| 1. |
- Hedner, Thomas, 1949, et al.
(författare)
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Gammahydroxybutyric acid: central biochemical and behavioral effects in neonatal rats.
- 1985
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Ingår i: Pharmacology, biochemistry, and behavior. - 0091-3057. ; 23:2, s. 185-9
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Tidskriftsartikel (refereegranskat)abstract
- Administration of gammahydroxybutyric acid (GHBA) to 4 days old animals caused a dose dependent decrease in locomotor activity. GHBA also induced a marked hypoventilation, irregular breathing and finally apnea, while heart rate was slightly increased. Changes in monoamine neurotransmitter turnover indicated an inhibition of dopamine (DA) neurotransmission. It is concluded that GHBA mechanisms in the neonatal rat brain are biochemically as well as functionally mature at an early age and that the effects on locomotor activity and respiratory regulation at least partly may involve interactions with central DA neurotransmission.
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| 2. |
- Carling, Malin S, et al.
(författare)
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Preoperative Fibrinogen Plasma Concentration Is Associated With Perioperative Bleeding and Transfusion Requirements in Scoliosis Surgery.
- 2011
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Ingår i: Spine. - 1528-1159. ; 36:7, s. 549-55
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Tidskriftsartikel (refereegranskat)abstract
- STUDY DESIGN.: Prospective observational study. OBJECTIVE.: To investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery. SUMMARY OF BACKGROUND DATA.: Bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. Early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk. METHODS.: A total of 82 otherwise healthy patients (mean age: 15 ± 3 years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. Patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. Correlations between laboratory variables and bleeding volume were calculated with Pearson test. Patient variables and laboratory variables were compared with Student t test between patients with bleeding volume in the upper quartile ("bleeders") and the remaining patients, and between patients with extensive transfusion (defined as >2 U of packed red cells) and no or limited transfusions (≤2 U). RESULTS.: Mean fibrinogen concentration was 3.0 ± 0.7 g/L (range, 1.3-4.9). Mean total perioperative bleeding volume was 1552 ± 1019 mL (range, 100-5800 mL). Total bleeding volume correlated significantly with preoperative fibrinogen concentration (r = -0.31, P = 0.005) but neither with platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 ± 0.6 vs. 3.1 ± 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were transfused with >2 U of packed red cells.Patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 ± 0.7 vs. 3.1 ± 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT did not differ. CONCLUSION.: The results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. Preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.
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| 3. |
- Fritzell, Peter, 1948, et al.
(författare)
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2001 Volvo Award Winner in Clinical Studies: Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish Lumbar Spine Study Group.
- 2001
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Ingår i: Spine. - 0362-2436. ; 26:23
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Tidskriftsartikel (refereegranskat)abstract
- A randomized controlled multicenter study with a 2-year follow-up by an independent observer.To determine whether fusion of the lower lumbar spine could reduce pain and diminish disability more effectively when compared with nonsurgical treatment in patients with severe chronic low back pain (CLBP).The reported results after fusion surgery on patients with CLBP vary considerably, and the evidence of treatment efficacy is weak in the absence of randomized controlled studies.A total of 294 patients referred to 19 spinal centers from 1992 through 1998 were randomized blindly into four treatment groups. Patients aged 25-65 years with CLBP for at least 2 years and with radiologic evidence of disc degeneration at L4-L5, L5-S1, or both were eligible to participate in the study. The surgical group (n=222) included three different fusion techniques, not analyzed separately in this study. Patients in the nonsurgical group (n=72) were treated with different kinds of physical therapy. The surgical group comprised 49.5% men, and the mean age was 43 years. The corresponding figures for the nonsurgical group were 48.6% and 44 years. The patients had suffered from low back pain for a mean of 7.8 and 8.5 years and been on sick leave due to back pain for a mean of 3.2 and 2.9 years, respectively. The Visual Analogue Scale (VAS) was used to measure pain. The Oswestry Low Back Pain Questionnaire, the Million Score and the General Function Score (GFS) were used to measure disability. The Zung Depression Scale was used to measure depressive symptoms. The overall result was assessed by the patient and by an independent observer. Records from the Swedish Social Insurance were used to evaluate work disability. Patients who changed groups were included in the analyses of significance according to the intention-to-treat principle.At the 2-year follow-up 289 of 294 (98%) patients, including 25 who had changed groups, were examined. Back pain was reduced in the surgical group by 33% (64 to 43), compared with 7% (63 to 58) in the nonsurgical group (P=0.0002). Pain improved most during the first 6 months and then gradually deteriorated. Disability according to Oswestry was reduced by 25% (47 to 36) compared with 6% (48 to 46) among nonsurgical patients (P=0.015), according to Million by 28% (64 to 46) compared with 8% (66 to 60) (P=0.004), and accordingtoGFS by 31% (49 to 34) compared with 4% (48 to 46) (P=0.005). The depressive symptoms, according to Zung, were reduced by 20% (39 to 31) in the surgical group compared with 7% (39 to 36) in the nonsurgical group (P=0.123). In the surgical group 63% (122/195) rated themselves as "much better" or "better" compared with 29% (18/62) in the nonsurgical group (P<0.0001). The "net back to work rate" was significantly in favor of surgical treatment, or 36% vs. 13% (P=0.002). The early complication rate in the surgical group was 17%.Lumbar fusion in a well-informed and selected group of patients with severe CLBP can diminish pain and decrease disability more efficiently than commonly used nonsurgical treatment.
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| 4. |
- Fritzell, Peter, 1948, et al.
(författare)
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Chronic low back pain and fusion: a comparison of three surgical techniques: a prospective multicenter randomized study from the Swedish lumbar spine study group.
- 2002
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Ingår i: Spine. - 1528-1159. ; 27:11, s. 1131-41
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Tidskriftsartikel (refereegranskat)abstract
- A multicenter randomized study with a 2-year follow-up period and an independent observer was conducted.To compare three commonly used surgical techniques to achieve lumbar fusion primarily in terms of their ability to reduce pain and decrease disability in patients with severe chronic low back pain.Lumbar fusion can be used to reduce pain and decrease disability in patients with chronic low back pain, and different surgical techniques are available. The reported results after fusion surgery vary considerably, but most studies are retrospective and/or performed on heterogeneous patient groups. Spine surgeons commonly use the techniques presented in this report. However, in the absence of randomized trials it is difficult to know whether any one of them is better than the others for these patients.From 1992 through 1998, 294 patients referred to 19 spinal centers were blindly randomized into four treatment groups: three surgical groups (n = 222) and one nonsurgical group (n = 72). The sociodemographic and clinical characteristics did not differ among the groups. Eligibility included patients 25 to 65 years of age with therapy-resistant chronic low back pain that had persisted for at least 2 years and radiologic evidence of disc degeneration (spondylosis) at L4-L5, L5-S1, or both. Only patients randomized to one of three surgical groups were analyzed in the current study: Group 1 (posterolateral fusion; n = 73), Group 2 (posterolateral fusion combined with variable screw placement, an internal fixation device; n = 74), and Group 3 (posterolateral fusion combined with variable screw placement and interbody fusion; n = 75). The "circumferential fusion" in Group 3 was performed either as an anterior lumbar interbody fusion (n = 56) or as a biomechanically similar posterior lumbar interbody fusion (n = 19). The groups were composed of 51%, 58%, and 40% men respectively, and the respective mean ages were 44, 43, and 42 years. The patients had experienced low back pain for at least 2 years (mean, approximately 8 years). They had been on sick leave for approximately 3 years. Pain was measured by a visual analog scale, and disability was assessed by the Oswestry Low Back Pain Questionnaire, the Million Visual Analogue Score, and the General Function Score. Depressive symptoms were measured by the Zung Depression Scale. The global overall rating of the result was assessed by the patient and an independent observer after 2 years. Hospitalization data including operation time, blood loss, blood transfusion, and days of hospitalization in connection with surgery were reported, along with complications and the fusion rate. Records from the Swedish Social Insurance Board providing information on sick leave and economic compensation for Swedish residents were used to evaluate the patients' work status.An independent observer examined 201 (91%) of 222 patients after 2 years, after 18 "group changers" and 3 dropouts had been excluded from the analyses. All surgical techniques were found to reduce pain and decrease disability substantially, but no significant differences were found among the groups. In all three groups, the patients rated the overall outcome similarly, as did the independent observer. The more demanding techniques in Groups 2 and 3 consumed significantly more resources in terms of operation time, blood transfusions, and days in hospital after surgery. The early complication rate was 6% in Group 1, 16% in Group 2, and 31% in Group 3. The fusion rate, as evaluated by plain radiograph, was 72% in Group 1, 87% in Group 2, and 91% in Group 3.All the fusion techniques used in the study could reduce pain and improve function in this selected group of patients with severe chronic low back pain. There was no obvious disadvantage in using the least demanding surgical technique of posterolateral fusion without internal fixation.
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| 5. |
- Hedner, Jan A, 1953, et al.
(författare)
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An analysis of the mechanism by which gamma-aminobutyric acid depresses ventilation in the rat.
- 1984
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Ingår i: Journal of applied physiology: respiratory, environmental and exercise physiology. - : American Physiological Society. - 0161-7567. ; 56:4, s. 849-56
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Tidskriftsartikel (refereegranskat)abstract
- Intracerebroventricular administration of gamma-aminobutyric acid (GABA) or intraperitoneal injection of the GABA transaminase A inhibitor aminooxyacetic acid (AOAA) depressed ventilation in halothane-anesthetized rats. The depression was due to changes in both respiratory frequency (f) and tidal volume (VT) after GABA, whereas AOAA decreased only f. Intracerebroventricular GABA decreased inspiratory drive (VT/TI; intrapulmonary pressure at 100 ms) but did not change the bulbopontine setting of inspiratory duration (TI). Moreover, respiratory duty cycle (TI/TT) was decreased, and the ventilatory response to CO2 exposure was blunted. The ventilatory depression induced by GABA was reversed by the GABA antagonist bicuculline. The GABA content measured 45 min after AOAA administration was significantly increased in the whole brain, the hemispheres, striatum, and lower spinal cord regions. Whole-brain GABA content was significantly correlated to the changes in f, minute ventilation, TI, expiratory duration (TE), and total cycle duration. Furthermore, there was a significant negative correlation between brain stem GABA content and TI/TT but not VT/TI. In summary, GABA seems to interact with the central regulation of respiration at different levels in the brain. The main effect of increased endogenous concentrations of GABA is, however, a decrease in respiratory frequency due to a prolongation in TE.
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| 6. |
- Hedner, Jan A, 1953, et al.
(författare)
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Effects of TRH and TRH analogues on the central regulation of breathing in the rat.
- 1983
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Ingår i: Acta physiologica Scandinavica. - : Wiley. - 0001-6772 .- 1365-201X. ; 117:3, s. 427-37
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Tidskriftsartikel (refereegranskat)abstract
- Respiratory activity was studied in rats during light halothane anesthesia. Thyrotropin releasing hormone (TRH) and two TRH analogues: the desamidated form (TRH-OH) and gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate (DN 1417) were administered intracerebroventricularly. TRH 0.5-5 micrograms induced a marked tachypnoea with a rapid onset and a duration of at least 20 min. DN 1417, a potent analogue of TRH with a very low TSH (thyroid stimulating hormone) releasing activity was more effective in stimulating respiratory frequency, while TRH-OH, regarded to have neither TSH releasing nor extra hypothalamic effects, at equimolar doses was unable to induce any changes in the respiratory pattern. When TRH was given into the fourth ventricle the dose response curve was slightly shifted to the left. In experiments employing the occluded breath technique, P0.1 was increased in the same magnitude as the mean inspiratory flow (VT/T1). The results also indicated an increase in the gain of the inflation reflex loop whereas the central bulbopontine setting for T1 and TTOT were not significantly changed. Local injection of TRH into the nucleus tractus solitarii induced a stimulation of respiratory frequency which was slower in onset compared to the response seen after injection into the lateral or fourth ventricles. Concomitantly to the respiratory changes, i.c.v. TRH injection induced a hypocarbia and an alkalosis. No changes in blood pressure or heart rate were seen. The respiratory stimulant effect of TRH could be potentiated by pretreatment with naloxone, methylatropine or a low dose of GABA. Haloperidol or propranolol did not significantly change the respiratory effects of TRH, while reserpine pretreatment seemed to blunt some of the ventilatory effects of TRH. It seems likely that TRH has few direct effects on brain stem neurones involved in the central regulation of respiration, but the main effects seem to be elicited in areas rostral to the brain stem. The respiratory stimulating effect of TRH is unrelated to TSH. Furthermore, other neurotransmitter systems might also be involved in modulation of the respiratory stimulation evoked by TRH.
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| 7. |
- Hedner, Jan A, 1953, et al.
(författare)
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Interaction of substance P with the respiratory control system in the rat.
- 1984
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Ingår i: The Journal of pharmacology and experimental therapeutics. - 0022-3565. ; 228:1, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- The effects of substance P (SP) on respiratory regulation were studied in halothane-anesthetized rats. Intracerebroventricular injections of SP in the dose range 3 to 30 micrograms (3 X 10(-9) to 3 X 10(-8) mol) induced a dose-dependent stimulation of minute ventilation due to an increase in tidal volume although respiratory frequency was slightly decreased. Inspiratory drive (tidal volume/inspiratory time; P0.1) increased whereas respiratory duty cycle (inspiratory time/total cycle duration) remained unchanged. Animals subjected to bilateral vagotomy showed a similar response to i.c.v. SP with the exception that the increase in tidal volume was less pronounced and inspiratory time/total cycle duration was decreased. When applying the occluded breath technique it was found that maximum pressure indicating inspiratory off-switch threshold mechanisms was increased in vagi-intact animals after SP. Furthermore, SP altered the vagally mediated control of the length of the inspiratory phase and induced a shortening of the bulbopontine setting for inspiratory time. A biphasic circulatory response with an initial depressor effect followed by a slight pressor effect was also seen after i.c.v. SP. It is concluded that SP interacts with the respiratory control system by at least two different mechanisms, bulbopontine time setting and inspiratory off-switch mechanisms. SP may also directly increase central inspiratory activity.
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| 8. |
- Hedner, Thomas, 1949, et al.
(författare)
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Effects of theophylline on adenosine-induced respiratory depression in the preterm rabbit.
- 1984
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Ingår i: European journal of respiratory diseases. - 0106-4339. ; 65:2, s. 153-6
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Tidskriftsartikel (refereegranskat)abstract
- The adenosine agonist N6-phenylisopropyladenosine (PIA) was given intraperitoneally to preterm rabbit neonates (29 days gestational age). 1 mg i.p. induced a marked respiratory depression and irregular breathing which could be prevented or antagonized by administration of theophylline. The results indicated a central nervous site of action and it is hypothesized that central adenosine overactivity may have a pathophysiological significance for the irregular breathing or apnea of prematurity sometimes seen in the human neonate.
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| 9. |
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| 10. |
- Kaigle Holm, Allison, 1964, et al.
(författare)
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Muscular and kinematic behavior of the lumbar spine during flexion-extension.
- 1998
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Ingår i: Journal of spinal disorders. - 0895-0385. ; 11:2, s. 163-74
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Tidskriftsartikel (refereegranskat)abstract
- Reduction in lumbar muscular activity at full body flexion, known as flexion relaxation, has been studied in relation to overall trunk, lumbar spine, and hip flexion, but has not been evaluated in conjunction with motion on the segmental level. In this study, intervertebral motion in a lumbar motion segment, trunk flexion, and the electromyographic activity in the lumbar erector spinae muscles were simultaneously measured during dynamic flexion-extension in seven patients with chronic low back pain with symptoms suggesting segmental instability and in six asymptomatic controls. A linkage system, which attached directly to the spinous processes of a lumbar motion segment, was used to continuously measure the sagittal plane intervertebral motion, while a potentiometric goniometer measured trunk flexion; myoelectric activity was measured using surface electrodes. It was found that intervertebral motions, as well as trunk mobility, were significantly less in the patients, both in terms of range and pattern of motion. Flexion relaxation was demonstrated in the controls by a 78% decrease in myoelectric activity at full flexion, whereas in the patients, only a 13% reduction was found, with most of the patients experiencing no reduction at all. Flexion relaxation occurred only in subjects in whom intervertebral rotation had reached a stage of completion considerably before full trunk flexion was achieved. These findings suggest that persistent muscle activation, which restricts intervertebral motion, is a means by which the neuromuscular system provides stability to help protect diseased passive spinal structures from movements that may cause pain.
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