Asymmetrical attenuation of vibration sensation in unilateral diabetic Charcot foot neuroarthropathy.

AIMS: To further characterize the distal sensory neuropathy in subjects with unilateral diabetic Charcot foot neuroarthropathy. METHODS: A retrospective cohort study to assess the level to which the sensory modalities of pinprick, light touch, vibration, joint position and temperature were attenuated in the affected and unaffected limbs in subjects with unilateral Charcot. The level to which the sensory modality was attenuated in each limb was assigned a score. The Wilcoxon signed rank test was used to compare the scores in the affected and unaffected limbs and also to compare the scores of the different sensory modalities in the affected and unaffected limbs. RESULTS: Fifty subjects with unilateral Charcot foot neuroarthropathy were assessed. Mean age was 45 ± SD 6 years for the 17 subjects with Type 1 diabetes and 62 ± 10 years for the 33 subjects with Type 2 diabetes. Duration of diabetes was 21 ± 13 years, HbA(1c) was 70 ± 19 mmol/mol [8.6 ± 1.8 %] and 15 subjects (30%) required renal replacement therapy. The level of attenuation of vibration sensation was more proximal in the affected compared with the unaffected limbs (P = 0.002). Pinprick, light touch, joint position and temperature sensations were not different. Joint position sensation was less attenuated bilaterally than the other sensory modalities. CONCLUSIONS: Asymmetrical attenuation of vibration sensation may predict the side that will develop a Charcot joint and may suggest a more important role for vibration sense loss than loss of other sensory modalities in the pathophysiology of Charcot.

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

The effect on myocardial energy balance of increasing oxygen demand without altering basal myocardial perfusion rate was assessed in isolated, isovolumic, retrograde blood perfused rabbit hearts. Myocardial energy requirements were increased with paired stimulation. The capacity of rapid paired stimulation to increase mechanical energy consumption was demonstrated in the presence of increased perfusion with the rate X pressure product and oxygen consumption increasing 86 and 148%, respectively, compared with control values. In contrast, rapid paired stimulation under constant, basal flow conditions did not alter the rate X pressure product, while oxygen extraction and consumption increased only 40% relative to control. Myocardial ATP, creatine-phosphate, and lactate content were identical under control and constant flow-paired stimulation conditions. The results of this study indicate that no detectable energy imbalance was produced by rapid paired stimulation with flow held constant at basal rates. These results suggest that the myocardium does not increase mechanical energy expenditure in response to inotropic or rate stimulation in the presence of restricted flow reserve and are inconsistent with the concept of "demand-induced" or "relative" myocardial ischemia.

Performance of subjects with and without severe mental illness on a clinical test of problem solving.

Severe mental illness is associated with impairments in executive functions, such as conceptual reasoning, planning, and strategic thinking all of which impact problem solving. The present study examined the utility of a novel assessment tool for problem solving, the Rapid Assessment of Problem Solving Test (RAPS) in persons with severe mental illness. Subjects were 47 outpatients with severe mental illness and an equal number healthy controls matched for age and gender. Results confirmed all hypotheses with respect to how subjects with severe mental illness would perform on the RAPS. Specifically, the severely mentally ill subjects (1) solved fewer problems on the RAPS, (2) when they did solve problems on the test, they did so far less efficiently than their healthy counterparts, and (3) the two groups differed markedly in the types of questions asked on the RAPS. The healthy control subjects tended to take a systematic, organized, but not always optimal approach to solving problems on the RAPS. The subjects with severe mental illness used some of the problem solving strategies of the healthy controls, but their performance was less consistent and tended to deteriorate when the complexity of the problem solving task increased. This was reflected by a high degree of guessing in lieu of asking constraint questions, particularly if a category-limited question was insufficient to continue the problem solving effort.

Characterization of the proteins of human hair and nail by electrophoresis.

Low-sulfur and high-sulfur proteins from human hair and nail were characterized by two-dimensional polyacrylamide gel electrophoresis. Apparent molecular weights (estimated by SDS electrophoresis) of low-sulfur and high-sulfur proteins were in the ranges 55,500-76,000 and 26,500-43,000, respectively, but these are probably higher than the real values (12-30% for low-sulfur, 75-150% for high-sulfur) because corresponding wool proteins behave anomalously in SDS electrophoresis. Isoelectric points of the low-sulfur proteins ranged from 4.9-5.4. Six low-sulfur and 7 high-sulfur major proteins were common to hair and nail from the same individual, but each keratin contained 1 additional major low-sulfur component which was not common. Variation, presumably of genetic origin, was observed in the low-sulfur and high-sulfur proteins of hair and nail.

Genetic variation in the proteins of human nail.

In a survey of the proteins from human nail, genetic variation has been observed in both the low-sulfur and high-sulfur protein fractions. The low-sulfur proteins were examined by polyacrylamide gel electrophoresis at pH 7 in the presence of sodium dodecyl sulfate, whilst the high-sulfur proteins were characterized by gel electrophoresis at pH 2.6 in 3 M urea. Of 106 samples of apparently normal nail, 69% showed a characteristic pattern of 3 major low-sulfur and 5 major high-sulfur proteins. The remaining samples showed an additional high-sulfur band, and about half of these samples also manifested an additional major low-sulfur band. The proportion of nail samples containing the variant proteins was much higher in some families. Two-dimensional eletrophoresis of the low-sulfur proteins showed five major low-sulfur components in the normal nail with an additional component in the variant sample. Peptide maps of the proteins showed that the additional protein was sufficiently different in amino acid sequence to the other proteins to indicate that a mutation in a structural gene had not occurred. In the high-sulfur protein fractions, over 30 proteins were observed in the two-dimensional electrophoretic patterns and there were at least 3 additional components in the variant fraction.

Studies of developing human hair shaft cells in vitro.

Methods for studying aspects of hair formation in vitro have been devised on the basis of isolating developing hair shaft cells. These cells were obtained using a sterile microdissection technique. Plucked anagen follicles were dissected free of surrounding tissues (inner and outer root sheaths), and presumptive hair shaft cells (including germinal epithelia) were cultured directly on mammalian fibroblasts or in media preconditioned by fibroblasts. Specimens were cultured either as dispersions or in whole tissue pieces. Trypsinized whole tissue specimens in culture were sometimes observed to form increased bulk, while dispersed cells appeared to elongate and form larger colonies. In sections of these colonies examined by transmission electron microscopy, intracellular hard keratin intermediate filaments (IFs) together with IF-matrix hard keratin complexes were observed. Radiolabelled cysteine [35S] was added to cultures (3-20 days), showing a continuing but reduced synthesis of hard keratin IF proteins (low-sulfur) over the period of study. Matrix protein (high-sulfur) production was drastically reduced after 3 days. Monoclonal antibodies directed against hair keratin IF components were used in Western transfers and immunofluorescent studies to help assess the specificity of proteins synthesized in culture. Our observations indicate that, with some refinement, the presently described methods enable preparation of hair shaft precursor cells suitable for observing certain hair-forming processes in vitro.

Changes in the proteins of wool following treatment of sheep with epidermal growth factor.

Administration of epidermal growth factor (EGF) extracted from mouse submaxillary gland to Merino sheep resulted in a temporary inhibition of the activity of the wool follicles. Subsequently, either complete discontinuities appeared in the fibers resulting in shedding of the entire fleece, or incomplete, in which case the fleece was retained but bore a zone of weakness. The protein composition of the first sample of wool harvested from 1 sheep following infusion for 66 hr with 27.5 mg EGF (0-2 weeks posttreatment) was similar to pretreatment wool. This represented wool fibers which were already present in the follicles at the beginning of infusion. Thereafter, the composition of the wool changed progressively, reaching a maximum divergence from the control in the 3-4 week regrowth period followed by a return to normal by about 10 weeks. Over this period the content of high-sulfur proteins first rose from an initial 19% to a maximum of 30%, then returned to 19%, while the high-tyrosine protein content initially decreased from 12% to 5% and then slowly increased to 12%. In addition to changes in overall protein composition, two-dimensional electrophoresis revealed alterations in the proportions of some individual protein components. These changes were similar to those observed with many other wool growth inhibitors. Smaller doses of EGF (5.8 and 2.9 mg but not 1 mg) had similar effects on wool composition but these were of lower magnitude and there was a delay in reaching a maximum response. Even after 16-18 weeks the wool from these treated sheep differed slightly in composition from the pretreatment samples.

The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart.

In order to evaluate the accuracy of blood flow measurement, the single-pass extraction, retention/wash-out and relative net uptake of 99mTc-teboroxime (SQ30217) and 201Tl were evaluated and compared in 20 isolated blood-perfused rabbit hearts at coronary flow rates ranging from 0.49 to 2.85 ml/g wet wt min-1. The average peak extraction of 201Tl (+/- s.d.) (0.67 +/- 0.11) marginally exceeded that of SQ30217 (0.62 +/- 0.12) (p = 0.06). Flow significantly affected the maximum net extraction of 201Tl and the 40-min net extractions of both 201Tl and SQ30217. Unexpectedly, the rate of 201Tl myocardial washout was significantly faster (p less than 0.05) than SQ30217 washout at all flow rates evaluated. Increasing coronary blood flow rate was associated with a more rapid clearance of both tracers from the myocardium (p less than 0.05 for both comparisons). The slope of the linear correlations between relative net SQ30217 uptake versus flow and relative net 201Tl uptake versus flow were found to be similar for up to 10 min after isotope injection. These data were interpreted to indicate that: 1. Thallium-201 might be slightly better extracted than SQ30217. 2. SQ30217 is cleared more slowly from the myocardium. 3. Thallium-201 and SQ30217 appear to be comparable tracers of myocardial perfusion for up to 10 min after injection under the single-pass conditions currently employed. 4. Additional studies are needed to clarify myocardial SQ30217 kinetics.

Assessment of the [18F]fluorodeoxyglucose kinetic model in calculations of myocardial glucose metabolism during ischemia.

The lumped constant--a term in the operational equation of the Sokoloff tracer kinetic model for deoxyglucose that accounts for the difference in transport and phosphorylation between glucose and its analog, deoxyglucose--could potentially vary from normal to ischemic conditions in the heart. To test the stability of the lumped constant during ischemia, we evaluated the ratio of the extraction fraction for (F-18)-fluorodeoxyglucose (FDG) to that for glucose (a measure of the lumped constant if there is no significant dephosphorylation of FDG-6-PO4) and the rate constant for dephosphorylation of FDG-6-PO4 (k4*) in the isolated, arterially perfused interventricular septum of the rabbit during moderate and severe demand-induced and reduced-flow ischemias. The lumped constant and k4* in each of the four ischemic experimental conditions were found not to be significantly different from the value obtained from the nonischemic controls.

Kinetic analysis of 125I-iodorotenone as a deposited myocardial flow tracer: comparison with 99mTc-sestamibi.

UNLABELLED: The goal of this investigation was to assess the accuracy of 7'-Z-[125I]iodorotenone (125I-iodorotenone) as a new deposited myocardial flow tracer and compare the results with those for 99mTc-sestamibi. METHODS: The kinetics of these two flow tracers were evaluated in 25 isolated, erythrocyte- and albumin-perfused rabbit hearts over a flow range relevant to patients. The two flow tracers and a vascular reference tracer (131I-albumin) were introduced simultaneously as a compact bolus through a port just above the aortic cannula in the absence of tracer recirculation. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves using the multiple-indicator dilution technique and spectral analysis. RESULTS: The extraction of 125I-iodorotenone was much higher than the extraction of 99mTc-sestamibi (0.84 +/- 0.05 vs. 0.48 +/- 0.10, respectively, P < 0.001). 125I-iodorotenone extraction was also less affected by flow than was 99mTc-sestamibi (P < 0.001). Net retention of 125I-iodorotenone was significantly greater than 99mTc-sestamibi net retention at 1 min (0.77 +/- 0.08 vs. 0.41 +/- 0.11, respectively, P < 0.001) and 26 min (0.46 +/- 0.13 vs. 0.27 +/- 0.11, respectively, P < 0.001) after tracer injection. Flow had less effect on 125I-iodorotenone net retention than on 99mTc-sestamibi net retention 1 min after tracer injection (P < 0.04). However, at 26 min, flow had an equivalent effect on the retention of both flow tracers (P < 0.4). The relationship between 125I-iodorotenone and 99mTc-sestamibi washout was complex and depended on elapsed time after isotope introduction and perfusion rate. Reflecting the favorable extraction and retention characteristics of 125I-iodorotenone, both its maximum myocardial uptake and its 26-min uptake were more closely related to flow than were those of 99mTc-sestamibi (P < 0.001 for both comparisons). CONCLUSION: The extraction and retention of 125I-iodorotenone were greater than those of 99mTc-sestamibi, making 125I-iodorotenone the superior flow tracer in the isolated rabbit heart.

Planar imaging versus gated blood-pool SPECT for the assessment of ventricular performance: a multicenter study.

UNLABELLED: Gated blood-pool SPECT (GBPS), inherently 3-dimensional (3D), has the potential to replace planar equilibrium radionuclide angiography (ERNA) for computation of left ventricular ejection fraction (LVEF), analysis of regional wall motion (RWM), and analysis of right heart function. The purpose of this study was to compare GBPS and ERNA for the assessment of ventricular function in a large, multicenter cohort of patients. METHODS: One hundred seventy-eight patients referred in the usual manner for nuclear medicine studies underwent ERNA followed by GBPS. Each clinical site followed a GBPS acquisition protocol that included 180 degrees rotation, a 64 by 64 matrix, and 64 or 32 views using single- or double-head cameras. Transverse GBPS images were reconstructed with a Butterworth filter (cutoff frequency, 0.45-0.55 Nyquist; order, 7), and short-axis images were created. All GBPS studies were processed with a new GBPS program, and LVEF was computed from the isolated left ventricular chamber and compared with standard ERNA LVEF. Reproducibility of GBPS LVEF was evaluated, and right ventricular ejection fraction (RVEF) was computed in a subset of patients (n = 33). Using GBPS, RWM and image quality from 3D surface-shaded and volume-rendered cine displays were evaluated qualitatively in a subset of patients (n = 30). RESULTS: The correlation between GBPS LVEF and planar LVEF was excellent (r = 0.92). Mean LVEF was 62.2% for GBPS and 54.1% for ERNA. The line of linear regression was GBPS LVEF = (1.04 x ERNA LVEF) + 6.1. Bland-Altman plotting revealed an increasing bias in GBPS LVEF with increasing LVEF (Y = 0.13x + 0.61; r = 0.30; mean difference = 8.1% +/- 7.0%). Interoperator reproducibility of GBPS LVEF was good (r = 0.92). RVEF values averaged 59.8%. RWM assessment using 3D cine display was enhanced in 27% of the studies, equivalent in 67%, and inferior in 7%. CONCLUSION: GBPS LVEF was reproducible and correlated well with planar ERNA. GBPS LVEF values were somewhat higher than planar ERNA, likely because of the exclusion of the left atrium.

Assessment of cardiac performance with quantitative radionuclide angiocardiography: right ventricular ejection fraction with reference to findings in chronic obstructive pulmonary disease.

A reproducible noninvasive technique for measuring righ ventricular ejection fraction was developed using first pass quantitative radionuclide angiocardiography. Studies were obtained in the anterior position with a computerized multicrystal scintillation camera with high count rate capabilities. Right ventricular ejection fraction was calculated on a beat to beat basis from the high frequency components of the background-corrected right ventricular time-activity curve. In 50 normal adults, right ventricular ejection fraction averaged 55 percent (range of 45 to 65 percent). This radionuclide measure of right ventricular function was reproducible, with minimal inter- and intraobserver variability, and was sensitive to changes in inotropic state induced with isoproterenol. In 36 patients with chronic obstructive pulmonary disease, right ventricular ejection fraction ranged from 19 to 71 percent. All 10 patients with corpulmonale, as well as 9 additional patients, had an abnormal right ventricular ejection fraction. Arterial oxygen tension and forced expiratory volume were depressed significantly more in patients with abnormal right ventricular ejection fraction than in subjects with normal right ventricular function. There was no relation between abnormalities in right and left ventricular ejection fraction.

Variability in sequential measures of left ventricular performance assessed with radionuclide angiocardiography.

The variability of left ventricular ejection fraction, normalized mean ejection rate and regional wall motion was evaluated from first pass quantitative radionuclide angiocardiograms obtained with a computerized multicrystal scintillation camera. Three radionuclide studies separated by an average of 4.3 days were obtained in each of 20 patients. Ejection fraction and ejection rate obtained on the first, second and third studies did not differ significantly. The mean (+/- standard deviation) variability of sequential ejection fraction measurement was 4.4 +/- 3.6 percent, and of sequential ejection rate was 0.56 +/- 0.47 sec(-1). Variations in measurements were not related to fluctuations in heart rate or blood pressure. Variability in ejection rate was significantly greater in patients with normal function than in those with abnormal function. Regional wall motion analysis was constant in 19 of 20 patients. Thus, sequential quantitative radionuclide angiocardiography allows reproducible serial assessment of left ventricular performance that can be performed with a low level of intrinsic variability.

Response to exercise after withdrawal from chronic alcoholism.

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.

Identification of persons at risk for sudden cardiac death.

Before any more progress is made in reducing the incidence of sudden cardiac death, our ability to identify those at risk must be refined further. The close association with coronary artery disease necessitates that the first step must be the identification of those with underlying coronary artery disease. This is underscored by the disturbing fact that, in many, sudden death is the first sign of coronary disease. An aggressive evaluation of those with significant risk factors appears justified. The second part of the problem is the identification of those with coronary artery disease who are at especially high risk. The current diagnostic modalities available suffer from a relative lack of specificity to be applied indiscriminately in light of the expense and morbidity of effective therapies (that is, coronary artery bypass surgery, antiarrhythmic drugs, implantable defibrillators, surgical or catheter ablation). At the present time, we can identify certain subsets that warrant aggressive therapy: survivors of sudden death events or sustained ventricular tachycardia, obstructive cardiomyopathies, aortic stenosis, left main coronary artery disease, and congenital QT prolongation. Less aggressive but also less specific therapies, such as beta-blockers in myocardial infarction survivors, can be given more indiscriminately. Ultimately, of course, the greatest impact will come from prevention of coronary artery disease.

Selective impairment of phonation: a case study.

A 47-year-old right-handed man underwent craniotomy for clipping of an aneurism at the trifurcation of the left middle cerebral artery. Subsequently, he suffered a left hemisphere CVA after which his speech and language resembled that of Broca's aphasia with accompanying apraxia of speech. Medical, behavioral, and acoustical data amassed over a period of several months indicated numerous contraindications to traditional diagnoses of Broca's aphasia, apraxia of speech, and dysarthria. Ultimately, it was determined that the patient had a selective impairement of phonation or laryngeal apraxia. This was illustrated dramatically when he was taught to use an electrolarynx which allowed him to bypass his disrupted phonatory system. Speaking with the electrolarynx, the patient communicated normally. Any semblance of Broca's aphasia disappeared. Supralaryngeal articulation was normal; apraxia of speech behaviors were absent. This case report indicates that dissociation of oral and laryngeal gestures due to brain injury is possible. Mechanisms underlying such a dissociation for this case are reviewed. The possibility of discrete center lesions in the frontal motor association area causing different types of apraxia of speech is discussed.

Idiosyncratic strategies in sentence production: a case report.

In their case study of a patient with selective apraxia of phonation, Marshall, Gandour, and Windsor (1988, Brain and Language, 35, 313-339) reported that many of his utterances were ill-formed syntactically. In this note, a detailed syntactic analysis of his speech is presented. Although the patient's syntax is deviant, it is seen to result from the application of certain consistent, identifiable, compensatory strategies. Moreover, it is shown that the particular, abnormal syntactic structures are internally consistent with his phonatory apraxia coupled with the normal rules of English prosody.

Self-monitoring behavior in a case of severe auditory agnosia with aphasia.

This case report describes an unusual combination of speech and language deficits secondary to bilateral infarctions in a 62-year-old woman. The patient was administered an extensive series of speech, language, and audiologic tests and was found to exhibit a fluent aphasia in which reading and writing were extremely well preserved in comparison to auditory comprehension and oral expression, and a severe auditory agnosia. In spite of her auditory processing deficits, the patient exhibited unexpected self-monitoring ability and the capacity to form acoustic images on visual tasks. The manner in which she corrected and attempted to correct her phonemic errors, while ignoring semantic errors, suggests that different mechanisms may underlie the monitoring of these errors.

Korean hemorrhagic fever: environmental health and medical surveillance measures.

Throughout history, battles, campaigns, and wars have often been decided by diseases, rather than bullets and tacticians. During the Korean War, Korean hemorrhagic fever (KHF) afflicted several thousand allied soldiers and an unknown number of Communist soldiers. This disease, and other members of a closely related group, the hemorrhagic fevers with renal syndrome, represent a continuing worldwide military and civilian threat. Through inexpensive and flexible environmental health measures, and readily available medical surveillance and testing, it is now possible to reduce the risk from this disease. In this paper, we will outline various environmental health measures developed to reduce the risk of contracting KHF and the justification for their use. We will also discuss a medical surveillance and testing program designed to get at-risk and symptomatic individuals to definitive care quickly in order to reduce overall morbidity and mortality.