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Biomedical subjects

F Nilsson

Publications and source records attributed to F Nilsson.

At least 19 recordsLinked to original sources
PubMed2006

Expanding the donor pool: lung transplantation with donors 55 years and older.

The scarcity of donor organs is one of the major limitations to lung transplantation. This has led to a progressive expansion of criteria for donor selection in lung transplantation. This study evaluated the outcome of recipients of lungs from donors >/=55 years. We performed a retrospective analysis of 212 consecutive lung transplantations. Recipients were divided into two groups, those receiving lungs from donors >/=55 years (older donor group) and those receiving lungs from donors <55 years (younger donor group). Recipient baseline characteristics, time in the intensive care unit (ICU), early mortality, and long-term survival (Kaplan-Meier) were compared between the groups. Forty-one donors (19%) were >/=55 years. Mean recipient age in the older donor group was higher than in the younger donor group (52 +/- 8 vs. 47 +/- 12 years; P = .015). Indication for transplantation did not differ between the groups. ICU stay was comparable between the two groups (6 +/- 12 vs. 7 +/- 11 days; P = .64). Actual 30-day mortality (10.8% vs. 6.4%; P = .32), 1-year mortality (17.1 vs. 19.6%; P = .50), and cumulative long-term survival (65% and 62% at 5 years, P = 1.00) did not differ between the older and younger donor group. This study indicated that transplantation of lungs from selected donors aged >/=55 years did not impair short-or long-term results. The use of lungs from elderly donors may help to increase the number of donor organs for lung transplantation.

Age Factors↗
PubMed2006

Long-term outcome in heart failure patients evaluated for heart transplantation but considered too well.

Patients referred for heart transplantation evaluation may be accepted for transplantation, or denied due to existing contraindications or judged to be too well. There is little knowledge about long-term outcome in patients considered too well for transplantation. Ninety-five patients (mean age 47 +/- 12 years, 73% men) judged "too well" at evaluation were included in this study. Acceptance for transplantation followed international guidelines. The follow-up (mean 4.5 years) was complete. Twenty of the 95 patients (21%) were eventually accepted for transplantation during the follow-up period. Twenty-one patients (22%) died, 13 without preceding acceptance for transplantation, 4 on the waiting list for transplantation, and 4 after transplantation. Cumulative and transplant-free survival at 1, 5, and 10 years were 91%, 82%, and 65%, and 90%, 70%, and 50%, respectively. In conclusion, long-term survival in patients considered too well for transplantation is better than in most contemporary series of heart transplant recipients, which suggests that the guidelines for acceptance are appropriate. However, almost one fifth of the patients die without preceding acceptance for transplantation or while on the waiting list, which illustrates the need for frequent reevaluation and tools to identify heart failure patients with an increased risk for sudden death.

Adult↗
PubMed2005

Bridge to heart transplantation with the HeartMate device in Gothenburg, Sweden.

BACKGROUND: Patients rapidly deteriorating while waiting for heart transplantation present a major problem. Our strategy for this entity is the HeartMate left ventricular assist device (LVAD) VELVAS, an electrically driven implantable LVAD. Herein we report our initial experience. METHODS: The medical records of all the patients who received HeartMate LVAS at our institution were reviewed. RESULTS: From January 1997 through May 2004, 19 patients received a HeartMate. The mean age was 39 (15 to 61) years and 84% were men. The diagnoses were: dilated cardiomyopathy (n = 8), ischemic heart disease (n = 6), myocarditis (n = 3), congenital heart disease (n = 1), and hypertrophic cardiomyopathy (n = 1). Mean time on LVAD was 113 (10 to 353) days. Ten patients were discharged from the hospital to their homes awaiting transplant or recovery. Three patients showed recovery of heart function and were subsequently weaned from mechanical support. Thirteen patients underwent heart transplantation. Three patients died during LVAD treatment. Major adverse events occurred in nine patients, including severe right heart failure (n = 3), severe bleeding (n = 3), stroke (n = 1), hepatic failure (n = 1), and septicemia (n = 2). Nine of the 13 transplanted patients are alive and well today. CONCLUSION: HeartMate LVAS is a valuable option for patients rapidly deteriorating while awaiting a heart transplant. Our results are comparable with those reported from larger centers.

Adolescent↗
PubMed2003

Clinical trial comparing nicotine replacement therapy (NRT) plus brief counselling, brief counselling alone, and minimal intervention on smoking cessation in hospital inpatients.

BACKGROUND: Guidelines recommend that smoking cessation interventions are offered in all clinical settings to all smokers willing to make a quit attempt. Since the effectiveness of routine provision of behavioural counselling and nicotine replacement therapy (NRT) to smokers admitted to hospital has not been established, a randomised controlled trial of these interventions given together compared with counselling alone or minimal intervention was performed in hospital inpatients. METHODS: Medical and surgical inpatients who were current smokers at the time of admission were randomised to receive either usual care (no additional advice at admission), counselling alone (20 minute intervention with written materials), or NRT plus counselling (counselling intervention with a 6 week course of NRT). Continuous and point prevalence abstinence from smoking (validated by exhaled carbon monoxide <10 ppm) was measured at discharge from hospital and at 3 and 12 months, and self-reported reduction in cigarette consumption in smokers was assessed at 3 and 12 months. RESULTS: 274 inpatient smokers were enrolled. Abstinence was higher in the NRT plus counselling group (n=91) than in the counselling alone (n=91) or usual care (n=92) groups. The difference between the groups was significant for validated point prevalence abstinence at discharge (55%, 43%, 37% respectively, p=0.045) and at 12 months (17%, 6%, 8%, p=0.03). The respective differences in continuous validated abstinence at 12 months were 11%, 4%, 8% (p=0.25). There was no significant difference between counselling alone and usual care, or in reduction in cigarette consumption between the treatment groups. CONCLUSIONS: NRT given with brief counselling to hospital inpatients is an effective routine smoking cessation intervention.

Administration, Intranasal↗
PubMed2002

Cerebral physiological and biochemical changes during vasogenic brain oedema induced by intrathecal injection of bacterial lipopolysaccharides in piglets.

BACKGROUND: The objective of the study was to evaluate biochemical and physiological changes in an experimental model of vasogenic brain oedema utilising techniques also used in routine neurointensive care. METHOD: 32 piglets were randomised to control or experimental group. The latter received an intrathecal injection of lipopolysaccharide (LPS) from E. coli (LPS group). Intracranial pressure (ICP)and mean arterial pressure (MAP) were measured continuously. Intracerebral microdialysis was used for analysing interstitial levels of glucose, pyruvate, lactate, glutamate, glycerol and urea every 30 min. Repeated calculations of mean hemispheric CBF were performed utilising an extracranial scintillation detector and Intra-carotid injection of (133)Xe. Cerebral specific gravity was measured and the brains were fixed for histological examinations. FINDINGS: After LPS injection ICP increased reaching a plateau phase after 4-7 hours and CBF increased by 46%. Histological examination showed inflammation with pronounced extravasation of granulocytes. A significant decrease in brain specific gravity (p =0.022) was obtained. LPS caused a significant decrease in cerebral interstitial concentration of glucose (p = 0.0035), and significant increases in lactate concentration (p = 0.002) and lactate/pyruvate ratio (p = 0.0017). A small but significant increase in glutamate was obtained (p = 0.0219). Glycerol did not change significantly. INTERPRETATION: Intrathecal LPS caused an inflammatory reaction with extravasation of granulocytes, increased blood-brain barrier permeability and cerebral oedema. Biochemical analyses indicate increased glycolysis but no signs of cell membrane degradation.

Animals↗
PubMed2002

Enhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculature.

Interleukin-12 (IL-12) is a heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. Its clinical applications are limited, however, by severe side-effects. Here we report that an IL-12 fusion protein, consisting of IL-12 fused to a human antibody fragment specific to the oncofetal ED-B domain of fibronectin, markedly enhances the antitumor activity of this cytokine, as demonstrated in a mouse lung-metastasis model and in two models of mice bearing different aggressive murine tumors. The residual small tumor masses seen in the treated mice were infiltrated with lymphocytes, macrophages, and natural killer cells and had elevated interferon gamma (IFN-gamma). These results are of therapeutic relevance as the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is not detectable in normal vessels and tissues.

Animals↗
PubMed2001

Targeted delivery of tissue factor to the ED-B domain of fibronectin, a marker of angiogenesis, mediates the infarction of solid tumors in mice.

The selective thrombosis of tumor blood vessels, leading to the starvation and subsequent death of tumor cells, is an attractive anticancer strategy. Here we report that a fusion protein, consisting of an antibody fragment specific for the oncofoetal ED-B domain of fibronectin fused to the extracellular domain of tissue factor, selectively targets tumor blood vessels in vivo. Furthermore, this fusion protein mediates the complete and selective infarction of three different types of solid tumors in mice. At the highest doses administered, complete tumor eradication was observed in 30% of the mice treated without apparent side effects. These results are of therapeutic relevance because the ED-B domain of fibronectin, a naturally occurring marker of angiogenesis identical in mouse and man, is expressed in the majority of aggressive solid tumors but is undetectable in normal vessels and tissues.

Animals↗
PubMed2001

Individual differences in preferences for and responses to four nicotine replacement products.

RATIONALE: With several different forms of nicotine replacement therapy available for smokers, it is useful to know about factors that may influence choice of form. OBJECTIVE: To examine factors associated with preference for different nicotine replacement products and effectiveness of these products. The simple comparison of success rates between the products has been reported previously. METHODS: Five hundred and four smokers were invited to rank order four products (gum, patch, nasal spray and inhaler) in terms of preference and were then randomly allocated to receive one of the products for a smoking cessation attempt. They were followed up 1 week, 4 weeks, 12 weeks and 15 weeks later. Ratings of the products were repeated 1 week after the quit date. Mood and physical symptoms were assessed at baseline and at each follow-up visit. Urges to smoke were assessed at all post-quit date sessions. Abstinence was assessed by self-report with expired air carbon monoxide verification. RESULTS: The patch was the most popular product initially, followed by the spray and inhaler and then the gum. The difference was greater for women than men. However, all smokers quickly came to like whichever product they had been allocated. Smokers who initially preferred the spray or inhaler were heavier smokers than those who preferred the gum or patch. Prior experience of the gum was associated with lower initial preference for it, but did not affect outcome. Prior experience with the patch had no effect on preference or outcome. Being allocated to the preferred product did not increase success at stopping smoking. Women were more successful at stopping smoking on the inhaler than the gum. Among highly dependent smokers, those on the inhaler had a lower relapse rate than those on the other products. CONCLUSIONS: Regardless of initial preferences, whether patients obtain their preferred form of NRT or one selected for them did not seem to affect outcome. This may be because smokers came to like particular products as they got used to them. Other things being equal, women may be better advised to use inhaler rather than gum and men vice versa.

Administration, Cutaneous↗
PubMed2001

Thiourea enhances mapping of the proteome from murine white adipose tissue.

Adipose tissue imposes problems in two-dimensional (2-D) analysis due to its extremely high content of fat. To improve protein separation detergents and chaotropes were varied in the IEF step. The most important factor for obtaining distinct spots in the 2-D gel was whether thiourea was included or not. Many high molecular weight spots became resolved by using thiourea, while no spots disappeared or showed inferior characteristics, thus approximately twice as many spots were possible to quantify. Hydrophobic indices were compared for a set of proteins that gave rise to sharper spots with proteins that were not improved on the use of thiourea. The comparison did not give any statistically significant difference between the two groups of proteins. One of the effects obtained by inclusion of thiourea was that the dominating protein, serum albumin, appeared as more condensed spots allowing other minor proteins to be detected. This work resulted in a protocol which greatly enhances the resolution of proteins in adipose tissue. A 2-D map of mouse white adipose tissue from epididymal fat pads was constructed in which 140 spots were identified by mass spectrometry. This work lays the ground for our further studies on white adipose tissue in metabolic diseases such as obesity and dyslipidemia.

Adipose Tissue↗
PubMed2001

The importance of grade 2 ischemic mitral regurgitation in coronary artery bypass grafting.

OBJECTIVE: To study if grade 2 ischemic mitral regurgitation (MR) influences outcome after coronary artery bypass grafting (CABG). METHODS: Results of all CABG patients with grade 2/4 ischemic MR operated during 1995--1998 (n = 89) were compared with all CABG patients without MR (n = 4709) during the same period. To further evaluate patients with grade 2 ischemic MR, a case-control study focusing on functional status was performed. Control patients without MR (n = 89) were matched for age, gender and left ventricular ejection fraction. All patients were interviewed regarding angina symptoms and functional status. RESULTS: Survival according to Kaplan--Meier at 1 and 3 years were inferior in the MR group compared to all CABG patients (91 vs 96% and 84 vs 92%, respectively (P = 0.0017). However, MR patients were older (68 +/- 9 vs 65 +/- 9 years (mean +/- SD), P = 0.008) and had an inferior preoperative left ventricular ejection fraction (42 +/- 14 vs 58 +/- 14%, P < 0.0001). In the case-control study, New York Heart Association (NYHA) class and Higgins' risk score differed preoperatively between the MR group and controls. Neither 30-day mortality (4,5% in both groups) nor survival at 1 (91 vs 93%) and 3 years (84 vs 88%) differed significantly. NYHA class and angina class (Canadian Cardiovascular Society, CCS) improved similarly in both groups. Postoperatively, 62% of the patients in the MR group had reduced, 36% unchanged and 2% increased MR. CONCLUSIONS: CABG on patients with grade 2 ischemic MR reduces angina pectoris and improves functional status to the same extent as in CABG patients without MR. Postoperative morbidity and mortality do not differ significantly between the groups. Grade of MR is reduced or unchanged after CABG in patients with grade 2 ischemic MR. The study supports an operative strategy where grade 2 ischemic mitral regurgitation is treated by CABG alone but the result do not exclude that there might be individual patients that would benefit from a valvular or annular procedure in combination with CABG. How these patients should be identified remains unclear.

Aged↗
PubMed2000

Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Nicotine replacement therapy is an effective treatment for nicotine-dependent smokers. However, cessation rates are modest, and preliminary studies suggest that combination therapy may be superior. We compared the efficacy of the nicotine inhaler plus nicotine patch vs nicotine inhaler plus placebo patch for smoking cessation. METHODS: A double-blind, randomized, placebo-controlled trial was conducted in 400 subjects who had smoked 10 or more cigarettes per day for 3 years or longer. Group 1 (n = 200) received the nicotine inhaler plus nicotine patch (delivering 15 mg of nicotine per 16 hours) for 6 weeks, then inhaler plus placebo patch for 6 weeks, then inhaler alone for 14 weeks. Group 2 (n = 200) received the nicotine inhaler plus placebo patch for 12 weeks, then inhaler for 14 weeks. Inhaler was used at a rate of 6 to 12 cartridges per day ad libitum for 3 months and then tapered off. Main outcome measures were complete abstinence (self-reported) and expired carbon dioxide concentration less than 10 ppm. RESULTS: Group 1 vs group 2 complete abstinence rates were 60.5% and 47.5% at 6 weeks (P =.009), 42.0% and 31.0% at 12 weeks (P =.02), 25.0% and 22.5% at 6 months (P =.56), and 19.5% and 14.0% at 12 months (P =. 14). One-year survival analysis showed a significant association between abstinence and treatment with nicotine inhaler plus nicotine patch (P =.04). Mean nicotine substitution at week 6 was 60.1% (group 1) and 24.6% (group 2) (P<.001). At 12 months, the frequency of respiratory symptoms in abstinent subjects fell significantly and lung function showed a trend toward improvement. The most common adverse events were throat irritation (inhaler) and itching (patch). CONCLUSIONS: Treatment with the nicotine inhaler plus nicotine patch resulted in significantly higher cessation rates than inhaler plus placebo patch.

Administration, Inhalation↗
PubMed2000

The use of phage display for the development of tumour targeting agents.

One way to improve the selectivity of therapeutic molecules in clinical oncology would be to target them on the tumour site, thereby sparing normal tissues. The development of targeted therapeutic methodologies relies in most cases on the availability of binding molecules specific for tumour-associated markers. The display of repertoires of polypeptides on the surface of filamentous phage, together with the efficient selection-amplification of the desired binding specificities using affinity capture, represents an efficient route towards the isolation of specific peptides and proteins that could act as vehicles for tumour targeting applications. Most investigations in this area of research have so far been performed with phage derived recombinant antibodies, which have been shown to selectively target tumour-associated markers both in preclinical animal models and in the clinic. However, future developments with other classes of polypeptides (small constrained peptides, small globular proteins) promise to be important for the selective delivery of therapeutic agents to the tumour site.

Animals↗
PubMed2000

A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler.

RATIONALE: Nicotine replacement therapy (NRT) in varying forms is becoming widely used. Clinicians, therapists and regulatory authorities are interested in the abuse liability and dependence potential of the different forms. OBJECTIVES: To compare the abuse liability and dependence potential of nicotine gum, transdermal patch, spray and inhaler. METHODS: 504 male and female smokers seeking help with stopping smoking were randomly allocated to the four products. Measures were taken at the designated quit date, then 1 week, 4 weeks, 12 weeks and 15 weeks later. Smokers were advised to use the product for up to 12 weeks. Those still using the product at the 12-week visit were advised to cease use by week 14. Measures included: pleasantness and satisfaction ratings at weeks 1 and 4 (used as a marker of abuse liability); ratings of feeling dependent on NRT at weeks 1, 4, 12 and 15 (used as a marker of subjective dependence); mood and physical symptoms ratings at weeks 12 and 15 (the change being used to assess physical dependence on NRT), continued usage of NRT at week 15 (used as an marker of behavioural dependence). RESULTS: Average ratings of pleasantness were low. The nicotine patch was rated as less unpleasant to use than all other products. There were no significant differences between the products in terms of satisfaction or subjective dependence except at week 15 when no patch users rated themselves as dependent. Continued use of NRT at week 15 was related to rate of delivery of nicotine from the products - 2% for patch, 7% for gum and inhaler, 10% for spray (P<0.05 for linear association). Among those

Adult↗
PubMed2000

Renal effects of amino acid infusion in cardiac surgery.

OBJECTIVE: To evaluate effects of amino acids on renal function and oxygen consumption and the role of individual amino acids on renal blood flow (RBF) changes. DESIGN: Prospective, randomized, controlled study. SETTING: Operating room in cardiothoracic surgery department, university hospital. PARTICIPANTS: Twenty-two male patients submitted to elective first-time coronary artery bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution RBF measurements and blood sampling. In 11 patients, a balanced mixed amino acid infusion was infused (200 mL/hr) for 30 minutes immediately after the operation. MEASUREMENTS AND MAIN RESULTS: RBF and glomerular filtration rate increased during amino acid infusion compared with the control group. Renal oxygen consumption increased in the amino acid group and correlated with the increase in RBF (r = 0.70, p<0.001). Amino acid infusion induced two- to fourfold increases in plasma concentrations of individual amino acid concentrations and promoted renal extraction of aspartate, glutamate, glycine, and histidine. No correlation was observed between arterial concentration or uptake of individual amino acids and RBF. CONCLUSIONS: The increase in RBF from a mixed amino acid infusion was associated with increased glomerular filtration rate and renal consumption of oxygen. Changes in RBF of a mixed amino acid infusion could not be linked to plasma level or renal uptake of any individual amino acids.

Adult↗
PubMed2000

Properties of three isoforms of the 116-kDa subunit of vacuolar H+-ATPase from a single vertebrate species. Cloning, gene expression and protein characterization of functionally distinct isoforms in Gallus gallus.

Vacuolar H+-ATPases (V-ATPases) are involved in a wide variety of essential cellular processes. An unresolved question is how the cell regulates the activity of these proton pumps and their targeting to distinct cellular compartments. There is growing evidence for the presence of subunit diversity amongst V-pumps, particularly regarding the 116-kDa subunit (called the a subunit). We have cloned and characterized three isoforms (a1, a2 and a3) of this subunit from chicken. The amino-acid sequences of these homologues are approximately 50% similar and their nucleotide differences indicate that they are products of distinct genes. The levels of mRNA expression of these isoforms was quantified by ribonuclease protection analysis. The a1 and a2 isoforms have a similar tissue distribution, with the highest level of mRNA expression in brain, an intermediate level in kidney and relatively low levels in liver and bone. In contrast, the highest level of expression of the a3 isoform is in bone and liver, with a moderate level in kidney, and the lowest level in brain. An antibody against the a1 isoform reacted with a 116 kDa protein in a brain V-ATPase preparation that was not detected in bone or liver V-ATPase preparations, whereas an antibody against the a3 isoform reacted with a 116-kDa peptide in bone and liver, but not brain V-ATPases preparations. The bone and brain V-ATPases showed differential sensitivity to the inhibitors bafilomycin and (2Z,4E)-5-(5,6-dichloro-2-indolyl)-2-methoxy-N-[4-(2, 2,6,6-tetramethyl)piperidinyl]-2,4-pentadienamide. Thus, this work demonstrates the presence of structurally and functionally distinct V-ATPases in a single vertebrate species.

Amino Acid Sequence↗