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Journal of Neural Transmission (Vienna,... Nov 2023This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's... (Review)
Review
This article provides an overview of the various screening and selection tools which have been developed over the past 25 years to identify patients with Parkinson's disease (PD) possibly eligible for device-aided therapies (DATs). For the available screening tools, we describe the target therapies (subtypes of DAT), development methods, validation data, and their use in clinical practice. In addition, the historical background and potential utility of these screening tools are discussed. The challenges in developing and validating these tools are also addressed, taking into account the differences in population, the local health care organization, and resource availability.
Topics: Humans; Parkinson Disease; Antiparkinson Agents; Carbidopa; Levodopa; Drug Combinations; Gels
PubMed: 37500937
DOI: 10.1007/s00702-023-02656-z -
Annals of Medicine and Surgery (2012) Aug 2023Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This...
UNLABELLED
Wunderlich syndrome is a rare and life-threatening condition that is characterized by spontaneous renal hemorrhage into the subcapsular and perinephric regions. This case report describes the diagnosis and management of bilateral Wunderlich syndrome during pregnancy, resulting in Page kidney.
CASE PRESENTATION
The patient presented with complaints of left flank pain and breathlessness. After stabilization, an emergency lower cesarean delivery was performed, and a percutaneous drainage procedure was carried out to alleviate the compression on the left kidney. The patient was treated with blood transfusion, methyldopa, and perindopril. Follow-up examinations performed 3 months later revealed a significant decrease in fluid volume surrounding the left kidney.
CLINICAL DISCUSSION
Lenk's triad provides the primary description of the classical manifestations of this syndrome. Some instances have been connected to the Page kidney phenomenon. The relationship between pregnancy and Wunderlich syndrome has not been extensively studied, primarily because the symptoms can resemble other complications related to pregnancy. Due to the scarcity of evidence in the literature, there is no definitive guideline for managing Wunderlich syndrome during pregnancy. Consequently, each patient is treated on an individual basis. Conservative treatment is recommended once malignancy has been ruled out.
CONCLUSION
The case highlights the importance of considering Wunderlich syndrome as a differential diagnosis in pregnant patients with abdominal or flank pain, a palpable mass, and hypovolemia. Furthermore, the case illustrates the successful management of Wunderlich syndrome during pregnancy.
PubMed: 37554856
DOI: 10.1097/MS9.0000000000001062 -
Genes Sep 2023Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the...
Aromatic L-Amino-Acid Decarboxylase Deficiency Screening by Analysis of 3-O-Methyldopa in Dried Blood Spots: Results of a Multicentric Study in Neurodevelopmental Disorders.
Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd.
Topics: Humans; Infant, Newborn; Carboxy-Lyases; Malnutrition; Muscle Hypotonia; Neurodevelopmental Disorders
PubMed: 37761968
DOI: 10.3390/genes14091828 -
Pharmaceutics Sep 2023The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending...
The present study aimed to evaluate the stability of active pharmaceutical ingredients (APIs) from different pharmacological classes in a compounded oral suspending vehicle. Oral suspensions of amoxicillin trihydrate (50 mg/mL), clozapine (25 mg/mL), indomethacin (5.0 mg/mL), levodopa/carbidopa (10.0/2.5 mg/mL), levothyroxine sodium (T4, 25 µg/mL), lomustine (4.0 and 10.0 mg/mL), methyldopa (25 mg/mL) and procarbazine (10.0 mg/mL) were formulated in SyrSpend SF PH4 and the stability was monitored for up to 90 days, except for amoxicillin trihydrate, which was evaluated for 30 days only. The APIs' stability was determined by measuring percent recovery using stability-indicating high-performance liquid chromatography (HPLC or UHPLC) or titration (amoxicillin trihydrate only). The stability of amoxicillin trihydrate, clozapine, indomethacin and levodopa/carbidopa were studied at both refrigerated (2-8 °C) and room temperature (20-25 °C). Lomustine, procarbazine, and methyldopa were studied at refrigerated temperature only. Our data demonstrated promising stability for the compounded suspensions containing various APIs, investigated in SyrSpend SF PH4, as all APIs exhibited stability throughout the study duration and met content uniformity criteria. These findings lead to the conclusion that the tested compounded oral suspensions present a viable approach for creating personalized, age-appropriate formulations. The capacity to ensure dose consistency and stability using APIs from diverse pharmacological classes renders them suitable choices for both pediatric and geriatric patients.
PubMed: 37896148
DOI: 10.3390/pharmaceutics15102388 -
International Journal of Molecular... Oct 2023Antihypertensive therapy is an essential part of management of patients with preeclampsia (PE). Methyldopa (Dopegyt) and nifedipine (Cordaflex) are basic medications of...
Features and Comparative Characteristics of Fucosylated Glycans Expression in Endothelial Glycocalyx of Placental Terminal Villi in Patients with Preeclampsia Treated with Different Antihypertensive Regimens.
Antihypertensive therapy is an essential part of management of patients with preeclampsia (PE). Methyldopa (Dopegyt) and nifedipine (Cordaflex) are basic medications of therapy since they stabilize blood pressure without affecting the fetus. Their effect on the endothelium of placental vessels has not yet been studied. In this study, we analyzed the effect of antihypertensive therapy on the expression of fucosylated glycans in fetal capillaries of placental terminal villi in patients with early-onset PE (EOPE) and late-onset PE (LOPE), and determined correlation between their expression and mother's hemodynamic parameters, fetoplacental system, factors reflecting inflammatory response, and destructive processes in the endothelial glycocalyx (eGC). A total of 76 women were enrolled in the study: the comparison group consisted of 15 women with healthy pregnancy, and the main group comprised 61 women with early-onset and late-onset PE, who received one-component or two-component antihypertensive therapy. Hemodynamic status was assessed by daily blood pressure monitoring, dopplerometry of maternal placental and fetoplacental blood flows, and the levels of IL-18, IL-6, TNFα, galectin-3, endocan-1, syndecan-1, and hyaluronan in the blood of the mother. Expression of fucosylated glycans was assessed by staining placental sections with AAL, UEA-I, LTL lectins, and anti-Le MAbs. It was found that (i) expression patterns of fucosylated glycans in eGC capillaries of placental terminal villi in EOPE and LOPE are characterized by predominant expression of structures with a type 2 core and have a similar pattern of quantitative changes, which seems to be due to the impact of one-component and two-component antihypertensive therapy on their expression; (ii) correlation patterns indicate interrelated changes in the molecular composition of eGC fucoglycans and indicators reflecting changes in maternal hemodynamics, fetoplacental hemodynamics, and humoral factors associated with eGC damage. The presented study is the first to demonstrate the features of placental eGC in women with PE treated with antihypertensive therapy. This study also considers placental fucoglycans as a functional part of the eGC, which affects hemodynamics in the mother-placenta-fetus system.
Topics: Humans; Pregnancy; Female; Placenta; Pre-Eclampsia; Antihypertensive Agents; Glycocalyx; Methyldopa; Polysaccharides
PubMed: 37958597
DOI: 10.3390/ijms242115611 -
CNS Neuroscience & Therapeutics Apr 2024This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs).
AIMS
This study aimed to systematically compare the effectiveness, safety, and costs of different anti-Parkinson drugs (APDs).
METHODS
This is a multi-center study that retrospectively analyzed the data of 8420 outpatients with PD from 2014 to 2019 across 30 tertiary hospitals in China. The effectiveness was evaluated by changes in total dosages of APDs, normalized by levodopa equivalent dose (LED) and presented as ΔLEDs; levodopa equivalent dose cost (LEDc) represented the daily cost of APDs; and newly added diagnostics were represented as APDs-related adverse events.
RESULTS
A total of 384 patients with eligible medical records for three consecutive years were enrolled. Patients treated with carbidopa/levodopa or levodopa/benserazide had significantly lower mean ΔLEDs than other groups (p < 0.01), followed by pramipexole and selegiline. The piribedil group had the highest ΔLEDs, with mean differences of 112.56-355.04 mg compared to other groups (p < 0.01). Meanwhile, LEDc in the levodopa/benserazide, carbidopa/levodopa, and piribedil groups were significantly lower than those in pramipexole or selegiline groups ($0.088-0.135/day for levodopa/benserazide; $0.070-0.126/day for carbidopa/levodopa; $0.112-0.138/day for piribedil; $0.290-0.332/day for pramipexole; $0.229-0.544/day for selegiline; p < 0.01). Patients with piribedil had more adverse events, with an incidence rate of 35.7%, followed by levodopa/benserazide (25.6%), selegiline (23.5%), carbidopa/levodopa (23.3%), and pramipexole (16.4%). Pramipexole showed a lower incidence rate of adverse events than piribedil, including neuropsychiatric symptoms (p = 0.006), headache/dizziness (p = 0.016), and gastrointestinal symptoms (p = 0.031).
CONCLUSIONS
Carbidopa/levodopa or levodopa/benserazide might exhibit better clinical improvement with less medical cost, while piribedil presented less clinical improvement but a higher risk of headache/dizziness, gastrointestinal, and neuropsychiatric symptoms.
Topics: Humans; Levodopa; Carbidopa; Benserazide; Retrospective Studies; Pramipexole; Parkinson Disease; Piribedil; Selegiline; Dizziness; Antiparkinson Agents; Headache
PubMed: 37983933
DOI: 10.1111/cns.14531 -
Electrochemical sensor based on bio-inspired molecularly imprinted polymer for sofosbuvir detection.RSC Advances Aug 2023The electropolymerized molecularly imprinted polymers (MIP) have enabled the utilization of various functional monomers with superior selective recognition of the target...
The electropolymerized molecularly imprinted polymers (MIP) have enabled the utilization of various functional monomers with superior selective recognition of the target analyte template. Methyldopa is an attractive synthetic dopamine analogue which has phenolic, carboxylic, and aminic functional groups. In this research, methyldopa was exploited to fabricate selective MIPs, for the detection of sofosbuvir (SFB), by a simple electropolymerization step onto a disposable pencil graphite electrode (PGE) substrate. The interaction between methyldopa, as a functional monomer, and a template has been investigated experimentally by UV spectroscopy. A polymethyldopa (PMD) polymer was electrografted onto PGE in the presence of SFB as a template. X-ray photoelectron spectroscopy (XPS), electrochemical impedance spectroscopy (ESI), and cyclic voltammetry (CV) were used for the characterization of the fabricated sensor. Differential pulse voltammetry (DPV) of a ferrocyanide/ferricyanide redox probe was employed to indirectly detect the SFB binding to the MIP cavities. The sensor shows a reproducible and linear response over a dynamic linear range from 1.0 × 10 M to 1.0 × 10 M of SFB with a limit of detection of 3.1 × 10 M. The sensor showed high selectivity for the target drug over structurally similar and co-administered interfering drugs, and this enabled its application to detect SFB in its pharmaceutical dosage form and in spiked human plasma samples.
PubMed: 37614794
DOI: 10.1039/d3ra03870j -
Journal of Pregnancy 2023Hypertensive disorders in pregnancy (HDPs) are no longer seen as "transitory diseases cured by delivery." It accounts for up to 50% of maternal deaths. Information...
Hypertensive disorders in pregnancy (HDPs) are no longer seen as "transitory diseases cured by delivery." It accounts for up to 50% of maternal deaths. Information concerning HDPs is less in developing countries like Ghana. This study was conducted to find out the prevalence, awareness, risk factors, control, and the birth outcomes of HDPs. This was a retrospective cohort study conducted among pregnant women seeking care in selected health facilities in the Ashanti Region. Data on demographics, HDPs, and its associated birth outcomes were collected. Logistic regression models were used to examine the association of the independent variables with HDPs. The burden of HDPs was 37.2% among the 500 mothers enrolled with chronic hypertension superimposed with preeclampsia accounting for 17.6%, chronic hypertension, 10.2%, and preeclampsia 6.8% whilst gestational hypertension was 2.6%. It was observed that 44% (220) of the mothers had excellent knowledge on HDPs. Oral nifedipine and methyldopa were frequently used for HDP management, and it resulted in a significant reduction in HDP burden from 37.2% to 26.6%. Factors that influenced the increased risk of HDPs were grand multigravida (AOR = 4.53; CI = 1.42-14.42), family history of hypertension (AOR = 3.61; CI = 1.89-6.90), and the consumption of herbal preparations (AOR = 2.92; CI = 1.15-7.41) and alcohol (AOR = 4.10; CI = 1.34-12.62) during pregnancy. HDPs increased the risk of preterm delivery (AOR = 2.66; CI = 1.29-5.89), stillbirth (AOR = 12.47; CI = 2.72-57.24), and undergoing caesarean section (AOR = 1.70; CI = 1.10-2.61) amongst mothers during delivery. The burden of HDPs is high amongst pregnant mothers seeking care in selected facilities. There is the need for intensified campaign on HDPs in the Ashanti Region of Ghana.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Pregnant Women; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Ghana; Prevalence; Cesarean Section; Retrospective Studies; Health Facilities; Delivery of Health Care
PubMed: 37732166
DOI: 10.1155/2023/4194443 -
American Journal of Obstetrics &... May 2024Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely...
The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.
BACKGROUND
Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values.
OBJECTIVE
This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings.
STUDY DESIGN
This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy.
RESULTS
A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02).
CONCLUSION
In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.
Topics: Humans; Female; Pregnancy; Antihypertensive Agents; Prospective Studies; Adult; Hemodynamics; Pre-Eclampsia; Labetalol; Cardiac Output; Nifedipine; Vascular Resistance; Methyldopa; Blood Pressure; Hypertension, Pregnancy-Induced; Treatment Outcome; Heart Rate; Stroke Volume; Vasodilator Agents
PubMed: 38574856
DOI: 10.1016/j.ajogmf.2024.101368 -
Journal of Neural Transmission (Vienna,... Nov 2023Pump-guided intrajejunal levodopa administration is one of the indispensable forms of therapy in advanced Parkinson's syndrome, along with deep brain stimulation and...
Pump-guided intrajejunal levodopa administration is one of the indispensable forms of therapy in advanced Parkinson's syndrome, along with deep brain stimulation and subcutaneous apomorphine injection. The standard application of levodopa gel via a JET-PEG, i.e. a percutaneous endoscopic gastrostomy (PEG) with an inserted internal catheter into the jejunum, has not been unproblematic due to the restricted absorption area of the drug in the region of the flexura duodenojejunalis and especially due to the sometimes considerable accumulated complication rates of a JET-PEG. Causes of complications are mainly a non-optimal application technique of PEG and internal catheter as well as the often missing adequate follow-up care. This article presents the details of a-compared to the conventional technique-modified and optimised application technique, which has been clinically proven successfully for years. However, many details derived from anatomical, physiological, surgical and endoscopic aspects must be strictly observed during the application to reduce or avoid minor and major complications. Local infections and buried bumper syndrome cause particular problems. The relatively frequent dislocations of the internal catheter (which can ultimately be avoided by clip-fixing the catheter tip) also prove to be particularly troublesome. Finally, using the Hybrid technique, a new combination of an endoscopically controlled gastropexy with 3 sutures and subsequent central thread pull-through (TPT) of the PEG tube, the complication rate can be dramatically reduced and thus a decisive improvement achieved for patients. The aspects discussed here are highly relevant for all those involved in the therapy of advanced Parkinson's syndrome.
Topics: Humans; Levodopa; Parkinson Disease; Carbidopa; Enteral Nutrition; Gastrostomy
PubMed: 36809488
DOI: 10.1007/s00702-023-02601-0