 4.4 nM and antagonized NKB-induced Ca(2+) mobilization in HEK 293 cells stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC(50) = 18.4 nM. SB-222200 was selective for hNK-3 receptors compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 250 nM). In HEK 293 cells transiently expressing murine NK-3 receptors (HEK 293-mNK-3R), SB-222200 inhibited binding of (125)I-[MePhe(7)]NKB (K(i) = 174 nM) and antagonized NKB (1 nM)-induced calcium mobilization (IC(50) = 265 nM). In mice oral administration of SB-222200 produced dose-dependent inhibition of behavioral responses induced by i.p. or intracerebral ventricular administration of the NK-3 receptor-selective agonist, senktide, with ED(50) values of approximately 5 mg/kg. SB-222200 effectively crossed the blood-brain barrier in the mouse and rat. The inhibitory effect of SB-222200 against senktide-induced behavioral responses in the mouse correlated significantly with brain, but not plasma, concentrations of the compound. Pharmacokinetic evaluation of SB-222200 in rat after oral administration (8 mg/kg) indicated sustained plasma concentrations (C(max) = about 400 ng/ml) and bioavailability of 46%. The preclinical profile of SB-222200, demonstrating high affinity, selectivity, reversibility, oral activity, and central nervous system penetration, suggests that it will be a useful tool compound to define the physiological and pathophysiological roles of NK-3 receptors, in particular in the central nervous system.

Animals↗
PubMed1999

Acute confusion and unreal experiences in intensive care patients in relation to the ICU syndrome. Part II.

The intensive care unit syndrome (ICU syndrome) is defined as an altered emotional state occurring in a highly stressful environment, which may manifest itself in various forms such as delirium, confusion, crazy dreams or unreal experiences. The purpose of this part of a study of patients' experiences is to describe and illuminate patients' experiences of acute confusion, disorientation, wakefulness, dreams and nightmares during and after their stay in the ICU. The data were obtained from 19 ventilated patients, who were interviewed twice and had stayed at least 36 hours in the ICU, the first interview being about one week after discharge from the ICU, and the second 4-8 weeks later. The hermeneutic approach used when interpreting and analysing the text from the interviews revealed that patients' experiences of unreal experiences were often associated with intense fear. Intense or continuous unbearable fear seems to result in frightening unreal experiences, which further increase the level of fear. Care actions or caring relationships with relatives or nurses can reduce this fear, which can help to prevent the occurrence and/or duration and intensity of the unreal experiences. Trust and confidence in nurses or significant others and feelings of self-control or trust in self-control seemed to reduce the risk of unreal experiences so that adverse stimuli might only trigger a mild confusion.

Acute Disease↗
PubMed1999

Preclinical pharmacokinetics and interspecies scaling of a novel vitronectin receptor antagonist.

Allometric scaling may be used in drug development to predict the pharmacokinetics of xenobiotics in humans from animal data. Although allometry may be successful for compounds that are excreted unchanged or that are oxidatively metabolized (with corrections for metabolic capacity), it has been more challenging for compounds excreted primarily as conjugates in bile. (S)-10, 11-Dihydro-3-[3-(pyridin-2-ylamino)-1-propyloxy]-5H-dibenzo[ a, d]cycloheptene-10-acetic acid (SB-265123) is a novel alphavbeta3 ("vitronectin receptor") antagonist. In this study, the in vivo pharmacokinetics and in vitro plasma protein binding of SB-265123 were examined in four species: mice, rats, dogs, and monkeys. In monkeys and dogs, SB-265123 exhibited moderate clearance, whereas low clearance (<20% hepatic blood flow) was observed in the rat, and high clearance (>70% hepatic blood flow) was seen in the mouse. The concentration-time profiles indicated the possibility of enterohepatic recirculation; subsequent studies in bile duct-cannulated rats demonstrated extensive biliary excretion of an acyl-glucuronide of SB-265123. In allometric scaling to predict the disposition of SB-265123 in humans, various standard correction factors were applied, including protein binding, maximum lifespan potential, and brain weight; each failed to produce adequate interspecies scaling of clearance (r(2) < 0.72). Consequently, a novel correction factor incorporating bile flow and microsomal UDP-glucuronosyltransferase activity in each species was applied, demonstrating substantial improvement in the correlation of the allometric plot (r(2) = 0.96). This study demonstrates a novel allometric correction that may be applicable to compounds that undergo conjugation and biliary excretion.

Acetates↗
PubMed1998

Pharmacokinetics of intravenously and orally administered eprosartan in healthy males: absolute bioavailability and effect of food.

Eighteen healthy males received a single 300 mg oral dose of eprosartan as the commercial wet granulation formulation under fasting conditions and following a high-fat breakfast and a single 20 mg intravenous (i.v.) dose. The pharmacokinetics of i.v. eprosartan (mean +/- S.D.) were characterized by a low systemic plasma clearance (131.8 +/- 36.2 mL min(-1)) and a small steady-state volume of distribution (12.6 +/- 2.6 L). Oral bioavailability averaged 13.1%, due to incomplete absorption. In vitro dynamic flow cell dissolution data showed that pH-dependent aqueous solubility of eprosartan is one factor which limits absorption. Eprosartan terminal half-life was shorter after i.v. (approximately 2 h) versus oral (approximately 5-7 h) administration, which may be due to detection of an additional elimination phase or absorption rate-limited elimination following oral administration. Oral administration of eprosartan following a high-fat meal compared with fasting conditions resulted in a similar extent of absorption (based on AUC), but a decreased absorption rate. Cmax was approximately 25% lower, and a median delay of 1.25 h in time to Cmax was observed when eprosartan was administered with food. These minor changes in exposure are unlikely to be of clinical consequence; therefore, eprosartan may be administered without regard to meal times.

Acrylates↗
PubMed1998

Patients' experience of being critically ill or severely injured and cared for in an intensive care unit in relation to the ICU syndrome. Part I.

The intensive care unit (ICU) syndrome is regarded principally as a complex interaction of several contributory factors, all of which can be seen as partly responsible for the development of the syndrome. The purpose of this study was to describe and give a deeper insight into patients' experiences and memory recall, both during and after their stay in the ICU. Nineteen patients who had been respirator treated (ventilated), and had stayed at least 36 hours in the ICU, were interviewed about one week after discharge, and again 4-8 weeks after their discharge from the ICU. Patients' experiences are interpreted and related to previous views held concerning the syndrome, together with an awareness of other important and significant phenomena, i.e. a hermeneutic approach. This study partly confirms the findings of earlier studies concerning the ICU syndrome, but also reveals some new aspects, which have not previously been considered. The patients described themselves as experiencing some sort of state of chaos following the onset of their sickness, injury or accident, which resulted in feelings of extreme instability, vulnerability and fear, often experienced as prolonged inner tension. It was reported that even the most trivial events in circumstances or routines could trigger changes-either an increase or decrease-in patients' feelings of fear or inner tension. The caring relationship was perceived as providing an important degree of security and comfort. Nursing care actions can therefore be seen as vital factors in patients overcoming the accompanying horrific experiences to which they can be subjected. This state of chaotic feeling, and how it is combated and treated, appear to be one critical factor in the development and progression of the ICU syndrome.

Acute Disease↗
PubMed1998

Coronary stenting for coronary artery disease in a cardiac transplant recipient.

Accelerated coronary artery disease in the transplanted heart remains the leading cause of death in heart transplant recipients. Traditional treatment modalities have generally yielded sub-optimal results. Coronary artery stents are used frequently in the non-transplanted heart to treat coronary artery disease. Only a few cases using this approach in the cardiac transplant recipient have been reported. This report details the use of this modality in a transplant recipient with significant two-vessel coronary artery disease 11 years after orthotopic cardiac transplantation.

Angioplasty↗
PubMed1997

Disposable CO2-detector, a reliable tool for determination of correct tracheal tube position during resuscitation of a neonate.

Undetected displacement of the endotracheal tube may lead to death of the patient. The present report illustrates the benefits of using a disposable carbon dioxide detector, designed for adults, also in a new-nate during resuscitation. The infant had asystole after delivery by caesarean section. The trachea was intubated, but the tube was displaced soon after return of spontaneous circulation. The oesophageal position of the tube was, however, discovered before bradycardia had occurred, thanks to the use of the CO2 detector.

Adult↗
PubMed1997

Decisions not to resuscitate in a Swedish university hospital.

BACKGROUND: Cardiopulmonary resuscitation (CPR) has the potential to save many lives. Used indiscriminately though, it may be harmful and not in the best interest of the patient. An advance directive to refrain from resuscitation in selected patients is probably not uncommon in Sweden, but guidelines ruling this are still generally lacking. This study was performed to evaluate the use and documentation of do-not-resuscitate orders in a Swedish university hospital. METHODS: Adult inpatients at 7 medical, 3 surgical and 2 neurological wards, a total of 220, were investigated on one specific day by interviewing the physicians and nurses responsible for their care. RESULTS: We found a discrepancy in doctors' and nurses' perception concerning the appropriateness of CPR in selected patients. CPR was judged by doctors to be inappropriate for 45 patients (20%). Out of these 45 patients, only 24 had a written do-not-resuscitate order in their medical record, in most cases noted as a code word or sign only. Rarely were the patient or his/her relatives involved in the decision-making process. CONCLUSION: We conclude that a decision to refrain from resuscitation is often not made, even when considered medically and ethically justifiable. Also, the use of coded information as a sole indicator for a patient not to be resuscitated is still common practice. The patient or his/her relatives are rarely involved in this decision.

Adult↗