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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 181 records · Page 10Linked to original sources

Acupuncture treatment of patients with radiation-induced xerostomia.

Xerostomia is a common and usually irreversible side effects in patients receiving radiation therapy (> 50 Gy) for head and neck cancer. Of 38 patients with radiation-induced xerostomia, 20 in the experimental group were treated with classical acupuncture and 18 patients in the control group received superficial acupuncture as placebo. Within both groups the patients showed significantly increased salivary flow rates after the acupuncture treatment. In the experimental group 68% and in the control group 50% of the patients had increased salivary flow rates at the end of the observation period. Among those patients who had had all their salivary glands irradiated, 50% in both groups showed increased salivary flow rates (> 20%) by the end of the observation period of 1 year. The study indicates that among the patients who had increased salivary flow rates already after the first 12 acupuncture sessions, the majority had high probability of continual improvement after the completion of acupuncture treatment. The improved salivary flow rates usually persisted during the observation year. The changes observed in the control group were somewhat smaller and appeared after a longer latency phase. Significant differences for salivary flow rates could be observed only within each group, and there were no statistically significant differences between the groups. There were no differences in the improvement of salivary flow rates between those patients who were irradiated within a year before the acupuncture treatment and those who had received radiation therapy several years earlier. The results indicate that acupuncture might be a useful method for the treatment of radiation-induced xerostomia, and that superficial acupuncture should preferably not be used as placebo acupuncture.

Acupuncture Therapy↗

Technetium 99m-Q12 kinetics in perfused rat myocardium: effects of hypoxia and low flow.

Technetium 99m-Q12 is a new cationic myocardial perfusion imaging agent that produces excellent images in human beings. The purpose of this study was to examine the separate effects of hypoxia and low flow on myocardial clearance kinetics. After a 1 mCi bolus injection, myocardial 99mTc-Q12 clearance was monitored for 1 hour by using an Nal detector in 24 isolated perfused rat hearts. In 6 control hearts, flow was 12 ml/min, and oxygenation was normal. In 6 hypoxic hearts, flow was normal, but oxygenation was reduced (<5% 02). In 6 low-flow hearts, flow was 3 ml/min, and oxygenation was normal. In 6 very low flow hearts, flow was 1 ml/min, and oxygenation was normal. 99mTc-Q12 myocardial clearance was biphasic in all four groups, consisting of a rapid early phase and a second slow phase that began after 10 minutes. Myocardial retention between 1 and 10 minutes was 56.8% +/- 1.8% for control, 49.2% +/- 2.2% (p < 0.05 compared with control) for hypoxic, 56.8% +/- 2.6% (p = NS compared with control) for low flow (3 ml/min), and 63.7% +/- 2.1 % (p < 0.05 compared with control) for very low flow hearts (1 ml/min). Myocardial retention between 10 and 60 minutes was 90.5% +/- 0.2% for control, 90.2% +/- 1.6% for hypoxic, 90.0% +/- 0.8% for low-flow hearts (3 ml/min), and 87.6% +/- 0.3% (p < 0.05 compared with other groups) for very low flow hearts (1 ml/min). In conclusion, 99mTc-012 demonstrates biphasic clearance from normal, hypoxic, low-flow, and very low flow ischemic myocardium. Early-phase myocardial retention is decreased by hypoxia and increased by very low flow.

Animals↗

Management and outcome of chronic atherosclerotic infrarenal aortic occlusion.

PURPOSE: To evaluate the management and outcome of chronic atherosclerotic infrarenal aortic occlusion (IRAO), a review of 48 patients who were treated for angiographically documented IRAO between January 1980 and December 1994 was undertaken. Mean follow-up was 45 months. Mean age was 57 years (range, 33 to 88 years). Forty-seven patients were heavy smokers. Symptoms included claudication in 81%, rest pain in 25%, and tissue loss in 15%. Impotence was documented in 73% of men. Associated arterial disease included inferior mesenteric artery occlusion in 31 patients, renal artery stenosis or occlusion in 12, superior mesenteric artery stenosis in two, and celiac artery stenosis in one. METHODS: Forty inflow procedures were performed, including 17 thoracobifemoral bypass (TBF) procedures, 15 aortobifemoral/iliac bypass (ABFI) procedures, and eight axillobifemoral bypass (AXBF) procedures. Eight patients were managed without surgery. The thoracic aorta was chosen as the inflow source in 17 patients because of previous abdominal aortic surgery in eight, poor status of the abdominal aorta in eight, and horseshoe kidney in one. RESULTS: The overall operative mortality rate was 5%, and the perioperative morbidity rate was 18%. There was no statistical difference in perioperative mortality and morbidity rates among the operative groups. The five-year survival rate (life-table) for all IRAO patients was 67%. TBF and ABFI revascularization procedures yielded 5-year patency rates of 71% and 79%, respectively (p < 0.05). All eight patients who underwent AXBF died or had occluded grafts at 3 years after surgery. Two-year patency rates (life-table) for TBF, ABFI, and AXBF were 92%, 92%, and 44%, respectively. The AXBF patency rate was significantly inferior to those of TBF and ABFI (p < 0.05). Changes in ankle-brachial indexes after TBF or ABFI were similar, but were significantly greater than changes after AXBF (p < 0.05). Three patients in the nonoperative group died, and two underwent major amputation. Acute renal failure did not occur in our study population. Follow-up creatinine levels > 2.0 mg/dl were documented in three operative patients and in one nonoperative patient, and none required dialysis. CONCLUSIONS: In patients who have IRAO, aorta-based inflow procedures are superior to AXBF both in hemodynamic outcome and in patency rates. Treatment of IRAO with TBF or ABFI yields similar long-term results; the descending thoracic aorta represents an excellent inflow alternative to the abdominal aorta. Clinically significant renal impairment is rarely associated with IRAO. Nonoperative management of IRAO is associated with an increased mortality rate and a high rate of limb loss.

Adult↗

Synthesis and biological evaluation of an iodinated iberiotoxin analogue, [mono-iodo-Tyr5, Phe36]-iberiotoxin.

The synthesis and iodination of a structural analogue of the specific large-conductance calcium-activated potassium (BK) channel blocker, iberiotoxin (IbTX), a 37-amino acid scorpion neurotoxin, is reported. The synthesis of this analogue, [Tyr5, Phe36]-IbTX, was accomplished using standard solid-phase Fmoc (9-fluorenylmethoxycarbonyl) chemistry protocols. The linear peptide was cyclized via the formation of three intramolecular disulfide bridges and subsequently iodinated at the Tyr5 position. Upon purification, the iodinated analogue, [mono-iodo-Tyr5, Phe36]-IbTX, exhibited comparable biological activity to native IbTX in blocking BK-mediated currents. These findings suggest the synthesis and use of an 125I labelled IbTX analogue for BK channel localization in autoradiography experiments.

Amino Acid Sequence↗

Vision testing in atrophic macular degeneration.

PURPOSE: To determine the correlation between a group of vision tests in atrophic macular degeneration (AMD) in an office setting. METHODS: Patients with documented vision loss from atrophic macular degeneration in one eye were invited to attend an eye clinic every three months for a series of six vision tests for their good eye followed by fundus photography. Modified contrast sensitivity, blue/yellow anomaloscopy, flicker fusion frequency, Amsler grid, and photostress recovery time were correlated with Snellen acuity using the Pearson correlation coefficient. The regression of the Snellen acuity on sex, age and the presence of disciform macular degeneration in the other eye was obtained using a general linear model. RESULTS: The correlation with Snellen acuity result was low for all tests. It was highest for Amsler grid abnormality (r = -0.33345) and blue/yellow anomaloscopy matching range (r = -0.20742), where r denotes the correlation coefficient. Patient age was strongly correlated with Snellen results (P = 0.0001), but it was not significantly related to sex (P = 0.1187) or the presence of disciform macular degeneration in the other eye (P = 0.9989). The photostress recovery time showed enormous inter-visit variations and poor correlation with Snellen acuity (P = 0.0526). CONCLUSIONS: The course of AMD is routinely assessed by Snellen acuity and any of several additional tests. When employing a test battery in an office setting, a clinician needs to know the relative utility and correlation between the tests at his disposal. Of the tests used in this study, the Amsler grid was the most useful addition to the Snellen acuity at all stages of atrophic macular degeneration, and blue/yellow anomaloscopy was useful only in mild macular degeneration where Snellen acuity was 6/12 or better.

Aged↗

Hyperextension soft tissue injuries of the cervical spine--a review.

While a full understanding of continuing symptoms following a soft tissue hyperextension injury of the cervical spine remains elusive, recent research has shown that the explanation may lie with occult lesions beyond the musculoskeletal structures of the neck. The balance of the roles of injury, psychological factors, and the effects of litigation has shifted towards the former. However this injury would be unique if the latter two played only a minor role in determining recovery. It seems likely that among the large numbers of patients presenting with symptoms after hyperextension soft tissue injuries, a proportion will have occult bone, joint, or intervertebral disc lesions. Improvements in medical imaging techniques may allow better definition of these specific injuries and the development of more appropriate treatment. The search for a central nervous system lesion in humans continues and until this is demonstrated, many will dispute the existence of an organic brain syndrome. Evidence for significant injury to the temporomandibular joints, ear, and ophthalmic system has been found and this may be amenable to specialist intervention. While there is little evidence for effective treatments of the established injury, reduction in related disability appears most likely to be achieved by prevention. Improvements in automobile design, with particular reference to head restraints, could limit the cost to society of this common and disabling injury.

Biomechanical Phenomena↗

Traumatic pneumothorax: is a chest drain always necessary?

OBJECTIVE: To examine the management of traumatic pneumothorax in a department where some of these injuries do not receive chest drains. METHODS: A retrospective study of the management of traumatic pneumothorax was performed on a unit where historically many of these injuries have been treated conservatively. RESULTS: 54 pneumothoraces in a three year period were identified. Of these, 29 injuries (54.7%) were initially managed without drainage. Two patients subsequently had chest drains inserted as a result of asymptomatic radiological enlargement of the pneumothorax while inpatients. No patients deteriorated clinically during conservative treatment. CONCLUSIONS: Chest drain insertion for small or moderate sized traumatic pneumothoraces, in the absence of other significant injuries or the need for intermittent positive pressure ventilation (IPPV), may be unnecessary.

Drainage↗

MR sialography. Work in progress.

PURPOSE: To develop a noninvasive method for demonstrating the main salivary gland duct systems. MATERIALS AND METHODS: The authors developed a magnetic resonance (MR) imaging protocol that uses a heavily T2-weighted (echo time, 750 msec), fat-suppressed pulse sequence and rapid acquisition with relaxation enhancement. The technique was optimized to depict fluid within a two-dimensional thick slab. A preliminary evaluation was performed by examining the major salivary gland ducts in 10 asymptomatic volunteers and three symptomatic patients with known salivary duct abnormalities. RESULTS: The main parotid gland ducts were clearly demonstrated in all volunteers. The submandibular ducts were visible in all cases, although not always on projection images. In the three patients, the MR technique clearly demonstrated bilateral sialectasis, a calculus obstructing the left submandibular duct, and a fluid-filled ranula, respectively. CONCLUSION: Preliminary work indicates that this MR technique can successfully demonstrate both normal and abnormal parotid and submandibular gland duct systems and has several advantages over conventional x-ray sialography.

Adolescent↗

Measurement of cell adhesion and migration using phosphor-screen autoradiography.

This study demonstrates the use of phosphor-screen autoradiography as a means of measuring cell adhesion and cell expansion on polymer surfaces. The method has particular merit in cases where a specific substrate may be opaque or biochemically incompatible with colorimetric assay methodologies. With the phosphor-screen autoradiography method, there was a linear relationship between cell number and quantitated radioactivity. The technique has also been validated by comparison with a colorimetric assay of adhesion conducted for attachment to conventional culture substrata. The data supported the view that the use of phosphor-screen autoradiography was a valid method for detecting cell attachment, and it gave equivalent results to the colorimetric assay. Furthermore, a comparison between phosphor-screen autoradiography and a dye-staining method showed that this technique can be used as a means of quantifying cellular expansion over surfaces.

Autoradiography↗

The role of lithium in the affective disorders.

The current status of lithium in the treatment of mania and recurrent affective disorder is considered. The potential usefulness of lithium in clinical practice is not being realised. There is a need for information on clinical monitoring practices in the community. Long-term effects of lithium on renal function are reviewed and guidelines for monitoring are presented.

Antidepressive Agents↗

Acetylcholinesterase of human intestinal tissue affected by Hirschsprung's disease: effect of magnesium chloride on isoforms.

Acetylcholinesterase (AChE) molecular isoforms from anglionic and adjacent unaffected (control) colonic tissue in patients with Hirschsprung's disease (HD) were analysed by density gradient centrifugation in order to determine the major AChE isoforms and the effect of a reported MgCl2 inactivation assay method upon them, with a view to improving the AChE assay used in the diagnosis of Hirschsprung's disease. The total AChE level was greater in the HD-affected colonic tissue than the control tissue (HD: 9.0 vs. control: 7.3 units/g tissue) and this was due to a consistently greater elevation of the globular tetrameric form, G4 (HD: 48.8% vs. control: 35.5% of total AChE). The inactivation of whole tissue homogenates by brief exposure to 4 mol/l MgCl2 followed the same pattern (HD: 48.4% vs. control: 28.7% inactivation). The detergent-extractable G4 is inhibited to a greater extent than the low salt-soluble G4 by exposure to 4 mol/l MgCl2 (83.8% vs. 51.1%). These results imply that the elevated AChE levels in HD are mainly due to increases of the hydrophobic globular tetrameric form of AChE of the same type that is found in differentiating nervous tissue before synapse formation. The monomeric globular isoform G1 is not inhibited but the asymmetric A4, A8 and A12 isoforms are completely inhibited by exposure to 4 mol/l MgCl2. All isoforms of Torpedo (electric ray) electroplax and human erythrocyte AChE, mainly amphiphilic G2, are almost completely inhibited. The inhibition by 4 mol/l MgCl2 of the main G4 isoform in HD-affected intestine accentuates the difference between aganglionic and unaffected intestine in fractionated samples, but does not provide a sufficiently specific G4 isoform assay. The use of 2-4 mol/l MgCl2 in histochemical AChE staining reduces the activity slightly but does not differentiate the tetrameric AChE isoform that is increased in Hirschsprung's disease but does reduce contaminating erythrocyte AChE levels that can obscure the result in blood-stained biopsies. A specific immunochemical stain for hydrophobic AChE tetramers or the associated 20 kDa membrane associated subunit is therefore needed to provide specificity.

Acetylcholinesterase↗

A prospective randomized evaluation of implantable cardioverter-defibrillator size on unipolar defibrillation system efficacy.

BACKGROUND: The active can unipolar implantable cardioverter-defibrillator (ICD) has been shown to defibrillate efficiently, but its current 80-cc size limits use in the pectoral position in many patients. Decreasing can size will facilitate pectoral insertion and will soon be feasible as an inevitable consequence of technological advancements. However, decreasing the can size has the potential to compromise unipolar defibrillation efficacy. It is the purpose of this study, therefore, to prospectively and randomly compare unipolar defibrillation efficacy with 80-cc, 60-cc, and 40-cc can sizes in patients immediately before ICD surgery in anticipation of advances in technology that will make smaller ICDs possible. METHODS AND RESULTS: Twenty-four consecutive patients underwent prospective, randomized evaluation of the effect of ICD can size on defibrillation efficacy during standard ICD surgery. Each patient had the unipolar defibrillation threshold (DFT) measured with 80-cc, 60-cc, or 40-cc active can placed in the left subcutaneous infraclavicular region. The system included a 10.5F tripolar right ventricular electrode that served as the shock anode. The shock waveform used in each instance was a single capacitor biphasic 65% pulse delivered from a 120-microF capacitor. Stored energy at the DFT for the 80-cc, 60-cc, and 40-cc cans were 8.1 +/- 4.7 J, 8.7 +/- 5.8 J, and 9.5 +/- 4.8 J, respectively. There was no statistical significant difference between the DFTs for the three unipolar can electrodes (P = 39). Leading edge voltage also did not differ significantly among the three unipolar cans (356 +/- 92 V, 365 +/- 110 V, and 387 +/- 94 V, respectively, P = .29). There was, however, a slight progressive increase in resistance with decreasing can size (57 +/- 7 omega, 60 +/- 9 omega, and 65 +/- 9 omega, respectively, P < .001). CONCLUSIONS: Decreasing can volume from 80 cc to 60 cc to 40 cc does not compromise unipolar defibrillation efficacy despite a slight rise in shock resistance. These findings indicate that technological advances that allow for smaller-volume ICDs will not compromise defibrillation efficacy for unipolar systems.

Defibrillators, Implantable↗

Proline in a transmembrane helix compensates for cavities in the photosynthetic reaction center.

A site-specific double mutant, in which the large aromatic residues M208Tyr and L181Phe in the interior of the photosynthetic reaction center (RC) complex were replaced by smaller threonine residues, showed a dramatic reduction in the number of assembled complexes and was incapable of photosynthetic growth. The cavity created by the smaller side-chains was thought to interfere with the stability and/or assembly of the complex. Phenotypic revertants were recovered in which a spontaneous second-site mutation restored photocompetence in the presence of the original site-specific mutations. In these strains, an Ala-->Pro substitution in a neighboring transmembrane helix (at M271) resulted in an increased yield of RC complexes. To test the hypothesis that the original phenotype was due to a cavity, other mutants were constructed that created similar-sized voids at other positions in the membrane-spanning interior. These substitutions caused the same phenotype. Coupling of the above proline substitution to these new cavity mutants also resulted in photocompetent strains that carry increased levels of RC complexes. Therefore, the proline substitution at M271 serves as a global suppressor of the phenotype caused by these internal cavities. The proline substitution slightly increases the thermal stability of the complex at higher temperatures, but the mutant and suppressor strains have about the same stability at the optimal culture temperature, where both are less stable than the wild-type strain. Therefore, the proline substitution may suppress the non-photosynthetic phenotype of cavity mutants by facilitating folding of the nascent polypeptides as they assemble with cofactors to form the transmembranar RC complex. The proline replacement occurs at a pre-existing kink in a transmembrane helix where it can be accommodated without introducing a strain in the structure. The function of proline residues in transmembrane helices might be to promote folding and/or assembly in general.

Cell Membrane↗

Truncated biphasic pulses for transthoracic defibrillation.

BACKGROUND: Early defibrillation is the single most important factor for improving out-of-hospital ventricular fibrillation resuscitation rates. To achieve the earlier response times required for survival, typically < 6 minutes from time of collapse, it will be necessary to equip a far wider network of first responders (firefighters, police, and other individuals with responsibility for public safety) with small, lightweight, and inexpensive automatic external defibrillators (AEDs). An important step in reducing the size and cost of AEDs will be to improve defibrillation efficacy. Because biphasic waveform defibrillation has had a favorable impact on implantable cardioverter-defibrillators (ICDs), there are reasons to believe that biphasic waveforms would also improve transthoracic defibrillators. Our purpose, therefore, was to examine the efficacy of two different low-energy biphasic truncated waveforms referenced to a standard damped sine waveform for transthoracic defibrillation in humans. METHODS AND RESULTS: We prospectively and randomly compared the transthoracic defibrillation efficacy of two different truncated biphasic waveforms, 115 J (70 microF) and 130 J (105 microF), with that of a standard 200-J (36-microF, 28-mH) damped sine wave pulse using right anterior and left lateral thoracic pads (R2 Medical Systems) in 30 cardiac arrest survivors during transvenous ICD surgery. The right anterior patch electrode was used as the cathode and the left lateral thoracic pad as the anode. Transthoracic ventricular defibrillation rescue shocks were tested after a failed transvenous defibrillation shock delivered in the course of ICD testing. Each of the three different rescue shocks was tested in random order in each patient. All shocks were delivered at end expiration. The investigators responsible for determining transthoracic shock efficacy were blinded throughout the study to the transthoracic rescue waveform used. A total of 33 patients were considered for study, but three patients failed to satisfy all entry criteria or did not have a sufficient number of ventricular fibrillation inductions to allow for testing of all three waveforms. Percent efficacy for the three waveforms was then compared in the 30 patients who satisfied entry criteria and completed the protocol. The study population had a mean age of 61 +/- 11 years, with 22 (73%) being men. The mean left ventricular ejection fraction was 0.39 +/- 0.14. Coronary artery disease was present in 22 (73%). The 115-J (70-microF) biphasic pulse, the 130-J (105-microF) biphasic pulse, and the 200-J (36-microF, 28-mH) damped sine wave pulse were equally effective, resulting in a 97% first-shock ventricular defibrillation efficacy rate. Each waveform failed to defibrillate once, with each waveform failing in a different patient. CONCLUSIONS: The results of this study suggest that biphasic truncated transthoracic shocks of low energy (115 and 130 J) are as effective as 200-J damped sine wave shocks used in standard transthoracic defibrillators. This finding may contribute significantly to the miniaturization and cost reduction of transthoracic defibrillators, which could enable the development of a new generation of AEDs appropriate for an expanded group of out-of-hospital first responders and, eventually, layperson use.

Adult↗

A prospective randomized comparison in humans of biphasic waveform 60-microF and 120-microF capacitance pulses using a unipolar defibrillation system.

BACKGROUND: Improving unipolar implantable cardioverter-defibrillator (ICD) effectiveness has favorable implications for ICD safety, efficacy, and size. Advances in defibrillation efficacy would accelerate ICD ease of use by decreasing device size and by minimizing morbidity and mortality related to an improved defibrillation safety margin. The specific purpose of the present study was to determine whether unipolar defibrillation efficacy could be improved further in humans by lowering biphasic waveform capacitance. METHODS AND RESULTS: We prospectively and randomly compared the defibrillation efficacy of a 60-microF and a 120-microF capacitance asymmetrical 65% tilt biphasic waveform using a unipolar defibrillation system in 38 consecutive cardiac arrest survivors before implantation of a presently available standard transvenous defibrillation system. The right ventricular defibrillation electrode had a 5-cm coil located on a 10.5F lead and was used as the anode. The system cathode was the electrically active 108-cm2 surface area shell (or "can") of a prototype titanium alloy pulse generator placed in a left infraclavicular pocket. The defibrillation pulse was derived from either a 60-microF or a 120-microF capacitance and was delivered from RV-->CAN. Defibrillation threshold (DFT) stored energy, delivered energy, leading-edge voltage and current, pulse resistance, and pulse width were measured for both capacitances examined. The 60-microF capacitance biphasic pulse resulted in a stored-energy DFT of 8.5 +/- 4.1 J and a delivered-energy DFT of 8.4 +/- 4.0 J. In 34 of 38 patients (89%), the stored-energy DFT was < 15 J. Leading-edge voltage at the DFT was 517 +/- 128 V. Mean pulse impedance for the 60-microF waveform was 60.6 +/- 7.1 omega. The 120-microF capacitance biphasic pulse resulted in a stored-energy DFT of 10.1 +/- 7.4 J and a delivered-energy DFT of 10.0 +/- 7.2 J (P = .13 and .13, respectively). In 28 of 38 patients (74%), the stored-energy DFT was < 15 J (P = .052). Leading-edge voltage at the DFT with the 120-microF capacitance pulse was 386 +/- 142 (P < .00001). Mean pulse impedance for the 120-microF waveform was 60.7 +/- 7.0 omega (P = .80). CONCLUSIONS: The results of the present study suggest that a relatively small capacitance, 60 microF, can be used for unipolar defibrillation systems without compromising defibrillation energy requirements compared with more typical ICD capacitance values, but this will require a higher circuit voltage. The use of lower capacitance also provides a modest increase in the percent of patients who have very low energy defibrillation requirements, an important issue should maximum ICD energy be decreased from the present level of 34 J. Such a move to smaller output devices could allow significant decreases in device size, a necessary feature of making cardioverter-defibrillator implantation comparable to that of standard pacemaker surgery.

Adult↗

Anti-acetylcholinesterase antibodies display cholinesterase-like activity.

A monoclonal antibody (mAb) raised against human acetylcholinesterase (AChE) was found to have catalytic activity. A similar phenomenon was observed in a polyclonal antibody raised against the same antigen. The antibodies were demonstrated to be pure, and no contamination with either AChE or butyrylcholinesterase was found. Both antibodies hydrolyzed acetylthiocholine, an AChE substrate, and the mAb followed Michaelis-Menten kinetics. Six other mAb and one other polyclonal antibody showed no evidence of catalytic activity. This development of cholinesterase-like behavior by certain anti-AChE antibodies may have arisen by stable complexation of the enzyme with a substrate or inhibitor during antigen presentation. This phenomenon may have implications for the diagnostic measurement of AChE activity as well as in assessing the immunological reasons for the markedly raised AChE level in developmental conditions such as Hirschsprung's disease.

Acetylcholinesterase↗