Effects of antihypertensive drugs on ultrasound production and cardiovascular responses in 15-day-old rats

When exposed to extreme cold or injected with the alpha(2)-adrenoceptor agonist, clonidine, infant rats emit ultrasonic vocalizations (USVs). Based upon the cardiovascular changes that accompany these two manipulations, especially decreased venous return, it was hypothesized that USVs are the acoustic by-product of the abdominal compression reaction (ACR), a maneuver that increases venous return. If this hypothesis is correct, then other anithypertensive drugs that decrease venous return should evoke USVs. In Experiment 1, sodium nitroprusside (SNP, 400 microg/kg), a direct-acting dilator of arteries and veins, was administered to 15-day-old rats under thermoneutral conditions while cardiac rate and ultrasound production were monitored. In Experiment 2, femoral artery pressure was monitored after SNP administration. Infants responded to SNP administration with decreased arterial pressure and tachycardia and, in addition, significantly increased ultrasound production. In Experiment 3, chlorisondamine (5 mg/kg), a ganglionic blocker that causes vasodilation and bradycardia, and hydralazine (20 mg/kg), a selective dilator of arteries, was administered to 15-day-olds. As predicted, chlorisondamine evoked ultrasound production and hydralazine did not. These results introduce SNP and chlorisondamine as only the second and third known agents capable of independently evoking USVs in thermoneutral conditions, and provide further support for the notion that ultrasound production is triggered by decreased venous return.     

Lower Extremity Injury While Undergoing Urology Procedures in the Trendelenburg with Lithotomy Position: Three Case Reports

PurposeTo report and discuss the incidence of severe lower extremity injuries associated with robotic procedures in Trendelenburg with lithotomy position.Design and MethodsA case study method was used to describe three cases of patients who underwent robotically assisted urological procedures in Trendelenburg with lithotomy position and developed serious lower extremities injuries resulting in fasciotomies. Furthermore, a literature review was conducted to evaluate risk factors and possible interventions for the prevention of similar injuries.FindingsCase analysis revealed multifactorial causes, including patient comorbidities, long surgical procedures, and blood pressure decreases below the baseline for more than 30 minutes. The severity of lower extremity injury associated with lithotomy position may be underestimated. The etiology of peripheral nerve injury can be attributed to patient comorbidities, positioning, and surgical conditions. Injury prevention should include careful patient and procedural risk assessment, staff education, and communication strategies.ConclusionsExtreme Trendelenburg with lithotomy position for longer periods can lead to serious lower extremities injuries. Preanesthetic screening and multidisciplinary team discussions for additional precautions for high-risk patients are crucial interventions to decrease incidence and severity of lower extremities injuries.     

Changes in cerebral oxygen saturation during transcatheter aortic valve replacement

Cerebral oxygen saturation (rSO₂) is a non-invasive monitor used to monitor cerebral oxygen balance and perfusion. Decreases in rSO₂ >20 % from baseline have been associated with cerebral ischemia and increased perioperative morbidity. During transcatheter aortic valve replacement (TAVR), hemodynamic manipulation with ventricular pacing up to 180 beats per minute is necessary for valve deployment. The magnitude and duration of rSO₂ change during this manipulation is unclear. In this small case series, changes in rSO₂ in patients undergoing TAVR are investigated. Ten ASA IV patients undergoing TAVR with general anesthesia at a university hospital were prospectively observed. Cerebral oximetry values were analyzed at four points: pre-procedure (baseline), after tracheal intubation, during valve deployment, and at procedure end. Baseline rSO₂ values were 54.5 ± 6.9 %. After induction of general anesthesia, rSO₂ increased to a mean of 66.0 ± 6.7 %. During valve deployment, the mean rSO₂ decreased <20 % below baseline to 48.5 ± 13.4 %. In two patients, rSO₂ decreased >20 % of baseline. Cerebral oxygenation returned to post-induction values in all patients 13 ± 10 min after valve deployment. At procedure end, the mean rSO₂ was 67.6 ± 8.1 %. As expected, rapid ventricular pacing resulting in the desired decrease in cardiac output during valve deployment was associated with a significant decrease in rSO₂ compared to post-induction values. However, despite increased post-induction values in all patients, whether related to increased inspired oxygen fraction or reduced cerebral oxygen consumption under anesthesia, two patients experienced a significant decrease in rSO₂ compared to baseline. Recovery to baseline was not immediate, and took up to 20 min in three patients. Furthermore, baseline rSO₂ in this population was at the lower limit of the published normal range. Significant cerebral desaturation during valve deployment may potentially be limited by maximizing rSO₂ after anesthetic induction. Future studies should attempt to correlate recovery in rSO₂ with recovery of hemodynamics and cardiac function, provide detailed neurological assessments pre and post procedure, determine the most effective method of maximizing rSO₂ prior to hemodynamic manipulation, and provide the most rapid method of recovery of rSO₂ following valve deployment.     

Isoelectronic perturbations to f-d-electron hybridization and the enhancement of hidden order in URu2Si2

Electrical resistivity measurements were performed on single crystals of URu_2–xOs_xSi₂ up to x = 0.28 under hydrostatic pressure up to P = 2 GPa. As the Os concentration, x, is increased, 1) the lattice expands, creating an effective negative chemical pressure P_ch(x); 2) the hidden-order (HO) phase is enhanced and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase; and 3) less external pressure P_c is required to induce the HO→LMAFM phase transition. We compare the behavior of the T(x, P) phase boundary reported here for the URu_2-xOs_xSi₂ system with previous reports of enhanced HO in URu₂Si₂ upon tuning with P or similarly in URu_2–xFe_xSi₂ upon tuning with positive P_ch(x). It is noteworthy that pressure, Fe substitution, and Os substitution are the only known perturbations that enhance the HO phase and induce the first-order transition to the LMAFM phase in URu₂Si₂. We present a scenario in which the application of pressure or the isoelectronic substitution of Fe and Os ions for Ru results in an increase in the hybridization of the U-5f-electron and transition metal d-electron states which leads to electronic instability in the paramagnetic phase and the concurrent formation of HO (and LMAFM) in URu₂Si₂. Calculations in the tight-binding approximation are included to determine the strength of hybridization between the U-5f-electron states and the d-electron states of Ru and its isoelectronic Fe and Os substituents in URu₂Si₂.

The heavy-fermion superconducting compound URu2Si2 is known for its second-order phase transition into the so-called “hidden-order” (HO) phase at a transition temperature T0 ≈17.5 K. Extensive investigation of the phase space in proximity to the HO phase transition has provided a detailed picture of the electronic and magnetic structure of this unique phase (1–42). However, more than three decades after the initial characterization of URu2Si2 (1–3), the order parameter for the HO phase is still unidentified.Most perturbations to the URu2Si2 compound have the effect of suppressing HO. The application of an external magnetic field (H) suppresses the HO phase (41, 43) and many of the chemical substitutions (x) at the U, Ru, or Si sites that have been explored significantly reduce T0, even at modest levels of substituent concentration (44–52). At present, only three perturbations are known to consistently enhance the HO phase in URu2Si2: 1) external pressure P, 2) isoelectronic substitution of Fe ions for Ru, and 3) isoelectronic substitution of Os ions for Ru. Upon applying pressure P, the HO phase in pure URu2Si2 is enhanced (6) and the system is driven toward a large-moment antiferromagnetic (LMAFM) phase (53). The HO→LMAFM phase transition is identified indirectly by a characteristic “kink” at a critical pressure Pc ≈1.5 GPa in the T0 (P) phase boundary (18, 53, 54) and also directly by neutron diffraction experiments, which reveal an increase in the magnetic moment from μ ∼ (0.03±0.02)μB/U in the HO phase to μ ∼ 0.4 μB/U in the LMAFM phase (13, 55, 56).Recent reports indicate that the isoelectronic substitution of Fe ions for Ru in URu2Si2 replicates the T0(P) behavior in URu2Si2 (57–59). An increase in x in URu2−xFexSi2 enhances the HO phase and drives the system toward the HO→LMAFM phase transition at a critical Fe concentration xc ≈0.15 (58, 60). The decrease in the volume of the unit cell due to substitution of smaller Fe ions for Ru may be interpreted as a chemical pressure, Pch, where the Fe concentration x can be converted to Pch (x) (57, 59). In addition, the induced HO→LMAFM phase transition in URu2−xFexSi2 occurs at combinations of x and P that consistently obey the additive relationship: Pch(x) + Pc ≈1.5 GPa (57, 59). These results have led to the suggestion that Pch is equivalent to P in affecting the HO and LMAFM phases (58, 59).Reports of the isoelectronic substitution of larger Os ions for Ru have shown that an increase in x in URu2−xOsxSi2 1) expands the volume of the unit cell, thus creating an effective negative chemical pressure (Pch ≤0); 2) enhances the HO phase; and 3) drives the system toward a similar HO→LMAFM phase transition at a critical Os concentration of xc ≈0.065 (60–62). These results are contrary to the expectation that a negative Pch would lead to a suppression of HO and complicate the view of chemical pressure as a mechanism affecting the evolution of phases in URu2Si2.In this paper, we report on the behavior of the T(x, P) boundary for the URu2−xOsxSi2 system based on ρ(T) measurements of single crystals of URu2−xOsxSi2 as a function of Os concentration x and applied pressure P. The T(x, P) phase boundary observed here for the URu2−xOsxSi2 system (57–59) is compared to that of the URu2−xFexSi2 system and also with the behavior of T(P) in pure URu2Si2. As an explanation for the enhancement of HO toward the HO→LMAFM phase transition, we suggest a scenario in which each of the perturbations of Os substitution, Fe substitution, and pressure P favors delocalization of the 5f electrons and increases the hybridization of the uranium 5f-electron and transition metal (Fe, Ru, Os) d-electron states. To avoid an ad hoc explanation of the effect of increasing the Os concentration x in URu2−xOsxSi2, compared to the effects of pressure P and Fe substitution, we explain how pressure P, Fe substitution, and Os substitution are three perturbative routes to enhancement of the U-5f- and d-electron hybridization. The importance of the 5f- and d-electron hybridization to the emergence of HO/LMAFM is presented in the context of the Fermi surface (FS) instability that leads to a reconstruction and partial gapping of the FS during the transition from the paramagnetic (PM) phase to the HO and LMAFM phases (2, 6, 20, 22, 24–26, 37, 38, 63).In an effort to further understand the effect of isoelectronic substitution on the 5f- and d-electron hybridization, calculations in the tight-binding approximation were made for compounds from the series UM2Si2 (M = Fe, Ru, and Os). The calculations indicate that the degree of hybridization is largely dependent on the magnitude of the difference between the binding energy of the localized U-5f electrons and that of the transition metal d electrons.     

Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study

INTRODUCTION: In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. METHODS: Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. RESULTS: Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). CONCLUSIONS: A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.     

Communication on end-of-life decisions with patients wishing to die at home: the making of a guideline for GPs in Flanders, Belgium

BACKGROUND: Communication with patients on end-of-life decisions is a delicate topic for which there is little guidance.AIM: To describe the development of a guideline for GPs on end-of-life communication with patients who wish to die at home, in a context where patient autonomy and euthanasia are legally regulated. DESIGN OF STUDY: A three-phase process (generation, elaboration and validation). In the generation phase, literature findings were structured and then prioritised in a focus group with GPs of a palliative care consultation network. In the elaboration phase, qualitative data on patients' and caregivers' perspectives were gathered through a focus group with next-of-kin, in-depth interviews with terminal patients, and four quality circle sessions with representatives of all constituencies. In the validation phase, the acceptability of the draft guideline was reviewed in bipolar focus groups (GPs-nurses and GPs-specialists). Finally, comments were solicited from experts by mail. SETTING: Primary home care in Belgium. SUBJECTS: Participants in this study were terminal patients (n = 17), next-of-kin of terminal patients (n = 17), GPs (n = 25), specialists (n = 3), nurses (n = 8), other caregivers (n = 2) and experts (n = 41). RESULTS: Caregivers and patients expressed a need for a comprehensive guideline on communication in end-of-life decisions. Four major communication themes were prioritised: truth telling; exploration of the patient's wishes regarding the end of life; dealing with disproportionate interventions; and dealing with requests for euthanasia in the terminal phase of life. Additional themes required special attention in the guideline: continuity of care by the GP; communication on foregoing food and fluid; and technical aspects of euthanasia. CONCLUSION: It was feasible to develop a guideline by combining the three cornerstones of evidence-based medicine: literature search, patient values and professional experience.     

Evidence-based assessment of attention deficit hyperactivity disorder in children and adolescents.

This article examines evidence-based assessment practices for attention deficit hyperactivity disorder (ADHD). The nature, symptoms, associated features, and comorbidity of ADHD are briefly described, followed by a selective review of the literature on the reliability and validity of ADHD assessment methods. It is concluded that symptom rating scales based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994), empirically and rationally derived ADHD rating scales, structured interviews, global impairment measures, and behavioral observations are evidence-based ADHD assessment methods. The most efficient assessment method is obtaining information through parent and teacher rating scales; both parent and teacher ratings are needed for clinical purposes. Brief, non-DSM based rating scales are highly correlated with DSM scales but are much more efficient and just as effective at diagnosing ADHD. No incremental validity or utility is conferred by structured interviews when parent and teacher ratings are utilized. Observational procedures are empirically valid but not practical for clinical use. However, individualized assessments of specific target behaviors approximate observations and have both validity and treatment utility. Measures of impairment that report functioning in key domains (peer, family, school) as well as globally have more treatment utility than nonspecific global measures of impairment. DSM diagnosis per se has not been demonstrated to have treatment utility, so the diagnostic phase of assessment should be completed with minimal time and expense so that resources can be focused on other aspects of assessment, particularly treatment planning. We argue that the main focus of assessment should be on target behavior selection, contextual factors, functional analyses, treatment planning, and outcome monitoring.     

Facioscapulohumeral muscular dystrophy: new insights from compound heterozygotes and implication for prenatal genetic counselling

Background Facioscapulohumeral muscular dystrophy (FSHD) is considered an autosomal dominant disease with a prevalence of 1 in 20?000. Almost all patients with FSHD carry deletions of integral copies of tandem 3.3 kb repeats (D4Z4) located on chromosome 4q35. However, FSHD families have been reported in which individuals carrying a D4Z4-reduced allele remain asymptomatic. Recently, it has been proposed that the D4Z4-reduced allele is pathogenic only in association with the permissive haplotype, 4APAS. Methods and results Through the Italian National Registry for FSHD (INRF), genotype-phenotype correlations were extensively studied in 11 non-consanguineous families in which two D4Z4-reduced alleles segregate. Overall, 68 subjects carrying D4Z4-reduced alleles were examined, including 15 compound heterozygotes. It was found that in four families the only FSHD-affected subject was the compound heterozygote for the D4Z4-reduced allele, and 52.6% of subjects carrying a single D4Z4-reduced 4A161PAS haplotype were non-penetrant carriers; moreover, the population frequency of the 4A161PAS haplotype associated with a D4Z4-reduced allele was found to be as high as 1.2%. Conclusions This study reveals a high frequency of compound heterozygotes in the Italian population and the presence of D4Z4-reduced alleles with the 4A161PAS pathogenic haplotype in the majority of non-penetrant subjects in FSHD families with compound heterozygosity. These data suggest that carriers of FSHD-sized alleles with 4A161PAS haplotype are more common in the general population than expected on the basis of FSHD prevalence. These findings challenge the notion that FSHD is a fully penetrant autosomal dominant disorder uniquely associated with the 4A161PAS haplotype, with relevant repercussions for genetic counselling and prenatal diagnosis.