Wojciech Dabrowski

Fast CMOS binary front-end for silicon strip detectors at LHC experiments

We present design and test results of the front-end circuit developed in a 0.25 mum complementary metal-oxide semiconductor technology. The aim of this work is to study the performance of a deep submicron process in applications for fast binary front ends for silicon strip detectors. The channel comprises a fast transimpedance preamplifier working with an active feedback loop, two stages of the amplifier-integrator circuits providing 22 ns peaking time, and a two-stage differential discriminator. A particular effort has been made to minimize the current and the power consumption of the preamplifier, while keeping the required noise and timing performance. For a detector capacitance of 20 pF noise below 1500 e- equivalent noise charge (ENC) has been achieved for 300 muA bias current in the input transistor, which is comparable with the levels achieved in the past for the front end using a bipolar input transistor. The total supply current of the front end is 600 muA and the power dissipation is 1.5 mW per channel. The offset spread of the comparator is below 3 mV rms

The use of bio-electrical impedance analysis (BIA) to guide fluid management, resuscitation and deresuscitation in critically ill patients: a bench-to-bedside review

The impact of a positive fluid balance on morbidity and mortality has been well established. However, little is known about how to monitor fluid status and fluid overload. This narrative review summarises the recent literature and discusses the different parameters related to bio-electrical impedance analysis (BIA) and how they might be used to guide fluid management in critically ill patients. Definitions are listed for the different parameters that can be obtained with BIA; these include among others total body water (TBW), intracellular water (ICW), extracellular water (ECW), ECW/ICW ratio and volume excess (VE). BIA allows calculation of body composition and volumes by means of a current going through the body considered as a cylinder. Reproducible measurements can be obtained with tetrapolar electrodes with two current and two detection electrodes placed on hands and feet. Modern devices also apply multiple frequencies, further improving the accuracy and reproducibility of the results. Some pitfalls and conditions are discussed that need to be taken into account for correct BIA interpretation. Although BIA is a simple, noninvasive, rapid, portable, reproducible, and convenient method of measuring body composition and fluid distribution with fewer physical demands than other techniques, it is still unclear whether it is sufficiently accurate for clinical use in critically ill patients. However, the potential clinical applications are numerous. An overview regarding the use of BIA parameters in critically ill patients is given, based on the available literature. BIA seems a promising tool if performed correctly. It is non-invasive and relatively inexpensive and can be performed at bedside, and it does not expose to ionising radiation. Modern devices have very limited between-observer variations, but BIA parameters are population-specific and one must be aware of clinical situations that may interfere with the measurement such as visible oedema, nutritional status, or fluid and salt administration. BIA can help guide fluid management, resuscitation and de-resuscitation. The latter is especially important in patients not progressing spontaneously from the Ebb to the Flow phase of shock. More research is needed in critically ill patients before widespread use of BIA can be suggested in this patient population.

Volatile Anesthetics Reduce Biochemical Markers of Brain Injury and Brain Magnesium Disorders in Patients Undergoing Coronary Artery Bypass Graft Surgery

OBJECTIVES Neuropsychological disorders are some of the most common complications of coronary artery bypass graft (CABG) surgery. The early diagnosis of postoperative brain damage is difficult and mainly based on the observation of specific brain injury markers. The aim of this study was to analyze the effects of volatile anesthesia (VA) on plasma total and ionized arteriovenous magnesium concentrations in the brain circulation (a-vtMg and a-viMg), plasma matrix metalloproteinase-9 (MMP-9), and glial fibrillary acidic protein (GFAP) in adult patients undergoing CABG surgery. DESIGN An observational study. SETTING The Department of Cardiac Surgery in a Medical University Hospital. PATIENTS AND METHODS Studied parameters were measured during surgery and in the early postoperative period. Patients were assigned to 3 groups: group O, patients who did not receive VA; group ISO, patients who received isoflurane; and group SEV, patients who received sevoflurane. RESULTS Ninety-two patients were examined. CABG surgery increased MMP-9 and GFAP. The highest MMP-9, GFAP, and the most dramatic disorders in a-vtMg and a-viMg were noted in group O. CONCLUSIONS Cardiac surgery increased plasma MMP-9 and GFAP concentrations. Changes in MMP-9, GFAP, and arteriovenous tMg and iMg were significantly higher in group O. Volatile anesthetics, such as ISO or SEV, reduced plasma MMP-9, GFAP concentrations, and disturbances in a-vtMg and a-viMg.

Disturbance in Venous Outflow From the Cerebral Circulation Intensifies the Release of Blood-Brain Barrier Injury Biomarkers in Patients Undergoing Cardiac Surgery

OBJECTIVE Disturbances in venous outflow from the cerebral circulation may result in brain injury. Severe increases in brain venous pressure lead to brain ischemia and, subsequently, brain edema and intracranial hemorrhages. The purpose of this study was to determine the effect of changes in jugular venous bulb pressure (JVBP) on plasma blood brain-barrier biomarkers concentration and disturbances in arteriovenous total and ionized magnesium (a-vtMg and a-viMg) in brain circulation in patients undergoing coronary artery bypass grafting surgery (CABG) with cardiopulmonary bypass (CPB). DESIGN Prospective observational study. SETTING Department of Cardiac Surgery at a Medical University Hospital. PARTICIPANTS Ninety-two adult patients undergoing elective CABG with CPB under general anaesthesia were studied. METHODS Central venous pressure (CVP) was measured using a pulmonary artery catheter. The right jugular vein was cannulized retrogradely for jugular venous bulb pressure (JVBP) measurement. Concentrations of plasma S100β protein, matrix metalloproteinase 9 (MMP-9), creatine kinase isoenzyme BB (CK-BB) a-vtMg and a-viMg were measured as the markers of blood-brain barrier dysfunction. All of them were analyzed in comparison with JVBP during surgery and the early postoperative period. RESULTS Elevated JVBP was noted after CPB and after surgery. Its increase above 12 mmHg intensified release of S100β, MMP-9 and CK-BB as well as disorders in a-vtMg and a-viMg. CVP correlated with JVBP, S100β, and MMP-9. Moreover, JVBP correlated with S100β and MMP-9. CONCLUSIONS Cardiac surgery increased JVBP, and JVBP elevated above 12 mmHg intensified an increase in biomarkers of plasma blood-brain barrier disruption.

Fluid therapy and perfusional considerations during resuscitation in critically ill patients with intra-abdominal hypertension

Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are consistently associated with morbidity and mortality among the critically ill or injured. Thus, avoiding or potentially treating these conditions may improve patient outcomes. With the aim of improving the outcomes for patients with IAH/ACS, the World Society of the Abdominal Compartment Syndrome recently updated its clinical practice guidelines. In this article, we review the association between a positive fluid balance and outcomes among patients with IAH/ACS and how optimisation of fluid administration and systemic/regional perfusion may potentially lead to improved outcomes among this patient population.Evidence consistently associates secondary IAH with a positive fluid balance. However, despite increased research in the area of non-surgical management of patients with IAH and ACS, evidence supporting this approach is limited. Some evidence exists to support implementing goal-directed resuscitation protocols and restrictive fluid therapy protocols in shocked and recovering critically ill patients with IAH. Data from animal experiments and clinical trials has shown that the early use of vasopressors and inotropic agents is likely to be safe and may help reduce excessive fluid administration, especially in patients with IAH. Studies using furosemide and/or renal replacement therapy to achieve a negative fluid balance in patients with IAH are encouraging. The type of fluid to be administered in patients with IAH remains far from resolved. There is currently insufficient evidence to recommend the use of abdominal perfusion pressure as a resuscitation endpoint in patients with IAH. However, it is important to recognise that IAH either abolishes or increases threshold values for pulse pressure variation and stroke volume variation to predict fluid responsiveness, while the presence of IAH may also result in a false negative passive leg raising test.Correct fluid therapy and perfusional support during resuscitation form the cornerstone of medical management in patients with abdominal hypertension. Controlled studies determining whether the above medical interventions may improve outcomes among those with IAH/ACS are urgently required.

Prolonged Subdural Infusion of Kynurenic Acid Is Associated with Dose-Dependent Myelin Damage in the Rat Spinal Cord.

Background Kynurenic acid (KYNA) is the end stage metabolite of tryptophan produced mainly by astrocytes in the central nervous system (CNS). It has neuroprotective activities but can be elevated in the neuropsychiatric disorders. Toxic effects of KYNA in the CNS are unknown. The aim of this study was to assess the effect of the subdural KYNA infusion on the spinal cord in adult rats. Methods A total of 42 healthy adult rats were randomly assigned into six groups and were infused for 7 days with PBS (control) or 0.0002 pmol/min, 0.01 nmol/min, 0.1 nmol/min, 1 nmol/min, and 10 nmol/min of KYNA per 7 days. The effect of KYNA on spinal cord was determined using histological and electron microscopy examination. Myelin oligodendrocyte glycoprotein (MOG) was measured in the blood serum to assess a degree of myelin damage. Result In all rats continuous long-lasting subdural KYNA infusion was associated with myelin damage and myelin loss that was increasingly widespread in a dose-depended fashion in peripheral, sub-pial areas. Damage to myelin sheaths was uniquely related to the separation of lamellae at the intraperiod line. The damaged myelin sheaths and areas with complete loss of myelin were associated with limited loss of scattered axons while vast majority of axons in affected areas were morphologically intact. The myelin loss-causing effect of KYNA occurred with no necrosis of oligodendrocytes, with locally severe astrogliosis and no cellular inflammatory response. Additionally, subdural KYNA infusion increased blood MOG concentration. Moreover, the rats infused with the highest doses of KYNA (1 and 10 nmol/min) demonstrated adverse neurological signs including weakness and quadriplegia. Conclusions We suggest, that subdural infusion of high dose of KYNA can be used as an experimental tool for the study of mechanisms of myelin damage and regeneration. On the other hand, the administration of low, physiologically relevant doses of KYNA may help to discover the role of KYNA in control of physiological myelination process.

Plasma matrix metalloproteinase 9 correlates with disorders of brain magnesium homeostasis in patients undergoing coronary artery bypass surgery

BACKGROUND Changes in plasma matrix metalloproteinase 9 (MMP-9) concentrations and parallel changes in brain magnesium homeostasis have not been examined in cardiac surgery patients. The purpose of the present study was to analyse these relationships in patients undergoing coronary artery bypass surgery (CABG) with extracorporeal circulation (ECC). Additionally, the effect of volatile anaesthetics was considered. PATIENTS AND METHODS Adult patients undergoing CABG with ECC under general anaesthesia were studied. Plasma MMP-9 and total (tMg) and ionized (iMg) magnesium concentrations were measured during surgery and during the early postoperative period. The plasma arteriovenous (a-v) tMg and iMg differences in the brain circulation were considered to be markers for brain magnesium homeostasis. The Mini-Mental State Examination test and computer tomography were used to diagnose postoperative neuropsychological disorders (PNPDs). RESULTS In total, 92 patients were examined. PNPDs were noted in 17 cases. Cardiac surgery resulted in increased plasma levels of MMP-9. The highest MMP-9 concentrations were observed in patients with PNPDs. MMP-9 concentrations strongly correlated with a-v tMg and a-v iMg differences. Compared with arterial measurements, venous tMg and iMg concentrations were higher during and immediately after surgery and lower during the early postoperative period. The most severe differences in a-v tMg and iMg were noted in patients with PNPDs. CONCLUSION 1. Cardiac surgery resulted in an increase in plasma MMP-9 concentrations. 2. This increase in MMP-9 was significantly greater in patients with PNPDs. 3. The plasma MMP-9 concentration was correlated with disorders of brain Mg homeostasis.

An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury

Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un-phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125-2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125-2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process.

Increase in intra-abdominal pressure raises brain venous pressure, leads to brain ischaemia and decreases brain magnesium content.

BACKGROUND Intra-abdominal hypertension (IAH) may increase brain venous pressure, which may lead to brain injury. The aim of the present study was to analyse the effect of IAH on brain venous pressure and brain total and ionised magnesium (tMg and iMg), calcium (Ca) and zinc (Zn) contents in rats. MATERIAL AND METHODS Forty four adult Wistar rats were examined. Animals were divided into two groups: control, and IAH: rats with intra-abdominal pressure (IAP) elevated to 25 mmHg. IAP was measured directly in the abdominal cavity. After retrograde cannulation of the jugular vein, the jugular venous pressure (JVP) was measured as the brain venous pressure. JVP and IAP were noted after induction of anaesthesia, immediately following induction of IAH and 90 min after induction of IAH. In all rats, brains were removed for biochemical and histological analysis. RESULTS Biochemical analysis was performed in 30 rats, histological visualisation in 14. IAP elevated to 25 mmHg increased JVP in the IAH group. After 90 min, JVP decreased; however, its value was still higher compared with pre-IAH. In the IAH group, tMg and iMg were significantly lower than in the control group. Moreover, Ca and Zn levels were higher in the IAH group compared with the control group. The histological examination showed changes indicative of ischaemic neuronal cell stress. CONCLUSIONS Firstly, increase in IAP elevates JVP. Secondly, raised JVP decreases tMg and iMg. Thirdly, raised JVP increases the Ca and Zn content in the rat brain. Fourthly, IAH leads to changed characteristics of brain ischaemia.

Raised Jugular Venous Pressure Intensifies Release of Brain Injury Biomarkers in Patients Undergoing Cardiac Surgery

OBJECTIVES Neurologic damage after cardiac surgery with extracorporeal circulation is multifactorial. Despite several studies, its pathophysiology is poorly understood. The purpose of this study was to determine the changes in jugular venous pressure and to analyze their effect on perioperative brain injury measured by biomarkers in patients undergoing coronary artery bypass grafting. DESIGN Observational study. SETTING Department of cardiac surgery in a medical university hospital. PARTICIPANTS Adult patients undergoing elective coronary artery bypass grafting with extracorporeal circulation under general anesthesia. INTERVENTIONS The right jugular vein was cannulated in retrograde fashion. Jugular venous pressure was measured in the jugular vein bulb (JVBP). Concentrations of plasma glial fibrillary acidic protein, tau protein, arteriovenous lactate, and jugular vein saturation were measured as the markers of brain injury during the surgery and early postoperative period. All were analyzed in relation to JVBP. MEASUREMENTS AND MAIN RESULTS Increased JVBP was noted after extracorporeal circulation and after surgery. A significant increase >12 mmHg for JVBP, increased plasma glial fibrillary acidic protein, tau protein, arteriovenous lactate concentrations, and decreased jugular vein saturation were observed. CONCLUSIONS Cardiac surgery increased JVBP and an increased JVBP > 12 mmHg intensified an increase in brain injury biomarker concentrations.