Concentration andpH dependent steady-state volume of distribution of methotrexate estimated by a simple physiologically based method

The effects of plasma concentration and pH on the steady-state volume of distribution, V_ss,of methotrexate (MTX) were studied in five conditioned male beagle-mongrel dogs. Steady-state plasma MTX concentrations of approximately 1, 20, and 100g/ml were targeted for by i.v. bolus doses followed by i.v. infusions. An isotonic solution of sodium bicarbonate or ammonium chloride was simultaneously infused for the purpose of inducing plasma pH change, while the infusion of an isotonic solution of sodium chloride served as a control. Plasma and urine concentrations of MTX were quantitated by a sensitive high-performance liquid chromatographic method, and the V_ss of MTX was estimated by a recently reported physiologically based method of Chiou and Lam. Statistically significant (p<0.05) concentration and plasma pHdependent V_ss of MTX were observed. Concentration dependence of V_ss was noted in sodium chloride and ammonium chloride infused dogs, but not in bicarbonate treated dogs. There was an average 50.0 and 44.8% increase in V_ss at 1 g/ ml relative to the two higher concentrations (20 and 100 g/ ml) for dogs treated with ammonium and sodium chloride, respectively. However, V_ss of MTX at the targeted concentrations of 20 and 100 g/ml was relatively constant. Plasma pHdependence of V_ss was observed only at the plasma concentration of 1 g/ml, and on the average, ammonium chloride and sodium chloride treatments resulted in 50.0 and 31.3% higher V_ss,respectively, when compared with the bicarbonate treatment. These phenomena appear to be adequately explained by the reported tissue uptake kinetics of MTX.This research was supported in part by a grant from the National Cancer Institute, CA-29754.Abstracted from a dissertation submitted in 1984 by Chung Y. Lui to the Graduate College, University of Illinois at Chicago, in partial fulfillment of Doctor of Philosophy Degree requirements.     

乳酸及降钙素原对一氧化碳中毒后迟发性脑病的预测价值

目的探讨检测血乳酸、降钙素原和联合检测对急性一氧化碳中毒后迟发性脑病(DEACMP)的预测价值。 方法随机抽取我院在急诊科收住院的ACMP患者70例,随访3个月,以其中发生DEACMP患者10例为DEACMP组,其余60例为非DEACMP组,随机抽取同期笔者医院40例健康体检者为对照组。对患者立即行动脉血Lac和血清PCT检测,并计算Lac和PCT诊断DEACMP的灵敏度、特异度。 结果DEACMP组血Lac和PCT检测值均明显高于非DEACMP和对照组,差异有统计学意义(采用秩和检验,P<0.05);检测异常率亦明显高于非DEACMP组及对照组,差异有统计学意义(采用χ²检验,P<0.05)。Lac和PCT升高预测DEACMP的敏感度均为90.0% ,特异度分别为50.0%和65.0% ,准确性分别为55.7%和68.6%。联合检测时若其中1个指标为阳性时即预测DEACMP发病,则联合检测的敏感度为100.0%,特异度为41.7%,阳性预测值为21.7%,阴性预测值为100.0%,准确性为71.4%。 结论DEACMP患者早期动脉血Lac和PCT均明显升高,PCT诊断价值优于Lac,联合检测较单项指标检测对DEACMP发病预测价值更理想。     

Risks of AKI and Major Adverse Clinical Outcomes in Patients with Severe Acute Respiratory Syndrome or Coronavirus Disease 2019

BackgroundSevere acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) are closely related. The effect of AKI on the clinical outcomes of these two conditions is unclear.MethodsThis retrospective, territory-wide cohort study used an electronic public healthcare database in Hong Kong to identify patients with SARS or COVID-19 by diagnosis codes, virologic results, or both. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death.ResultsWe identified 1670 patients with SARS and 1040 patients with COVID-19 (median ages, 41 versus 35 years, respectively). Among patients with SARS, 26% met the primary endpoint versus 5.3% of those with COVID-19. Diabetes mellitus, abnormal liver function, and AKI were factors significantly associated with the primary endpoint among patients with either SARS or COVID-19. Among patients with SARS, 7.9%, 2.1%, and 3.7% developed stage 1, stage 2, and stage 3 AKI, respectively; among those with COVID-19, 6.6%, 0.4%, and 1.1% developed stage 1, stage 2, and stage 3 AKI, respectively. In both groups, factors significantly associated with AKI included diabetes mellitus and hypertension. Among patients with AKI, those with COVID-19 had a lower rate of major adverse clinical outcomes versus patients with SARS. Renal function recovery usually occurred within 30 days after an initial AKI event.ConclusionsAKI rates were higher among patients with SARS than those with COVID-19. AKI was associated with major adverse clinical outcomes for both diseases. Patients with diabetes mellitus and abnormal liver function were also at risk of developing severe consequences after SARS and COVID-19 infection.     

Concomitant Lateral Ankle and Peroneal Tendon Instability Treated With Simultaneous Arthroscopic Broström and Tendoscopic Superior Peroneal Retinaculum Repair: A Case Report

Chronic lateral ankle instability is a prevalent condition, and it is commonly associated with other foot and ankle injuries. Among the associated injuries, peroneal tendon pathologies and anterolateral ankle impingement are frequently encountered. In this report, a case of concomitant chronic lateral ankle instability and dislocation of the peroneal tendons is described. While this combination of injuries is not uncommon, the method of treatment entailed arthroscopic repair of the anterior talofibular ligament and endoscopic repair of the superior peroneal retinaculum, procedures that eliminated the anterior drawer instability that had been present, and the patient remained symptom free after 24 months of follow-up.     

Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers

BACKGROUND/AIM: A mechanism suggested to cause injury to preserved organs is the generation of oxygen free radicals. Lipid peroxidation is one of the biological damages caused by oxygen free radicals. It is our aim to investigate whether magnolol, a strong antioxidant, suppresses the generation of oxygen free radicals and improves the viability of cold-preserved warm-reperfused rat livers. MATERIALS AND METHODS: In vitro lipid peroxidation was induced in rat hepatic mitochondria with ADP and FeSO4. The inhibitory effect of magnolol on lipid peroxidation was measured with oxygen consumption and malondialdehyde (MDA) formation. Subsequently, we preserved and reperfused rat livers in preservation solutions that contained magnolol. The hepatic enzymes and liver MDA were measured to assess the protective effect of magnolol on isolated rat livers. RESULTS: In rat hepatic mitochondria, magnolol was 470 times more potent than alpha-tocopherol in inhibiting oxygen consumption and 340 times more potent than alpha-tocopherol in inhibiting MDA formation. Addition of magnolol to Ringer's lactate solution had a protective effect, in terms of MDA formation and leakage of hepatic enzymes, on warm-reperfused but not cold-stored liver tissue. Addition of magnolol to University of Wisconsin (UW) solution, a widely used preservation solution, did not modify the effect of this solution on isolated liver tissues. CONCLUSIONS: We conclude that magnolol is an effective antioxidant and suppresses lipid peroxidation in rat liver mitochondria and can be used as a rinsing solution in protecting transplanted organs from lipid peroxidation during reperfusion, especially for those organs not preserved with UW solution.     

Perfusion sphincterometry for objective evaluation of postprostatectomy intrinsic sphincter deficiency

OBJECTIVES: Male urinary incontinence secondary to intrinsic sphincter deficiency (ISD) is a possible complication of transurethral resection of the prostate (TURP) or radical prostatectomy (RP). For objective assessment of urinary sphincteric competence, we used perfusion sphincterometry (PS) to measure the retrograde urethral perfusion pressure (RUPP). METHODS: A retrospective and prospective analysis of 60 neurologically normal patients of varying continence status was performed. The subjects were divided into three groups: continent patients with no previous prostate surgery (group 1), continent patients after prostatectomy (group 2), and incontinent patients after prostatectomy (group 3). All patients underwent PS with the technique described. All incontinent patients (group 3) had a filling cystometrogram (CMG) to rule out detrusor instability. RESULTS: Continent patients with no prior prostate surgery (group 1) had a mean RUPP of 101 +/- 16 cm H2O; continent postprostatectomy patients (group 2) had a mean RUPP of 77 +/- 14 cm H2O; and incontinent postprostatectomy patients (group 3) had a mean RUPP of 36 +/- 11 cm H2O. The differences were statistically significant (P <0.001). There was no statistically significant difference in RUPP when the patients in groups 2 and 3 were stratified into TURP and RP groups. CONCLUSIONS: PS is a simple and accurate technique for objective evaluation of lower sphincter competence. Patients with stress incontinence after prostatectomy have a statistically significant decrease in RUPP compared with continent controls. In combination with cystourethroscopy and filling CMG, PS can be useful in the evaluation of postprostatectomy incontinence.     

Tissue potassium,selenium, and iron levels associated with gastric cancer progression

The contents of 10 minor and trace elements in histologically confirmed gastric adenocarcinomas and their corresponding normal gastric mucosal tissues obtained from 39 patients at the time of gastric resection were simultaneously determined by instrumental neutron activation analysis. Specimens were irradiated by reactor neutrons and subsequently subject to direct analysis using a high-resolution HPGe -spectrometer. Univariate analysis revealed that gastric cancer tissues had significantly higher concentrations of Fe, K, Mg, Na, Rb, Se, and Zn than normal gastric mucosal tissues. However, multivariate analysis found that Fe, K, and Se were independent elements that associated with gastric cancer. Upon further evaluation of their clinical significance, we found a high tissue K level was related to lymphatic duct metastasis. High Se tissue levels were linked to intestinal type adenocarcinoma. A positive correlation was found between high Fe levels and vascular involvement. These findings suggest that Fe and K are associated with gastric cancer progression. Se is involved in carcinogenesis of stomach in high-risk areas. The mechanisms that underlie the corresponding pathohistological features deserve further study.     

Surgical Mortality, Survival, and Quality of Life after Resection for Gastric Cancer in the Elderly

Although there were some studies on clinicopathologic characteristics, operative morbidity, and mortality in elderly patients with gastric cancer, no reports have specifically focused on survival and quality of life after resection. A total of 433 patients aged ≥ 65 years (1987–1994) who underwent gastric resection for gastric adenocarcinoma were studied. Two groups were considered: patients aged 65 to 74 years and those > 74 years. Most of the patients (78.1%) had advanced diseases, and nearly half (41.3%) had associated chronic disease(s). Resections with curative intention were performed in 362 patients (83.6%). The overall operative morbidity rate was 21.7% and mortality rate 5.1%. Although operative procedures were similar in both groups, patients aged >74 years had a higher mortality rate than those aged 65 to 74 years (10.1% vs. 3.5%; p= 0.034). Age and extent of gastric resection were two independent factors negatively affecting mortality. The cumulative survival rates for patients who underwent curative resection were 86.2%, 72.4%, 67.2%, 62.9%, and 60.0% at 1, 2, 3, 4, and 5 years, respectively. Nearly all patients (96%) after surgery had normal work and daily activities. Some patients appeared to lack energy (16%) or experienced a period of anxiety or depression. There was no statistical difference in survival and quality of life assessed by the Spitzer index after curative resection between the two groups. Therefore resection with curative intention can be performed for the elderly with acceptable morbidity and mortality rates, possible long-term survival, and good quality of life, but a limited operation should be considered in the very elderly patients.