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Biomedical subjects

J Holmberg

Publications and source records attributed to J Holmberg.

At least 19 recordsLinked to original sources
PubMed2006

Up to 21-day banked red blood cells collected by apheresis and stored for 14 days after automated wash at different times of storage.

BACKGROUND AND OBJECTIVES: A closed-system technology (ACP-215, Haemonetics, Braintree, MA) enables automated washing and extended storage of frozen red blood cells (RBC). This technology was applied to wash banked RBC for removal of undesirable protein and metabolites before transfusion. We studied protein and metabolite depletion as well as RBC metabolism and viability up to 14 days postwash with regard to various pre-storage times. MATERIALS AND METHODS: Thirty RBC units were collected by means of apheresis and subdivided into three arms based on prewash storage time period (6 days/group 1, 14 days/group 2, 21 days/group 3). Wash efficacy (protein depletion, IgA), RBC metabolism (pH, lactate, potassium, haemolysis) and cell viability (ATP) were analysed immediately and 14 days after washing. RESULTS: Total protein and IgA postwash were lowered by automated wash in all groups and uniformly met EC guidelines. Potassium (mmol/l) was below 1.2 mmol/l postwash and significantly below prewash values in all groups, even after 14 days of storage (prewash vs. postwash; P < 0.05). RBCs washed after 14 and 21 days, respectively, showed significantly lower pH values and lower ATP content than RBCs washed after only 6 days of storage. Haemolysis rate remained significantly below 0.8%, the maximum level recommended by the EC guidelines, immediately and 14 days after washing in all units. CONCLUSION: Our data confirm that RBC units banked up to 21 days can be effectively protein- and potassium-depleted with the ACP-215 independent from prewash storage time. With respect to high ATP levels and pH, postwash storage of 2 weeks should be limited to units not older than 7 days before wash. This new washing technology ensures better standardization in washed RBC and provides blood centres with a logistical alternative to 24-h washed RBC products.

Blood Component Removal↗
PubMed2005

Treatment of phobic postural vertigo. A controlled study of cognitive-behavioral therapy and self-controlled desensitization.

In balance clinic practice, phobic postural vertigo is a term used to define a population with dizziness and avoidance behavior often as a consequence of a vestibular disorder. It has been described as the most common form of dizziness in middle aged patients in dizziness units. Anxiety disorders are common among patients with vestibular disorders. Cognitive-behavioral therapy is an effective treatment for anxiety disorders, and vestibular rehabilitation exercises are effective for vestibular disorders. This study compared the effect of additional cognitive-behavioral therapy for a population with phobic postural vertigo with the effect of self-administered vestibular rehabilitation exercises. 39 patients were recruited from a population referred for otoneurological investigation. Treatment effects were evaluated with the Dizziness Handicap Inventory, Vertigo Symptom Scale, Vertigo Handicap Questionnaire, and Hospital Anxiety and Depression Scale. All patients had a self treatment intervention based on education about the condition and recommendation of self exposure by vestibular rehabilitation exercises. Every second patient included was offered additional cognitive behavioral therapy. Fifteen patients with self treatment and 16 patients with cognitive- behavioral treatment completed the study. There was significantly larger effect in the group who received cognitive behavioral therapy than in the self treatment group in Vertigo Handicap Questionnaire and the Hospital Anxiety and Depression scale and its subscales. Cognitive-behavioral therapy has an additional effect as treatment for a population with phobic postural vertigo. A multidisciplinary approach including medical treatment, cognitive-behavioral therapy and physiotherapy is suggested.

Adult↗
PubMed2004

Tubular repair of the median or ulnar nerve in the human forearm: a 5-year follow-up.

The long-term outcome from silicone tube nerve repair was compared with the outcome from routine microsurgical repair in a clinical randomized prospective study, comprising 30 patients with median or ulnar nerve injuries in the distal forearm. Postoperatively, the patients underwent neurophysiological and clinical assessments of sensory and motor function regularly over a 5-year period. After 5 years there was no significant difference in outcome between the two techniques except that cold intolerance was significantly less severe with the tubular technique. In the total group there was ongoing improvement of functional sensibility throughout the 5 years after repair. It is concluded that tubular repair of the median and ulnar nerves is at least as good as routine microsurgical repair, and results in less cold intolerance.

Adolescent↗
PubMed2001

Pharmacodynamic modelling of reversible gastric acid pump inhibition in dog and man.

H 335/25, a 4-amino quinoline, belongs to a new class of reversible gastric acid pump inhibitors. A potential advantage of such drugs over the irreversible proton pump inhibitors (PPIs) is better control over the effect-time profile. Dose escalation studies were performed to characterize the effect on acid secretion in dogs (n=24) and healthy male subjects (n=12). The effect-time profile was delayed compared to the concentration-time profile. A model-based approach, using non-linear mixed effects modelling, was applied to quantify and elucidate the mechanism for the delayed effect. Three different models were investigated: (1) a slow equilibration preceding the formation of drug-enzyme complex, modelled by an effect-compartment, (2) a slow equilibration between free drug, free enzyme and drug-enzyme complex, described by a kinetic binding model, and (3) a delay between enzyme inhibition and the measured response, described by an indirect response model. Model 2 was shown to be superior to models 1 and 3, for both dog and human data. The dissociation rate constant, k(off), was estimated to be 0.85 and 0.88 h and the calculated equilibration constant, K(d), was 160 and 250 nM in dog and man, respectively. Simulations of the predicted time-course of the effect beyond the 4-5-h observation period was similar for the three models.

Administration, Oral↗
PubMed2001

Arthritis induced in rats with nonimmunogenic adjuvants as models for rheumatoid arthritis.

Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.

Adjuvants, Immunologic↗
PubMed2000

Regulation of repulsion versus adhesion by different splice forms of an Eph receptor.

Eph tyrosine kinase receptors and their membrane-bound ephrin ligands mediate cell interactions and participate in several developmental processes. Ligand binding to an Eph receptor results in tyrosine phosphorylation of the kinase domain, and repulsion of axonal growth cones and migrating cells. Here we report that a subpopulation of ephrin-A5 null mice display neural tube defects resembling anencephaly in man. This is caused by the failure of the neural folds to fuse in the dorsal midline, suggesting that ephrin-A5, in addition to its involvement in cell repulsion, can participate in cell adhesion. During neurulation, ephrin-A5 is co-expressed with its cognate receptor EphA7 in cells at the edges of the dorsal neural folds. Three different EphA7 splice variants, a full-length form and two truncated versions lacking kinase domains, are expressed in the neural folds. Co-expression of an endogenously expressed truncated form of EphA7 suppresses tyrosine phosphorylation of the full-length EphA7 receptor and shifts the cellular response from repulsion to adhesion in vitro. We conclude that alternative usage of different splice forms of a tyrosine kinase receptor can mediate cellular adhesion or repulsion during embryonic development.

Alternative Splicing↗
PubMed2000

Esomeprazole provides improved acid control vs. omeprazole In patients with symptoms of gastro-oesophageal reflux disease.

BACKGROUND: Esomeprazole (Nexium) is a new proton pump inhibitor for the treatment of acid-related diseases. METHODS: In this double-blind crossover study, 38 patients with gastro-oesophageal reflux disease (GERD) symptoms were randomized to esomeprazole 40 and 20 mg and omeprazole 20 mg once daily for 5 days. On day 5 of each dosing period, 24-h intragastric pH and pharmacokinetic variables were measured. RESULTS: Thirty-six patients aged 29-58 (mean 45) years completed the study. Esomeprazole 40 and 20 mg maintained intragastric pH > 4 for (mean) 16.8 and 12.7 h, respectively, vs. 10.5 h for omeprazole 20 mg (P < 0.001 and P < 0. 01). Twenty-four-hour median intragastric pH was significantly higher with esomeprazole 40 mg (4.9) and 20 mg (4.1) than with omeprazole 20 mg (3.6) (P < 0.001 and P < 0.01). Area under the plasma concentration-time curve (AUC) was 80% higher for esomeprazole 20 mg vs. omeprazole, while that for esomeprazole 40 mg was more than five times higher (each P < 0.0001). Interpatient variability in intragastric pH and AUC was less with esomeprazole than with omeprazole. Esomeprazole was well tolerated and there were no safety concerns. CONCLUSIONS: Esomeprazole provides more effective acid control than omeprazole, with reduced interpatient variability, thereby offering the potential for improved efficacy in acid-related diseases.

Adult↗
PubMed1998

Pharmacokinetics and effect on caffeine metabolism of the proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole.

AIMS: To study the pharmacokinetics of three proton pump inhibitors, omeprazole, lansoprazole, and pantoprazole, as well as any potential influence on CYP1A2 activity (measured by means of rate of caffeine metabolism) of these compounds at single dose and repeated dose administration. METHODS: Fourteen healthy males, classified as 12 extensive metabolizers (EMs) and two poor metabolizers (PMs) according to the urinary S/R mephenytoin ratio, completed this open, randomized, three-way cross-over study. In each of the three 7-day treatment periods either omeprazole (20 mg), lansoprazole (30 mg) or pantoprazole (40 mg) in therapeutically recommended doses was administered once daily, and the pharmacokinetics of the proton pump inhibitors as well as the rate of caffeine metabolism was measured on days 1 and 7. RESULTS: In the EMs there was an increase in AUC from day 1 to day 7 for omeprazole. In the PMs the AUC of both omeprazole and lansoprazole was unchanged during repeated dosing, while for pantoprazole there was a tendency to a slight decrease. The AUC at steady state was for all three proton pump inhibitors 5 fold higher in PMs compared with EMs, indicating that the same proportion of the dose, irrespective of compound, is metabolized by CYP2C19. No induction of CYP1A2 was evident for any of the compounds in either EMs or PMs. CONCLUSIONS: The approximately 5 fold difference in AUC between EMs and PMs indicates that approximately 80% of the dose for all three proton pump inhibitors is metabolized by the polymorphically expressed CYP2C19. None of the three proton pump inhibitors, administered in therapeutically recommended doses, is an inducer of CYP1A2--neither in PMs nor in EMs.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Tubular versus conventional repair of median and ulnar nerves in the human forearm: early results from a prospective, randomized, clinical study.

Injury to a peripheral nerve is followed by local synthesis and release of neurotrophic factors of importance for the regeneration process. This concept was adopted for repair of transected human median and ulnar nerves in the forearm. As an alternative to conventional microsurgical repair of the nerve trunk, silicone tubes of appropriate size were used to enclose the injury zone, intentionally leaving a gap measuring 3-4 mm between the nerve ends inside the tube. The early results from a prospective, randomized, clinical study comparing this principle with conventional microsurgical technique for repair of human median and ulnar nerves, is presented. Eighteen patients (14 men and 4 women), aged 12-72 (mean, 29.5) years, were randomized to either tubulization (11 cases) or conventional microsurgical repair (7 cases). A battery of tests for sensory and motor functions of the hand were carried out at regular intervals for up to 1 year after surgery. The results show no difference between the both techniques, with the exception of perception of touch, which showed a significant difference (p < .05) at the 3-month checkup in favor of the tubulization technique. At re-exploration 11 months after the initial procedure (1 case), the former gap was replaced by regenerated nerve tissue in direct continuity with the proximal and distal parts of the nerve trunk, the exact level of the former injury being impossible to identify. Study data demonstrate an intrinsic capacity of human major nerve trunks to reconstruct themselves in a preformed space when an optimal environment is offered and the surgical trauma is minimized.

Adolescent↗
PubMed1996

Replantation-revascularization and primary amputation in major hand injuries. Resources spent on treatment and the indirect costs of sick leave in Sweden.

Thirty consecutive patients with amputation or devascularizing injuries of the thumb or two or more fingers proximal to the PIP joint were reviewed. Replantation or revascularization had been done in 27 patients, in 24 successfully. Three patients had primary amputation. The distribution of calculable costs was dominated by those for sick leave (49%), operation (26%) and ward costs (20%). Out-patient care, physiotherapy and travel together constituted only 6%. The cost of a successful replantation was equal to 1.6 times the mean annual salary of these patients and that of primary amputation about half as much. Mobility, power and performance of a standardized grip test were better for the successfully replanted or revascularized patients. Subjective evaluation of 23 parameters of function, cosmesis and quality of life did not disclose any differences. All patients except three had returned to their original work within 2 years.

Adolescent↗
PubMed1996

Osteotomy of the first metacarpal for osteoarthrosis of the basal joints of the thumb.

A radial, 30 degrees wedge osteotomy was used for treatment of osteoarthrosis of the trapeziometacarpal joint in 18 patients, 16 women and two men, mean age of 61 years (range 38-74). Six of them had involvement of the scaphotrapezial joint. After a mean follow-up of 8.5 months (range 2-21) one of the patients were completely satisfied with the result of the operation, seven were quite satisfied, and two considered themselves unchanged. None was made worse. Of the 12 patients who did not have involvement of the scaphotrapezial joint nine were completely satisfied and three quite satisfied. Grip strength on the operated side was 75.5% (32%-100%), and pulp pinch was 74.5% (30%-100%) of that in the contralateral one. The mobility of the thumb was influenced little by the operation. Wedge osteotomy of the first metacarpal is a simple and safe way of relieving pain, particularly in the early stages of osteoarthrosis of the basal thumb joint.

Adult↗
PubMed1994

Nerve repair: correlation of restitution of functional sensibility with specific cognitive capacities.

To test the hypothesis that cognitive capacity is correlated with the outcome of functional sensibility after nerve repair, 19 patients were evaluated 2 to 5 years after median or ulnar nerve repair at the distal forearm level. The sensory evaluation included tests for functional sensibility as well as assessments addressing perception thresholds for touch/pressure and vibration. Psychometric tests for cognitive capacity were also carried out. Multiple regression analysis, correcting for the effect of age and the ability to perceive touch/vibration, was used to investigate the relationship between functional sensibility and cognitive capacity, and to determine which of the tested central nervous factors had the greatest influence on the outcome of recovery of functional sensibility. On a ranking list of such factors verbal learning and visuo-spatial logic capacity were the most important ones, indicating significant correlations with functional sensibility. It is concluded that cognitive capacity factors may play an important role for the functional outcome following nerve repair and that variations in such factors may help to explain the variability in the outcome of nerve repair.

Adolescent↗
PubMed1994

Effect of digital edge-enhancement on the visibility of normal parenchymal lung markings.

Digital 'conventional-like' (C-L) and edge-enhanced (E-E) posteroanterior chest roentgenograms of 42 healthy individuals were ranked twice (interval of at least 5 days) in the order of increasing lung parenchymal markings (a total of four rankings). This was done by three radiologists, two residents, one medical student and one radiographer. There was a good general consistency of rankings for both the C-L and E-E images. The correlation coefficients were best (median 0.600) (P < 0.05) between the consequent rankings of C-L images compared to the subsequent rankings of E-E images (median 0.440) and to the various combinations between the rankings of both kinds of images. Subtle differences in normal lung parenchyma could, therefore, generally (five of the seven observers) best be demonstrated in C-L images, but two observers managed best with the E-E images.

Adult↗
PubMed1994

Sixty five thumb replantations. A retrospective analysis of factors influencing survival.

Sixty five isolated thumb replantations and revascularisations for survival done at our department between 1977 and 1991 were studied retrospectively. The overall failure rate was 20% (13/65). The most important influence on outcome was the mechanism of injury. The failure rate for avulsed thumbs was 38% (6/16), for all other mechanisms of injury 14% (7/49). The failure rates for replantations and revascularisations for survival were similar, 18% (6/33) and 22% (7/32), respectively. The survival rate was independent on the level of injury, the failure rates for amputations at the levels of the proximal and distal phalangeal levels being 19% (6/31) and 21% (7/33), respectively. The presence of two patent arteries at the end of the operation (n = 11) was favourable for the prognosis, as all these thumbs survived. There was no corresponding relationship on the venous side. The use of vein grafts on the arterial or venous side was not associated with lower failure rate. Nine patients were reoperated on, one of them twice. Reoperation was worthwhile, the failure rate in reoperated thumbs being only 11%.

Adolescent↗