| 1. |
- Luhr, O., et al.
(författare)
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A retrospective analysis of nitric oxide inhalation in patients with severe acute lung injury in Sweden and Norway 1991-1994
- 1997
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 41:10, s. 1238-46
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with severe acute lung injury (ALI) have been treated compassionately on doctors' initiative with inhaled nitric oxide (INO) in Sweden and Norway since 1991. In 1994 the previously used technical grade nitric oxide was replaced by medical grade nitric oxide. METHODS: We have carried out a retrospective data collection on all identified adult patients treated with INO for >4 h during the period 1991-1994 focusing on safety aspects and patient outcome. We used the following exclusion criteria (1) Age <18 years, (2) Simultaneous treatment with extracorporeal removal of CO2 (3) NO inhalation period <4 h, (4) Incomplete or missing patient charts, (5) Use of INO in order to treat pulmonary hypertension following cardiac surgery, with little or no acute lung injury. RESULTS: Inclusion criteria were met by 56 out of 73 identified patients. Mean age was 48+/-19 years and the median duration of INO treatment was 102 h. PaO2/FIO2 ratio at start of treatment was 85 +/- 33 mm Hg with a lung injury score (LIS) of 3.2+/-0.8. The aetiology of the lung injury was pneumonia (n= 27), sepsis (n=12) and trauma (n=8). Survival to hospital discharge was 41% and survival after 180 d was 38%. Three serious adverse events were identified, two from technical failures of the INO delivery device and one withdrawal reaction necessitating slow weaning from INO. No methaemoglobin values >5% were reported during treatment. CONCLUSION: The overall mortality did not differ dramatically from historical controls with high mortality. Only a randomised study may determine whether INO as an adjunct to treatment alters the outcome in severe ALI. One cannot at present advocate the routine use of INO in patients with ALI outside such studies.
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| 3. |
- Eklund, Arne, et al.
(författare)
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Recurrent inguinal hernia : randomized multicenter trial comparing laparoscopic and Lichtenstein repair
- 2007
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 21:4, s. 634-640
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The optimal treatment for recurrent inguinal hernia is of concern due to the high frequency of recurrence. METHODS: This randomized multicenter study compared the short- and long-term results for recurrent inguinal hernia repair by either the laparoscopic transabdominal preperitoneal patch (TAPP) procedure or the Lichtenstein technique. RESULTS: A total of 147 patients underwent surgery (73 TAPP and 74 Lichtenstein). The operating time was 65 min (range, 23-165 min) for the TAPP group and 64 min (range, 25-135 min) for the Lichtenstein group. Patients who underwent TAPP reported significantly less postoperative pain and shorter sick leave (8 vs 16 days). The recurrence rate 5 years after surgery was 19% for the TAPP group and 18% for the Lichtenstein group. CONCLUSION: The short-term advantage for patients who undergo the laparoscopic technique is less postoperative pain and shorter sick leave. In the long term, no differences were observed in the chronic pain or recurrence rate.
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| 4. |
- Eklund, Arne, 1957-, et al.
(författare)
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Short-term results of a randomized clinical trial comparing Lichtenstein open repair with totally extraperitoneal laparoscopic inguinal hernia repair
- 2006
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 0007-1323 .- 1365-2168. ; 93:9, s. 1060-1068
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Tidskriftsartikel (refereegranskat)abstract
- Background: Laparoscopic herniorrhaphy has emerged as a recognized operative method for inguinal hernia repair. This study compared the short-term results of two tension-free methods of repair: totally extraperitoneal (TEP) laparoscopic patch repair and the open Lichtenstein mesh technique. Methods: A total of 1513 men from 11 hospitals who presented with a primary unilateral inguinal hernia were randomized to one of the two methods. Operating time, short-term complications, reoperations, postoperative pain, consumption of analgesics, sick leave and time to resumption of normal physical activities were recorded. Results: Some 1371 of the 1513 men underwent surgery, 665 in the TEP group and 706 in the Lichtenstein group. The median duration of operation was 55 min for both procedures and 91.0 per cent of die patients in both groups were discharged on the day of operation. Patients in the TEP group experienced less postoperative pain (P < 0.001), consumed fewer analgesics (P < 0.001), had a shorter period of sick leave (7 versus 12 days; P < 0.001) and a shorter time to resumption of normal physical activity (20 versus 31 days; P < 0.001). Conclusion: The TEP technique took no longer to perform, and was associated with less postoperative pain, a shorter period of sick leave and a faster recovery, compared with open Lichtenstein hernia repair.
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| 6. |
- Arvidsson, D, et al.
(författare)
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Randomized clinical trial comparing 5-year recurrence rate after laparoscopic versus Shouldice repair of primary inguinal hernia
- 2005
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Ingår i: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; 92:9, s. 1085-1091
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Shouldice technique is the 'gold standard' of open non-mesh hernia repair. The aim of this study was to compare 5-year recurrence rates after Shouldice and laparoscopic transabdominal preperitoneal patch (TAPP) repair for primary inguinal hernia. Method: Men with a primary unilateral inguinal hernia were randomized to either Shouldice or TAPP operation. An independent observer scored the surgeons' performance. Follow-up comprised clinical examination after 1 year, a questionnaire after 2 and 3 years, and a clinical examination after 5 years. Results: Between February 1993 and March 1996, 1183 patients were included. Nine hundred and twenty patients were followed for 5 years, 454 in the TAPP group and 466 in the Shouldice group. Recurrences were evenly distributed between groups throughout the follow-up period. The cumulative recurrence rate after 5 years was 6.6 per cent in the TAPP group and 6.7 per cent in the Shouldice group. Postoperative pain was a risk factor for recurrence after Shouldice operation but not after TAPP repair. There was a correlation between a low surgeon's performance score and recurrence. Conclusion: The 5-year recurrence rate is acceptable, with no difference between TAPP and Shouldice repair. Poor operative performance resulted in a higher recurrence rate. The TAPP operation represents an excellent alternative for primary inguinal hernia repair.
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| 9. |
- Eklund, Arne, 1957-, et al.
(författare)
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Low Recurrence Rate After Laparoscopic (TEP) and Open(Lichtenstein) Inguinal Hernia RepairA Randomized, Multicenter Trial With 5-Year Follow-Up
- 2009
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 249:1, s. 33-38
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare a laparoscopic (totally extraperitoneal patch (TEP)) and an open technique (Lichtenstein) for inguinal hernia repair regarding recurrence rate and possible risk factors for recurrence. Summary Background Data: Laparoscopic hernia repair has been introduced as an alternative to open repair. Short-term follow-up suggests benefits for those patients operated with a laparoscopic approach compared with open techniques; ie, less postoperative pain and a shorter convalescence period. Long-term results, however, are less well known. Methods: The study was conducted as a multicenter randomized trial with a 5-year follow-up. A total of 1512 men aged 30 to 70 years, with a primary unilateral inguinal hernia, were randomized to either TEP or Lichtenstein repair. Results: Overall, 665 patients in the TEP group and 705 patients in the Lichtenstein group were evaluable. The cumulative recurrence rate was 3.5% in the TEP group and 1.2% in the Lichtenstein group (P = 0.008). Test for heterogeneity revealed significant differences between individual surgeons. The exclusion of 1 surgeon, who was responsible for 33% (7 of 21) of all recurrences in the TEP group, lowered the cumulative recurrence rate to 2.4% in this group, which was not statistically different from that of the Lichtenstein group. Conclusions: The recurrence rate for both TEP and Lichtenstein repair was low. A higher cumulative recurrence rate in the TEP group was seen at 5 years. Further analysis revealed that this could be attributable to incorrect surgical technique.
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| 10. |
- Enochsson, L, et al.
(författare)
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Laparoscopic vs open appendectomy in overweight patients
- 2001
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 15:4, s. 387-392
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Tidskriftsartikel (refereegranskat)abstract
- Background: Laparoscopic appendectomy (LA) has been associated with a faster recovery and less postoperative pain than the open technique. However, few data are available on the clinical outcome of LA in overweight patients. Methods: A group of 106 patients with a body mass index (BMI) > 26.4, representing the upper quintile of 500 prospectively randomized patients, were included in the study. They were randomized to undergo either laparoscopic or open appendectomy (OA). Operating and anesthesia times, postoperative pain, complications, hospital stay, functional index (1 week postoperatively), sick leave, and time to full recovery were documented. Results: In OA, the operating time for overweight patients was significantly longer than that for patients in the normal weight range (40 vs 35 min, p < 0.05). In LA, there was no difference in operating time between the normal and overweight patients. Overweight patients who underwent LA had longer operating and anesthesia times than their OA counterparts (55 vs 40 min, p < 0.001, and 125 vs 100 min, p < 0.001, respectively). Postoperative pain was significantly greater in overweight patients who underwent OA than in those treated with the laparoscopic technique. Postoperative pain was also significantly greater in overweight patients subjected to OA than in patients of normal weight after 4 weeks, the clinical significance may, however, be of less importance since the values are low (0.26 vs 0.09, p < 0.05). There were no significant differences between the two operating techniques in terms of complications. Hospital stay was longer for overweight patients than for normal-weight patients undergoing OA (3.0 vs 2.0, p < 0.01). The functional index did not differ between any group of patients. Sick leave was longer for overweight patients who underwent OA than for normal-weight patients treated with the same technique (17 vs 13 days, p < 0.01). In the laparoscopic group, however, there were no differences between the overweight and normal-weight patients. Time to full recovery was greater in overweight patients subjected to OA than in the overweight patients in the LA group (22 vs 15 days, p < 0.001). Conclusion: In this study, overweight patients who were submitted to LA had less postoperative pain and a faster postoperative recovery than overweight patients who had OA. LA also abolished some of the negative effects that overweight had on operating time, hospital stay, and sick leave with the open technique. However, anesthesia and operating times were significantly longer in LA for both overweight patients and those with a normal BMI.
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| 11. |
- Enochsson, L, et al.
(författare)
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The Fenyo-Lindberg scoring system for appendicitis increases positive predictive value in fertile women - A prospective study in 455 patients randomized to either laparoscopic or open appendectomy
- 2004
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Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 18:10, s. 1509-1513
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Tidskriftsartikel (refereegranskat)abstract
- Background: Suspected appendicitis is one of the most common indications for acute laparotomy or laparoscopy. The negative laparotomy and laparoscopy rates are high, often in the range of 15-30%, and especially high in some groups of patients such as women of child-bearing age and young patients. Different scoring systems have been introduced in order to improve diagnostic accuracy. The aim of the present study was to analyse the outcome of the Fenyo-Lindberg scoring system in a prospectively randomized multicenter trial and to analyze how well the score performed in stratified subgroups. Methods: The variables of the Fenyo-Lindberg scoring system were collected in a prospective study comparing laparoscopic and open surgery in suspected appendicitis and with four participating centers. None of the hospitals had used the scoring system previously. Since surgeons were unfamiliar with the score, they could not use it as a diagnostic aid. When comparing the score with the clinical outcome, retrospectively, the investigators interpreting the score were blinded regarding the surgical outcome. Results: Positive predictive value (PPV) of the Fenyo-Lindberg score was higher than that of the surgeon's clinical diagnosis in the patient cohort [0.90 vs 0.79 (p < 0.001)]. The score demonstrated an improvement of PPV in women [0.83 vs 0.70 (p < 0.01)]. PPV was increased in women between 15 and 50 years of age. In women aged 15-30 years and 31-50 years PPV increased from 0.69 to 0.82 and 0.68 to 0.86, respectively (p < 0.01). Both the sensitivity (0.77) and the specificity (0.69) of the score were, however, low. Conclusion: The Fenyo-Lindberg score is an inexpensive clinical tool that may improve the diagnostic accuracy for acute appendicitis in women of childbearing age, which is a group of patients where the diagnostic accuracy usually is low and where the arsenal of diagnostic tools such Lis Computed tomography is limited because of radiation. The low specificity of the score in women of childbearing age must, however, be kept in mind.
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| 12. |
- Graham, C., et al.
(författare)
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The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : Statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis
- 2017
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Ingår i: Trials. - : BioMed Central Ltd.. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. Methods/Design: The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Discussion: Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020.
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| 23. |
- Pansell, J, et al.
(författare)
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Optic nerve sheath diameter is associated with outcome in severe Covid-19
- 2022
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 17255-
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Tidskriftsartikel (refereegranskat)abstract
- Neurological symptoms are common in Covid-19 and cerebral edema has been shown post-mortem. The mechanism behind this is unclear. Elevated intracranial pressure (ICP) has not been extensively studied in Covid-19. ICP can be estimated noninvasively with measurements of the optic nerve sheath diameter (ONSD). We performed a cohort study with ONSD ultrasound measurements in severe cases of Covid-19 at an intensive care unit (ICU). We measured ONSD with ultrasound in adults with severe Covid-19 in the ICU at Karolinska University Hospital in Sweden. Patients were classified as either having normal or elevated ONSD. We compared ICU length of stay (ICU-LOS) and 90 day mortality between the groups. 54 patients were included. 11 of these (20.4%) had elevated ONSD. Patients with elevated ONSD had 12 days longer ICU-LOS (95% CI 2 to 23 p = 0.03) and a risk ratio of 2.3 for ICU-LOS ≥ 30 days. There were no significant differences in baseline data or 90 day mortality between the groups. Elevated ONSD is common in severe Covid-19 and is associated with adverse outcome. This may be caused by elevated ICP. This is a clinically important finding that needs to be considered when deciding upon various treatment strategies.
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| 29. |
- Rudberg, A. -S, et al.
(författare)
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Stroke survivors’ priorities for research related to life after stroke
- 2020
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Ingår i: Topics in Stroke Rehabilitation. - : Taylor & Francis. - 1074-9357 .- 1945-5119. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke has transitioned from an untreatable, unpreventable disease to a highly treatable and preventable disease over recent decades, and the number of stroke survivors is expected to increase. The number is also foreseen to grow larger as a result of an aging population. With an escalating number of stroke survivors, research on how to improve life after stroke is needed. Aims: The primary aim was to determine which area of research related to life after stroke that stroke patients and their informal carers prioritized as being relevant and valuable. Methods: A cross-sectional study of all patients who had completed the 12 months of follow-up in the EFFECTS trial. In the questionnaire the stroke patients and their informal carers were asked to prioritize areas of research they considered important and valuable with respect to their life after stroke. Results: Of the 731 patients who were still alive after the 12 months-follow-up, 589 responded. The most prioritized areas of research were Balance and walking difficulties (290 (49%) responders) and Post-stroke fatigue (173 (29%) responders). Women answered the undefined alternative “other” more often than men (43 women (11%) versus 11 men (6%), p = .04). Younger patients prioritized Post-stroke fatigue to a higher extent (88 (45%) versus (22%), p < .001), and elderly prioritized Balance and walking difficulties (214 (54%) versus 76 (40%), p = .002) and Speech difficulties (38 (10%) versus 9 (5%), p = .045). Conclusions: Life after stroke is perceived differentely with aging. Future research should address strategies to face challenges such as imbalance and walking difficulties and post-stroke-fatigue.
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| 31. |
- Rudberg, P C, et al.
(författare)
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Leukotriene A(4) hydrolase - Identification of a common carboxylate recognition site for the epoxide hydrolase and aminopeptidase substrates
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 279:26, s. 27376-27382
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Tidskriftsartikel (refereegranskat)abstract
- Leukotriene ( LT) A(4) hydrolase is a bifunctional zinc metalloenzyme, which converts LTA(4) into the neutrophil chemoattractant LTB4 and also exhibits an anion-dependent aminopeptidase activity. In the x-ray crystal structure of LTA(4) hydrolase, Arg(563) and Lys(565) are found at the entrance of the active center. Here we report that replacement of Arg(563), but not Lys(565), leads to complete abrogation of the epoxide hydrolase activity. However, mutations of Arg(563) do not seem to affect substrate binding strength, because values of K-i for LTA(4) are almost identical for wild type and ( R563K) LTA(4) hydrolase. These results are supported by the 2.3-Angstrom crystal structure of (R563A) LTA(4) hydrolase, which does not reveal structural changes that can explain the complete loss of enzyme function. For the aminopeptidase reaction, mutations of Arg(563) reduce the catalytic activity (V-max = 0.3 - 20%), whereas mutations of Lys(565) have limited effect on catalysis (V-max = 58 - 108%). However, in (K565A)- and (K565M) LTA(4) hydrolase, i.e. mutants lacking a positive charge, values of the Michaelis constant for alanine-p-nitroanilide increase significantly (K-m = 480 - 640%). Together, our data indicate that Arg(563) plays an unexpected, critical role in the epoxide hydrolase reaction, presumably in the positioning of the carboxylate tail to ensure perfect substrate alignment along the catalytic elements of the active site. In the aminopeptidase reaction, Arg(563) and Lys(565) seem to cooperate to provide sufficient binding strength and productive alignment of the substrate. In conclusion, Arg(563) and Lys(565) possess distinct roles as carboxylate recognition sites for two chemically different substrates, each of which is turned over in separate enzymatic reactions catalyzed by LTA(4) hydrolase.
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| 32. |
- Rudberg, Peter C
(författare)
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Leukotriene A4 hydrolase : studies of structure-function relationships by site-directed mutagenesis and X-ray crystallography
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Inflammation is the pathophysiological mechanism by which an organism clears and rebuilds a site of infection or injury. It is also the characteristic feature of a multitude of severe diseases, with the potential of afflicting almost any organ system. The inflammatory process is a complex array of interactions between cells and soluble factors, among which are the leukotrienes, a family of lipid mediators. Leukotriene (LT) B4 is a chemical mediator of inflammation. It is a potent chemotactic agent for polymorphonuclear leukocytes and T-lymphocytes, and thus constitutes an important link between the innate and adaptive immune responses. LTB4 is formed from arachidonic acid by the sequential action of 5-lipoxygenase and LTA4 hydrolase (LTA4H), which yield the unstable epoxide intermediate LTA4 and LT134, respectively. LTA4H is a ubiquitous 69 kDa dual-activity zinc metalloenzyme. In addition to the epoxide hydrolase activity, i.e. the conversion of LTA4 into LT134, it exhibits an anion-dependent aminopeptidase activity, for which the physiologic substrate(s) is currently not known. LTA4H belongs to the MI family of metallopeptidases and shares conserved sequence motifs with members of this family. Inhibition studies and the recently solved crystal structure of LTA4H showed that the epoxide hydrolase and aminopeptidase reactions occur in a common active site. For the aminopeptidase reaction, certain structural determinants had been characterized, but for the epoxide hydrolase reaction, the catalytic determinants in LTA4H were largely unknown. In this thesis we present studies of structure-function relationships in LTA4H using site-directed mutagenesis and X-ray crystallography. A conserved GXMEN motif was identified in sequence alignments of members of the M1 family of metallopeptidases. In addition, in the LTA4H crystal structure, Glu-271 of the GXMEN motif seemed to interact with the free amine of the inhibitor bestatin. We show that Glu-271 is crucial for both catalytic reactions of LTA4H, and support these findings with the crystal structure of [E271 Q]LTA4H. For the aminopeptidase reaction, Glu-271 acts as an N-terminal recognition site for peptide substrates. For the epoxide hydrolase reaction, we propose a reaction mechanism in which Glu-271 assists the catalytic zinc in the opening of the substrate's epoxide. Hence, Glu-271 is a unique example of an amino acid residue with dual and distinct functions in two catalytic reactions, involving chemically diverse substrates. The 12(R)-hydroxyl group is required for the biologic activity of LT134- In the LTA4H crystal structure, a group of hydrophilic residues was identified in predominantly lipophilic surroundings in the active site. The polar side-groups of these residues were catalytic candidates for substrate hydroxylation. We show that mutagenetic exchange of Asp-375 selectively eliminates the epoxide hydrolase reaction and support the critical role of Asp-375 with crystallographic data of [D375N]LTA4H. We propose a mechanism model, in which this residue acts as a general base in substrate 12(R)-hydroxylation. In this role, Asp-375 is a critical element for LTB4 formation and bioactivity. In the LTA4H crystal structure, the carboxylate of the complexed inhibitor bestatin is located in vicinity of Arg-563 and Lys-565. When the substrate LTA4 is modelled in the active site, electrostatic interactions seem possible between its carboxylate and these two residues. Our mutagenetic data suggest that Arg-563 alone plays a critical role for substrate alignment in the epoxide hydrolase reaction, whereas for the aminopeptidase reaction, Arg-563 cooperates with Lys565 for substrate alignment and binding. These findings are supported by the [R563A]LTA4H crystal structure. Together, these residues constitute a common carboxylate recognition site, with distinct roles for the two reaction mechanisms in LTA4H. Based on the crystal structure and the characterization of active site catalytic residues, we aimed to design novel inhibitors of LTA4H by computer-assisted molecular modelling and automated docking. We present the design, synthesis and analysis of a novel inhibitor designated HACAP, with IC50 values in the nanomolar range towards both the aminopeptidase and epoxide hydrolase reaction of LTA4H. Furthermore, protein-ligand interactions are confirmed by the LTA4H-HACAP crystal structure complex at 2.0 A resolution.
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