Successful coronary angiography with adequate image acquisition using a combination of gadolinium and a power injector in a patient with severe iodine contrast allergy

A history of severe allergic reaction to iodine contrast leading to anaphylactic shock presents a dilemma in patients requiring cardiac catheterization. As an alternative, gadolinium has been an interesting and potentially useful agent. However, gadolinium produces poor image quality and has been associated with significant arrhythmias in small case series. Furthermore, there is no consensus about the maximal allowable dose that can be administered to a patient. In the present report, a successful combination of gadolinium contrast with a power injector that produced adequate image quality in a patient with severe allergy to iodine contrast is described. The case was complicated by the occurrence of ventricular fibrillation when damping occurred during injection of contrast into the right coronary artery. This complication has been reported previously with intracoronary gadolinium injection. The report is followed by a brief literature review.     

Bromuconazole-induced hepatotoxicity is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1 gene expression

Despite widespread use of bromuconazole as a pesticide for food crops and fruits, limited studies have been done to evaluate its toxic effects. Here, we evaluated the hepatotoxic effect of bromuconazole using classical toxicological (biochemical analysis and histopathological examination) and gene-based molecular methods. Male rats were treated either orally or topically with bromuconazole at doses equal to no observed adverse effect level (NOAEL) and 1/10 LD50 for 90?d. Bromuconazole increased activities of liver enzymes (ALT, AST, ALP, and ACP), and levels of bilirubin. It also induced hepatic oxidative stress as evidenced by significant decrease in the activities of superoxide dismutase (SOD), and significant increase in levels of malondialdehyde (MDA) in liver. In addition, bromuconazole caused an increase in liver weights and necrobiotic changes (vacuolation and hepatocellular hypertrophy). It also strongly induced the expression of PXR and its downstream target CYP3A1 gene as well as the activity of CYP3A1. However, it inhibited the expression of CAR and its downstream target CYP2B1 gene without significant changing in CYP2B1 activity. Overall, the oral route showed higher hepatotoxic effect and molecular changes than the dermal route and all changes were dose dependent. This is the first investigation to report that bromuconazole-induced liver oxidative damage is accompanied by upregulation of PXR/CYP3A1 and downregulation of CAR/CYP2B1.     

Impact of Spinal Manipulation on Lower Extremity Motor Control in Lumbar Spinal Stenosis Patients: A Small-Scale Assessor-Blind Randomized Clinical Trial

ObjectiveThe purpose of this study was to quantify the impact of a single lumbar spinal manipulation (SM) intervention on the leg movement performance of degenerative lumbar spinal stenosis (LSS) patients in a small-scale registered randomized clinical trial.MethodsParticipants with LSS (n = 14) were tested at baseline for pain, lumbar range of motion, and behavioral or kinematic motor performance (using an established Fitts’ Law foot-pointing task), then underwent covariate adaptive randomization to receive SM or no intervention. Postintervention all dependent measures were repeated. Experimenters were blinded to patient group allocation. University ethics board approval was attained.ResultsFor the primary outcome movement time, there was no significant difference between groups. As predicted by Fitts’ Law, all participants had longer movement times as task difficulty increased. Secondary kinematic outcomes yielded no significant between-group differences. Consistent with Fitts’ Law, kinematic measures changed significantly with task difficulty. Pairwise comparisons revealed the kinematic variables were more adversely affected by greater movement amplitudes than target size changes. No exploratory differences in pain or lumbar range of motion were observed.ConclusionChanges in motor performance were not observed in this chronic pain population after a single SM intervention compared with a control group. Given the sample size, the study may have been underpowered to detect meaningful differences. Fitts’ Law was observed for the lower extremity–pointing task for an LSS population and may provide an objective measure of motor performance.     

Biosimilars in rheumatology: recommendations for regulation and use in Middle Eastern countries

The increasing availability of biosimilar medicines in Middle Eastern regions may provide an opportunity to increase the number of rheumatology patients who have access to traditionally more expensive biologic medicines. However, as well as a lack of real-world data on the use of biosimilar medicines in practice, the availability of intended copies in the region may undermine physician confidence in prescribing legitimate biosimilar medicines. There is a need for regional recommendations for healthcare professionals to ensure that biosimilar drugs can be used safely. Therefore, a literature search was performed with the aim of providing important recommendations for the regulation and use of biosimilar medicines in the Middle East from key opinion leaders in rheumatology from the region. These recommendations focus on improving the availability of relevant real-world data, ensuring that physicians are aware of the difference between intended copies and true biosimilars and ensuring that physicians are responsible for making any prescribing and switching decisions.     

Anabolic androgenic steroid induced necrotising myopathy

We describe the case of a 23-year-old gentleman who developed a severe generalised necrotising myopathy. Initially presenting with features of a virus-induced polymyositis, both symptomatic and biochemical improvements were initially achieved with glucocorticoid-based immunosuppression. Subsequently he represented with evidence of severe generalised rhabdomyolysis (creatinine kinase peaking at 210,000 U/L). Rendered anuric from the myogloburic assault, he required intensive care support from the development of multi-organ failure. Subsequent investigations failed to demonstrate an infective, inflammatory, metabolic or inherited aetiology. Muscle biopsy demonstrated severe generalised necrotising myopathy in the notable absence of inflammation. Confidential discussion with the patient and relatives confirmed a suspicion of anabolic androgenic steroid (AAS) abuse. There is limited literature as to the toxic effect of AAS compounds on muscle tissue, and these tend to focus on localised disease. Indeed, AAS have consistently been shown in animal models to produce a generalised myotrophic state. Apart from the social uses of such compounds, the scope for their supervised use in various medical conditions has been established since the 1960s.     

Yohimbine Depresses Excitatory Transmission in BNST and Impairs Extinction of Cocaine Place Preference Through Orexin-Dependent,Norepinephrine-Independent Processes

The alpha2 adrenergic receptor (α₂-AR) antagonist yohimbine is a widely used tool for the study of anxiogenesis and stress-induced drug-seeking behavior. We previously demonstrated that yohimbine paradoxically depresses excitatory transmission in the bed nucleus of the stria terminalis (BNST), a region critical to the integration of stress and reward pathways, and produces an impairment of extinction of cocaine-conditioned place preference (cocaine-CPP) independent of α₂-AR signaling. Recent studies show yohimbine-induced drug-seeking behavior is attenuated by orexin receptor 1 (OX₁R) antagonists. Moreover, yohimbine-induced cocaine-seeking behavior is BNST-dependent. Here, we investigated yohimbine-orexin interactions. Our results demonstrate yohimbine-induced depression of excitatory transmission in the BNST is unaffected by alpha1-AR and corticotropin-releasing factor receptor-1 (CRFR₁) antagonists, but is (1) blocked by OxR antagonists and (2) absent in brain slices from orexin knockout mice. Although the actions of yohimbine were not mimicked by the norepinephrine transporter blocker reboxetine, they were by exogenously applied orexin A. We find that, as with yohimbine, orexin A depression of excitatory transmission in BNST is OX₁R–dependent. Finally, we find these ex vivo effects are paralleled in vivo, as yohimbine-induced impairment of cocaine-CPP extinction is blocked by a systemically administered OX₁R antagonist. These data highlight a new mechanism for orexin on excitatory anxiety circuits and demonstrate that some of the actions of yohimbine may be directly dependent upon orexin signaling and independent of norepinephrine and CRF in the BNST.     

Differences in mean and variability of heart rate and ambulatory rate-pressure product when valsartan or carvedilol is added to lisinopril

Guidelines recommend combining β-blockers and angiotensin-converting enzyme (ACE) inhibitors in high-risk heart disease but not in the initial treatment of hypertension. The mechanism of this benefit has not been determined. After 3 weeks of lisinopril (L, 40 mg/day) run-in, 30 subjects entered a single-blinded, forced-titration, crossover study in which carvedilol (C, 20 then 40 mg/day) or a control renin-angiotensin blocker, valsartan (V, 160 then 320 mg/day) were added to L. Ambulatory blood pressure (ABP) and heart rate monitoring was performed at the end of each period. Rate-pressure product (RPP, systolic BP × heart rate, an indicator of cardiac oxygen consumption) was measured over 24 hours, daytime (6 am to midnight), and nighttime (midnight to 6 am) periods. Variability (standard deviation and range) of RPP, BP, and heart rate was also investigated. After 4 weeks, mean 24-hour systolic BP was about 8 mm Hg lower when either V or C was added to L (P < .01 each). Heart rate was consistently lower with C (8 beats/min over 24 hours, P < .000) but was slightly increased with V (about 2 beats/min, P = NS). Consequently, C lowered RPP to a greater degree than V over 24 hours (about 8% vs. 2%, P < .000) and during daytime and nighttime periods (P < .000 each). In addition, RPP variability (SD but not range) was consistently lower on C than V. When added to L, C reduces the mean and variability (SD) of 24-hour heart rate and cardiac workload to a greater degree than valsartan. These effects may contribute to the outcome benefits observed with β-blocker–ACE inhibitor combinations.