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Biomedical subjects

R G Miller

Publications and source records attributed to R G Miller.

At least 217 records · Page 12Linked to original sources

Subacute structural myopathy associated with human immunodeficiency virus infection.

An unusual myopathy characterized by selective loss of thick filaments and widespread formation of rod bodies is described in two men, both seropositive for human immunodeficiency virus. We were unable to find any previous reports documenting this combination of morphological abnormalities, which we believe may be related to human immunodeficiency virus infection. Both patients responded to treatment: one, to steroid therapy; the other, to plasmapheresis.

Acquired Immunodeficiency Syndrome↗

Failure of antiviral therapy for acquired immunodeficiency syndrome-related cytomegalovirus myelitis.

We report the first published case (to our knowledge) of histopathologically documented acquired immunodeficiency syndrome-related cytomegalovirus (CMV) myelitis in which antiviral drug therapy was administered. Despite sensitivity of the patient's CMV isolate to therapy with both ganciclovir and foscarnet, use of neither of these agents halted progression of central nervous system CMV disease. Higher doses of these drugs or combination therapy may be required to treat acquired immunodeficiency syndrome-related CMV myelitis effectively.

Acquired Immunodeficiency Syndrome↗

Motor conduction studies in Guillain-Barré syndrome: description and prognostic value.

The North American study of plasmapheresis in Guillain-Barré syndrome (GBS) included early, standardized electrodiagnostic testing in 210 of the 245 patients. To determine the types of abnormalities and the relation to outcome, we analyzed the prospectively collected motor conduction data obtained during the first 30 days of illness. For each parameter of motor conduction data, means were computed based on institutional normal data. Mean distal motor and F wave latencies commonly were abnormal in these early studies. In univariate analysis, mean compound muscle action potential (CMAP) amplitude from distal and proximal stimulation and mean motor conduction velocity were found to be related to the four predetermined outcome measures. In multivariate analysis of the motor conduction parameters, mean distal CMAP amplitude was the single best predictor of prognosis; other measures did not add to its predictive value. In further multivariate analysis of all factors relating to outcome, mean distal CMAP amplitude was determined to be the most powerful predictor of outcome, followed by plasmapheresis. These two factors were always statistically significant over and above all other variables. Our results indicate that prognostic information can be obtained from motor conduction studies even when performed early in the course of GBS; a mean distal CMAP amplitude of 0 to 20% of the lower limit of normal is associated with a markedly increased probability of a poor outcome. Nevertheless, even in patients with a low mean distal CMAP amplitude, the predicted outcome is improved with plasmapheresis therapy.

Action Potentials↗

Prognostic value of electrodiagnosis in Guillain-Barré syndrome.

This study was designed to identify clinical and electrodiagnostic indicators of prognosis in Guillain-Barré syndrome (GBS). Sixty severe GBS patients (all bedfast, 22 ventilator dependent) were analyzed clinically and with standard electromyography and nerve conduction studies. Both ventilator dependence and rapid evolution of weakness were more common in patients with a poor prognosis. The most powerful predictor of a poor outcome was reduced mean compound muscle action potential amplitude (less than 10% of the lower limit of normal).

Action Potentials↗

The spectrum of peripheral neuropathy associated with ARC and AIDS.

Peripheral neuropathy is increasingly recognized as a complication of the Acquired Immune Deficiency Syndrome (AIDS) and AIDS-related complex (ARC), but the varied clinical features have been incompletely described. Thirty homosexual men with peripheral neuropathy were evaluated in this study. Twenty-one had ARC and nine had AIDS. Four distinct clinical syndromes were recognized: distal sensorimotor polyneuropathy, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), mononeuropathy multiplex, and progressive polyradiculopathy. Four patients with clinical, electrophysiologic, and histologic evidence of CIDP and severe progressive weakness improved with plasma exchange, three regaining normal function.

AIDS-Related Complex↗

Reactivity of T-cells from patients with rheumatoid arthritis to anti-CD3 antibody.

The ability of an anti-CD3 monoclonal antibody (OKT3) to induce proliferation was examined in peripheral blood mononuclear cells (PBM) from 30 patients with rheumatoid arthritis (RA). Controls consisted of 10 patients with osteoarthritis, 12 patients with psoriatic arthritis, and 12 healthy subjects. The results revealed enhanced PBM reactivity in patients with active RA relative to inactive RA patients and all control groups. PBM of patients with mild/moderate clinical disease activity exhibited augmented anti-CD3 reactivity while those with severe disease demonstrated impaired reactivity. Enhanced reactivity was also observed in the active RA group using another anti-CD3 monoclonal antibody (Leu-4). Differences in anti-CD3 dose-response or time kinetics could not account for the results. Studies of enriched T-cell preparations revealed a markedly enhanced anti-CD3 reactivity of RA T-cells relative to normal control T-cells. Monocyte/T-cell mixing experiments revealed no enhanced reactivity of RA monocytes in the anti-CD3 response. RA T-cell preparations depleted of monocytes by limiting dilution reacted significantly more to anti-CD3 in the presence of IL-2 relative to controls. The enhanced reactivity could be accounted for in part by hyperreactivity of the OKT8-bearing subpopulation of T-cells.

Antibodies, Monoclonal↗

Atomic force microscopy of purple membranes.

The surface structure of purple membranes was imaged using an atomic force probe mounted in a scanning tunnelling microscope. One of the two different membrane surfaces showed protruding, disc-shaped features forming an hexagonal lattice with about 6 nm centre to centre spacing. These are identified as the cytoplasmic surfaces of trimers of bacteriorhodopsin molecules and are correlated with the structural information on bacteriorhodopsin obtained from numerous earlier electron microscope and diffraction studies.

Bacteriorhodopsins↗

31P nuclear magnetic resonance studies of high energy phosphates and pH in human muscle fatigue. Comparison of aerobic and anaerobic exercise.

The goal of these experiments was to investigate the relationship of ATP, phosphocreatine (PCr), inorganic phosphate (Pi), monobasic phosphate (H2PO4-), and pH to human muscle fatigue. Phosphates and pH were measured in adductor pollicis using 31P nuclear magnetic resonance at 2.0 Tesla. The force of muscle contraction was simultaneously measured with a force transducer. The effects of aerobic and anaerobic exercise were compared using two exercise protocols: 4 min sustained maximal voluntary contraction (MVC) and 40 min of repeated intermittent contractions (75% MVC). The sustained maximal contraction produced a rapid decline of MVC and PCr, and was accompanied by a rapid rise of Pi, H+, and H2PO4-. Intermittent exercise produced steady state changes of MVC, pH, and phosphates. No significant changes of ATP were found in either protocol. During fatiguing exercise, PCr and Pi had a nonlinear relationship with MVC. H+ showed a more linear correlation, while H2PO4- showed the best correlation with MVC. Furthermore, the correlations between MVC and H2PO4- were similar in sustained (r = 0.70) and intermittent (r = 0.73) exercise. The highly significant linear relationship between increases of H+ and H2PO4- and the decline of MVC strongly suggests that both H+ and H2PO4- are important determinants of human muscle fatigue.

Adenosine Triphosphate↗

Muscle strengthening through electric stimulation combined with low-resistance weights in patients with neuromuscular disorders.

Ten patients with gradually progressive neuromuscular disorders underwent (1) unilateral electric stimulation of anterior tibialis muscles and (2) unilateral stimulation of quadriceps femoris muscles, in combination with voluntary knee extension against ankle weights. After electric stimulation two hours/day, five days/week for two to 14 months, the mean maximum force (muscle strength) of knee extension increased significantly (p less than 0.005), by 108% +/- 56%. The contralateral nonexercised knee extensors also showed some increase in muscle strength. Electric stimulation of ankle dorsiflexors was ineffective; the maximum force of ankle dorsiflexion increased by only 11% +/- 27% (p greater than 0.3). In general, severely weak muscles (less than 10% normal strength) did not improve with either stimulation program. Electric neuromuscular stimulation combined with low-resistance weights can significantly increase muscle strength in patients with neuromuscular disorders if disease progression is gradual and initial muscle strength is greater than 15% normal.

Adolescent↗

Muscle strengthening through high-resistance weight training in patients with neuromuscular disorders.

The effects of weight training on muscle performance were quantified by measuring (1) maximum force (muscle strength), (2) force-time integral--area under force-time plot during 60 seconds of sustained maximum force (work done), and (3) fatigue index--percentage reduction in maximum force. Subjects included 16 patients with gradually progressive neuromuscular disorders. The muscle strength of these patients ranged from 2% to 75% normal before the program. For patients with markedly to moderately weak muscles, maximum force increased by 80% +/- 48%, force-time integral increased by 132% +/- 93%, and mean fatigue index was significantly reduced from 53% +/- 18% to 34% +/- 7.7% during the study period. Severely weak muscles (less than 10% normal strength) generally did not improve. High-resistance weight training can significantly increase muscle performance of patients with neuromuscular disease if disease progression is slow and initial muscle strength is greater than 15% normal.

Adult↗

Dopaminergic regulation of horizontal cell gap junction particle density in goldfish retina.

Light- or dark-adapted goldfish (Carassius auratus) retinas were treated with dopamine, which is believed to uncouple horizontal cells via D1 receptors, or with the dopamine antagonist haloperidol. Aldehyde-fixed retinas were freeze-fractured and the replicas examined by electron microscopy to identify horizontal gap junctions. The density (number per micron2) of intra-membrane particles of horizontal cell soma gap junctions was significantly lower in light-adapted and dopamine-treated retinas than in dark-adapted and haloperidol-treated retinas. There was no statistically significant difference between gap junction particles densities in (I) light-adapted (untreated) and in dopamine-treated (light- or dark-adapted) retinas, or between (II) dark-adapted (untreated) and haloperidol-treated (light- or dark-adapted). These results suggest that the uncoupling of horizontal cell somas by dopamine is accompanied by a decrease in gap junction particle density and that there is a greater release of dopamine during light-adaptation than dark-adaptation. Unlike horizontal cell somas, horizontal cell axon terminals did not show consistent changes in gap junction particle density with light- or dark-adaptation. Although the data suggests that there may be a reduction in axon terminal gap junction particle density with dopamine treatment, this effect is not reversible with haloperidol treatment. Our results suggest that the regulation of gap junctions may differ at two sites within the same cell.

Adaptation, Ocular↗

Three-dimensional architecture of sarcoplasmic reticulum and T-system in human skeletal muscle.

A modified Golgi method combined with stereoscopy has been used to demonstrate the three-dimensional architecture of the sarcoplasmic reticulum (SR) and the T-system in human skeletal muscle. SR formed a continuous repeating network with a different structure dependent upon the sarcomere position. Intermyofibrillar SR contained three regions: 1) fenestrated collars overlying the M-band region, 2) terminal cisternae overlying the A-I region, and 3) a three-dimensional anastomosed tubular network overlying the Z-band region. Longitudinal and/or transverse SR tubules connected these regions. Subsarcolemmal SR was also composed of three regions: 1) transversely oriented polygonal meshes overlying the M-band, 2) single-layered tubules overlying the Z-band region, and 3) a loose network between the two. In the subsarcolemmal sarcoplasm, where mitochondria were aggregated, SR anastomosed loosely and showed nonfenestrated cisternae beneath the plasma membrane. The T-system was composed of transversely oriented networks overlying the A-I region with occasional longitudinal tubules connecting these networks.

Adolescent↗

AAEE minimonograph #28: injury to peripheral motor nerves.

Nerve injury triggers a sequence of electrophysiological events dependent upon changes occurring both at the neuromuscular junction and the muscle membrane. The time course of these physiologic and morphologic alterations is reviewed in light of recent information provided by studies of extrajunctional acetylcholine receptors, axoplasmic transport, and freeze-fracture electron microscopy. A thorough knowledge of these changes is essential to understanding the clinical impact of nerve injury.

Animals↗

The effect of temporal dispersion on compound action potential area in human peripheral nerve.

In 32 ulnar nerves of healthy volunteers, the mean area of the compound muscle action potential recorded over abductor digiti minimi was reduced by 7.4% when comparing above-elbow with wrist stimulation and by 1.9% when comparing above-elbow with below-elbow stimulation. In 20 of these nerves, the mean area of the compound nerve action potential (CNAP) recorded over the fifth digit was reduced by 36% when comparing above-elbow with wrist stimulation. Area reduction of the compound action potential, especially of the CNAP, appears to be a characteristic effect of temporal dispersion in peripheral nerve when utilizing the bipolar recording technique routinely employed in clinical neurophysiology. A thorough understanding of the effects caused by temporal dispersion and of their quantitative limits in normal peripheral nerve is important for the proper interpretation of nerve conduction studies.

Adult↗

AIDS and apheresis procedures--therapeutic and safety considerations.

The role of therapeutic apheresis was assessed in a number of clinical syndromes associated with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). Four groups of patients were studied: AIDS with opportunistic infections, AIDS with Kaposi's sarcoma, AIDS/ARC patients with peripheral neuropathy and a patient with AIDS-related immune thrombocytopenia. Intensive plasmapheresis was shown to have no significant effects on the disease course of patients with full-blown AIDS. However, intensive plasma exchange restored normal neurologic function in the majority of patients with AIDS/ARC-related peripheral neuropathy. Selective immunoadsorption by means of protein A columns led to a sustained normalization of platelet counts in a patient with severe immune thrombocytopenia. A phase I study of AIDS-related Kaposi's sarcoma demonstrated that protein A immunoadsorption was tolerated well and was accompanied by partial responses. Patients being plasmapheresed for conditions other than AIDS were not found to be at any greater risk for acquiring AIDS-related viruses. Finally, health care professionals performing apheresis procedures on AIDS patients were not shown to be at increased risk of contracting AIDS-related viruses provided reasonable blood precautions were exercised.

AIDS-Related Complex↗

Quantitative correlation between plasma pyridostigmine levels and neuromuscular function in myasthenia gravis.

In 10 patients with myasthenia gravis, we studied the relationship between plasma pyridostigmine levels and five measures of neuromuscular function (NMF) following single oral doses of 60 to 120 mg. The NMF measures were percent decrement of the evoked muscle compound potential, maximum force, force-time integral, vital capacity, and outstretched-arm time. The combined mean improvement was most significant 2 hours after pyridostigmine ingestion and coincided with the peak plasma pyridostigmine levels in eight patients. In seven patients, there was a positive correlation between plasma pyridostigmine levels and the mean percent improvement.

Adult↗

Specific labelling by peanut agglutinin of the outer acrosomal membrane of the human spermatozoon.

Experiments to bind fluorescein-conjugated Arachis hypogea (peanut) agglutinin (FITC-PNA) to washed human spermatozoa demonstrated that this lectin binds to the acrosome region in air-dried preparations. Since there was no binding when labelling was performed in suspension, and comparable labelling to that seen in air-dried preparations was seen when spermatozoa treated with saponin (to lyse the plasma membrane) were labelled in suspension, the lectin must bind to an intracellular structure, probably the outer acrosomal membrane. This was confirmed by ultrastructural localization of colloidal gold-conjugated lectin in saponin-treated spermatozoa. Treatment of spermatozoa with the detergent Nonidet P-40 caused a marked change in the binding pattern: more spermatozoa showed binding in the equatorial segment of the acrosome with no binding in the anterior cap region. A comparable, less marked, change was seen when spermatozoa were incubated overnight under conditions known to support the capacitation and spontaneous acrosome reactions. Treatment with the calcium ionophore A23187 for 1 h to induce acrosome reactions artificially in uncapacitated spermatozoa resulted in the appearance of patchy acrosome fluorescence. From these experiments it is concluded that PNA binds specifically to the outer acrosomal membrane, and that FITC-PNA-labelling may be used to monitor the human sperm acrosome reaction.

Acrosome↗