Cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy, a randomized controlled trial (CAPTURE) protocol.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) is the standard surgical treatment method for large kidney stones. Its aim is to achieve a stone-free status, since any residual fragments (RFs) after PCNL are likely to cause additional morbidity or stone growth. Enhancing intraoperative detectability of RFs could lead to increased stone-free rates and decreased re-intervention rates. Cone beam computed tomography (CBCT) has recently been introduced in urology as a feasible method for intraoperatively imaging RFs. The aim of this trial is to determine the added value of CBCT in percutaneous nephrolithotomy, by measuring differences in stone-related morbidity for patients with procedures in which a CBCT is used versus patients with procedures without the use of CBCT. METHODS: The CAPTURE trial is an investigator-initiated single-center, randomized controlled trial (RCT) in adult patients who have an indication for percutaneous nephrolithotomy. A contemporary percutaneous nephrolithotomy is performed. Once the surgeon is convinced of a stone-free status by means of fluoroscopy and nephroscopy, randomization allocates patients to either the study group in whom an intraoperative CBCT scan is performed or to the control group in whom no intraoperative CBCT scan is performed. The main endpoint is the stone-free status as assessed four weeks postoperatively by low-dose non-contrast abdominal CT, as a standard follow-up procedure. Secondary endpoints include the number of PCNL procedures required and the number of stone-related events (SREs) registered. The total study population will consist of 320 patients that undergo PCNL and are eligible for randomization for an intraoperative CBCT scan. DISCUSSION: We deem a randomized controlled trial to be the most effective and reliable method to assess the efficacy of CBCT in PCNL. Though some bias may occur due to the impossibility of blinding the urologist at randomization, we estimate that the pragmatic nature of the study, standardized circumstances, and follow-up methods with pre-defined outcome measures will result in a high level of evidence. TRIAL REGISTRATION: Netherlands Trial Register (NTR) NL8168 , ABR NL70728.042.19. Registered on 15 October 2019. Prospectively registered.

Intraoperative cone beam computed tomography for detecting residual stones in percutaneous nephrolithotomy: a feasibility study.

Cone beam computed tomography (CBCT) provides multiplanar cross-sectional imaging and three-dimensional reconstructions and can be used intraoperatively in a hybrid operating room. In this study, we investigated the feasibility of using a CBCT-scanner for detecting residual stones during percutaneous nephrolithotomy (PCNL). Intraoperative CBCT-scans were made during PCNL procedures from November 2018 until March 2019 in a university hospital. At the point where the urologist would have otherwise ended the procedure, a CBCT-scan was made to image any residual fragments that could not be detected by either nephroscopy or conventional C-arm fluoroscopy. Residual fragments that were visualized on the CBCT-scan were attempted to be extracted additionally. To evaluate the effect of this additional extraction, each CBCT-scan was compared with a regular follow-up CT-scan that was made 4 weeks postoperatively. A total of 19 procedures were analyzed in this study. The mean duration of performing the CBCT-scan, including preparation and interpretation, was 8 min. Additional stone extraction, if applicable, had a mean duration of 11 min. The mean effective dose per CBCT-scan was 7.25 mSv. Additional extraction of residual fragments as imaged on the CBCT-scan occurred in nine procedures (47%). Of the follow-up CT-scans, 63% showed a stone-free status as compared to 47% of the intraoperative CBCT-scans. We conclude that the use of CBCT for the detection of residual stones in PCNL is meaningful, safe, and feasible.

Clinical outcomes of Ghanaian Buruli ulcer patients who defaulted from antimicrobial therapy.

OBJECTIVES: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy. METHODS: A number of days of antimicrobial therapy and patient and lesion characteristics were recorded from charts from a cohort of BU patients treated at Nkawie-Toase hospital between 2008 and 2012. Patients who defaulted from treatment were retrieved, and lesion characteristics and functional limitations were recorded. RESULTS: About 54% of patients defaulted from therapy or wound care. Forty-seven defaulters with follow-up completed had received <56 days of antibiotics. 84% of these patients healed after 32 days or less of antibiotics. There appeared to be an increased rate of healing in smaller lesions; 94% of WHO category I lesions had healed after 32 days or less of antibiotics. CONCLUSION: Although numbers were small, and a potential for bias exists, our findings suggest that a reduction in the duration of antimicrobial therapy in BU in small, early lesions is feasible. These findings can serve as a basis for future well-designed studies.

Intracranial penetration of a halo pin causing an epileptic seizure.

A 71-year-old man with ankylosing spondylitis and an unstable fracture of the 6th and 7th cervical vertebrae was managed with a halo vest. Eight weeks following application the halo had shifted because of a loose pin. The patient's only complaint at the time was a headache but this was followed two days later by a seizure. An MR scan of the brain showed a swollen cortex under the right dorsal pin as a result of a perforation of the internal lamina by the pin. The halo was removed and anti-epileptic medication commenced. The patient had no further seizures.

Measures of cardiovascular autonomic nervous function: agreement, reproducibility, and reference values in middle age and elderly subjects.

AIMS/HYPOTHESIS: Currently, three categories of cardiovascular autonomic nervous function measures are used: classic Ewing-test measures, measures of heart-rate variability (HRV), and measures of baroreflex sensitivity (BRS). Little is known about the agreement between these measures, and reference and reproducibility values for these measures have not been reported within the same group. METHODS: As part of the Hoorn Study, 631 subjects aged 50 to 75 participated in a study of autonomic nervous function. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during spontaneous breathing, during six deep breaths over 1 min, and during an active change in position from lying to standing. From these readings, ten measures of autonomic function were assessed (mean heart rate, three Ewing test measures, five HRV measures and one BRS measure). RESULTS: Regression analysis in a healthy subgroup (n=191) showed sex differences for two of the ten measures and seven measures decreased with age. Therefore, appropriate age-specific and sex-specific reference values were calculated. Reproducibility (n=39) of most measures was moderate, with a reliability coefficient of around 50%. Agreement between the measures of autonomic nervous function varied greatly, between 0% and 87%. The HRV-power ratio measure and the blood pressure changes in the lying-to-standing test showed the lowest agreement with all other measures. CONCLUSION/INTERPRETATION: This study provides age-specific and sex-specific reference values for a wide range of different autonomic function measures in an elderly population. Agreement among the different measures varied widely and reproducibility was only moderate.

Structural investigations of the active-site mutant Asn156Ala of outer membrane phospholipase A: function of the Asn-His interaction in the catalytic triad.

Outer membrane phospholipase A (OMPLA) from Escherichia coli is an integral-membrane enzyme with a unique His-Ser-Asn catalytic triad. In serine proteases and serine esterases usually an Asp occurs in the catalytic triad; its role has been the subject of much debate. Here the role of the uncharged asparagine in the active site of OMPLA is investigated by structural characterization of the Asn156Ala mutant. Asparagine 156 is not involved in maintaining the overall active-site configuration and does not contribute significantly to the thermal stability of OMPLA. The active-site histidine retains an active conformation in the mutant notwithstanding the loss of the hydrogen bond to the asparagine side chain. Instead, stabilization of the correct tautomeric form of the histidine can account for the observed decrease in activity of the Asn156Ala mutant.

Structural investigations of calcium binding and its role in activity and activation of outer membrane phospholipase A from Escherichia coli.

Outer membrane phospholipase A (OMPLA) is an integral membrane enzyme that catalyses the hydrolysis of phospholipids. Enzymatic activity is regulated by reversible dimerisation and calcium-binding. We have investigated the role of calcium by X-ray crystallography. In monomeric OMPLA, one calcium ion binds between two external loops (L3L4 site) at 10 A from the active site. After dimerisation, a new calcium-binding site (catalytic site) is formed at the dimer interface in the active site of each molecule at 6 A from the L3L4 calcium site. The close spacing and the difference in calcium affinity of both sites suggests that the L3L4 site may function as a storage site for a calcium ion, which relocates to the catalytic site upon dimerisation. A sequence alignment demonstrates conservation of the catalytic calcium site but evolutionary variation of the L3L4 site. The residues in the dimer interface are conserved as well, suggesting that all outer membrane phospholipases require dimerisation and calcium in the catalytic site for activity. For this family of phospholipases, we have characterised a consensus sequence motif (YTQ-X(n)-G-X(2)-H-X-SNG) that contains conserved residues involved in dimerisation and catalysis.

A baroreflex model of short term blood pressure and heart rate variability.

Parameters based on heart rate variability alone or on both heart rate and blood pressure variability (baroreflex sensitivity) are becoming increasingly clinical relevant. Nevertheless a complete insight in physiological mechanisms underlying these parameters is still lacking. A computer model may help to fill up some of the gaps. We present a model which consists of a simple beat-to-beat hemodynamic part (Starling heart and Windkessel) linked to a detailed continuous modelled neural control part. The intermediate between continuous and beat-to-beat part is an integral pulse frequency modulator (IPFM) acting as cardiac pacemaker. Input for the IPFM is a "sympathovagal" balance signal, with different dynamics for sympathetic and vagal branches. Low-frequency variability is supposed to arise from resonance of existing noise, while high-frequency variability (respiration) is assumed to enter the closed loop at the hemodynamic (blood pressure) site. Results of three studies have been used for validation: (1) spontaneous variability in heart rate and blood pressure (baroreflex transfer functions), (2) vagal blockade with atropine, (3) a modified Valsalva manoeuvre performed in normal and quadriplegic man. Steady state as well as dynamic properties of the model reasonably well fitted to these experimental data.

Unusual catalytic triad of Escherichia coli outer membrane phospholipase A.

Escherichia coli outer membrane phospholipase A (OMPLA) is an integral membrane enzyme. OMPLA is active as a homodimer and requires calcium as a cofactor. The crystal structures of the monomeric and the inhibited dimeric enzymes were recently determined [Snijder, H. J., et al. (1999) Nature 401, 717-721] and revealed that OMPLA monomers are folded into a 12-stranded antiparallel beta-barrel. The active site consists of previously identified essential residues Ser144 and His142 in an arrangement resembling the corresponding residues of a serine hydrolase catalytic triad. However, instead of an Asp or Glu that normally is present in the triad of serine hydrolases, a neutral asparagine (Asn156) was found in OMPLA. In this paper, the importance of the catalytic Asn156 is addressed by site-directed mutagenesis studies. All variants were purified at a 30 mg scale, and were shown to be properly folded using SDS-PAGE and circular dichroism spectroscopy. Using chemical cross-linking, it was shown that all variants were not affected in their calcium-dependent dimerization properties. The Asn156Asp variant exhibited a 2-fold lower activity than wild-type OMPLA at neutral pH. Interestingly, the activity of the variant is 1 order of magnitude higher than that of the wild type at pH >10. Modest residual activities (5 and 2.5%, respectively) were obtained for the Asn156Ala and Asn156Gln mutants, showing that the active site of OMPLA is more tolerant toward replacements of this third residue of the catalytic triad than other serine hydrolases, and that the serine and histidine residues are minimally required for catalysis. In the X-ray structure of dimeric OMPLA, the cofactor calcium is coordinating the putative oxyanion via two water molecules. We propose that this may lessen the importance for the asparagine in the catalytic triad of OMPLA.

Evaluation of catheter-mounted transducers for intra-oesophageal pressure recording in respiratory function tests.

Oesophageal pressure measurements in respiratory function tests are commonly performed using a balloon-catheter system. This study investigates the usefulness of catheter-mounted pressure transducers as an alternative to balloon-catheter systems. Calibration related physical properties of the catheter mounted pressure transducers are evaluated in vitro. The behaviour of these transducers in vivo is evaluated in ten volunteers by relating pressures measured in the oesophagus to airway opening pressures and by comparing these relationships with those sequentially obtained by a balloon-catheter system. The catheter-mounted pressure transducers show no drift after a proper preparation procedure. These catheters, with integrated pressure transducers, are tolerated significantly better by the subjects than are balloon catheters. The catheter-mounted pressure transducers are found to give an equivalent performance compared with the balloon-catheter system, if relative pressures are of interest. However, unpredictable and uncontrollable shifts in offset occur during the in vivo measurements, disturbing absolute pressure readings. Possible explanations for these shifts are the presence of bubbles and adhesion of mucus to the transducers, exerting Van der Waals forces, and contact with the tissue of the oesophageal wall. These shifts are found to be quite stable throughout a period of measurement and therefore of minor disturbance to relative pressure measurements, for instance in assessing the elastic properties of lungs.

On the quantification of heart rate changes in autonomic function tests: relations between measures in beats per minute, seconds and dimensionless ratios.

1. Disorders of the autonomic nervous system are frequently diagnosed by measuring heart rate changes in response to deep-breathing and lying-to-standing manoeuvres. The heart rate changes in these manoeuvres are quantified in measures using various units, like beats per minute, seconds and dimensionless ratios. 2. In the present study we mathematically derived relationships between the measures which quantify heart rate changes in beats per minute, seconds and dimensionless ratios. The theoretical outcomes were experimentally confirmed by the results of the deep-breathing and the lying-to-standing test in 525 healthy and diabetic subjects. The measures were found to be non-equivalent, because the mean RR interval duration influenced the measures in different ways. 3. It is argued that measures in seconds are preferable to measures in beats per minute or ratios, because the physiological interpretation of this measure is easier, and the sensitivity of measures in seconds is expected to be greater. 4. Finally, we recommend that measures of heart rate variation in the deep-breathing and lying-to-standing manoeuvre are accompanied by information on the mean RR interval duration or mean heart rate to allow correct interpretation of the measures.

Effects of ketanserin on heart rate and blood pressure variability: implications for the effect on the baroreflex mechanisms.

Ketanserin is an antihypertensive drug with affinity to both serotonin S2- and alpha 1-adrenoceptors. The specific effects of ketanserin on the baroreflex are not fully understood. We, therefore, studied baroreflex regulation based on blood pressure (BP) and heart rate (HR) responses to several maneuvers before and after the administration of 2 x 5 mg of ketanserin i.v. both in supine and in standing posture. Seven young healthy volunteers were investigated. We measured spontaneous variability in HR and BP (Finapres), and performed deep inspiration, Valsalva, and lying-to-standing tests. We also used a modified Valsalva maneuver that consist of Deep Inspiration Breath-holding with closed glottis and EXpiration: DIBEX maneuver. From the BP recordings, peripheral resistance (TPR) and stroke volume (SV) were estimated by the Modelflow method. Thirty minutes after the administration of ketanserin, there was no significant change in mean HR, BP, spectral power of HR and BP variability, baroreflex sensitivity, or Valsalva ratio. Thus ketanserin did not affect the cardiac baroreflex mechanism. However, in standing position, SV increased and TPR decreased under the influence of ketanserin, and BP overshoot after the Valsalva and DIBEX maneuver was significantly decreased as well. There was also no reflex recovery of BP during the DIBEX maneuver in three volunteers, who felt faint. These observations indicate that there is a lack of vasoconstriction. We conclude that ketanserin is not a vasodilator but seems to inhibit vasoconstriction.

Revising death education.

Current nursing education approaches toward death and dying are outdated and need revision. Inadequate preparation in this critical area causes problems for students after they graduate. Practicing nurses report they are unprepared academically to cope with the stresses of working with dying clients and their families. The author reviews the role of formalized death education programs for students in lowering personal anxiety and discomfort while teaching skillful interventions for professional practice.

Comparison of two techniques to measure the motor nerve refractory period distribution.

The techniques introduced by Ingram et al. and by Kimura to assess the motor nerve refractory period distribution were compared in the peroneal nerve of 28 healthy subjects. Twenty of these subjects were examined twice with an interval of 6-20 days. Results obtained with Ingram's technique yielded a narrower refractory period distribution, displayed less inter-individual variability, and were more reproducible than those obtained with Kimura's technique. The mean refractory period for the 5% slowest recovering fibres (MRP95) was 1.51 msec (S.D. 0.14) for Ingram's technique and 2.15 msec (S.D. 0.72) for Kimura's technique. The coefficient of variation of the MRP95 was 8% for Ingram's technique, and 22% for Kimura's technique. The present data do not allow a definite conclusion concerning the association of refractory period with age, gender and height. Ingram's technique would be favoured for practical application over Kimura's technique on the basis of this study.

Comparison of two techniques to measure the motor nerve conduction velocity distribution.

Hopf's technique to measure the distribution of motor nerve conduction velocities (DMCV) has been compared with the technique introduced by Ingram et al. in the peroneal nerve of 28 healthy subjects 41.2 (S.D. 8.4) years. Twenty subjects were examined twice. Both techniques yielded an equal DMCV and equally reproducible results. Group mean velocities for the slowest examined (MNCV95) motor nerve fibres were 39.0 m/sec (S.D. 3.3) for Ingram's technique and 38.6 (S.D. 3.6) for Hopf's technique. The conventional MNCV was always slower than the velocity of the 5% fastest fibres estimated from the DMCV. Ingram's technique may have a number of merits which may have been obscured by measurement in the peroneal nerve, which may be of advantage in shorter nerve segments or faster nerve fibres. On the basis of our data in the peroneal nerve of healthy subjects no preference can be given for either of the techniques.