PubMed Health⌕ Search

Biomedical subjects

D K Menon

Publications and source records attributed to D K Menon.

At least 19 recordsLinked to original sources
PubMed2003

Hyperoxia and the cerebral hemodynamic responses to moderate hyperventilation.

BACKGROUND: A reduction in the arterial partial pressure of CO2 (PaCO2) leads to a rapid reduction in cerebral blood flow (CBF). However, despite continuing hypocapnia there is secondary recovery of CBF over time as a result of increases in lactic acid production. Hyperoxia is thought to modulate the production of lactic acid. This study examined the kinetics of middle cerebral artery flow velocity (MCA FV) reduction during hyperventilation, and its modulation by hyperoxia. METHODS: Cerebral blood flow was assessed using transcranial Doppler ultrasound in nine healthy, awake human volunteers. Subjects were ventilated, via a mouthpiece, to achieve a stable end-tidal CO2 (PETCO2). After a 20-min baseline period the minute volume on the ventilator was passively increased by approximately 20% to reduce PETCO2 by 0.75-1 kPa. After a 10-min stabilization period the new PETCO2 level was maintained at a constant level for 20 min, and MCA FV recovery was measured during this 20-min period. Subjects undertook the protocol breathing air and breathing 100% oxygen. RESULTS: The PETCO2 level was (mean +/- SD) 4.9 +/- 0.4 kPa (normoxia baseline), 4.0 +/- 0.3 kPa (normoxia hyperventilation), 4.6 +/- 0.4 kPa (hyperoxia baseline) and 3.9 +/- 0.4 kPa (hyperoxia hyperventilation). CO2 reactivity was significantly lower with normoxia than hyperoxia (16.5 +/- 3.8 vs. 21.2 +/- 4.6 % kPa-1; P< 0.05). Middle cerebral artery FV recovery was significantly more rapid with normoxia than hyperoxia (0.23 +/- 0.17 vs. 0.08 +/- 0.1 % baseline min-1; P< 0.01). CONCLUSIONS: Our results suggest that cerebral hemodynamic responses to moderate hyperventilation are different in normoxic and hyperoxic conditions. Clinical assessment of CO2 reactivity and CBF recovery during hyperventilation should take the degree of arterial oxygenation into account.

Adult↗
PubMed2003

Assessment of the Ventrix parenchymal intracranial pressure monitoring probe (NL950-P) and Monitor (NL950-100) in a 3 Tesla magnetic resonance scanner.

Magnetic resonance (MR) imaging and spectroscopy provide important information in patients with acute head injury. However, optimal patient management requires intracranial pressure (ICP) monitoring. There are few reports on the use of ICP sensors in an MR environment. We tested the Ventrix parenchymal intracranial pressure monitoring probe and monitor (Integra Neurosciences, USA), modified by the use of a fibre-optic extension cable, within a 3 Tesla MR system. The device performed well in the MR environment, but one element within the fibre-optic extension was significantly ferromagnetic. The ICP probe produced a small susceptibility artefact on spin echo images, and a larger artefact on gradient echo images. The MR safety of the integrated system is probably acceptable, but could be easily improved with minor modifications. Although the system is MR compatible and produces generally acceptable imaging even at 3 Tesla, there is significant degradation of image quality during gradient echo sequences.

Artifacts↗
PubMed2003

Validation of a tonometric noninvasive arterial blood pressure monitor in the intensive care setting.

Intra-arterial measurement is considered the gold standard for continuous, beat-to-beat arterial blood pressure monitoring. However, arterial cannulation can be difficult and may cause complications such as thrombosis and ischaemia. Recently, a tonometric system, the Colin CBM-7000 has been developed for noninvasive beat-to-beat measurement of arterial blood pressure from the radial artery. We assessed the level of agreement between the CBM-7000 and invasive radial artery measurements in 15 patients on a neuro-intensive care unit. Agreement of systolic, diastolic and mean arterial pressure values was limited, with approximately 34% of mean arterial pressures differing by over 10 mmHg. In many cases, this was due to a downward drift of the noninvasive measurements over time. Furthermore, there was a tendency to underestimate low pressures and overestimate high pressures. In our opinion, the Colin CBM-7000 cannot be recommended for continuous blood pressure monitoring in the intensive care setting.

Adult↗
PubMed2003

Cerebral oxygen vasoreactivity and cerebral tissue oxygen reactivity.

There has long been an appreciation that cerebral blood flow is modulated to ensure adequate cerebral oxygen delivery in the face of systemic hypoxaemia. There is increasing appreciation of the modulatory role of hyperoxia in the cerebral circulation and a consideration of the effects of such modulation on the maintenance of cerebral tissue oxygen concentration. These newer findings are particularly important in view of the fact that cerebrovascular and tissue oxygen responses to hyperoxia may change in disease. Such alterations provide important insights into pathophysiological mechanisms and may provide novel targets for therapy. However, before the modulatory effects of hyperoxia can be used for diagnosis, to predict prognosis or to direct therapy, a more detailed analysis and understanding of the physiological concepts behind this modulation are required, as are the limitations of the measurement tools used to define the modulation. This overview summarizes the available information in this area and suggests some avenues for further research.

Animals↗
PubMed2003

Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury.

BACKGROUND: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO(2)) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO(2), to allow assessment of oxygen supply and demand relations. OBJECTIVES: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. METHODS: Using positron emission tomography, global cerebral blood flow, CMRO(2), and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. RESULTS: Low CMRO(2) was associated with disturbed pressure reactivity (inverse function, R(2) = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R(2) = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO(2) or oxygen extraction fraction. CONCLUSIONS: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome.

Adolescent↗
PubMed2002

Assessment of the Caradyne WhisperFlow for administration of continuous positive airway pressure in a 3 Tesla magnetic resonance scanner.

Demand for magnetic resonance investigations in critically ill patients is increasing. While these patients frequently need ventilatory support, not all of them require controlled ventilation and many may be treated with continuous positive airway pressure. Controlled ventilation, with the concurrent need for sedation, may be inappropriate when airway physiology is being studied and may retard weaning. No commercially available ventilator designed for the magnetic resonance environment can deliver high flow continuous positive airway pressure. We tested the Caradyne Whisperflow flow generator and five Whisperflow valves (2.5-15 cmH2O airway pressure) within a 3 Tesla environment for safety and possible dysfunction. All components had minimal ferromagnetic properties and tests showed no clinically relevant change in flow delivery or oxygen concentration in the magnetic field. In addition, the airway pressure generated by the valves was not affected by the magnetic field. We conclude that the tested system can be safely used in a 3 Tesla magnetic resonance environment.

Critical Care↗
PubMed2002

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.

Adult↗
PubMed2002

Deliberate release of biological agents.

Deliberate release of biological agents is a growing threat, but clinical recognition of the resulting diseases is hampered by their rarity and similar presentation to more common illnesses. Despite substantial publicity, access to information may be difficult. Further, the available data are fragmented and not always relevant to critical care settings. We describe the clinical presentations of some important infections, highlighting the features that are relevant to critically ill patients. We provide an integrated set of guidelines for diagnosis, patient care and infection control and have attempted to list important print- and web-based resources for further information.

Bioterrorism↗
PubMed2002

Discordant temporal patterns of S100beta and cleaved tau protein elevation after head injury: a pilot study.

There is considerable interest in S100beta protein as a potential marker that can be used to quantify central nervous system injury. However, increasing appreciation that S100beta may be produced by non-neural tissue (specifically adipocytes), has led to a search for more specific markers of brain injury. Recent interests have focused on a cleaved form of tau protein (c tauP) which is elevated in CSF from patients suffering traumatic brain injury. We have investigated whether levels in peripheral blood are a satisfactory alternative to provide an accessible marker of CNS injury severity. We measured levels of S100beta and c tauP in arterial blood from 20 patients with severe head injury. When compared with normal values S100beta was elevated 10-fold in the first 24 hours and c tauP was elevated at all time points, but showed a reversal of the temporal trend observed with S100beta. Patients with a poor outcome (GOS 1-3) had significantly higher S100beta levels on day one. Plasma c tauP levels did not correlate with outcome following head injury.

Adolescent↗
PubMed2002

Unilateral transplantation of human primary fetal tissue in four patients with Huntington's disease: NEST-UK safety report ISRCTN no 36485475.

OBJECTIVES: Huntington's disease (HD) is an inherited autosomal dominant condition in which there is a CAG repeat expansion in the huntingtin gene of 36 or more. Patients display progressive motor, cognitive, and behavioural deterioration associated with progressive cell loss and atrophy in the striatum. Currently there are no disease modifying treatments and current symptomatic treatments are only partially effective in the early to moderate stages. Neural transplantation is effective in animal models of HD and offers a potential strategy for brain repair in patients. The authors report a safety study of unilateral transplantation of human fetal striatal tissue into the striatum of four patients with HD. SUBJECTS AND METHODS: Stereotaxic placements of cell suspensions of human fetal ganglionic eminence were made unilaterally into the striatum of four patients with early to moderate HD. All patients received immunotherapy with cyclosporin A, azathioprine, and prednisolone for at least six months postoperatively. Patients were assessed for safety of the procedure using magnetic resonance imaging (MRI), regular recording of serum biochemistry and haematology to monitor immunotherapy, and clinical assessment according to the Core Assessment Protocol For Intrastriatal Transplantation in HD (CAPIT-HD). RESULTS: During the six month post-transplantation period, the only adverse events related to the procedure were associated with the immunotherapy. MRI demonstrated tissue at the site of implantation, but there was no sign of tissue overgrowth. Furthermore, there was no evidence that the procedure accelerated the course of the disease. CONCLUSIONS: Unilateral transplantation of human fetal striatal tissue in patients with HD is safe and feasible. Assessment of efficacy will require longer follow up in a larger number of patients.

Adult↗
PubMed2001

Further characterisation of a thromboembolic model of stroke in the rat.

We have used magnetic resonance imaging (MRI) techniques to characterise a rat model of thromboembolic stroke. The consequences of acute perfusion deficit associated with a middle cerebral artery occlusion (MCAo) by a newly formed thrombus was mapped by interrogation of the tissue oxygenation status using gradient echo methods and production of T2* maps. Final infarct size was subsequently assessed at 24-h post-ischaemia by histology with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Animals displayed an infarct volume of 178.7+/-84.2 mm(3) (mean+/-S.D.) with a large coefficient of variation (47%) and range of values (85.6--265.5 mm(3)). This variability provided us with an opportunity to assess the relationships between early imaging observations and eventual infarct size. For a single cerebral slice, at the centre of the MCA territory, a relationship between the area of reduced T2* at 1 and 2 h post MCAo correlated highly with final lesion area (Spearman rank correlation, r=0.98, P<0.01, n=9). Lesion volumes in the thromboembolic MCAo model were compared with a 120-min occlusion, 22-h reperfusion protocol using an intraluminal thread MCAo approach. For the thromboembolic model, the total lesion volume was found to be smaller (178.7+/-84.2 vs. 243.3+/-50.1 mm(3), mean+/-S.D., Student's t-test P=0.046) and showed a greater variability (coefficient of variations: 47% vs. 21%). These data underline the relative variability of this embolic model and provide important preliminary information regarding the value of early changes in T2* in predicting eventual infarct size.

Animals↗
PubMed2001

Management of comatose head-injured patients: are we getting any better?

This re-survey of neurosurgical centres was conducted to determine whether the publication of management guidelines has resulted in changes in the intensive care management of severely head-injured patients (defined as Glasgow Coma Score < 9) in the UK and Ireland. Results were compared with data collected from a similar survey conducted 2 years earlier. Almost 75% of centres monitor intracranial pressure in the majority of patients and 80% now set a target cerebral perfusion pressure of > 70 mmHg. The use of prolonged hyperventilation (> 12 h) is declining and the target PaCO2 is now most commonly > 4 kPa. More centres maintain core temperature < 36.5 degrees C. Although wide variations in the management of severely head-injured patients still exist, we found evidence of practice changing to comply with published guidelines.

Coma↗
PubMed2001

Neuroprotection in ischemia-reperfusion injury: an antiinflammatory approach using a novel broad-spectrum chemokine inhibitor.

Cerebral ischemia-reperfusion injury is associated with a developing inflammatory response with pathologic contributions from vascular leukocytes and endogenous microglia. Signaling chemokines orchestrate the communication between the different inflammatory cell types and the damaged tissue leading to cellular chemotaxis and lesion occupation. Several therapies aimed at preventing this inflammatory response have demonstrated neuroprotective efficacy in experimental models of stroke, but to date, few investigators have used the chemokines as potential therapeutic targets. In the current study, the authors investigate the neuroprotective action of NR58-3.14.3, a novel broad-spectrum inhibitor of chemokine function (both CXC and CC types), in a rat model of cerebral ischemia-reperfusion injury. Rats were subjected to 90 minutes of focal ischemia by the filament method followed by 72 hours of reperfusion. Both the lesion volume, measured by serial magnetic resonance imaging, and the neurologic function were assessed daily. Intravenous NR58-3.14.3 was administered, 2 mg/kg bolus followed by 0.5 mg/kg hour constant infusion for the entire 72-hour period. At 72 hours, the cerebral leukocytic infiltrate, tumor necrosis factor-alpha (TNF-alpha), and interleukin-8 (IL-8)-like cytokines were analyzed by quantitative immunofluorescence. NR58-3.14.3 significantly reduced the lesion volume by up to 50% at 24, 48, and 72 hours post-middle cerebral artery occlusion, which was associated with a marked functional improvement to 48 hours. In NR58-3.14.3-treated rats, the number of infiltrating granulocytes and macrophages within perilesional regions were reduced, but there were no detectable differences in inflammatory cell numbers within core ischemic areas. The authors reported increased expression of the cytokines, TNF-alpha, and IL-8-like cytokines within the ischemic lesion, but no differences between the NR58-3.14.3-treated rats and controls were reported. Although chemokines can have pro- or antiinflammatory action, these data suggest the overall effect of chemokine up-regulation and expression in ischemia-reperfusion injury is detrimental to outcome.

Animals↗
PubMed2000

Multimodality monitoring and the diagnosis of traumatic caroticocavernous fistula following head injury.

Increases in jugular bulb saturations (SjO2) following head injury are usually due to hyperaemia. Less commonly this may be due to the development of an arteriovenous fistula. We describe how SjO2 monitoring can be used in conjunction with transcranial Doppler ultrasound to make the distinction between these two conditions, which require distinct therapies. Multimodality monitoring in acute injury provides information regarding underlying pathophysiology and permits individualization of therapy.

Adult↗