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Biomedical subjects

D Grob

Publications and source records attributed to D Grob.

At least 55 records · Page 3Linked to original sources

Effect of ethanol on function of the rat heart and skeletal muscles.

The present study was undertaken to evaluate the acute effects of ethanol on responses of the rat heart and skeletal muscles both in vivo and in vitro. In the anesthetized rat, intravenous infusion of ethanol at 0.1-0.5 g/kg body weight (33-167 mM) decreased the breathing rate by 8-83%, heart rate by 4-52%, and QRS amplitude by 5-27%, and increased the P-R interval by 1-49%. In the anterior tibialis muscle subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, ethanol at 0.1 g/kg increased the amplitude of the muscle action potential (AP) by 7%, whereas at 0.5 g/kg it decreased the muscle AP by 32%. The nerve-evoked tetanic tension was reduced by 7-34% at 0.1-0.5 g/kg ethanol. In the isolated rat heart, perfusion of ethanol at 0.1-3.0% (22-651 mM) decreased the heart rate by 8-48% and QRS amplitude by 10-39%, and increased the P-R interval by 5-61%. Left ventricular pressure was increased by 10% at 0.1% ethanol, and decreased by 80% at 3.0% ethanol. In the isolated rat phrenic nerve-diaphragm muscle preparation subjected to repetitive nerve stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the nerve AP by 5-89%, nerve-evoked muscle AP by 2-96%, and peak tetanic tension by 1-87%. On repetitive direct muscle stimulation at 100 Hz for 0.5 sec, 0.1-3.0% ethanol decreased the amplitude of the muscle-evoked muscle AP by 8-65%, and muscle-evoked tetanic tension by 2-65%. These studies indicate that ethanol causes smaller reduction in responses of the heart and skeletal muscles at clinical concentrations, but marked reduction in these responses at higher concentrations due to direct action on excitability of these tissues. At higher concentrations, ethanol causes greater reduction in excitability of the skeletal muscle than of the heart.

Animals

Treatment of myasthenia gravis by immunoadsorption of plasma.

We treated 16 patients with moderately severe to severe generalized myasthenia gravis (MG) by immunoadsorption (perfusion through a resin that adsorbs proteins) of 2,500 ml plasma on each of four alternate days. Fourteen patients who completed treatment all had significant improvement in strength (6 excellent, 6 good, and 2 fair), which began a mean of 42 hours after the first immunoadsorption, reached a maximum 4 days after the fourth immunoadsorption (mean, 250% of baseline strength), and returned to baseline over a mean of 2 months. Thirty-seven grams of plasma proteins were removed during each immunoadsorption, which required no replacement, compared with 175 grams during plasma exchange, which requires replacement with albumin. Serum or plasma concentration of all proteins fell, more so for most of the larger proteins than for the smaller ones: acetylcholine receptor antibody (AChR Ab) fell to a mean of 23% of original level, fibrinogen to 26%, C4 to 29%, IgM to 33%, IgG to 35%, CH50 to 41%, C3 to 42%, IgA to 54%, and albumin to 76%. All proteins, including AChR Ab, returned to their original levels within 1 to 3 weeks after the last immunoadsorption, while improvement in strength lasted a mean of 6 weeks longer. One seronegative patient had excellent improvement lasting more than a month. Activated complement C5a and white blood cell count rose during each immunoadsorption, while activated complement C3a fell, and each returned to its original level within hours. Eight patients had transient symptomatic hypotension attributable to withdrawal of blood more rapidly than it was returned; this hypotension was prevented or ameliorated by intravenous saline.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies

Degenerative lumbar spinal stenosis. Decompression with and without arthrodesis.

We prospectively evaluated the results of decompression of the spine, with and without arthrodesis, for the treatment of lumbar spinal stenosis without instability in forty-five patients (twenty-one men and twenty-four women) who had been managed between November 1989 and November 1990. The average age at the time of the operation was sixty-seven years (range, forty-eight to eighty-seven years). The patients were randomly assigned to one of three treatment groups (fifteen patients in each group) according to when they were admitted to the hospital. Group I was treated with decompression with laminotomy and medial facetectomy; Group II, with decompression and arthrodesis of the most stenotic segment; and Group III, with decompression and arthrodesis of all of the decompressed vertebral segments. All of the operations were performed by the same surgeon. The average duration of follow-up was twenty-eight months (range, twenty-four to thirty-two months). All three groups had a significant improvement in the distance that the patients were able to walk at the time of the latest follow-up examination compared with before the operation (p < 0.001 for Group I, p < 0.002 for Group II, and p < 0.005 for Group III). With the numbers available, there were no significant differences in the results among the three groups with regard to the relief of pain (p = 0.25 for Group I compared with Group II, p = 0.36 for Group II compared with Group III, and p = 0.92 for Group I compared with Group III).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

On the understanding of clinical instability.

STUDY DESIGN: Three-dimensional flexibility changes due to the application of an external fixator at C4-C5 were studied in cervical spine specimens. OBJECTIVES: To evaluate the biomechanical effects of applying a cervical external fixator to a patient using an in vitro model. SUMMARY OF BACKGROUND DATA: There is controversy regarding the relationship between the changes in spinal motion and clinical instability. METHODS: Using fresh cadaveric C4-C7 specimens, multidirectional flexibility was measured at all vertebral levels, before and after the fixator application at C4-C5, C5-C6, and C4-C6. RESULTS: The average ranges of motion for flexion, extension, lateral bending, and axial rotation were 8.3 degrees, 7.2 degrees, 5.3 degrees, and 5.6 degrees, which decreased by 40%, 27%, 32%, and 58%, respectively, because of the fixator application. The corresponding neutral zones were 3.4 degrees, 3.4 degrees, 3.0 degrees, and 2.0 degrees, which decreased by 76%, 76%, 54% and 69%, respectively. The decreases with the fixation at C4-C5 were similar to those for fixation at C5-C6. CONCLUSIONS: This in vitro study documented that the application of an external fixator to the cervical spine decreases the intervertebral motion in general, and decreases flexion, extension and torsional neutral zones in particular. The findings help explain the clinical instability of the spine and support the hypothesis that the neutral zone is more closely associated with the clinical instability than is the range of motion.

Adult

The role of plate and screw fixation in occipitocervical fusion in rheumatoid arthritis.

STUDY DESIGN: In a clinical retrospective study, the results of occipitocervical fusion in patients with rheumatoid arthritis were studied and analyzed. OBJECTIVES: The results of two different operative techniques were compared. The advantages of screw fixation compared with wiring techniques in this population of patients were investigated. SUMMARY OF BACKGROUND DATA: Numerous different implants have been presented in the literature for occipitocervical fusion in patients with rheumatoid arthritis. The use of wires being the standard fixation technique. METHODS: Occipitocervical fusion was performed in patients with rheumatoid arthritis: 26 patients with the wiring technique and 33 patients with a new Y-plate fixation. The results were compared at a follow-up period of 24 months and 50 months, respectively. Clinical and radiologic results were investigated. RESULTS: The atlantodental distance could be significantly better reduced in the group with the Y-plate fixation and the neurologic improvement in the wiring group was 40%, whereas in the Y-plate fixation 86% of neurologic improvement was observed. Pseudarthrosis was seen in 27% of the wiring technique and in 6% in the plate and screw fixation technique. CONCLUSIONS: In occipitocervical fusion for patients with rheumatoid arthritis, the screw and plate fixation technique provides superior results than other techniques using wire fixations.

Arthritis, Rheumatoid

Defective production of anti-inflammatory cytokine, TGF-beta by T cell lines of patients with active multiple sclerosis.

Activated T lymphocytes play an important role in the pathogenesis of multiple sclerosis (MS). These T cells secrete both pro- and anti-inflammatory cytokines. We have studied the production of these two kinds of cytokines by PBL of patients with MS and compared it with normal controls and other autoimmune diseases (OAD). PBL of 29 patients with MS, 14 patients with OAD, and 14 healthy normal controls were cultured for 5 wk. PBL of MS patients produced more pro-inflammatory cytokines, IL-2, IFN-gamma and TNF/lymphotoxin, and less anti-inflammatory cytokine, TGF-beta, during wk 2 to 4 in culture than PBL of normal controls. PBL of MS patients also produced more IL-2 and TNF/lymphotoxin than PBL of OAD patients. Decreased TGF-beta production by lymphocytes of patients with MS correlated directly with disease activity. MS patients with active disease produced less TGF-beta than MS patients with stable disease. The cells producing TGF-beta were primarily CD8+ T cells and CD45RA+T cells. These findings emphasize the complexity of immune response in MS patients and suggest that the increased production of pro-inflammatory cytokines by lymphocytes of patients with MS, combined with the decreased production of TGF-beta (anti-inflammatory cytokine), may play an important role in the mechanisms and manifestations of MS.

Adult

Potassium and caffeine contractures of mouse muscles before and after fatiguing stimulation.

To assess the impairment of muscle membrane excitation, excitation-contraction (E-C) coupling, and contractility during muscle fatigue, we monitored the contracture responses of resting and fatigued muscles on exposure to high potassium and caffeine. On exposure to 140 mmol/L potassium, mouse extensor digitorum longus (EDL) developed a contracture which was 15.7% of tetanic tension before fatigue and 31.7% after fatigue, while soleus developed 59.4% contracture before and 68.8% after fatigue. Potassium causes contractures by depolarizing the muscle fiber membrane. Hence, membrane excitation is reduced in fatigued EDL and soleus. On exposure to 32 mmol/L caffeine, the contracture was 7.1% in resting EDL, 8.5% in fatigued EDL, 50.1% in resting soleus, and 43.7% in fatigued soleus. On exposure to 1 mmol/L caffeine followed by rapid cooling, the contracture was 3.0% in resting EDL, 3.2% in fatigued EDL, 21.5% in resting soleus, and 10.3% in fatigued soleus. Caffeine causes contracture by releasing Ca++ from the sarcoplasmic reticulum. Our results indicate reduced E-C coupling attributable to reduced membrane excitation in fatigued EDL, and reduced contractility in fatigued soleus.

Animals

Immune responses, and autoimmune outcome, during virus infection of the central nervous system.

A combined role of a virus infection of the central nervous system (CNS) and an autoimmune response to myelin basic protein (MBP), an autoantigen of the CNS, is suggested in the pathogenesis of multiple sclerosis (MS). SJL mice are highly susceptible while B6 mice are less susceptible to the induction of experimental autoimmune encephalomyelitis (EAE), the autoimmune model of MS. Peripheral inoculation of Semliki forest virus (SFV) into SJL and B6 mice resulted in: (1) Higher viral titers, more severe clinical disease, and hence a stronger nonspecific and SFV-specific lymphoproliferation, and production of IFN-gamma and TNF/LT was observed by splenocytes (SPL) of B6 than by those of SJL mice, on Day 7 postinfection. (2) Following viral clearance, however, proliferation to SFV, and to MBP, and the production of IFN-gamma and TNF/LT by SPL of SFV-infected SJL mice were significantly higher, while the production of TGF-beta was significantly lower than by those of B6 mice. In conclusion, the immune responses to SFV, and to MBP, which were triggered by SFV infection were significantly higher and more prolonged in the SPL of SJL mice, the EAE-susceptible mice, than by those of B6 mice after the infection was cleared.

Alphavirus Infections

The value of functional computed tomography in the evaluation of soft-tissue injury in the upper cervical spine.

A functional rotatory computed tomography (CT) study of 423 whiplash patients with cervical spine soft-tissue injury was undertaken to determine its diagnostic value. The results are correlated with previous CT studies on normal subjects, and an evaluation of paradox motion, in which the lower vertebra rotates more than the vertebra immediately superior to it, is given. Asymmetrical left/right rotation reached the pathological value in 36% of the patient population at the level of C0-1. Twice as many patients had hypermobile rotation to the left as compared with the right, perhaps indicating that the right alar ligament is more often damaged in injuries involving the whiplash mechanism. A higher percentage of pathological values for hypermobile rotation was found at the level of C0-1 than at C1-2. Patients exhibiting paradox rotation had a significantly higher amount of rotation to the contralateral side than did those who exhibited no paradox rotation. These findings validate the use of functional rotatory CT in the evaluation of soft-tissue damage of the upper cervical spine resulting from whiplash injury.

Adolescent

Hypersensitivity to molybdenum as a possible trigger of ANA-negative systemic lupus erythematosus.

After implantation of two metal plates a 24 year old woman developed fever of unknown origin and successively more symptoms of an ANA-negative systemic lupus erythematosus (SLE). These symptoms resolved after removal of the plates and recurred during patch testing of the metal components, which showed a reaction to molybdenum. A lymphocyte transformation test indicated a delayed-type hypersensitivity to molybdenum. Subsequent progressive flare ups of SLE appeared without molybdenum reexposure. This is the first report suggesting the existence of a hypersensitivity to molybdenum, which may act as another environmental trigger for SLE.

Adult

[The unstable spine--an "in vitro" and "in vivo study" on better understanding of clinical instability].

In cases of suspected painful instability of a cervical segment, temporary external fixation by means of external fixator was applied. The segmental immobilization caused immediate relief of pain. The pain reoccurred after removal of the immobilization. The effect of immobilization by external fixation was investigated in biomechanical tests using fresh cadaveric C4-7 specimens. Multidirectional flexibility was measured before and after application of the fixator at C4/C5, C5/C6 and C4-6. We measured the reduction in motion between the different segments. In every situation the neutral zone decreased more than the range of motion. The findings are helpful to understand the clinical instability of the spine and support the hypothesis that the neutral zone is more closely associated with clinical instability than range of motion. The combination of clinical application and biomechanical investigation allowed us to establish a direct correlation between instability and pain.

Accidents, Traffic

Production of anti-acetylcholine receptor-alpha antibody in vitro by peripheral blood lymphocytes of patients with myasthenia gravis: role of immunoregulatory T cells and monocytes.

To study the role of T cells in T and B cell interaction resulting in production of antibody (Ab) to the alpha chain of acetylcholine receptor (anti-AChR-alpha Ab) in myasthenia gravis (MG), we cocultured peripheral blood-purified B and T cells of patients with MG and of control subjects with and without multiple sclerosis in the presence of AChR-alpha or pokeweed mitogen. Under these conditions, a high level of anti-AChR-alpha Ab was produced by cells of patients with MG but not of control subjects. Production of anti-AChR-alpha Ab by B cells was stimulated by autologous purified or cloned CD4+ T cells, whereas autologous CD8+ T cells had no effect. CD8+ T cells did not suppress anti-AChR-alpha Ab production when added to B cells cocultured with CD4+ T cell clones. Anti-AChR-alpha Ab production was inhibited by monoclonal antibodies against CD4 and class II major histocompatibility complex (MHC) antigens, indicating that these antigens are required for productive T-B cell interactions resulting in anti-AChR-alpha Ab synthesis. Anti-AChR-alpha Ab production by peripheral blood lymphocytes of patients with MG was significantly lower than that by their purified or cloned T cells cultured with B cells. Cell-mixing experiments indicated that anti-AChR-alpha Ab synthesis was inhibited by monocytes. The prostaglandin synthetase inhibitor, indomethacin, partially restored the suppressive effect of monocytes on anti-AChR-alpha Ab synthesis. These results indicate that induction of anti-AChR-alpha Ab production by CD4+ T cell clones requires CD4 and class II MHC antigens and is inhibited by suppressor macrophages and not by CD8+ T cells.

Adult

Posture affects motion coupling patterns of the upper cervical spine.

Measurements of motions of the cervical spine are used to help diagnose the problems of clinical instability due to degenerative changes and trauma. For a better interpretation of the three-dimensional motions of the upper cervical spine, knowledge of the effects of posture on these motions is necessary. Seven fresh human cadaveric C0-C3 spinal specimens were utilized. Each specimen was put in three distinct sagittal plane postures: full flexion, neutral, and full extension. At each posture, two load types were applied: left and right axial torques, and left and right lateral bending moments up to 1.5 Nm. The resulting three-dimensional relative motions of C0-C1 and C1-C2 were measured, with use of nonconstraining stereophotogrammetry, in the form of load-displacement curves. We found that the curves were nonlinear. The most dramatic change due to modification in posture was found in coupled sagittal plane rotation, which changed from extension at extended posture to flexion at flexed posture at both levels and in response to both load types. For the axial torque, the main axial rotation and coupled lateral bending changed little with posture. For the lateral bending moment, the main lateral bending rotation and coupled axial rotation decreased; the latter changed direction at C1-C2 as the spine was put into flexed posture. The motions for the right and left load applications generally were mirror images, except for the coupled sagittal plane rotations, which did not change with the direction of the load.

Adult

Duration of pain and muscular adaptations in patients with dysfunction of the cervical spine.

Biopsies of the sternocleidomastoid and omohyoid muscle were taken from 24 patients who underwent arthrodesis for cervical dysfunction of different etiologies. The two muscles, which are involved differently in movements of the head and cervical spine, were investigated histochemically. Muscle fibers were classified as type I, IIA, IIB, or IIC (transitional fibers) according to the pH lability of myofibrillar ATPase and calculated relative distribution. In both muscles, fiber transformations (as evidenced by an increase in the relative amount of type-IIC fibers) were regularly observed within the first 2 years after the onset of the symptoms. The occurrence of the transformation processes was independent of the patient's age and sex and was the same for the different etiologies. Since the overall fiber composition of the muscles remained essentially unchanged, the fiber transformations must occur alternatingly in both directions (from "slow" to "fast" and the reverse). Muscles of patients with a long case history showed no greater signs of fiber transformation. Therefore, fiber transformations in response to cervical dysfunction occur in the initial stage of the disease and involve different types of muscles. The muscles then return to a "stable" condition, independent of the continuation of the dysfunction and the chronic neck pain.

Adaptation, Physiological

Mechanisms of fatigue in normal intercostal muscle and muscle from patients with myasthenia gravis.

Fatigue mechanisms in normal intercostal muscle and muscle from patients with myasthenia gravis (MG) were evaluated by monitoring the compound muscle action potential (CMAP) and tetanic tension responses to repetitive nerve or muscle stimulation in vitro. When fatigue was induced by nerve stimulation at 30 Hz for 0.5 s every 2.5 s, about half of the original tension decreased after 30 min in normal muscle and 5 min in MG muscle. Analysis of the changes in area of CMAPs and tension indicated that impairment of neuromuscular transmission, muscle membrane excitation, and excitation-contraction (E-C) coupling and contractility accounted for 40%, 29%, and 31% of fatigue in normal muscle, and 83%, 0%, and 17% of fatigue in MG muscle. When fatigue was induced by muscle stimulation at 30 Hz, tension declined by a quarter after 30 min in normal muscle, but by a half after 17 min in MG muscle. Impairment of muscle membrane excitation and E-C coupling and contractility accounted for 58% and 42% of fatigue in normal muscle, and 22% and 78% of fatigue in MG muscle. Thus, fatigue of normal muscle is caused by impairment of at least four processes, and enhanced fatigue of MG muscle is caused by greater impairment of neuromuscular transmission, E-C coupling, and contractility.

Action Potentials

Effect of cocaine on leakage of creatine kinase from isolated fast and slow muscles of rat.

Since patients with cocaine overdose were reported to develop rhabdomyolysis involving skeletal muscle damage leading to elevated levels of serum creatine kinase (CK), we determined whether cocaine can directly act on isolated rat skeletal muscles and increase the leakage of CK. In the fast-twitch muscle such as the extensor digitorum longus (EDL), following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 0.6, 0.7, 0.9, and 1.2 units/mg of muscle respectively. On exposure of EDL to 0.1, 0.5, and 1.0 mM cocaine, there was no significant change in CK leakage. In the slow-twitch muscle such as the soleus, following exposure to normal physiological solution for 1, 2, 3, and 4 hr, the mean leakage of CK was 1.5, 2.2, 2.7, and 3.1 units/mg, which was significantly greater (P < 0.001) than in EDL at each time interval. On exposure of soleus to 0.1 mM cocaine, the CK leakage did not increase significantly, but on exposure to 0.5 mM cocaine, it significantly increased to 2.4, 3.4, 4.4, and 5.7 units/mg, and on exposure to 1.0 mM cocaine, it further increased to 2.7, 4.9, 6.5, and 7.6 units/mg. The CK activity of fresh muscle homogenate was 115.5 units/mg in EDL and 51.9 units/mg in soleus. These results indicate that cocaine can directly act on skeletal muscle and increase the leakage of CK especially from slow-twitch muscle like soleus, but not from fast-twitch muscle like EDL.

Animals

Clinical validation of functional flexion/extension radiographs of the cervical spine.

The aim of this study was to determine the clinical validity of functional flexion/extension radiographs of the cervical spine in a defined patient population. Sixty-four adults with functional disorders of the cervical spine underwent passive flexion/extension radiographic examinations. The radiographs were analyzed using a computer assisted method to calculate segmental motion parameters, such as rotations, translations, and centers of rotation. The patients were separated into three groups based on their specific functional disorders, and their motion parameters were compared with those of a healthy population. The three groups consisted of patients with degenerative changes, those with radicular syndrome, and those with whiplash trauma. Most of the patients displayed trends toward hypomobile segmental motion. This trend is displayed more substantially in the groups with degeneration and radicular syndrome. Hypomobility in segmental rotation was significant at C6-C7 for the degenerative and radicular groups. The trauma group showed trends toward hypermobility in the upper and middle cervical levels, and the locations of the centers of rotation were shifted in the anterior direction when compared with those of the healthy population.

Adult