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Biomedical subjects

M Bengtsson

Publications and source records attributed to M Bengtsson.

At least 55 records · Page 3Linked to original sources

Intravenous phentolamine test--an aid in the evaluation of patients with persistent pain after low-back surgery?

BACKGROUND: Persistent pain following surgery in the treatment of chronic low-back pain patients is still relatively frequent. Most of these patients with persistent pain have clinical signs of neuropathic pain. The neuropathic pain might be sympathetically maintained pain (SMP) or sympathetically independent pain (SIP). Systemic administration of phentolamine, a competitive alpha-adrenergic antagonist, has been used as a diagnostic tool to identify patients with SMP. METHODS: Thirty-seven patients with persistent pain after low-back surgery (lumbar laminectomy, with or without discectomi, or a posterior fusion, with or without decompression) received intravenous phentolamine (0.5 mg/kg over 30 min) in a single-blind, placebo-controlled manner. Prior to this infusion the patients were classified clinically into different pain groups based on physical examination and imaging findings. An opioid epidural test blockade was used as a control. RESULTS: Clinical classification divided the patients into nociceptive pain (n = 7), neuropathic pain (n = 22) and mixed pain (n = 8). In the phentolamine test there were only one responder, 34 non-responders and 2 patients were placebo-responders. In the control epidural blockade there were 11 non-responders, 23 fentanyl/local anaesthetic-responders and 3 placebo-responders. CONCLUSIONS: SMP is either an uncommon cause of persistent pain in this type of failed back surgery patients or the phentolamine test, as we performed it, was unable to identify SMP.

Adrenergic alpha-Antagonists↗

Mobilization of CD34+ cells by glycosylated and nonglycosylated G-CSF in healthy volunteers--a comparative study.

In vitro studies indicate that lenograstim (glycosylated G-CSF) is more potent than filgrastim (nonglycosylated G-CSF) on a weight for weight basis. However, such a difference has not yet been shown in vivo. The primary objective of this trial was to compare the efficacy of equivalent doses (microgram) of lenograstim and filgrastim in mobilizing CD34+ cells. Thirty-two healthy male volunteers, median age 27 yr (19-44 yr), were randomized to receive either lenograstim 10 micrograms/kg followed by filgrastim 10 micrograms/kg or vice versa with a washout period of a minimum 4 wk. Both drugs were administered as s.c. injections once daily for 5 d (d 1-5). CD34+ cells were mobilized with a similar kinetics, peaking at median d 6 (5-6) for both drugs. A significant difference in favour of lenograstim was shown for peak number of CD34+ cells/microliter blood (104 +/- 38 vs. 82 +/- 35, mean +/- 1 SD, p < 0.0001, paired t-test, n = 30) and number of CFU-GM/microliter blood at d 6 (14.6 +/- 8.4 vs. 10.2 +/- 4.6, p < 0.0001), respectively. There was no difference in the d 6 number of CD3+ cells. Both drugs were generally well tolerated and did not differ with respect to number of adverse events. In conclusion, lenograstim 10 micrograms/kg/d mobilizes PBPC more efficiently than the identical dose of filgrastim, indicating a difference in in vivo potency between the two G-CSFs.

Adjuvants, Immunologic↗

Sound quality judgment during acclimatization of hearing aid.

This study included 10 subjects with sensorineural hearing loss. They had not previously used hearing aids. The hearing aid fitting with "behind-the-ear' aids was based on the NAL method. Judging the sounds in their ordinary home environment, three sound situations (programmes) were selected, permitting the subjects to listen to one programme with speech, another with music and a third with "background noise'. For the group as a whole, significant differences were found between the sound quality judgements with and without the hearing aid. When the judgements of the programmes with background noise were excluded in the analysis, there were significant differences over time in the group as a whole on the scales for clarity and total impression.

Follow-Up Studies↗

Fibromyalgia--are there different mechanisms in the processing of pain? A double blind crossover comparison of analgesic drugs.

OBJECTIVE: Pain was analyzed in patients with fibromyalgia (FM) in a randomized, double blind, crossover study using intravenous (i.v.) administration of different drugs. METHODS: In 18 patients with FM muscle pain to i.v. administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3 mg/kg), or saline was studied. Spontaneous pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and non-tender point areas were followed. Drug plasma concentrations and effects on physical functioning ability score (FIQ) were recorded. A personality inventory (KSP) was used to related pain response to personality traits. RESULTS: Thirteen patients responded to one or several of the drugs, but not to placebo. Two patients were placebo responders responding to all 4 infusions. Three were nonresponders responding to no infusions. Seven of the responders had a reduction in pain for 1-5 days. Pressure pain threshold and pain tolerance increased significantly in responders. Plasma concentrations were similar in responders and nonresponders. FIQ values improved significantly after the ketamine infusion. Responders scored higher on KSP scales for somatic anxiety, muscular tension, and psychasthenia compared with healthy controls. CONCLUSION: FM diagnosed according to the American College of Rheumatology criteria seems to include patients with different pain processing mechanisms. A pharmacological pain analysis with subdivision into responders and nonresponders might be considered before instituting therapeutic interventions or research.

Adult↗

Recipient-reactive antibodies occur during development of acute graft-versus-host reaction after small bowel transplantation.

After small bowel transplantation, not only rejection but also graft-versus-host reaction (GVHR) may occur. Donor T lymphocytes, transferred together with the graft, are a prerequisite for the development of GVHR. So far, however, little is known about the effector mechanisms in acute GVHR. It can be assumed that not only T lymphocytes but also other cells, i.e., B lymphocytes, monocytes/macrophages, and NK cells, together with inflammatory cytokines, are responsible for the lesions of recipient tissue. In the present study, the occurrence of recipient-reactive antibodies after semisyngeneic small bowel transplantation was investigated to elucidate the role of B lymphocytes in GVHR development. No antibodies reactive with recipient cells were detectable in serum from untreated, nontransplanted rats. Five days after transplantation, recipient-reactive antibodies started to appear in recipient serum. At the same time, a deposition of IgM antibodies became visible in the liver and native intestine, which are target organs for GVHR. No antibodies directed against either the donor strain or a third-party strain were detectable in serum. We conclude that a synthesis of antibodies against recipient tissue occurs during the development of GVHR. Whether these antibodies contribute to the disease remains unclear.

Acute Disease↗

Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells.

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to Kb- or Db-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central position on the carrier peptide. With two of these glycopeptides, with galabiose (Gal alpha 1-4Gal; Gal2) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to Kb), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal2 epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific Kb-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.

Amino Acid Sequence↗

Is kidney transplantation in sensitized recipients justified?

The objective of the study was to determine if it is justified to use the scarce resources of cadaveric kidneys on HLA-sensitized patients, by reviewing the initial and long-term outcome of cadaveric renal transplantation at Uppsala University Hospital, Sweden. Between January 1988 and December 1994, 402 renal transplantations were performed. The patients were divided into one group of sensitized recipients (peak panel antibody reactivity > or = 25%; n = 84) and a second of non-sensitized recipients (panel reactive antibodies < 25%; n = 318). The groups were comparable in terms of recipient and donor age, gender, HLA-A, -B and -DR mismatches and numbers of diabetics. None of the sensitized patients received a six-antigen-matched kidney. For the non-sensitized group, life table analysis showed a 1-year actuarial graft survival (GS) of 91.8% and a 4-year GS of 84.4%. The corresponding GSs for the sensitized group were 79.9% and 68.7%, respectively (P < 0.01). The statistical significance vanished if patients with primary non-function were excluded. When excluding donors above 55 years of age, kidneys with cold ischemia time above 20 h, and two-antigen (HLA-DR) mismatches, there was no detectable difference between the non-sensitized and sensitized groups at 1-year or 4-year GS. Although there is a statistical significance in GS between non-sensitized and sensitized recipients of a kidney transplant, this does not differ from other risk groups such as diabetics, rheumatoid disease sufferers or elderly recipients. We therefore conclude that the sensitized patient should be accepted on the waiting list for a kidney transplant and that it is worthwhile to do the utmost to transplant this category of patients. Our data indicate that kidney GS in sensitized recipients is more affected by negative risk factors such as older donors, long cold ischemia time and two-antigen HLA-DR mismatch, than the non-sensitized recipient. To improve the outcome, those negative factors should be avoided or reduced.

Adult↗

Can a pharmacological pain analysis be used in the assessment of chronic low back pain?

A battery of pharmacological tests was used to differentiate the pain in patients with chronic low back pain (CLBP) referred for pain diagnosis and assessment of whether surgery was indicated or not. Forty patients (mean age 39 years, range 22-51 years) suffering from CLBP (mean pain duration 5.9 years, range 1-12 years) participated. Three pharmacological approaches were used: (1) intravenous infusion of morphine, (2) intravenous infusion of lidocaine and (3) a diagnostic epidural opioid blockade. The patients were tested in a single-blind, placebo-controlled fashion. The pain was considered nociceptive if it decreased by 50% or more in response to both intravenous morphine and epidural fentanyl, but increased in response to intravenous naloxone. The pain was considered neuropathic if it decreased by 50% or more in response to both intravenous lidocaine and the epidural local anaesthetic. Patients who registered a pain decrease of 50% or more in response to saline were classified as placebo responders. Those who registered less than 50% pain decrease in all the tests were considered nonresponders. According to the results of the tests, 16 of the patients were classified as having nociceptive pain, 8 neuropathic pain, 2 were placebo responders, 10 non-responders and 4 were unclassified. The results support the idea that this battery of pharmacological tests can be used in the classification of CLBP patients into different pain categories. This approach may prove useful as a guide for further patient evaluation and as a basis for choice of a suitable treatment strategy.

Adult↗

Can a pharmacological pain analysis in patients with chronic low back pain predict the outcome of lumbar fusion? Preliminary report.

Chronic low back pain patients chosen for lumbar fusion surgery were entered into a prospective study with the aim of evaluating whether pre-operative pharmacological pain classification correlated with the outcome of surgical treatment. Twenty consecutive patients (mean age 39 years, range 29-50 years) with a mean pain duration of 4.6 years (range 1-8 years) participated. The patients' pain, disability and work situation were evaluated pre- and post-operatively. According to the results of pharmacological pain testing the patients were classified into five pain groups: (1) those with nociceptive pain, (2) those with neuropathic pain, (3) placebo responders, (4) non-responders and (5) unclassified. This classification was based on the following approaches: intravenous morphine, intravenous lidocaine, epidurally administered fentanyl and a local anaesthetic. Surgical treatment consisted of posterolateral fusion of the lower two functional lumbosacral spinal units combined, if necessary with appropriate decompression. The results of the pharmacological pain assessment were not disclosed until the end of the follow-up period and outcome was evaluated by an unbiased observer. The distribution of patients between pain groups was as follows; nine had nociceptive pain, two suffered neuropathic pain, there were no placebo responders and seven were non-responders. Two patients could not be classified into any of these groups. Outcome was rated at 6, 12 and 24 months as excellent/good in eight out of nine patients with nociceptive pain. In the group with non-responding pain surgical outcome was significantly poorer (P < 0.01), and was ranked as excellent/good in only one out of seven patients. There was a significant improvement (P < 0.05) concerning both pain and disability in the nociceptive group, but not in the non-responding group. Pre-operative pharmacological pain testing may be useful as a predictor of surgical outcome and we suggest that it can be employed as a means to identify patients with non-responding pain and poor surgical prognosis.

Adult↗

Measurement of dynamic wedge angles and beam profiles by means of MRI ferrous sulphate gel dosimetry.

The purpose of this study is to examine the possible value of measuring the dose distribution in dynamic wedge photon beams using ferrous sulphate gel phantoms analysed by MRI. The wedge angles and dose profiles were measured for a field size of 70 x 70 mm2 and for dynamic wedge angles of 15 degrees, 30 degrees, 45 degrees and 60 degrees using a 15 MV photon beam generated from a Clinac 2100 CD (Varian). The dose profiles obtained from MRI ferrous sulphate gel were in good agreement with the dose measurements performed with a diode detector array. Also, the wedge angles determined from the MRI ferrous sulphate gel agreed well with the values obtained by using film dosimetry and with calculations by use of TMS (treatment planning system) (Helax, Uppsala, Sweden). The study demonstrated that MRI ferrous sulphate gel dosimetry is an adequate tool for measurements of some beam characteristics of dynamic radiation fields.

Algorithms↗

Laser Doppler perfusion imager (LDPI)--for the assessment of skin blood flow changes following sympathetic blocks.

A laser Doppler perfusion imager (LDPI) for evaluation of skin blood flow is presented and its use illustrated in two cases with a presumptive diagnosis of reflex sympathetic dystrophy (RSD) treated with local anesthetic sympathetic blocks. Among the advantages are the good spatial resolution over the area measured (12 x 12 cm) and that measurements can be done without contact with the skin. Generating a complete image takes 4.5 min but if higher temporal resolution is needed continuous measurements at one point are possible by use of another software routine.

Adult↗

Dose-dependent mobilisation of haematopoietic progenitor cells in healthy volunteers receiving glycosylated rHuG-CSF.

In an attempt to optimise the dose of G-CSF for mobilisation of PBPC in allogeneic donors, four groups of six healthy male volunteers received lenograstim (glycosylated rHuG-CSF) at a dose of 3, 5, 7.5 or 10 micrograms/kg/day, respectively, for 6 days (days 1-6). All subjects underwent a 10 I leukapheresis. Lenograstim was well tolerated. Maximal mobilisation was observed on days 5 or 6, with a clear dose-response for all progenitor cell types (CD34+, CFU-GM, BFU-E, CFU-mix). The peak numbers of CD34+ cells/microlitre (mean, s.e.m.) were 30 +/- 5, 49 +/- 8, 44 +/- 5 and 122 +/- 30 in the 3, 5, 7.5 and 10 micrograms/kg groups, respectively. A good correlation was observed between the number of CD34+ cells in blood and leukapheresis product (LP), respectively. Increasing the dose of lenograstim did not increase the number of T cells in the LP. A comparison of LP and steady state BM CD34+ cells in paired samples from each individual, showed a higher proportion of primitive immunophenotypes (CDw90+, HLA-DR-, CD45RA-, CD33-) among LP CD34+ cells. We conclude that increased doses of G-CSF improve the mobilisation of PBPC, and that G-CSF favours mobilisation of primitive CD34+ cell subsets. Lenograstim 10 micrograms/kg/day for 6 days should provide a sufficiently effective mobilisation of PBPC in most healthy PBPC donors.

Adult↗

Major histocompatibility complex class I binding glycopeptides for the estimation of 'empty' class I molecules.

Different forms of major histocompatibility complex (MHC) class I heavy chains are known to be expressed on the cell surface, including molecules which are functionally 'empty'. Direct peptide binding to cells is obvious during sensitization of target cells in vitro for cytotoxic T lymphocyte killing and 'empty' MHC-I molecules are comparatively abundant on TAP-1/2 peptide transporter mutant cells. In the present work we have estimated the fraction of 'empty' MHC class I molecules using glycosylated peptides and cellular staining with carbohydrate specific monoclonal antibodies. Synthetic Db and Kb binding peptides were coupled at different positions with different di- or trisaccharides, using different spacing between the carbohydrate and the peptide backbone. Binding of sugar specific mAbs was compared in ELISA and cellular assays. An optimal Db binding glycopeptide was used for comparative staining with anti-Db and anti-carbohydrate monoclonal antibodies to estimate fractions of 'empty' molecules on different T lymphoid cells. On activated normal T cells, a large fraction of Db molecules were found to be 'empty'. The functional role of such 'empty' MHC class I molecules on T cells is presently unclear. However, on antigen presenting cells they might participate in the antigen presentation process.

Amino Acid Sequence↗

Autosomal dominant cerebellar ataxia deafness and narcolepsy.

A new autosomal dominant syndrome in a Swedish pedigree is described. Five patients were affected with cerebellar ataxia and sensorineural deafness. Four of these patients had symptoms of narcolepsy. Optic atrophy, other neurological abnormalities and psychiatric symptoms developed with increasing disease duration. Three patients had non-neurological disease in addition, including diabetes mellitus in two and hypertrophic cardiomyopathy in one. Autopsy with neuropathological examination was performed in one case. Molecular studies focused on the short arm of chromosome 6, including the HLA DR2 locus associated with narcolepsy and the (CAG)n repeat at the spinocerebellar ataxia type 1 (SCA1) locus. Biochemical investigation of muscle biopsy of one case indicated mitochondrial dysfunction with selective decrease in ATP production for substrates that normally give the highest rates. The activity of glutamate dehydrogenase was reduced, indicating a low mitochondrial density. We postulate an autosomal dominant genetic factor responsible for this syndrome. Linkage was excluded to HLA DR2, and a normal sized SCA1 repeat was observed. We conclude that a locus predisposing to ataxia, deafness and narcolepsy exists outside this region of chromosome 6.

Adolescent↗

Using the Potts glass for solving the clustering problem.

We present an application of a Potts glass to the clustering problem. Simulated annealing in the mean field approximation is used in order to avoid local minima. The resulting updating equations are completely parallel, and very easy to implement. The model has no free parameters except for the annealing parameters. We show how the model can be implemented for some special clustering problems. The T-->0 limit of the Potts glass is identical to the vector quantization algorithm with certain increments. A comparative study of the Potts glass and vector quantization is also made, and it is shown that for difficult clustering problems, the Potts glass is far better than vector quantization.

Algorithms↗

Pain analysis in patients with fibromyalgia. Effects of intravenous morphine, lidocaine, and ketamine.

Pain intensity, muscle strength, static muscle endurance, pressure pain threshold, and pain tolerance at tender points and control points were assessed in 31 patients with fibromyalgia (FM), before and after intravenous administration of morphine (9 patients), lidocaine (11 patients), and ketamine (11 patients). The three different studies were double-blind and placebo-controlled. The patients were classified as placebo-responders, responders (decrease in pain intensity by > 50%) and non-responders. The morphine test did not show any significant changes. The lidocaine test showed a pain decrease during and after the infusion. The ketamine test showed a significant reduction in pain intensity during and after the test period. Tenderness at tender points decreased and endurance increased significantly, while muscle strength remained unchanged. The present results support the hypothesis that the NMDA receptors are involved in pain mechanisms in fibromyalgia. These findings also suggest that central sensitization is present in FM and that tender points represent secondary hyperalgesia.

Adult↗

Liver function and halothane-diethyl-ether azeotrope anaesthesia. Re-evaluation of an obsolete drug with special reference to early postoperative effects.

A general anaesthetic drug that fulfils requirements for use under difficult circumstances is the inhalation agent halothane-diethyl-ether (HE) azeotrope. Although both halothane and diethyl ether have been described in detail, their effect on the liver when given together as an azeotrope has not been systematically characterised. The effect on liver function was evaluated and compared with the effects of halothane anaesthesia (H) and spinal anaesthesia with tetracaine (S), the last named serving as controls. The series consisted of 33 healthy men (ASA 1-2) receiving no medication and scheduled for inguinal hernia repair. The patients were randomly allocated to receive HE, H or S. The following parameters were estimated the day before surgery and on the first postoperative day: liver cell metabolism (bile acids, unconjugated bilirubin), cell integrity (aminotransferases), synthesizing capacity (Prothrombin complex), cholestasis (conjugated bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase), and global liver function (chenodeoxycholic load test). No major differences emerged between the groups. Unconjugated bilirubin was increased in all groups. Prothrombin complex activity was reduced in all groups. Conjugated bilirubin was increased in the H group. The oral bile acid load test and the fasting bile acid were unaltered by anaesthesia in all groups. No major impact on liver cell function was seen in the early post-operative period after HE azeotrope anaesthesia. The findings support our view that HE azeotrope could be considered as an alternative anaesthetic agent under field conditions.

Adult↗