Seven ACE inhibitors were studied for possible differences in distribution to aorta, brain, heart, lung, and kidney after administration of single oral doses to spontaneously hypertensive rats (SHR). Doses, normalized for differences in inhibitory potency and molecular weight, were expected to deliver equivalent levels of ACE-inhibitory activity to the circulation, and this was confirmed by preliminary dose-response studies. The relative potencies of the active moieties of the seven drugs and the normalized oral doses used were: SQ 29,852 (1.0), 100 mg/kg; captopril (3.5), 30 mg/kg; enalapril (12), 20 mg/kg; fosinopril (13), 25 mg/kg; zofenopril (20), 10 mg/kg; lisinopril (24), 10 mg/kg; and ramipril (51), 5 mg/kg. In these ex vivo studies, ACE activities were determined fluorometrically in SHR sera and in uncentrifuged homogenates of the solid tissues at various times after oral dosing with the ACE inhibitors. As expected, the normalized oral doses of the seven inhibitors had equivalent effects on serum ACE. In lung, where ACE has a vascular endothelial localization, and in aorta, where ACE inhibition correlates with antihypertensive action, ramipril, lisinopril, and zofenopril were distinguished by the magnitude and duration (three to four days) of their effects. In the brain, where ACE may affect central regulation of blood pressure and participate in the degradation of certain neuropeptides, ramipril and enalapril had no effect; captopril and zofenopril had modest, short-lasting effects, and fosinopril, lisinopril, and SQ 29,852 had delayed but long-lasting inhibitory actions. In the kidney, where ACE inhibition may have positive or negative effects on renal function, ramipril and fosinopril could be distinguished by their weak actions, perhaps associated with biliary routes of excretion. In the heart, where ACE inhibitors may prevent ischemic damage to the myocardium, single oral doses of captopril, fosinopril, and particularly zofenopril produced striking and long-lasting inhibition, whereas equivalent doses of ramipril and enalapril produced barely detectable inhibition.
1. Seven drugs (captopril, zofenopril, enalapril, ramipril, lisinopril, fosinopril, and SQ 29,852) were compared in vitro in homogenates of aorta, brain, heart, lung, and kidney and in sera of spontaneously hypertensive rats (SHR) both with respect to potencies of their active moieties as inhibitors of angiotensin‐converting enzyme (ACE), and, where applicable, rates of hydrolysis of their prodrug ester functions. 2. In ex vivo dose‐response and time‐course studies, the inhibitory effects of the seven drugs on tissue ACEs and their relative distributions to SHR tissues were compared following oral administration. 3. The relative potencies of the inhibitory moieties of the drugs (in parentheses) and the normalized ‘equiactive’ oral doses employed for time‐course studies were: SQ 29,852 (1.0), 100 mg kg‐1; captopril (3.5), 30 mg kg‐1; enalapril (12), 20 mg kg‐1; fosinopril (13), 25 mg kg‐1; zofenopril (20), 10 mg kg‐1; lisinopril (24), 10 mg kg‐1; and ramipril (51), 5 mg kg‐1. 4. Following oral administration of the drugs to SHR, the degree and duration of ACE inhibition in aorta and lung correlated with the antihypertensive actions, with ramipril, lisinopril, and zofenopril producing effects of the greatest magnitude and duration. 5. Ramipril and enalapril did not inhibit brain ACE ex vivo; captopril and zofenopril had modest but short‐lasting effects; and fosinopril, lisinopril, and SQ 29,852 had long‐lasting inhibitory actions, which, with the latter two, were delayed in onset. 6. All of the drugs produced significant inhibition of kidney ACE, with ramipril and fosinopril having somewhat weaker effects, perhaps due to biliary routes of excretion. 7. Captopril, fosinopril, and particularly zofenopril inhibited cardiac ACE ex vivo with degrees and durations that were marked compared with those of the other drugs; preliminary studies with isolated hearts suggest a possible relationship between inhibition of cardiac ACE and preservation of cardiac function subsequent to ischaemia.
Background Artificial intelligence is an emerging technology with rapid growth and increasing applications in orthopaedics. This study aimed to summarize the existing evidence and recent developments of artificial intelligence in diagnosing knee osteoarthritis and predicting outcomes of total knee arthroplasty. Methods PubMed and EMBASE databases were searched for articles published in peer-reviewed journals between January 1, 2010 and May 31, 2021. The terms included: ‘artificial intelligence’, ‘machine learning’, ‘knee’, ‘osteoarthritis’, and ‘arthroplasty’. We selected studies focusing on the use of AI in diagnosis of knee osteoarthritis, prediction of the need for total knee arthroplasty, and prediction of outcomes of total knee arthroplasty. Non-English language articles and articles with no English translation were excluded. A reviewer screened the articles for the relevance to the research questions and strength of evidence. Results Machine learning models demonstrated promising results for automatic grading of knee radiographs and predicting the need for total knee arthroplasty. The artificial intelligence algorithms could predict postoperative outcomes regarding patient-reported outcome measures, patient satisfaction and short-term complications. Important weaknesses of current artificial intelligence algorithms included the lack of external validation, the limitations of inherent biases in clinical data, the requirement of large datasets in training, and significant research gaps in the literature. Conclusions Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. Further research to overcome the weaknesses of machine learning models may enhance reliability and allow for future use in routine healthcare settings.
Background Surgical site infection following joint replacement surgery is still a significant complication, resulting in repeated surgery, prolonged antibiotic therapy, extended postoperative hospital stay, periprosthetic joint infection, and increased morbidity and mortality. This review discusses the risk factors associated with surgical site infection. Related risk factors The patient-related factors include sex, age, body mass index (BMI), obesity, nutritional status, comorbidities, primary diagnosis, living habits, and scores of the American Society of Anesthesiologists physical status classification system, etc. Surgery-related factors involve preoperative skin preparation, prolonged duration of surgery, one-stage bilateral joint replacement surgery, blood loss, glove changes, anti-microbial prophylaxis, topical anti-bacterial preparations, wound management, postoperative hematoma, etc. Those risk factors are detailed in the review. Conclusion Preventive measures must be taken from multiple perspectives to reduce the incidence of surgical site infection after joint replacement surgery.
Background: Knee osteoarthritis (OA) is one of the most common and debilitating degenerative joint diseases worldwide. While radiography is the most commonly used imaging modality, it is associated with drawbacks which newer modalities such as magnetic resonance imaging (MRI) and ultrasound could overcome. Nevertheless, the role of imaging in clinical practice and research in knee OA has not been clearly defined. Furthermore, guidelines on imaging in knee OA from different authoritative bodies have not been compared in previous studies. Therefore, the present review aims to summarise existing evidence and compare guidelines on the use of different imaging modalities in evaluating knee OA.Methods: This is a narrative review based on a search of published clinical guidelines and the PubMed database for articles published between 1 January 1990 and 31 May 2020. Results:There is no broad consensus on the value of imaging in patients with typical OA presentation. If imaging is required, current evidence and clinical guidelines support the use of radiography and MRI as first-and second-line diagnostic modalities respectively. Since radiographic OA features have limited sensitivity and do not manifest in early stages, MRI is the preferred option for whole-joint evaluation in OA research. Discrepancies exist regarding the use of alternative imaging modalities including ultrasound, computed tomography and nuclear medicine. Conclusion:Radiography and MRI are the imaging modalities of choice. Other modalities have their respective advantages, and more research is warranted for the standardisation of image acquisition and interpretation methodology, in order to evaluate their validity, reliability and responsiveness in OA research. K E Y W O R D S clinical guidelines, imaging, knee osteoarthritis 1 | INTRODUCTION Knee osteoarthritis (OA) is one of the most common and debilitating degenerative joint diseases worldwide, with 80% of OA patients suffering from movement limitations and 25% of them being unable to carry out major activities in their daily lives (Neogi, 2013).Although cartilage degeneration and osteophyte formation remain the structural hallmarks of knee OA, the disease is now increasingly recognised as a whole-organ disorder affecting tissues in the entire knee joint, such as the meniscus and synovium (Hayashi, Guermazi, & Hunter, 2011). Its clinical presentation is heterogeneous, with typical symptoms including pain, stiffness and movement restriction.
Background Dual-mobility hip component is widely used in Europe and North America, because it effectively reduces hip dislocation in primary and revision total hip arthroplasties. However, reports were limited on the use of dual-mobility articulation in Asian populations. Purpose The aim of this retrospective study was to review the use of modular dual-mobility hip articulation in Asian patients with the high risk factor for hip dislocation. We also discussed the potential concern on the use of dual-mobility articulation in Asian patients. Methods From Jan 2018 to June 2019, 17 patients were included in this study. The mean age of the patients was (73.8 ± 9.5) years (range: 57–88 years). The mean size of acetabular cup and modular DM liner were (49.5 ± 3.4) mm (range, 46–58 mm) and (40.7 ± 3.4) mm (range, 38–48 mm), respectively. The mean follow-up period was (15.8 ± 3.9) months (range, 11–24 months). The primary outcome was the rate of hip dislocation. The secondary outcomes included the Harris Hip Score. Differences were considered statistically significant at p < 0.05. Results Hip dislocation, loosening, peri-prosthetic fractures, or intra-prosthetic dislocation was not found in the series. The mean preoperative and postoperative Harris Hip Scores were 42.2 ± 17.2 (range, 15–80) and 74.7 ± 13.5 (range, 52–97), respectively, giving a mean improvement of 32.5 ± 17.2 (range, 4–72). The improvement was statistically significant (p < 0.05). Conclusions In Asian patients with high risk of hip dislocation, the use of modular dual-mobility hip component produces promising outcomes without hip dislocation, but the relatively small-sized acetabulum may limit it widespread application in other populations worldwide. Trial registration HKUCTR-2913.
Background Arthroplasty services worldwide have been significantly disrupted by the pandemic of coronavirus disease 2019 (COVID-19). This retrospective comparative study aimed to characterize its impact on arthroplasty services in Hong Kong. Methods From January 1 to June 30, 2020, the patients of “COVID-19 cohort” underwent elective total hip or knee replacement in Hong Kong public hospitals. The cohort was compared to the “control cohort” during the same period in 2019. Data analysis was performed to compare the two cohorts’ numbers of operations, hospital admission, orthopaedic clinic attendances, and waiting time. Results A total of 33,111 patient episodes were analyzed. During the study period, the elective arthroplasty operations and hospitalizations decreased by 53 and 54%, respectively (P < 0.05). Reductions were most drastic from February to April, with surgical volume declining by 86% (P < 0.05). The primary arthroplasty operations decreased by 91% (P < 0.05), while the revision operations remained similar. Nevertheless, 14 public hospitals continued performing elective arthroplasty for patients with semi-urgent indications, including infection, progressive bone loss, prosthesis loosening, dislocation or mechanical failure of arthroplasty, and tumor. At the institution with the highest arthroplasty surgical volume, infection (28%) was the primary reason for surgery, followed by prosthesis loosening (22%) and progressive bone loss (17%). The orthopaedic clinic attendances also decreased by 20% (P < 0.05). Increases were observed in waiting time and the total number of patients on the waiting list for elective arthroplasty. Conclusions Despite the challenges, public hospitals in Hong Kong managed to continue providing elective arthroplasty services for high-priority patients. Arthroplasty prioritization, infection control measures, and post-pandemic service planning can enhance hospital preparedness to mitigate the impact of current and future pandemics.
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