Guillain-Barré syndrome in a patient with neuropsychiatric systemic lupus erythematosus.

Guillain-Barré syndrome is a rare manifestation of neuropsychiatric systemic lupus erythematosus (SLE). Clinical and electrophysiological features of Guillain-Barré syndrome in patients with SLE are different from those in patients without SLE. There is considerable variation in the management and prognosis. We present a patient with Guillain-Barré syndrome and SLE and review the recent knowledge on the various manifestations of neuropsychiatric SLE.

CORRELATION OF CLINICAL AND ECHO-CARDIOGRAPHIC SCORES WITH BLOOD "BRAIN NATRIURETIC PEPTIDE" IN PAEDIATRIC PATIENTS WITH HEART FAILURE.

BACKGROUND: Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. OBJECTIVE: To evaluate two CHF scores: a modified clinical score and an echocardiographic score and compare them to BNP in paediatric patients. DESIGN: Prospective, hospital based study. SETTING: Two paediatric cardiac referral centres in Khartoum from April to July 2010. SUBJECTS: All patients one month to 18 years of age with the clinical diagnosis of CHF were included. RESULTS: Sixty seven patients were enrolled, 39 (58%) had congenital heart disease (CHD), 27 (32%) had rheumatic heart disease (RHD), and seven (10%) had dilated cardiomyopathy (DCM).Twenty four younger children (88%) and 29 older children (85%) had a high clinical score (severe CHF). Twenty one out of 23 younger children with high echo score (91%) had a high clinical score as well (p-value 0.001). In patients with RHD (all with a high clinical score), 81% had a high echo score. (p-value 0.001). All younger children with a high clinical score (n = 24) had a high level of BNP (p-value 0.00). In older children with a high clinical score 28 out of 29 (96%) had a high BNP level (p-value 0.00). Of patients with RHD and a high echo score (21), 16 (76.2%) patients had high BNP level and five (23.8%) had low level of BNP. All patients with DCM had high echo score and all of them had high levels of BNP (100%) (p-value.0.00). CONCLUSION: We tested clinical and echo scores and proved their value in assessment of CHF in children. The scores correlated well with BNP level. We recommend the use of these scores as well as BNP level in clinical practice.

Cost analysis of chronic heart failure management in Malaysia: A multi-centred retrospective study.

Background: Estimation of the economic burden of heart failure (HF) through a complete evaluation is essential for improved treatment planning in the future. This estimation also helps in reimbursement decisions for newer HF treatments. This study aims to estimate the cost of HF treatment in Malaysia from the Ministry of Health's perspective. Materials and methods: A prevalence-based, bottom-up cost analysis study was conducted in three tertiary hospitals in Malaysia. Chronic HF patients who received treatment between 1 January 2016 and 31 December 2018 were included in the study. The direct cost of HF was estimated from the patients' healthcare resource utilisation throughout a one-year follow-up period extracted from patients' medical records. The total costs consisted of outpatient, hospitalisation, medications, laboratory tests and procedure costs, categorised according to ejection fraction (EF) and the New York Heart Association (NYHA) functional classification. Results: A total of 329 patients were included in the study. The mean ± standard deviation of total cost per HF patient per-year (PPPY) was USD 1,971 ± USD 1,255, of which inpatient cost accounted for 74.7% of the total cost. Medication costs (42.0%) and procedure cost (40.8%) contributed to the largest proportion of outpatient and inpatient costs. HF patients with preserved EF had the highest mean total cost of PPPY, at USD 2,410 ± USD 1,226. The mean cost PPPY of NYHA class II was USD 2,044 ± USD 1,528, the highest among all the functional classes. Patients with underlying coronary artery disease had the highest mean total cost, at USD 2,438 ± USD 1,456, compared to other comorbidities. HF patients receiving angiotensin-receptor neprilysin-inhibitor (ARNi) had significantly higher total cost of HF PPPY in comparison to patients without ARNi consumption (USD 2,439 vs. USD 1,933, p < 0.001). Hospitalisation, percutaneous coronary intervention, coronary angiogram, and comorbidities were the cost predictors of HF. Conclusion: Inpatient cost was the main driver of healthcare cost for HF. Efficient strategies for preventing HF-related hospitalisation and improving HF management may potentially reduce the healthcare cost for HF treatment in Malaysia.

Treatment of Coronary De Novo Lesions by a Sirolimus- or Paclitaxel-Coated Balloon.

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: There is increasing clinical evidence for the treatment of coronary de novo disease using drug-coated balloons. However, it is unclear whether paclitaxel remains the drug of choice or if sirolimus is an alternative, in analogy to drug-eluting stents. METHODS: Seventy patients with coronary de novo lesions were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, B. Braun Melsungen; 4 µg/mm2) with a PCB (SeQuent Please, B. Braun Melsungen; 3 µg/mm2). The primary endpoint was angiographic late lumen loss (LLL) at 6 months. Secondary endpoints included major adverse cardiovascular events and individual clinical endpoints such as cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment LLL was 0.01 ± 0.33 mm in the PCB group versus 0.10 ± 0.32 mm in the SCB group. The mean difference between SCB and PCB was 0.08 (95% CI: -0.07 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. However, negative LLL was more frequent in the PCB group (60% of lesions vs 32% in the SCB group; P = 0.019). Major adverse cardiovascular events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-human comparison of a novel SCB with a crystalline coating showed similar angiographic outcomes in the treatment of coronary de novo disease compared with a clinically proven PCB. However, late luminal enlargement was more frequently observed after PCB treatment. (Treatment of Coronary De-Novo Stenosis by a Sirolimus Coated Balloon or a Paclitaxel Coated Balloon Catheter Malaysia [SCBDNMAL]; NCT04017364).

Combined Analysis of Two Parallel Randomized Trials of Sirolimus-Coated and Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis Lesions.

BACKGROUND: Paclitaxel-coated balloons (PCBs) are a preferred treatment option for coronary in-stent restenosis. To date, data from randomized trials of alternative drug coatings are lacking. The aim of the randomized Malaysian and German-Swiss randomized trials was to investigate a novel sirolimus-coated balloon (SCB) compared with a PCB in in-stent restenosis. METHODS: One hundred one patients with drug-eluting stent in-stent restenosis were enrolled in 2 identical randomized trials comparing the novel SCB (SeQuent SCB, 4 µg/mm²) with the clinically proven PCB (SeQuent Please, 3 µg/mm²). Primary end point was angiographic late lumen loss at 6 months. Secondary end points included procedural success, major adverse cardiac events, and individual clinical end points such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.25±0.57 mm in the PCB group versus 0.26±0.60 mm in the SCB group. Mean difference between SCB and PCB was 0.01 (95% CI, -0.23 to 0.24). Noninferiority at a predefined margin of 0.35 was shown. Clinical events up to 12 months did not differ between the groups. CONCLUSIONS: This first-in man comparison of a novel SCB with a crystalline coating showed similar angiographic and clinical outcomes in the treatment of coronary drug-eluting stent in-stent restenosis compared with PCB. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02996318, NCT03242096.

A multicentric, randomized, controlled phase III study of centhaquine (Lyfaquin ® ) as a resuscitative agent in hypovolemic shock patients.

INTRODUCTION: Centhaquine (Lyfaquin ® ) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock having systolic blood pressure (SBP) of ≤90 mm Hg and blood lactate levels of ≥2 mmol/L. Patients were randomized in a 2:1 ratio, 71 patients to the centhaquine group and 34 patients to the control (saline) group. Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine (0.01 mg/kg)) was administered in 100 mL of normal saline infusion over 1 hour. The primary objectives were to determine changes (mean through 48 hours) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, vasopressors administered in the first 48 hours, duration of hospital stay, time in ICU, time on the ventilator support, change in patient's Acute Respiratory Distress Syndrome (ARDS), Multiple Organ Dysfunction Syndrome (MODS) scores, and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. Trauma was the cause of hypovolemic shock in 29.41% of control and 47.06% of centhaquine, gastroenteritis in 44.12% of control, and 29.41% of centhaquine patients. An equal amount of fluids and blood products were administered in both groups during the first 48 hours of resuscitation. A lesser amount of vasopressors was needed in the first 48 hours of resuscitation in the centhaquine group. An increase in SBP from the baseline was consistently higher in the centhaquine group than in the control. A significant increase in pulse pressure in the centhaquine group than the control group suggests improved stroke volume due to centhaquine. The shock index was significantly lower in the centhaquine group than control from 1 hour (p=0.0320) till 4 hours (p=0.0494) of resuscitation. Resuscitation with centhaquine had a significantly greater number of patients with improved blood lactate and the base deficit than the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is a highly efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock due to sepsis and COVID-19 is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327 . KEY SUMMARY POINTS: A multicentric, randomized, controlled trial was conducted to evaluate the efficacy of centhaquine in hypovolemic shock patients.One hundred and five patients were randomized 2:1 to receive centhaquine or saline. Centhaquine was administered at a dose of 0.01 mg/kg in 100 mL saline and infused over 1 hour. The control group received 100 mL of saline over a 1-hour infusion.Centhaquine improved blood pressure, shock index, reduced blood lactate levels, and improved base deficit. Acute Respiratory Distress Syndrome (ARDS) and Multiple Organ Dysfunction Syndrome (MODS) score improved with centhaquine.An 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. There were no drug-related adverse events in the study.

A Multicentric, Randomized, Controlled Phase III Study of Centhaquine (Lyfaquin®) as a Resuscitative Agent in Hypovolemic Shock Patients.

INTRODUCTION: Centhaquine (Lyfaquin®) showed significant safety and efficacy in preclinical and clinical phase I and II studies. METHODS: A prospective, multicentric, randomized phase III study was conducted in patients with hypovolemic shock, systolic blood pressure (SBP) ≤ 90 mmHg, and blood lactate levels ≥ 2 mmol/L. Patients were randomized in a 2:1 ratio to the centhaquine group (n = 71) or the control (saline) group (n = 34). Every patient received standard of care (SOC) and was followed for 28 days. The study drug (normal saline or centhaquine 0.01 mg/kg) was administered in 100 mL of normal saline infusion over 1 h. The primary objectives were to determine changes (mean through 48 h) in SBP, diastolic blood pressure (DBP), blood lactate levels, and base deficit. The secondary objectives included the amount of fluids, blood products, and vasopressors administered in the first 48 h, duration of hospital stay, time in intensive care units, time on ventilator support, change in acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), and the proportion of patients with 28-day all-cause mortality. RESULTS: The demographics of patients and baseline vitals in both groups were comparable. The cause of hypovolemic shock was trauma in 29.4 and 47.1% of control group and centhaquine group patients, respectively, and gastroenteritis in 44.1 and 29.4%, respectively. Shock index (SI) and quick sequential organ failure assessment at baseline were similar in the two groups. An equal amount of fluids and blood products were administered in both groups during the first 48 h of resuscitation. A lesser amount of vasopressors was needed in the first 48 h of resuscitation in the centhaquine group. An increase in SBP from baseline was consistently higher up to 48 h (12.9% increase in area under the curve from 0 to 48 h [AUC0-48]) in the centhaquine group than in the control group. A significant increase in pulse pressure (48.1% increase in AUC0-48) in the centhaquine group compared with the control group suggests improved stroke volume due to centhaquine. The SI was significantly lower in the centhaquine group from 1 h (p = 0.032) to 4 h (p = 0.049) of resuscitation. Resuscitation with centhaquine resulted in a significantly greater number of patients with improved blood lactate (control 46.9%; centhaquine 69.3%; p = 0.03) and the base deficit (control 43.7%; centhaquine 69.8%; p = 0.01) than in the control group. ARDS and MODS improved with centhaquine, and an 8.8% absolute reduction in 28-day all-cause mortality was observed in the centhaquine group. CONCLUSION: Centhaquine is an efficacious resuscitative agent for treating hypovolemic shock. The efficacy of centhaquine in distributive shock is being explored. TRIAL REGISTRATION: Clinical Trials Registry, India; ctri.icmr.org.in, CTRI/2019/01/017196; clinicaltrials.gov, NCT04045327.

Factors that affect implementation of web-based faculty evaluation forms: residents' perspectives from a developing country.

CONTEXT: A web-based evaluation system for residents to provide feedback on faculty was piloted in four training programs at the Aga Khan University prior to institution-wide implementation. Of the four programs, less than 50% of forms were submitted by residents of three programs while more than 70% of forms were submitted by the residents of one program. This study was conducted to identify reasons for the varying participation rates of the four programs with a view to improving the system. METHODS: A qualitative approach was employed using focus group discussions (FGDs). Volunteers were invited and three groups of eight to ten residents each were formed. Participants for FGDs were selected from all residency years. FGDs were used to identify residents' perceptions regarding the web-based faculty evaluation system and to identify residents' problems and concerns with completing the web-based faculty evaluating forms. RESULTS: Technical issues in completing and submitting the forms online were identified to be the main deterrents to completing the evaluation forms. Non-accessibility of a resource person for resolving technical problems with the software and the burden of taking time out to complete the forms were considered as limiting factors by many residents. Residents recommended a focused orientation session to the new system within the departments. CONCLUSION: Residents' confidence and support are key to promoting adequate participation in web-based evaluations. Focused orientation sessions, reinforcement, reminders, assurances of confidentiality, and removal of technical glitches should help to improve resident participation.

Thorium decorporation efficacy of rationally-selected biocompatible compounds with relevance to human application.

During civil, nuclear or defense activities, internal contamination of actinides in humans and mitigation of their toxic impacts are of serious concern. Considering the health hazards of thorium (Th) internalization, an attempt was made to examine the potential of ten rationally-selected compounds/formulations to decorporate Th ions from physiological systems. The Th-induced hemolysis assay with human erythrocytes revealed good potential of tiron, silibin (SLB), phytic acid (PA) and Liv.52® (L52) for Th decorporation, in comparison to diethylenetriaminepentaacetic acid, an FDA-approved decorporation drug. This was further validated by decorporation experiments with relevant human cell models (erythrocytes and liver cells) and biological fluid (blood) under pre-/post-treatment conditions, using inductively coupled plasma mass spectrometry (ICP-MS) and transmission electron microscopy (TEM). Furthermore, density functional theory-based calculations and extended X-ray absorption fine structure (EXAFS) spectroscopy confirmed the formation of Th complex by these agents. Amongst the chosen biocompatible agents, tiron, SLB, PA and L52 hold promise to enhance Th decorporation for human application.

Treatment of Coronary Drug-Eluting Stent Restenosis by a Sirolimus- or Paclitaxel-Coated Balloon.

OBJECTIVES: The aim of this randomized controlled trial was to investigate a novel sirolimus-coated balloon (SCB) compared with the best investigated paclitaxel-coated balloon (PCB). BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging. PCBs are an established treatment option outside the United States with a Class I, Level of Evidence: A recommendation in the European guidelines. However, their efficacy is better in bare-metal stent (BMS) ISR compared with drug-eluting stent (DES) ISR. METHODS: Fifty patients with DES ISR were enrolled in a randomized, multicenter trial to compare a novel SCB (SeQuent SCB, 4 µg/mm2) with a clinically proven PCB (SeQuent Please Neo, 3 µg/mm2) in coronary DES ISR. The primary endpoint was angiographic late lumen loss at 6 months. Secondary endpoints included procedural success, major adverse cardiovascular events, and individual clinical endpoints such as stent thrombosis, cardiac death, target lesion myocardial infarction, clinically driven target lesion revascularization, and binary restenosis. RESULTS: Quantitative coronary angiography revealed no differences in baseline parameters. After 6 months, in-segment late lumen loss was 0.21 ± 0.54 mm in the PCB group versus 0.17 ± 0.55 mm in the SCB group (p = NS; per-protocol analysis). Clinical events up to 12 months also did not differ between the groups. CONCLUSIONS: This first-in-man comparison of a novel SCB with a crystalline coating shows similar angiographic outcomes in the treatment of coronary DES ISR compared with a clinically proven PCB. (Treatment of Coronary In-Stent Restenosis by a Sirolimus [Rapamycin] Coated Balloon or a Paclitaxel Coated Balloon [FIM LIMUS DCB]; NCT02996318).

Pharmacometabolomics analysis of plasma to phenotype clopidogrel high on treatment platelets reactivity in coronary artery disease patients.

Dual antiplatelet therapy (DAPT) of clopidogrel and aspirin is crucial for coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI). However, some patients may endure clopidogrel high on treatment platelets reactivity (HTPR) which may cause thromboembolic events. Clopidogrel HTPR is multifactorial with some genetic and non-genetic factors contributing to it. We aimed to use nuclear magnetic resonance (1H NMR) pharmacometabolomics analysis of plasma to investigate this multifactorial and identify metabolic phenotypes and pathways associated with clopidogrel HTPR. Blood samples were collected from 71 CAD patients planned for interventional angiographic procedure (IAP) before the administration of clopidogrel 600 mg loading dose (LD) and 6 h after the LD. Platelets function testing was done 6 h post-LD using VerifyNow® P2Y12 assay. Pre-dose and post-dose plasma samples were analysed using 1H NMR. Multivariate statistical analysis was used to indicate the discriminating metabolites. Two metabotypes, each with 34 metabolites (pre-dose and post-dose) were associated with clopidogrel HTPR. Pathway analysis of these metabotypes revealed that aminoacyl-tRNA biosynthesis, nitrogen metabolism and glycine-serine-threonine metabolism are the most perturbed metabolic pathways associated with clopidogrel HTPR. Furthermore, the identified biomarkers indicated that clopidogrel HTPR is multifactorial where the metabolic phenotypes of insulin resistance, type two diabetes mellitus, obesity, gut-microbiota and heart failure are associated with it. Pharmacometabolomics analysis of plasma revealed new insights on the implicated metabolic pathways and the predisposing factors of clopidogrel HTPR.

Toxicity of 3'-deamino-3'-(3-cyano-4-morpholinyl) doxorubicin and doxorubicin in nude mice bearing human tumour xenografts.

The toxicity of the intensely potent anthracycline 3'deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN) has been evaluated in nude mice bearing human colonic cancer xenografts. In addition to dose related toxicity manifested as weight loss and effects on the haematology profile, we obtained evidence of cardiotoxicity with MRA-CN, which has not been reported previously. Even a single dose of 0.012 mg kg-1 could induce significant myocardial changes as seen by electron microscopy. Our results suggest that nude mice bearing human tumour xenografts may offer a very sensitive model for the evaluation of anthracycline induced cardiomyopathy. In view of the potential of MRA-CN in cancer treatment, these results need to be confirmed and extended.

Familial intracranial gliomas.

The pedigree of two interrelated families with 10 affected members suffering from malignant supratentorial gliomas is reported. In addition, three other unrelated families with two members each who were treated for different types of brain tumors are described. Genetic implications are discussed.

Cancer esophagus Karachi 1995-2002: epidemiology, risk factors and trends.

OBJECTIVE: To study the trends of cancer esophagus in Karachi South during 1995-2002 and identify risk factors. METHODS: Incident esophageal cancer cases recorded at the Karachi Cancer Registry for Karachi South, during 1st January 1995 to 31st December 2003 were reviewed. For maximum completion of data, incident cases registered from 1st January 1995 to 31st December 2002 were included for final analyses. RESULTS: The Age Standardized Incidence Rates (ASIRs) of cancer esophagus in Karachi South for males were 6.5/100,000 (1995-1997) and 6.4/100,000 (1998-2002). In females the observed rates were 7.0/100,000 (1995-1997) and 8.6/100,000 (1998-2002). CONCLUSION: In the moderately high incidence, cancer esophagus zone of Karachi, the ASIRs in males remained stable during the last decade, but in females, an upward trend was observed suggesting a progressively higher exposure to risk factors in the latter. The potential risk factors in Karachi are use of all forms of tobacco, areca nut, infrequent consumption of raw fruits and vegetables and diet deficiencies. There is a necessity to actively control the proven risk factors and address the existence of other risk factors. The primary recommended strategy for the control of cancer esophagus would therefore be legislation against tobacco and areca nut in Pakistan and public health education. The risk factors of cancer esophagus identified in this article need to be further confirmed.

Cardiac abnormalities of Sudanese patients with Down's syndrome and their short-term outcome.

BACKGROUND: Congential heart disease (CHD) is an important cause of morbidity and mortality in patients with Down's syndrome (DS). METHODS: All patients with DS seen at the Sudan Heart Centre from July 2004 to November 2007 were included in the study. All patients were examined clinically and echocardiographically, and cardiac catheterisation was carried out in selected patients. All patients were prospectively followed up. RESULTS: In the study period, 1 566 patients were evaluated for heart disease. Of these, 80 patients with DS were identified (5%). Their ages ranged from 15 days to 18 years. Cardiac abnormalities included atrioventricular septal defect (AVSD) in 38 patients (48%), with the complete form in 25, a partial form in seven, AVSD with intact atrial septum in one, and complex AVSD in four patients. In one patient there was AVSD with right atrioventricular valve malformation with severe valve regurgitation and functional pulmonary atresia. The other main lesions were ventricular septal defect (VSD) in 19 patients (23%) and tetralogy of Fallot (TOF) in five (6%). Cardiac catheterisation was done in four patients with AVSD to measure pulmonary pressures and resistance, and in one patient with patent ductus arteriosus for device closure. Ten percent of the patients had Eisenmenger's syndrome at the time of presentation. Only 15% of patients who were in need of surgery were operated on; all had an uneventful postoperative course and a good outcome at a mean follow-up period of one year. CONCLUSION: The pattern of CHD in Sudanese patients with DS was comparable with that in the literature, including the rare occurrence of AVSD with intact atrial septum. In addition, we described an unreported association with right atrioventricular valve malformation. Although there was a significant delay in diagnosis and surgery, surgical results and short-term follow up were good.

Picolyl alkyl amines as novel tyrosinase inhibitors: influence of hydrophobicity and substitution.

Several novel picolyl alkyl amine derivatives (A-L) were synthesized, and the influence of hydrophobicity and substitution on the inhibition of mushroom tyrosinase toward both monophenolase and diphenolase activities are described. Alpha-, beta-, and gamma-picolyl amines are neither the substrates nor the inhibitors; however, the inhibition is induced by the incorporation of an alkyl chain. The inhibition was strongly dependent on the substitution on a pyridine ring, and the inhibition follows the trend of alpha-picolyl alkyl amines (A, D, G) < beta-picolyl alkyl amines (B, E, H) < gamma-picolyl alkyl amines (C, F, I). The inhibition kinetics have been investigated, and gamma-substituted derivatives were found to be a mixed type of inhibitor, whereas beta-substituted derivatives were found to exhibit uncompetitive inhibition toward the oxidation of L-DOPA.