-
Journal of Chromatography. B,... Jun 2024Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in...
Antiarrhythmic and antihypertensive drugs are frequently encountered in post mortem analysis, and the question may arise as to whether they were administered in therapeutic doses, and if they were taken in accidental, intentional, or suicidal overdose scenarios. Therefore, a novel analytical method was developed and validated for the quantification of 35 drugs with toxicological relevance, including antihypertensive and antiarrhythmic drugs (ajmaline, amlodipine, amiodarone, atenolol, bisoprolol, carvedilol, clonidine, desethylamiodarone, diltiazem, donepezil, doxazosin, dronedarone, esmolol, flecainide, lercanidipine, lidocaine, metoprolol, nebivolol, nimodipine, pindolol, prajmaline, propafenone, propranolol, sotalol, urapidil, and verapamil), as well as other medications commonly found in combination (sildenafil, tadalafil, atorvastatin, clopidogrel, dapoxetine, memantine, pentoxifylline, rivastigmine, and ivabradine). The method enables simultaneous identification and quantification in blood samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Validation exhibited excellent linearity across the concentration range for all analytes. Precision and accuracy were within acceptable limits, with bias and relative standard deviation (RSD) values consistently below 9 % and 10 %, respectively. Selectivity and specificity assessments confirmed the absence of any interference from contaminants or co-extracted drugs. The method demonstrated very high sensitivity, with limits of detection (LOD) as low as 0.01 ng/ml and limits of quantification (LOQ) as low as 0.04 ng/ml. Extraction recovery exceeded 57.5 % for all analytes except atenolol, and matrix effects were <17 % for all analytes except pindolol. Processed sample stability evaluations revealed consistent results with acceptable deviations for all analytes. In addition, the method was specifically tested for the use in post mortem analysis. The applicability of our method was demonstrated by the analysis of two authentic human autopsy blood samples.
PubMed: 38878710
DOI: 10.1016/j.jchromb.2024.124196 -
American Journal of Physiology.... May 2024The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder...
The transitional epithelial cells (urothelium) that line the lumen of the urinary bladder form a barrier between potentially harmful pathogens, toxins, and other bladder contents and the inner layers of the bladder wall. The urothelium, however, is not simply a passive barrier, as it can produce signaling factors, such as ATP, nitric oxide, prostaglandins and other prostanoids, that can modulate bladder function. We investigated whether select substances produced by the urothelium could directly modulate the contractility of the underlying urinary bladder smooth muscle. Force was measured in isolated strips of mouse urinary bladder with the urothelium intact or denuded. Bladder strips developed spontaneous tone and phasic contractions. In urothelium-intact strips, basal tone, as well as the frequency and amplitude of phasic contractions, were 25%, 32%, and 338% higher than in urothelium-denuded strips, respectively. Basal tone and phasic contractility in urothelium-intact bladder strips were abolished by the cyclooxygenase (COX) inhibitor indomethacin (10 mM) or the voltage-dependent Ca channel blocker diltiazem (50 mM), whereas blocking neuronal sodium channels with tetrodotoxin (1 mM) had no effect. These results suggest that prostanoids produced in the urothelium enhance smooth muscle tone and phasic contractions by activating voltage-dependent Ca channels in the underlying bladder smooth muscle. We went on to demonstrate that blocking COX inhibits the generation of transient pressure events in isolated pressurized bladders and greatly attenuates the afferent nerve activity during bladder filling, suggesting that urothelial prostanoids may also play a role in sensory nerve signaling.
PubMed: 38780425
DOI: 10.1152/ajpregu.00084.2024 -
Journal of the Anus, Rectum and Colon 2024Lateral internal sphincterotomy is a conventional surgical intervention for chronic anal fissures, yet the potential for postoperative anal incontinence underscores the...
OBJECTIVES
Lateral internal sphincterotomy is a conventional surgical intervention for chronic anal fissures, yet the potential for postoperative anal incontinence underscores the need for an alternative approach. This study aimed to evaluate the outcomes of patients with chronic fissures who underwent a combination of fissurectomy, vertical non-full thickness midline sphincterotomy (VNMS), and mucosal advancement flap (MAF), as a means of mitigating the risk of incontinence.
METHODS
This retrospective analysis included forty-six consecutive patients with chronic anal fissures, unresponsive to topical diltiazem, who underwent fissurectomy combined with VNMS and MAF between April 2018 and May 2023. Primary outcome measures encompassed fissure healing rates. Continence was assessed using the Fecal Incontinence Severity Index (FISI), and manometric assessments were conducted before the procedure and three months postoperatively.
RESULTS
With a median follow-up of 27 months, there were no postoperative complications, and the overall fissure healing rate reached 96% (44/46). At three months post-procedure, FISI scores were reduced to 0, with no instances of fecal soiling. Anal resting pressure exhibited a significant reduction at 3 months [pre-op: 133 (95% CI, 128-150) vs. 3 mo: 109 (95% CI, 100-117) cmHO; = 0.01]. Similarly, maximum anal squeeze pressure showed a significant decrease three months post-surgery [pre-op: 317 cmHO (95% CI, 294-380) vs. 3 mo: 291 cmHO (95% CI, 276-359), = 0.03].
CONCLUSIONS
The combination of fissurectomy, VNMS, and MAF proved to be an effective approach for chronic anal fissures, yielding favorable medium-term outcomes without postoperative anal incontinence.
PubMed: 38689786
DOI: 10.23922/jarc.2023-072 -
Cureus Mar 2024This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate,... (Review)
Review
This study aims to assess the association between intravenous diltiazem and metoprolol in rate control for atrial fibrillation (AF) patients with rapid ventricular rate, focusing on rate control efficacy and hemodynamic adverse events. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, electronic searches were conducted in Embase, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) until February 20, 2024. The primary outcome was achieving ventricular rate control < 110/min. Secondary outcomes included new hypotension (systolic blood pressure < 90 mm Hg) and bradycardia (heart rate < 60/min). Nineteen studies (three randomized controlled trials and 16 observational studies) were included in this meta-analysis. Pooled analysis showed intravenous metoprolol resulted in a 39% lower rate control attainment compared to diltiazem (OR: 0.61; 95% CI: 0.44 to 0.84; p = 0.002). There were no significant differences in bradycardia (OR: 0.51; 95% CI: 0.22 to 1.22; p = 0.13) or hypotension risk (OR: 1.08; 95% CI: 0.72 to 1.61; p = 0.72) between the two groups. Intravenous diltiazem demonstrated superior rate control efficacy compared to metoprolol in AF patients with rapid ventricular rate. However, no significant differences were observed in safety outcomes, namely, bradycardia and hypotension.
PubMed: 38646329
DOI: 10.7759/cureus.56560 -
Chemical & Pharmaceutical Bulletin May 2024This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated... (Comparative Study)
Comparative Study
This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca) using calcium chloride (CaCl). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO) heightened divalent cation reactivity, and crosslinking with CaCl produced Ca-CAP through -CH2-COO and Ca interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.
Topics: Diltiazem; Plant Gums; Tablets; Albizzia; Drug Liberation; Cross-Linking Reagents
PubMed: 38644216
DOI: 10.1248/cpb.c23-00652 -
Case Reports in Dermatological Medicine 2024Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases...
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem.
PubMed: 38596598
DOI: 10.1155/2024/9547206 -
BMC Medicine Apr 2024Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty...
Patterns of comorbidities in patients with atrial fibrillation and impact on management and long-term prognosis: an analysis from the Prospective Global GLORIA-AF Registry.
BACKGROUND
Clinical complexity, as the interaction between ageing, frailty, multimorbidity and polypharmacy, is an increasing concern in patients with AF. There remains uncertainty regarding how combinations of comorbidities influence management and prognosis of patients with atrial fibrillation (AF). We aimed to identify phenotypes of AF patients according to comorbidities and to assess associations between comorbidity patterns, drug use and risk of major outcomes.
METHODS
From the prospective GLORIA-AF Registry, we performed a latent class analysis based on 18 diseases, encompassing cardiovascular, metabolic, respiratory and other conditions; we then analysed the association between phenotypes of patients and (i) treatments received and (ii) the risk of major outcomes. Primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). Secondary exploratory outcomes were also analysed.
RESULTS
32,560 AF patients (mean age 70.0 ± 10.5 years, 45.4% females) were included. We identified 6 phenotypes: (i) low complexity (39.2% of patients); (ii) cardiovascular (CV) risk factors (28.2%); (iii) atherosclerotic (10.2%); (iv) thromboembolic (8.1%); (v) cardiometabolic (7.6%) and (vi) high complexity (6.6%). Higher use of oral anticoagulants was found in more complex groups, with highest magnitude observed for the cardiometabolic and high complexity phenotypes (odds ratio and 95% confidence interval CI): 1.76 [1.49-2.09] and 1.57 [1.35-1.81], respectively); similar results were observed for beta-blockers and verapamil or diltiazem. We found higher risk of the primary outcome in all phenotypes, except the CV risk factor one, with highest risk observed for the cardiometabolic and high complexity groups (hazard ratio and 95%CI: 1.37 [1.13-1.67] and 1.47 [1.24-1.75], respectively).
CONCLUSIONS
Comorbidities influence management and long-term prognosis of patients with AF. Patients with complex phenotypes may require comprehensive and holistic approaches to improve their prognosis.
Topics: Female; Humans; Middle Aged; Aged; Aged, 80 and over; Male; Atrial Fibrillation; Prospective Studies; Risk Factors; Treatment Outcome; Comorbidity; Anticoagulants; Registries; Stroke
PubMed: 38589864
DOI: 10.1186/s12916-024-03373-4 -
Cirugia Y Cirujanos 2024The aim of this study is to describe the effectiveness and safety of a magistral formulation of diltiazem 2% rectal gel as a treatment for chronic anal fissure. (Observational Study)
Observational Study
OBJECTIVE
The aim of this study is to describe the effectiveness and safety of a magistral formulation of diltiazem 2% rectal gel as a treatment for chronic anal fissure.
MATERIAL AND METHODS
A retrospective observational study of all patients that began treatment with diltiazem 2% gel during 2019. The primary endpoint of the study was anal fissure healing. We also looked for differences in effectiveness between those initiating treatment and those who had been previously treated, long-term effectiveness through a 2-year follow-up and frequency of adverse effects.
RESULTS
Of the 166 patients included in the study, anal fissure healed in 72.9%. We detected adverse effects in 12 patients, the most common was local irritation. After 2 years of follow-up, 88% of patients did not relapse.
CONCLUSION
In this study, use of topical diltiazem 2% has been shown to be effective and safe in the treatment of anal fissure and should be considered as the first line of therapy.
Topics: Humans; Diltiazem; Fissure in Ano; Administration, Topical; Chronic Disease; Wound Healing; Treatment Outcome
PubMed: 38537239
DOI: 10.24875/CIRU.22000626 -
Diagnostics (Basel, Switzerland) Mar 2024Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is...
Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.
PubMed: 38535057
DOI: 10.3390/diagnostics14060637 -
Hypertension in Pregnancy Dec 2024Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Preeclampsia (PE) is a pregnancy disorder that represents a major cause of maternal and perinatal morbidity and mortality.
METHODS
This network meta-analysis was registered with PROSPERO. We searched the PubMed, ClinicalTrials.gov. and Embase databases for studies published from inception to the 31 of March 2023. RevMan5.3 software provided by the Cochrane Collaboration was used for direct meta-analysis (DMA) statistical analysis. Funnel maps, network meta-analysis (NMA), the surface under the cumulative ranking curve (SUCRA) to rank the different interventions and publication bias were generated by STATA 17.0 software.
RESULTS
We included eight randomized controlled trials (RCTs) involving a total of 1192 women with PE; two studies were of high quality and six were of moderate quality. Eight interventions were addressed in the NMA. In the DMA, we found that blood pressure in the Ketanserin group were significantly higher than those in the Nicardipine group. NMA showed that blood pressure in the Dihydralazine group was significantly higher than that in the Methyldopa, Labetalol, Nicardipine and Diltiazem groups. And the blood pressure in the Labetalol group was significantly lower than that in the Nicardipine group. SUCRA values showed that Diltiazem was more effective in lowering blood pressure than other drugs looked at in this study.
CONCLUSION
According to the eight RCTs included in this study, Diltiazem was the most effective in reducing blood pressure in PE patients; Labetalol and Nicardipine also had good effects. Diltiazem is preferred for the treatment of patients with severe PE and high blood pressure.
Topics: Pregnancy; Female; Humans; Antihypertensive Agents; Labetalol; Pre-Eclampsia; Diltiazem; Nicardipine; Network Meta-Analysis
PubMed: 38488570
DOI: 10.1080/10641955.2024.2329068