Femoral Blood Research Articles

Oxycodone-Related Deaths: The Significance of Pharmacokinetic and Pharmacodynamic Drug Interactions.

Background and ObjectivesOxycodone is frequently prescribed as well as detected in postmortem cases. Concurrent use of pharmacodynamically or pharmacokinetically interacting drugs can cause adverse effects or even fatal intoxication. The aims of this study were to investigate differences in prescriptions for and toxicological findings of pharmacodynamically and pharmacokinetically interacting drugs in fatal oxycodone-related intoxications and other causes of death. We also aimed to investigate the differences in prevalence of oxycodone prescriptions, and the detected postmortem oxycodone concentrations between fatal oxycodone-related intoxications and other causes of death.MethodsForensic autopsy cases (2012–2018) where oxycodone was identified in femoral blood (n = 1236) were included. Medical history and prescription data were retrieved from national databases and linked to the forensic toxicology findings.ResultsOxycodone-related deaths were found to have higher blood concentrations of oxycodone (median 0.30 µg/g vs. 0.05 µg/g) and were less likely to have a prescription for oxycodone (OR 0.62) compared to nonintoxication deaths. Pharmacodynamically interacting drugs were prescribed in 79% and found in blood in 81% of the cases. Pharmacokinetically interacting drugs were rarely prescribed (1%). Oxycodone-related deaths were more likely to have prescriptions for a pharmacodynamically interacting drug (OR 1.7) and more often have co-findings of one or multiple pharmacodynamically interacting drugs (OR 5.6).ConclusionThe results suggest that combined use of oxycodone and pharmacodynamically interacting drugs is associated with oxycodone-related death and that non-medical use of oxycodone is a potential risk factor for oxycodone-related intoxication.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13318-021-00750-9.

Fatal Intoxication by the Novel Cathinone 4-Fluoro-3-methyl-α-PVP.

A 30 year old non-hispanic white male was found unresponsive at his workplace and admitted to the hospital in cardiac arrest. He was pronounced deceased shortly after arrival. At autopsy the pathologist noted a 176 pound, well-nourished, atraumatic, adult male with significant bilateral frothy pulmonary edema (right lung 930 g and left lung 1,130 g), cardiomegaly (430 g), dilated ventricles and slight cerebral edema. Upon completion of the systematic toxicological analysis scope for the Franklin County Coroner's Office Toxicology Laboratory, no known drugs were found. Further review of the gas chromatography--mass spectrometry (GC--MS) full-scan library summary reports showed an unknown peak in both the blood and urine solid phase extracts. An analogue of α-pyrrolidinovalerophenone (α-PVP) was identified, and a GC--MS selected ion monitoring method was developed to identify and quantitate the presence of 4-fluoro-3-methyl-α-PVP. This method quantified the drug at 26 ng/mL in gray top femoral blood, 30 ng/mL in purple top heart blood and 20 ng/mL in red top vitreous humor. Qualitative presence was also observed in the urine but was not detected in the liver. The decedent's cause of death was determined to be due to fluoro-methyl-PVP toxicity and the manner was ruled to be accidental. Investigational follow-up interviews corroborated drug use by the deceased with a preference of research chemicals and synthetic cannabinoids via the internet. No published literature is available currently, and to the author's knowledge this is the first incident of a fatal death solely attributed to this substituted cathinone.

Acute Citrulline Blunts Aortic Systolic Pressure during Exercise and Sympathoactivation in Hypertensive Postmenopausal Women.

Hypertensive postmenopausal women (PMW) have exaggerated exercise systolic blood pressure (SBP) due to impaired functional sympatholysis. l-Citrulline (CIT) supplementation attenuates aortic SBP responses to cold pressor test (CPT)-induced vasoconstriction in young men. We hypothesized that acute CIT ingestion would attenuate aortic SBP and leg hemodynamic responses during exercise and CPT (EX + CPT). Fifteen hypertensive PMW (61 ± 7 yr) were randomly assigned to consume either 6 g of CIT or placebo (PL) separated by a minimum 3-d washout phase. Brachial and aortic blood pressure, femoral artery blood flow (FBF), and vascular conductance (FVC) were measured at rest and during 5 min of unilateral plantarflexion exercise with a CPT applied during minutes 4 and 5. No differences between conditions were found in FBF, FVC, and brachial and aortic blood pressure at rest and during exercise alone. Changes in brachial SBP (CIT vs PL, 29 ± 12 vs 40 ± 10 mm Hg) and mean arterial pressure (CIT vs PL, 21 ± 10 vs 33 ± 11 mm Hg), and aortic SBP (CIT vs PL, 27 ± 11 vs 38 ± 9 mm Hg) and mean arterial pressure (CIT vs PL, 23 ± 9 vs 33 ± 11 mm Hg) to EX + CPT were lower in the CIT versus PL condition (P < 0.05). FBF, FVC, and functional sympatholysis (%ΔFVC) were not significantly different between conditions. Acute CIT ingestion attenuated aortic SBP response to exercise and cold-induced sympathetic activation that may prevent left ventricle overload in hypertensive PMW.

Application value of bedside ultrasound for assessing volume responsiveness in patients with septic shock

Background/Aim. Septic shock is a serious complication that can occur as consequence of infection. As the effective circulating blood volume is of vital importance in these cases, it is very important to keep track of this parameter constantly. The aim of this study was to explore the application value of bedside ultrasound for assessing volume responsiveness in patients with septic shock. Methods. A total of 102 patients with septic shock were selected. The volume load (VL) test was performed, and based on the results of the test, the patients were divided into the response group that had an increase in stroke volume (?SV ) ? 15% and non-response group (?SV &lt; 15%). Hemodynamic parameters were compared before and after the test. The correlation between ?SV and each hemodynamic index was explored by Pearson?s analysis. The receiver operating characteristic (ROC) curve was plotted. Results. There were 54 patients in response group and 48 patients in non-response group. Before VL test, retro-hepatic inferior vena cava (IVC) distensibility index (?IVC1), respiratory variation in IVC index (?IVC2), respiratory variation in aortic blood flow peak velocity index (?VpeakAO), respiratory variation in brachial artery blood flow peak velocity index (?VpeakBA) and respiratory variation in common femoral artery blood flow peak velocity index (?VpeakCFA) were all higher in response group than those in non-response group (p &lt; 0.05), while heart rate (HR), mean arterial pressure (MAP) and central venous pressure (CVP) were similar (p &gt; 0.05). After VL test, response group had significantly decreased HR, ?IVC1, ?IVC2, ?VpeakAO, ?VpeakBA and ?VpeakCFA, and increased MAP and CVP (p &lt; 0.05), while non-response group had significantly decreased CVP (p &lt; 0.05) and no significant changes in other indices. ?IVC1, ?IVC2, ?VpeakAO, ?VpeakBA and ?VpeakCFA significantly correlated with ?SV ( r= 0.589, r = 0.647, r = 0.697, r = 0.621, r = 0.766, p &lt; 0.05), but there was no correlation between CVP and ?SV (r = -0.345, p &gt; 0.05). The areas under the curves of ?IVC1, ?IVC2, ?VpeakAO, ?VpeakBA and ?VpeakCFA for predicting volume responsiveness were 0.839, 0.858, 0.878, 0.916 and 0.921, respectively, which were significantly larger than that of CVP (0.691), indicating higher sensitivity and specificity. Conclusion. Bedside ultrasound monitoring of ?IVC, ?VpeakAO, ?VpeakBA and ?VpeakCFA can better assess the volume responsiveness in patients with septic shock.

Savremeni tretman pacijenata sa karotidnom stenozom

Narrowing of the carotid arteries, carotid stenosis, (CS) is a frequent manifestation of atherosclerosis. It can be associated with other diseases of peripheral blood vessels, stenotic occlusive or aneurysmal, but also coronary arteries. Almost 15% of ischemic strokes are caused by this disease, which shares common risk factors with other atherosclerotic manifestations (age, male gender, hypertension, diabetes, smoking). The disease is progressive and with progression comes the progression of the degree of stenosis, the volume and morphological characteristics of the plaque. As these features progress, they increase the risk of clinical manifestations. Ischemic stroke, transient ischemic attack or transient blindness in the ipsilateral eye (amaurosis fugax) are the only clinical manifestations that can be directly related to carotid stenosis. Ischemic changes in the brain parenchyma, which can be seen on magnetic resonance imaging or computed tomography, are also associated with carotid stenosis. All the mentioned parameters are taken into account when making decisions about further treatment. Available drug therapy includes antiplatelet and statin therapy with control of risk factors (body weight correction, smoking cessation) and associated diseases (hypertension, diabetes, etc.). Invasive treatment includes carotid endarterectomy (CEA) as vascular or carotid stenting (CAS) as endovascular treatment. KEA is performed under local or general anesthesia, increasingly under local anesthesia, and after accessing the carotid arteries through a cervicotomy, they are clamped, the flow is interrupted, and after the artery is opened, plaque removal and endarterectomy are performed. In addition to the anesthesiological management of the patient and the performance of the surgical technique, the monitoring of cerebral perfusion during clamping is an important technical detail in these operations. KAS is performed through a percutaneous transfemoral approach under local anesthesia when a stent is implanted in the carotid artery at the site of the carotid stenosis. To perform this procedure, adequate access is required in terms of the quality of the femoral and iliac blood vessels, i.e. the aortic arch. KAS was introduced into practice much later, and in the last 20 years, there has been a significant improvement both in terms of performance and technology with the development of modern stents and the materials used in their installation. A special contribution to this technique was the introduction of embolization protection. KAS is a complementary method to CEA and an individual approach to the patient enables the choice of method, taking into account the advantages and disadvantages of one and the other method. When it comes to symptomatic patients, CEA certainly has a significantly greater advantage and when the use of CAS should be avoided. Complications of both methods are general, local and neurological, with the latter being the most important. Current recommendations state that performing these procedures is beneficial for the patient if the risk of neurological complications is less than 3% in asymptomatic patients, or less than 6% in symptomatic patients. At the Clinic for Vascular and Univascular Surgery of the Clinical Center of Serbia, in the last fifteen years, almost 9.000 procedures have been performed due to carotid stenosis, of which about 10% (960) were CAS. We opt for this method in patients who are at cardiorespiratory risk for CEA or in whom access to the carotid bifurcation is difficult. All, the CEA procedures are performed under conditions of the cervical block. The improvement of patient stratification and the use of artificial intelligence should in the future help doctors decide on the method of examination and treatment of these patients.

Informativeness of clinical and laboratory tests for the diagnosis of chronic renal failure in small animals

The study of the clinical and functional state of the kidneys revealed some aspects of the etiology, pathogenesis and diagnosis of chronic renal failure in dogs and cats. The course of the disease in animals at the beginning of the pathology was characterized by polyuria and polydipsia, then – oliguria and anuria, apathy, cachexia, dehydration, ulcers on the gums, salivation, bad breath, dull hair, debilitating vomiting (50% of cases), constipation or diarrhea. Sick animals were diagnosed with tachycardia with increased pulsation of the internal femoral artery and blood pressure from 150/100 to 180/100 mm Hg. art., signs of uremic pneumonia and pulmonary edema. Clinical and laboratory studies have shown that oliguria and anuria in 15 % of studied animals are accompanied by hypothermia up to 35.8 °C, pain in the kidneys, nephromegaly. In the study of urine and blood of animals with CRF, iso- and hypostenuria, proteinuria – in 85 %, glucosuria – in 15 %, hematuria – in 20 %, normochromic anemia. It has been found that the determination of microalbumins in urine is more informative than the determination of proteins, because their appearance precedes the appearance of protein in the urine, which can be considered a diagnostic test for this pathology. It has been proven that in chronic renal failure in dogs and cats develops a pronounced uremic syndrome, accompanied by clinical signs of intoxication – vomiting and hyperazotemia due to increased serum creatinine (up to 574.7 ± 62.5 μmol/l) and urea (37.8 ± 7.94 mmol/l), indicating the development of severe destructive processes in the kidneys. The terminal stages of renal failure are characterized by severe circulatory disorders with myocardial dysfunction and hypertension, progressive anemia. We associate the development of arterial hypertension with the formation of vasoconstrictor – angiotensin II, which can affect the systemic circulation through the defeat of the glomeruli of the renal corpuscles and proximal tubules. Suppression of erythropoietin production results in anemia, which we also associate with hematuria and bone marrow suppression by nitrogen-containing blood compounds.

Using noninvasive adjusted pulse transit time for tracking beat-to-beat systolic blood pressure during ventricular arrhythmia.

Tracking beat-to-beat blood pressure noninvasively during ventricular arrhythmia (VA) is of great importance but rarely reported. The goal of our study was to investigate the potential utility of the adjusted pulse transit time (APTT) to track beat-to-beat femoral systolic blood pressure (SBP) during VA. Patients who underwent radiofrequency ablation for arrhythmias at Fuwai Hospital were enrolled. Electrocardiograms (ECGs), finger photoplethysmograms, and femoral arterial blood pressure were recorded simultaneously during VA. The APTT was calculated as the ratio between the square of the conventional pulse transit time (cPTT) and the RR interval of the ECG waveform. Forty-five patients were enrolled in our study, and 22,849 beats were collected during their VA. The inverse of the APTT showed a good correlation with femoral SBP during VA (r = 0.70 ± 0.18). The APTT-derived SBP demonstrated acceptable accuracy in terms of the mean difference ± standard deviation (-0.01 ± 10.54 mmHg) from the invasive femoral SBP. The area under the receiver operating characteristic (ROC) curve for the ability of the APTT to detect ≥30% decreases in femoral SBP was 0.903 (95% confidential interval, 0.895-0.911). In addition, the APTT performed better than the cPTT and RR interval in the above analysis (all P < 0.05). Therefore, the APTT has acceptable accuracy in tracking beat-to-beat femoral SBP and could detect substantially decreased femoral SBP. These findings indicate that the APTT may be a promising noninvasive surrogate for invasive femoral SBP during VA. A multiparameter model combining APTT and other parameters is needed to further improve the accuracy.

Surgical hip dislocation for treatment of femoral head chondroblastoma: efficacy and safety.

Femoral head chondroblastoma poses a surgical challenge. Anatomical limitations may lead to increased risk of local recurrence, damage to the articular cartilage, growth disturbances, and/or avascular necrosis (AVN). We are presenting our results with surgical hip dislocation approach with the aim to evaluate its efficacy in preventing recurrence and its safety, preserving a functional hip joint and avoiding complications. Ten patients were managed using surgical hip dislocation with direct access to femoral head lesions, extended curettage through a modified trapdoor approach, and cement reconstruction. These were six males and four females, with a mean age of 17 ± 2.7years (range: 14-20) and a mean follow-up of 34 ± 12months (range: 17-57). The lesion extended into the neck in 60% of patients with the physis being either closed in seven or closing in three patients. We had a single case (10%) of recurrence at the trochanters for which re-curettage was done. However, all patients had their hips preserved with good function at the latest follow-up, and no serious complications recorded. The Musculoskeletal Tumor Society score improved significantly from a pre-operative median of 23.5 (range: 16-28) to a post-operative median of 29 (range: 26-30) (P = 0.005). This report describes a safe reproducible approach to effectively manage these locally aggressive lesions with good short-term results. This is done while maintaining the integrity of the articular surface, growth plate, as well as preserving the femoral head blood supply.

Twelve-Week Daily Gluteal and Hamstring Electrical Stimulation Improves Vascular Structure and Function, Limb Volume, and Sitting Pressure in Spinal Cord Injury: A Pilot Feasibility Study.

We examined the long-term effects of low-intensity electrical stimulation on (micro)vasculature and sitting pressure of a home-based, wearable electrical stimulation device in a pilot feasibility study. In a cohort observation before-after trial, nine middle-aged male (n = 8) and female (n = 1) individuals (48 ± 15 yrs) with American Spinal Injury Association A-C classified chronic (1-24 yrs) spinal cord injury underwent 12 wks of self-administered daily, low-intensity gluteal and hamstring electrical stimulation (50 Hz, 6 hrs [30-min electrical stimulation, 15-min rest]). Common femoral artery diameter and blood blow were determined with ultrasound, skin vascular function during local heating was assessed using Laser-Doppler flowmetry, thigh volume was estimated using leg circumferences and skinfolds, and interface sitting pressure was measured using pressure mapping. Resting common femoral artery diameter increased (0.73 ± 0.20 to 0.79 ± 0.22 cm, P < 0.001) and baseline common femoral artery blood flow increased (0.28 ± 0.12 to 0.40 ± 0.15 l/min, P < 0.002). Gluteal cutaneous vascular conductance showed a time*temperature interaction (P = 0.01) with higher conductance at 42°C after 12 wks. Ischial peak pressure decreased (P = 0.003) by 32 ± 23 mm Hg and pressure gradient decreased (23 ± 7 to 16 ± 6 mm Hg, P = 0.007). Thigh volume increased (+19%, P = 0.01). Twelve-week daily home-based gluteal and hamstring electrical stimulation is feasible and effective to improve (micro)vasculature and sitting pressure, and electrical stimulation may have clinical implications for ameliorating pressure ulcers and (micro)vascular complications in spinal cord injury.

Postmortem redistribution of morphine in humans: Important variables that might be influencing the central blood/peripheral blood ratio

IntroductionIn the field of forensic toxicology, many unexpected deaths are investigated as to whether toxicological substances may have caused or contributed to someone’s death. One of the factors that makes interpretation of the results of quantitative analysis in postmortem toxicology challenging, is that measured postmortem drugs levels may vary according to the sampling site and the interval between death and specimen collection. These site- and time-dependent variations are caused by ‘postmortem redistribution’ (PMR). Literature shows that there are several factors that determine the degree of PMR, such as cell and tissue changes after death, decomposition and the physicochemical characteristics of drugs. Blood from peripheral sites seems to be less affected by PMR than cardiac blood. Therefore, the ratio of cardiac blood concentration/peripheral blood concentration (C/P) of a drug is often used as a marker of the extent of postmortem redistribution. In this study, we investigated the relationship between different potentially important variables and the C/P ratio of morphine in humans in order to provide new insights that might assist in the interpretation of quantitative results in forensic casework. MethodToxicological results of all morphine positive postmortem cases investigated by the Netherlands Forensic Institute between January 1, 2010 and July 31, 2020 were reviewed. Morphine was quantified in both femoral and cardiac blood in a total of 103 cases. The C/P ratios were determined for all selected cases. To collect data for this study, all corresponding files were reviewed. C/P ratios were compared between subgroups by performing either a Mann-Whitney U test or a Kruskal-Wallis test, followed by a post-hoc Mann-Whitney U test. Bonferroni correction was performed to correct for the likelihood of a significant result by chance due to multiple testing. After Bonferroni correction, a p-value< 0.004 was considered statistically significant. ResultsThe data suggests a relationship between grade of decomposition at autopsy, position of the corpse at discovery, route of administration, attempted resuscitation and the C/P ratio of morphine with p-values of 0.010, 0.026, 0.035 and 0.046, respectively. ConclusionGrade of decomposition at autopsy, position of the corpse at discovery, route of administration and attempted resuscitation seem to be influencing the C/P ratio of morphine. Of these four variables, the route of administration seems to have the greatest impact.

Sex differences in muscle excitation and oxygenation, but not in force fluctuations or active hyperemia resulting from a fatiguing, bilateral isometric task

It remains to be fully elucidated if there are sex-specific physiological adjustments within the human neuromuscular and vascular systems that contribute to symptoms of fatigue during a sustained bilateral task. This, in part, is likely due to various limitations in experimental design such as an inability to independently record force fluctuations from each limb. Objective. Therefore, the purpose of the current study was to examine the fatigue-induced changes in muscle excitation, force fluctuations, skeletal muscle tissue saturation (StO2), and muscle blood flow resulting from a sustained, bilateral task. Approach. Thirty healthy, college-aged adults (15 males, 15 females) performed a bilateral leg task at 25% of maximum voluntary isometric (MVIC). Before and after the task, MVICs were completed. Resting and post-task femoral artery blood flow (FABF) were determined. Muscle excitation was quantified as electromyographic amplitude (EMG AMP) from the right and left vastus lateralis. During the task, force fluctuations were determined independently from each leg. The StO2 signal was collected with a near-infrared spectroscopy device attached to the right vastus lateralis. The rate of change in these variables was calculated via simple linear regression. The exercise-induced magnitude of change in MVIC (i.e. performance fatigability) and FABF (i.e. active hyperemia) was determined. Main Results. There was no sex difference in the percent decline in MVIC (20.5 ± 20.1% versus 16.4 ± 3.5%; p > 0.05). There were no inter-leg differences in EMG AMP or force fluctuations. The males exhibited a faster rate of increase in EMG AMP (b = 0.13 versus b = 0.08; p < 0.001), whereas the females exhibited a slower rate of decline in StO2 (b = −0.049 versus b = −0.080). There was no sex difference in force fluctuations or change in FABF. Significance. Males and females likely have different neuromuscular strategies and muscle characteristics, but these did not elicit a sex difference in performance fatigability.

Noninvasive Biomarkers for Cardiovascular Dysfunction Programmed in Male Offspring of Adverse Pregnancy.

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Hemodynamic Effect of Resuscitative Endovascular Balloon Occlusion of the Aorta in Hemodynamic Instability Secondary to Acute Cardiac Tamponade in a Porcine Model.

The pre-hospital use of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is increasing, although it remains controversial, in part because of suggested contraindications such as acute cardiac tamponade (ACT). As both the pre-hospital and in-hospital use of REBOA might potentially occur with concurrent ACT, knowledge of the hemodynamic effect of REBOA in this setting is crucial. This study, therefore, aimed at investigating the physiological effects of REBOA in hemodynamic instability secondary to ACT in a porcine model. We hypothesize that REBOA can temporarily increase systemic blood pressure and carotid blood flow, and prolong survival, in hemodynamic shock caused by ACT. Fourteen pigs (24-38 kg) underwent ACT, through true cardiac injury and hemorrhage into the pericardial space, and were allowed to hemodynamically deteriorate. At a systolic blood pressure (SBP) of 50 mm Hg (SBP50) they were randomized to total occlusion REBOA in zone 1 or to a control group. Survival, hemodynamic parameters, carotid blood flow (CBF), femoral blood flow (FBF), cardiac output (CO), end-tidal CO2, and arterial blood gas parameters were analyzed. REBOA intervention was associated with a significant increase in SBP (50 mm Hg to 74 mm Hg, P = 0.016) and CBF (110 mL/min to 195 mL/min, P = 0.031), with no change in CO, compared to the control group. At 20 min after SBP50, the survival rate in the intervention group was 86% and in the control group 14%, with time to death being significantly longer in the intervention group. This randomized animal study demonstrates that REBOA can help provide hemodynamic stabilization and prolong survival in hemodynamic shock provoked by ACT. It is important to stress that our study does not change the fact that urgent pericardiocentesis or cardiac surgery is, and should remain, the standard optimal treatment for ACT.Level of evidence: Prospective, randomized, experimental animal study. Basic science study, therapeutic.

Quantitative analysis of distal femoral epiphysis blood supply in healthy infants with superb microvascular imaging: a pilot study

This study aimed to determine the blood supply of the distal femoral epiphysis (DFE) using superb microvascular imaging in newborns and infants, and to investigate the correlation with ossification center (OC) length, sex, and age. A total of 140 cases were evaluated in this study. The cases were divided into 2 groups of less than 90 days and over 90 days. Cartilage blood supply was measured with vascularity index (%) (VI). The mean OC length and median VI values were measured as 10.20 ± 3.72 mm and 0.80% (0.58–1.50) for boys and 10.03 ± 3.36 mm and 0.70% (0.30–1.40) for girls, respectively. There was no significant difference in OC length and VI between sexes. The mean OC length in Group II was significantly higher than in Group I (12.14 ± 3.14 vs 8.09 ± 2.64) (p < 0.001). The median VI in Group I was higher than in Group II (1.40% vs 0.40%) (p < 0.001). There were positive correlations between age and OC length (r = 0 .716), negative correlations between age and VI (r = –0.822), and between VI and OC length (r = –0.657). Quantitative reference values for DFE blood supply and OC length can guide the diagnosis and follow-up of many skeletal diseases.

Intra-rater reliability of leg blood flow during dynamic exercise using Doppler ultrasound.

Developing an exercise model that resembles a traditional form of aerobic exercise and facilitates a complete simultaneous assessment of multiple parameters within the oxygen cascade is critically for understanding exercise intolerances in diseased populations. Measurement of muscle blood flow is a crucial component of such a model and previous studies have used invasive procedures to determine blood flow kinetics; however, this may not be appropriate in certain populations. Furthermore, current models utilizing Doppler ultrasound use isolated limb exercise and while these studies have provided useful data, the exercise model does not mimic the whole‐body physiological response to continuous dynamic exercise. Therefore, we aimed to measure common femoral artery blood flow using Doppler ultrasound during continuous dynamic stepping exercise performed at three independent workloads to assess the within day and between‐day reliability for such an exercise modality. We report a within‐session coefficient of variation of 5.8% from three combined workloads and a between‐day coefficient of variation of 12.7%. These values demonstrate acceptable measurement accuracy and support our intention of utilizing this noninvasive exercise model for an integrative assessment of the whole‐body physiological response to exercise in a range of populations.

Insights of posture dependent pressure characteristics in five rats

Abstract Current shunt treatments of hydrocephalus, a condition characterized by excessive accumulation of cerebrospinal fluid (CSF) and intracranial pressure (ICP) fluctuations, suffer malfunctions caused by changes in patient’s posture. Research toward a quantitative model describing posture dependent dynamics of CSF related pressures such as ICP and blood pressure (BP) shall provide relevant information that can lead to a better understanding of CSF dynamics and thus, improved treatment outcomes. In this pilot study, ICP and femoral blood pressure (FBP) were measured concurrently in anaesthetized as well as awake and freely moving rats using radio telemetry. It was shown that despite the inherent challenges of limited space for sensor implants and rapid movements leading to strong artefacts, influences on CSF related pressure fluctuations due to posture changes can be observed in individual rats

Postmortem Metabolomics: Strategies to Assess Time-Dependent Postmortem Changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

Postmortem redistribution (PMR) can result in artificial drug concentration changes following death and complicate forensic case interpretation. Currently, no accurate methods for PMR prediction exist. Hence, alternative strategies were developed investigating the time-dependent postmortem behavior of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram. For 477 authentic postmortem cases, femoral blood samples were collected at two postmortem time-points. All samples were quantified for drugs of abuse (targeted; liquid chromatography-tandem mass spectrometry LC-MS/MS) and characterized for small endogenous molecules (untargeted; gas chromatography-high resolution MS (GC-HRMS). Trends for significant time-dependent concentration decreases (diazepam (n = 137), nordiazepam (n = 126)), increases (mirtazapine (n = 55), citalopram (n = 50)) or minimal median postmortem changes (morphine (n = 122), codeine (n = 92)) could be observed. Robust mathematical mixed effect models were created for the generalized postmortem behavior of diazepam and nordiazepam, which could be used to back-calculate drug concentrations towards a time-point closer to the estimated time of death (caution: inter-individual variability). Significant correlations between time-dependent concentration changes of morphine, mirtazapine and citalopram with individual endogenous molecules could be determined; no correlation was deemed strong enough for successful a posteriori estimation on the occurrence of PMR for specific cases. The current dataset did successfully lead to a significant knowledge gain in further understanding the time-dependent postmortem behavior of the studied drugs (of abuse).

Evidence that Neuromuscular Fatigue Is not a Dogma in Patients with Parkinson's Disease.

Given the increased level of fatigue frequently reported by patients with Parkinson's disease (PD), this study investigated the interaction between central and peripheral components of neuromuscular fatigue (NF) in this population compared with healthy peers. Changes in maximal voluntary activation (ΔVA, central fatigue) and potentiated twitch force (ΔQtw,pot, peripheral fatigue) pre-post exercise were determined via the interpolated twitch technique in 10 patients with PD and 10 healthy controls (CTRL) matched for age, sex, and physical activity. Pulmonary gas exchange, femoral blood flow, and quadriceps EMG were measured during a fatiguing exercise (85% of peak power output [PPO]). For a specific comparison, on another day, CTRL repeat the fatiguing test matching the time to failure (TTF) and PPO of PD. At 85% of PPO (PD, 21 ± 7 W; CTRL, 37 ± 22 W), both groups have similar TTF (~5.9 min), pulmonary gas exchange, femoral blood flow, and EMG. After this exercise, the maximal voluntary contraction (MVC) force and Qtwpot decreased equally in both groups (-16%, P = 0.483; -43%, P = 0.932), whereas VA decreased in PD compared with CTRL (-3.8% vs -1.1%, P = 0.040). At the same PPO and TTF of PD (21 W; 5.4 min), CTRL showed a constant drop in MVC, and Qtwpot (-14%, P = 0.854; -39%, P = 0.540), instead VA decreased more in PD than in CTRL (-3.8% vs -0.7%, P = 0.028). In PD, central NF seems exacerbated by the fatiguing task which, however, does not alter peripheral fatigue. This, besides the TTF like CTRL, suggests that physical activity may limit NF and counterbalance PD-induced degeneration through peripheral adaptations.

Testing for Trenbolone, an Anabolic Steroid, in Biological Fluids and Head Hair in a Post-Mortem Case.

A 60-year-old man was found dead at home by his wife. The man was known to be a regular trainer in a fitness center and was described as a long-term user of anabolic steroids. The autopsy revealed heart failure with a cardiomegaly, a visceral congestion and a pulmonary edema. The local prosecutor ordered toxicological analyses but no anatomic pathology test. Initial analyses by UPLC-q-TOF-MS system indicated the presence in femoral blood of trenbolone, an anabolic steroid. Trenbolone was quantified with a liquid chromatography system coupled with a tandem mass spectrometer in various autopsy specimens, including hair. Concentrations of trenbolone were 3.9, 3.2, 231 and lower than 0.5 ng/mL in femoral blood, cardiac blood, bile and vitreous humor, respectively. Moreover, in head hair the concentration was 9 pg/mg. The presence of trenbolone in hair can be interpreted as repetitive exposures when compared to the limited literature data. Repetitive misuse of trenbolone can explain the advanced heart failure. This paper highlights the importance to test biological specimens for anabolic steroids in case of heart failure.

Sex- and Age-Related Physiological Profiles for Brachial, Vertebral, Carotid, and Femoral Arteries Blood Flow Velocity Parameters During Growth and Aging (4–76 Years): Comparison With Clinical Cut-Off Levels

Ultrasound-derived blood flow velocity (BFV) levels [e.g., peak systolic velocity (PSV)], intrabeat indexes (e.g., resistive), and intersegment ratios [e.g., internal/common carotid artery (ICA/CCA) PSV ratio] are assessed to describe cardiovascular physiology and health status (e.g., disease severity evaluation and/or risk stratification). In this respect, fixed cut-off values (disregard of age or sex) have been proposed to define “significant” vascular disease from BFV-derived data (parameters). However, the use of single fixed cut-off values has limitations. Accurate use of BFV-derived parameters requires knowing their physiological age-related profiles and the expected values for a specific subject. To our knowledge, there are no studies that have characterized BFV profiles in large populations taking into account: (i) data from different age-stages (as a continuous) and transitions (childhood–adolescence–adulthood), (ii) complementary parameters, (iii) data from different arteries, and (iv) potential sex- and hemibody-related differences. Furthermore, (v) there is little information regarding normative data [reference intervals (RIs)] for BFV indexes.Aims: The aims of this study are the following: (a) to determine the need for age-, body side-, and sex-specific profiles for BFV levels and derived parameters (intrabeat indexes and intersegment ratios), and (b) to define RIs for BFV levels and parameters, obtained from CCA, ICA, external carotid, vertebral, femoral, and brachial arteries records.Methods: A total of 3,619 subjects (3–90 years) were included; 1,152 were healthy (without cardiovascular disease and atheroma plaques) and non-exposed to cardiovascular risk factors. BFV data were acquired. The agreement between left and right data was analyzed (Concordance correlation, Bland–Altman). Mean and SD equations and age-related profiles were obtained for BFV levels and parameters (regression methods; fractional polynomials).Results: Left and right body-side derived data were not always equivalent. The need for sex-specific RIs was dependent on the parameter and/or age considered. RIs were defined for each studied artery and parameter. Percentile curves were compared with recommended fixed cut-off points. The equations for sex, body-side, and age-specific BFV physiological profiles obtained in the large population (of children, adolescents, and adults) studied were included (spreadsheet formats), enabling to determine for a particular subject, the expected values and potential data deviations.