International standardization of glycohemoglobin measurements: practical application.
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Chemistry, Clinical↗
Biomedical subjects
J D England
Publications and source records attributed to J D England.
Muscle denervation in peripheral arterial disease.
Muscle function is often severely impaired in peripheral arterial disease (PAD), but the effects of repeated ischemic events upon nerve and muscle are incompletely characterized. We performed comprehensive electrophysiologic studies and skeletal muscle histologic analysis in six patients with unilateral PAD and five control subjects matched for age and activity level. In the PAD patients, all ischemic legs showed both electrophysiologic and histologic evidence of chronic partial denervation-reinnervation restricted to distal muscles. Two of the PAD patients had evidence of milder distal denervation in the nonischemic legs. Two of the controls had denervation in at least one leg, but in each case electrophysiologic findings were pathognomonic of L-5 and S-1 radiculopathies. All other control legs and nonischemic legs were normal. These results suggest that recurrent ischemia associated with PAD may cause muscle denervation, which may be one of the mechanisms responsible for decreased exercise performance in these patients.
Action Potentials↗
Affinity binding assay of glycohemoglobin by two-dimensional centrifugation referenced to hemoglobin A1c.
We describe an automated assay of glycohemoglobin performed with the Abbott Vision analyzer. The assay is based on batch affinity-extraction with 3-aminophenylboronic acid-derivatized agarose beads. Reagents are packaged in a disposable test pack. Whole-blood specimens are hemolyzed with saponin within a glass capillary tube inserted into the test pack. The sample is automatically diluted with, mixed with, and separated from the solid-phase reagent. Bichromatic absorbance readings are used to calculate the percentage of hemoglobin bound. Based on the linear correlation between affinity-measured glycohemoglobin and HPLC-measured hemoglobin A1c, the percentage of hemoglobin bound is converted to a "standardized %HbA1c" result by use of regression parameters stored during a calibration run. The combination of affinity methodology with standardization by reference to HPLC produces values directly comparable with those obtained by methods specific for HbA1c. The method produces 10 results within 15 min. The assay operates with CVs < 5%, and the results correlate highly with those by ion-exchange and affinity minicolumn methods, and by ion-exchange HPLC.
Autoanalysis↗
Interlaboratory standardization of measurements of glycohemoglobins.
The diversity of methods used to measure glycohemoglobins (GHb) makes it difficult to compare patients' results among laboratories. We reported previously the feasibility of providing comparable results from different assays by use of common calibrators. We here compare results from seven different GHb methods calibrated by use of hemolysates assayed by a precise ion-exchange high-performance liquid-chromatographic (HPLC) method for hemoglobin A1c (HbA1c). Thus, regardless of the GHb species measured by the seven methods, results were referenced to the HbA1c content of the calibrators. Without this calibration, GHb values for single samples varied, e.g., from 4.0% to 8.1% and from 10% to 14.2% in the normal and high ranges, respectively. Calibration decreased between-method variability (single sample ranges of, e.g., 4.8% to 5.4% and 9.4% to 10.2% in the normal and high ranges, respectively) and improved interassay precision. We conclude that this approach to calibration of GHb measurements allows direct comparison of results obtained by different methods and improves precision.
Calibration↗
Liver side effects associated with simvastatin therapy.
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Anticholesteremic Agents↗
Increased numbers of sodium channels form along demyelinated axons.
Sodium channels, which are largely localized to the nodes of Ranvier in myelinated axons, appear to form new distributions along demyelinated axons. In this study a sensitive radioimmunoassay (RIA) was used to examine the changes in the total number of sodium channels that occur in nerves experimentally demyelinated in vivo with doxorubicin (adriamycin). The results clearly illustrate the development of an increased number of sodium channels during demyelination, suggesting that this process is associated with the formation of new sodium channels.
Animals↗
Dynamic F waves in neurogenic claudication.
Serial F waves were elicited before and after ambulation in 2 patients with neurogenic claudication. In both patients dynamic changes in F wave parameters consisting of either unelicitability or increased latencies occurred postexercise. The time course of these changes and their subsequent rapid reversibility over 15 minutes suggest ischemic-induced conduction block and slowing in proximal motor axons. These physiological changes may account for some of the dynamic neurological symptoms of this disorder. Moreover, F wave exercise testing may provide corroborative information for the diagnosis of neurogenic claudication.
Blood Circulation↗
Interlaboratory comparison of glycohemoglobin results: College of American Pathologists Survey data.
We describe recent changes in the College of American Pathologists Glycohemoglobin (gHb) Survey, made to improve the assessment of interlaboratory variability and the accuracy of results reported. The questionnaire portion of the survey was revised to include an updated list of current methods, and results for survey specimens were grouped according to the component measured (Hb A1, Hb A1c, or total gHb). The survey specimen material was changed to a material thought to give more reliable results with all available methods. After these changes, instituted in 1989, between-laboratory CVs decreased for some methods. Furthermore, gHb values between method types were more consistent with results obtained from fresh blood samples under very controlled laboratory conditions. However, these recent data also show that the interlaboratory variability is still quite high for some methods and that the variability within and between method types is still very great. We describe a pilot standardization program for gHb measurement.
Chromatography, Affinity↗
Muscle side effects associated with simvastatin therapy.
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Adolescent↗
A computer simulation of conduction block: effects produced by actual block versus interphase cancellation.
A reduction in compound muscle action potential (CMAP) amplitude and area following proximal versus distal stimulation is the accepted clinical hallmark of conduction block; however, quantitative criteria for determining conduction block remain ambiguous. In this study, digitized records of individual motor unit action potentials (MUAPs) elicited by incremental stimulation in vivo were arithmetically combined in a computer simulation of CMAP generation. Through simulation of possible phase interaction patterns of individual MUAPs, we have shown that abnormal temporal dispersion alone can produce reductions in CMAP area of up to 50%, values that are commonly thought to represent conduction block. Furthermore, by simulating conduction block without excessive temporal dispersion in defined subpopulations of axons, we have demonstrated the importance of the fastest conducting (largest MUAP) axons in determining CMAP amplitude and area. In conclusion, measurements of CMAP amplitude and area in determining conduction block may be misleading if there is significant abnormal temporal dispersion, and quantitation of the degree of conduction block is difficult without knowledge of which subpopulations of axons are affected.
Action Potentials↗
Changed distribution of sodium channels along demyelinated axons.
Voltage-gated sodium channels are largely localized to the nodes of Ranvier in myelinated axons, providing a physiological basis for saltatory conduction. What happens to these channels in demyelinated axons is not known with certainty. Experimentally demyelinated axons were examined by using a well-characterized, polyclonal antibody directed against sodium channels. Immunocytochemical and radioimmunoassay data were consistent with the distribution of an increased number of sodium channels along segments of previously internodal axon. These findings affirm the plasticity of sodium channels in demyelinated axolemma and may be relevant to understanding how axons recover conduction after demyelination.
Animals↗
Guillain-Barré syndrome.
Guillain-Barré syndrome is an acute inflammatory demyelinative neuropathy usually presenting as a symmetric areflexic paralysis. An immunologic pathogenesis is likely. Early diagnosis is important since good supportive care and plasmapheresis can decrease morbidity and hasten recovery.
Humans↗
Tellurium-induced demyelination: an electrophysiological and morphological study.
Tellurium (Te) is a naturally occurring element with many industrial uses. Microinjection of 0.3 micrograms of potassium tellurite [K(2)TeO(3)] into the endoneurial space of rat tibial nerve causes a rapidly progressing focal conduction block as measured by the disappearance of the evoked compound muscle action potential (CMAP) of the intrinsic foot muscles following stimulation proximal to the injection site. Conduction block was fully established within 6 hours and persisted for approximately 7 days, followed by the appearance of low amplitude, long latency, temporally dispersed potentials. The proximal CMAPs increased in amplitude and decreased in latency and temporal dispersion until normalization by 28 days after injection. The distal CMAP showed a minimal decline in amplitude. Morphological observations showed splitting of myelin, especially in the paranodal regions, followed by accumulation of myelin debris in Schwann cells and macrophages. Although the exact mechanism remains unknown, this in vivo model provides a unique opportunity to study the electrophysiological and morphological correlates of an acutely evolving demyelinative process.
Animals↗
Schwann cell degeneration induced by doxorubicin (adriamycin).
Doxorubicin is an anthracycline antineoplastic antibiotic that acts at the cell nucleus by intercalating between base pairs of DNA, thus inhibiting DNA-directed mRNA synthesis. Intraneural micro-injection of 0.19-0.38 micrograms of this substance into rat sciatic nerve results in a delayed subacute demyelination that is secondary to focal Schwann cell degeneration. Remyelination eventually occurs but is not complete until at least days 60-75 postinjection. Toxic Schwann cell disorders produced by agents such as doxorubicin may serve as useful models in understanding the pathogenesis of human demyelinative neuropathies.
Action Potentials↗
Lethal retrograde axoplasmic transport of doxorubicin (adriamycin) to motor neurons. A toxic motor neuronopathy.
Doxorubicin (Adriamycin) is an autofluorescent anthracycline antibiotic that acts as a DNA intercalator. Following intraneural microinjection of 3 micrograms of doxorubicin into rat tibial nerve, fluorescence microscopy indicated that it is transported retrogradely to anterior horn cell bodies. Subsequently, these motor neurons underwent a progressive subacute degeneration that occurred over a period of 35-39 days. Combined electrophysiological and neuropathological methods indicated that dorsal root ganglion cells were relatively unaffected by this dose of toxin. The selective motor neuron degeneration produced by this agent raises the possibility that abnormalities of nucleic acid metabolism may be involved in the aetiology of motor neuron diseases.
Action Potentials↗
Relationship of glycosylated hemoglobin to oral glucose tolerance. Implications for diabetes screening.
The oral glucose tolerance test (OGTT) for diagnosis of diabetes is inconvenient and requires a great deal of patient cooperation. Glycosylated hemoglobin (GHb), an index of long-term glycemic control, could offer several practical advantages over the OGTT for diabetes screening. We evaluated GHb as a screen for diabetes in 381 adults from a population with a high prevalence of non-insulin-dependent diabetes (Pima Indians). All individuals underwent a standard OGTT (75 g) and were separated into one of three groups: normal (N), impaired glucose tolerance (IGT), or diabetes mellitus (D) based on World Health Organization criteria. HbA1c, a GHb, was measured by highly precise high-performance liquid chromatography (interassay C.V. less than 4%). The normal range for HbA1c was 4.07-6.03% based on the 95% confidence interval for a nondiabetic, mostly Caucasian population. Compared with OGTT, HbA1c was highly specific (91%); an elevated HbA1c usually indicated D or IGT (sensitivity = 85 and 30%, respectively). A normal HbA1c did not, however, exclude a diagnosis of D or IGT. Based on previous epidemiological studies relating plasma glucose to chronic diabetic complications, GHb as measured in this study would properly identify the vast majority of subjects at risk. Long-term studies are necessary to determine the actual risk of complications in individuals with persistently normal HbA1c and D or IGT (based on OGTT).
Adolescent↗
Neuralgic amyotrophy: an increasingly diverse entity.
We describe nine cases of neuralgic amyotrophy whose clinical and electrophysiologic findings suggest lesions of individual peripheral nerves or peripheral nerve branches occurring singly (mononeuropathy) or in various combinations (mononeuropathy multiplex). There were four occurrences of isolated denervation of the pronator teres muscle; four occurrences of anterior interosseous nerve lesions; three occurrences of lateral antebrachial cutaneous nerve lesions; two occurrences of long thoracic nerve lesions; and one occurrence each of a median nerve trunk lesion, a median palmar cutaneous branch lesion, a suprascapular nerve lesion, and an axillary nerve lesion. "Neuralgic" pain was a prominent feature in all cases, and the location of the pain correlated with the location of the nerve lesions. We hypothesize that the specific course of certain nerves (especially their location across joints) selectively exposes them to mild focal trauma that increases their susceptibility to this disease. Whatever the etiology, this entity is considerably more diverse than generally appreciated.
Adult↗
Spondylotic high cervical spinal cord compression presenting with hand complaints.
Three patients with spondylotic compression of the upper cervical spinal cord presented with complaints of sensory dysfunction in their hands. Sensory dysfunction in the hands may signal a lesion in the upper cervical spinal cord if other common neurological causes can be excluded. Somatosensory evoked potentials may be useful in providing objective information to supplement subjective complaints in the hands caused by a high cervical lesion.
Adult↗