Lean body weight dosing avoids excessive systemic exposure to proton pump inhibitors for children with obesity.

BACKGROUND: Children with obesity are more likely to suffer gastroesophageal reflux disease, requiring acid-suppression therapy with proton pump inhibitors (PPIs) and no guidelines regarding dosing. OBJECTIVE: To prospectively evaluate lean-body-weight-based (LBW) dosing of the PPI pantoprazole for children with and without obesity. METHODS: Methods: Sixty-two children (6-17 years) received a one-time oral dose of liquid pantoprazole (1.2 mg kg-1 LBW). Plasma pantoprazole concentrations were measured at 10 time points over 8 h and pharmacokinetic (PK) profiles generated using non-compartmental techniques, in order to compare PK parameters of interest between children with and without obesity, while accounting for CYP2C19 genotype. RESULTS: Adjusted for milligram-per-kilogram total body weight (TBW) pantoprazole received, apparent drug clearance (CL/F) was reduced 50% in children with vs. without obesity (p=0.03). LBW-based dosing compensated for this reduction in CL/F (p = 0.15). CONCLUSION: To achieve comparable systemic PPI exposures for children with and without obesity, we recommend using LBW, rather than TBW-based dosing for pantoprazole.

[Cerebrovenous orthostatic reactivity in pathology of the craniovertebral junction (Chiari malformation)].

AIM: Chiari malformation is characterized by herniation of the cerebellar tonsils into the foramen magnum, which leads to disturbance of CSF circulation through the craniovertebral junction. Orthostatic stress, which leads to the movement of SCF through the craniovertebral junction, is an adequate method to detect these disorders. It is accompanied by changes in the intracranial pressure, affecting the cerebrovenous orthostatic reactivity (CVOR), which is noninvasively assessed in patients with Chiari malformation. MATERIAL AND METHODS: The study involved 35 patients with Chiari malformation (26 patients with Chiari I and 9 patients with Chiari II) aged 4 to 58 years (of them 12 males). Hydrocephalus was diagnosed in 4 examined patients and myelosyringosis was diagnosed in 6 patients. Transcranial Doppler sonography was used to record the venous blood flow in the tentorial sinus of the brain while changing body position on the fracture table from +90° to -30°. RESULTS: There is significant CVOR abnormality in most patients with Chiari malformation (more than 90%), which is characterized by either increased CVOR (sometimes 5-6-fold compared to the upper normal level (considerable hyperreactivity) or complete absence of any changes during the orthostatic load (areactivity). Before surgical treatment, CVOR of patients with Chiari malformation is often characterized by areactivity, as well as a moderate or significant hyperreactivity. After surgical treatment (decompression of the foramen magnum), patients with Chiari malformation demonstrate significant normalization of the craniovertebral volumetric ratios and CVOR if often characterized by normoreactivity (in 63%) or, more rarely, moderate hyperreactivity. The rate of venous blood flow in the tentorial sinus of the brain in patients with Chiari malformation can be increased before the surgery and normalizes after surgery. CONCLUSION: The high incidence of disturbance of CVOR (over 90%) in patients with Chiari malformation was revealed. After surgical treatment, complete normalization of CVOR was observed in more than half of these patients (63%).

Use of pharmacokinetic modelling to individualize FFP dosing in factor V deficiency.

Therapy with fresh frozen plasma (FFP) confers serious risks, such as contraction of blood-borne viruses, allergic reaction, volume overload and development of alloantibodies. The aim of this study was to apply principles of pharmacokinetic (PK) modelling to individual factor content of FFP to optimize individualized dosing, while minimizing potential risks of therapy. We used PK modelling to successfully target individual factor replacement in an 8-month-old patient receiving FFP for treatment of a severe congenital factor V (FV) deficiency. The model fit for the FV activity vs. time data was excellent (r = 0.98) and the model accurately predicted FV activity during the intraoperative and postoperative period. Accurate PK modelling of individual factor activity in FFP has the potential to provide better targeted therapy, enabling clinicians to more precisely dose patients requiring coagulation products, while avoiding wasteful and expensive product overtreatment, minimizing potentially life-threatening complications due to undertreatment and limiting harmful product-associated risks.

[The role of intraoperative flowmetry in surgery of cerebral aneurysms].

Aim of the study was to assess the capabilities of intraoperative ultrasonic flowmetry in cerebral aneurysm surgery for prevention and immediate correction of cerebral ischemia. Ultrasonic flowmeter (Model HT313/323, "ransonic Systems Inc.", USA) was used during surgery in patients with complicated, large and giant aneurysms for evaluation of cerebral blood flow in main arteries (internal carotid, anterior and middle cerebral) and their branches (branches of M2-M3 and A2 segments). The series included 20 adult patients (13 male and 7 female) operated in Burdenko Moscow Neurosurgery Institute during 2008-2011 years. Mean age was 47.4 +/- 8.6 years. Giant aneurysms (> 2.5 cm) were present in 12 (60%) patients, large (1.5-2.5 cm)--in 5 (25%). Aneurysms of internal carotid artery were found in 8 cases. 1 female patient was operated on giant aneurysm of anterior cerebral--anterior communicating artery. In 4 (20%) cases significant alterations of blood flow were registered after clipping (> 25% according to initial), the changes were not visible. This allowed to correct the position of clips. In 2 surgeries ('low' paraclinoid aneurysms) the collateral flow was sufficient during temporary clipping, this allowed trapping of aneurysms with good neurological outcome. In 3 cases flowmeter was used to evaluate blood flow after extracranial-intracranial bypass. Ultrasonic flowmetry is a simple, reproducible and safe technique for intraoperative assessment of blood flow. Despite visual sufficiency of arteries flowmetry allows detection of surgically significant alterations of blood flow after clipping.

[Multimodal neuromonitoring in the early diagnosis of brain ischemia during carotid arterial reconstruction].

The paper analyzes the efficiency of multimodal neuromonitoring (transcranial ultrasound Doppler study, cerebral oximetry, and electroencephalography) for the early intraoperative diagnosis of cerebral ischemia in patients during carotid reparative interventions. On the basis of the findings, the authors have developed a diagnostic algorithm of cerebral ischemia in this group of patients at surgery. Its basis is Doppler monitoring; the data of cerebral oximetry and EEG are taken into account with the borderline values of linear blood flow velocity. The diagnosis of cerebral ischemia during operation on the carotids is a direct indication for the usage of a temporary intraluminal shunt. During carotid reconstructive interventions made under general anesthesia, the application of multimodal neuromonitoring is a valid approach and it should make the most use.

[Impact of cerebral arteriovenous malformations on systemic and cerebral hemodynamics].

Shunt through cerebral arteriovenous malformations (AVMs) causes not only cerebral hemodynamic changes, but also affects the cardiovascular system as a whole. Forty-two patients aged 15 to 62 years were examined. Group 1 included 19 patients with AVM < 20 cm3; Group 2 comprised 23 patients with AVMs > 21 cm3. Cerebral angiography revealed AVMs afferents and stroma. Before and after surgery, total cerebral blood flow was estimated by color duplex scanning of cephalic large arteries; and the heart and systemic hemodynamics were evaluated by ECG, echoECG, and 24-hour blood pressure monitoring. Thus, small AVMs with insignificant arteriovenous shunt do not considerably affect cerebral and systemic hemodynamics (eukinetic hemodynamics). Large AVMs enhance functional load on the cardiovascular system whose hyperfunction as the basic mechanism of cerebral blood flow compensation in arteriovenous shunt through cerebral AVMs is effected by increasing cardiac and stroke, circulating blood volume, blood pressure, and tachycardia. These changes are functional.

[Stepwise surgical treatment in patients with multiple stenotic and occlusive lesions of the great arteries of the brain].

The study was conducted at the Academician N. N. Burdenko Institute of Neurosurgery, Moscow, in 1999 to 2006. The paper presents the results of stepwise surgical treatment in 84 patients with chronic cerebral ischemia, caused by multiple stenotic and occlusive lesions of the brachiocephalic arteries, who underwent 183 reparative operations. Six major groups of patients with various combinations of lesions of major cerebral arteries were identified. An attempt was made to create an algorithm of the optimum stepwise surgical treatment policy in the identified groups of patients on the basis of the site, degree, and nature of stenotic lesions, by taking into account the cerebral hemodynamics and collateral circulation at all stages of surgical treatment. At the same time, changes in the degree of neurological deficit as one of the major determinants of the results of surgical treatment could be evaluated. The study has demonstrated that the chosen tactics of employing series arterial reconstructions in multiple stenotic and occlusive lesions of major cerebral arteries is an effective treatment option in patients with chronic cerebral ischemia.

[Combined surgical treatment for carotid paraganglioma]. / Kombinirovannoe khirurgicheskoe lechenie karotidnoi paragangliomy.

The paper gives a clinical example of embolization of the vascular network of carotid paraganglioma with subsequent en-block tumor removal with bifurcation of the common carotid artery and with recovery of great blood flow along the internal carotid artery through alloprosthesis of the latter. The positive effects of a combination of endovascular embolization of the vascular network of the tumor with its subsequent removal are noted. Indications for endovascular embolization and its procedure, intraoperative evaluation of cerebral collateral circulation are discussed. Those for carotid repair during en-block removal of carotid paraganglioma with bifurcation of the common carotid artery are considered.

[Surgical treatment of occlusive and stenosing lesions of brachiocephalic arteries]. / Khirurgicheskoe lechenie bol'nykh s okkliuziruiushchimi i stenoziruiushchimi porazheniiami brakhiotsefal'nykh arterii.

The results of surgical treatment of patients with occlusive and stenosing lesions of brachiocephalic arteries implemented at Burdenko's Research Institute of Neurosurgery of the Russian Academy of Medical Sciences (RAMS) during 1999-2002 are described. A total of 164 operations were made in 128 patients. Different diagnostic methods and indications for various types of reconstructive and revascularization surgeries are under discussion. A variety of the carotid endarterectomy techniques and the conditions needed for their implementation (microsurgical equipment and intraoperative multi-modality neuromonitoring) are defined. Finally, the main complications and the methods of their prevention, correction and treatment are also described.

[Surgical treatment of chronic cerebral circulatory insufficiency due to traumatic carotid-jugular anastomosis]. / Khirurgicheskoe lechenie khronicheskoi nedostatochnosti mozgovogo krovoobrashcheniia, obuslovlennoi travmaticheskim karotidno-iuguliarnym soust'em.

The paper describes a clinical case of traumatic right carotid-jugular anastomosis, a rare abnormality of the great arteries in the neck. It presents data on its clinical and instrumental diagnosis, a procedure for a direct surgical intervention repairing the common carotid artery and the right internal jugular vein, which has yielded a good clinical result.

Noninvasive assessment of the elastance and reserve capacity of the craniovertebral contents via flow velocity measurements in the straight sinus by TCD during body tilting test.

Invasive recording of intracranial pressure (ICP) changes during cerebrospinal fluid (CSF) infusion-drainage tests have been used to estimate elastance and reserve capacity of craniovertebral contents. The increase in ICP and its pulse-related oscillations lead to "cuff constriction" of cerebral veins. The purpose of this study is noninvasive assessment of elastance and reserve capacity of craniovertebral contents (RCCC) by measurement of flow velocity (FV) in the straight sinus by transcranial Doppler (TCD) during body tilt tests, which cause changes in ICP. The study was performed in 14 healthy volunteers (age 12-49 y, 6 men) and 32 patients with Intracranial Hypertension (IH) (Benign Intracranial Hypertension, n = 14; Brain Tumors, n = 18). The straight sinus was insonated through the occipital window during body tilt tests (BTT). Tilt table position was changed gradually from head up (+75 degrees) to head down (-45 degrees). It was established that systolic flow velocity and amplitude of FV pulsations (Amp) in horizontal position in patients is usually higher than in healthy volunteers. We found that reserve capacity of craniovertebral contents in patients with IH was usually exhausted. Elastance in patients was usually significantly higher than in healthy volunteers. Evaluation of cerebral venous circulation during body tilt tests clearly differs between the patients with IH and the healthy volunteers. The degree of this difference depends on the localization and character of the pathologic process.

[Electrophysiologic analysis of the selectivity of action of anticholinesterase preparations in hereditary ataxias]. / Elektrofiziologicheskii analiz izbiratel'nosti deistviia antikholésteraznykh preparatov pri geredoataksiiakh.

The selectivity of action of anticholinesterase drugs (ACE drugs) in hereditary ataxias was studied using methods of registration of short latent stem-induced potentials to acoustic stimulation and assessment of the parameters of visual motor coordination. The findings obtained show the involvement in the pathological process of the brain stem in hereditary ataxias and the heterogeneity of action of ACE drugs. Thus, amiridine acted predominantly on efferent while galanthamine on afferent conduction of impulses.

[Short-latency brain stem evoked potentials to acoustic stimulation in patients with hereditary neuromuscular diseases]. / Korotkolatentnye stvolovye vyzvannye potentsialy na akusticheskuiu stimuliatsiiu u bol'nykh s nasledstvennymi nervno-myshechnymi zabolevaniiami.

Short-latent evoked potentials (SLEP) of the brain stem following acoustic stimulation (AS) were studied in 70 patients with hereditary neuromuscular diseases. The degree of changes in the components of brain stem SLEP in response to AS was found to correlate with disorders of impulse sensor conduction along the peripheral nerves in patients with the Roussy-Levy areflex distasia, the Charcot-Marie neural amyotrophy and Friedreich's spinocerebral ataxia. This method of recording brain stem SLEP following AS is a new modern highly informative tool of investigation allowing the physicians to assess the state of different portions of the brain stem in health and disease.

[Clinico-electrophysiologic studies of multiple sclerosis patients]. / Kliniko-élektrofiziologicheskie issledovaniia u bol'nykh rasseiannym sklerozom.

Clinical-electrophysiological examination of 108 patients with demyelinated diseases of the nervous system, which included electromyography, electroneuromyography and study of trunk evoked potentials, allowed the authors to identify criteria of the differential and topical diagnosis in multiple sclerosis, multiple encephalomyelitis and encephalomyelopolyradiculoneuritis. Data provided by a combined electrophysiological examination employing the above listed techniques expand our understanding of individual elements of the pathogenesis of demyelinated diseases involving the nervous system.

[Bulbar evoked potentials in multiple sclerosis]. / O stvolovykh vyzvannykh potentsialakh pri rasseiannom skleroze.

Clinical and electrophysiological examinations of 20 patients with disseminated sclerosis and 8 patients with disseminated encephalomyelitis were carried out. The data of the examinations were compared with those obtained from registering truncal evoked potentials. This comparison contributed to specifying the criteria for diagnostic differentiation between these two diseases. The changes of the truncal evoked potentials in disseminated sclerosis pointed to a process of demyelinization in the brain trunk. These changes, however, were not characteristic for disseminated encephalomyelitis.