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Biomedical subjects

D K Menon

Publications and source records attributed to D K Menon.

At least 73 records · Page 4Linked to original sources

Nonunion of the humerus after failure of surgical treatment. Management using the Ilizarov circular fixator.

We used the Ilizarov circular external fixator to treat 16 patients with persistent nonunion of the diaphysis of the humerus despite surgical treatment. All patients had pain and severe functional impairment of the affected arm. In ten, nonunion followed intramedullary nailing. We successfully treated these by a closed technique. The nail was left in place and the fracture compressed over it. The fractures of the other six patients had previously been fixed by various methods. We explored these nonunions, removed the fixation devices and excised fibrous tissue and dead bone before stabilising with the Ilizarov fixator. In five patients union was achieved. Bone grafting was not required. In the single patient in whom treatment failed, there had been a severely comminuted open fracture. All except one patient had reduction of pain, and all reported an improvement in function.

Adult↗

5- to 8-year results of the Freeman press-fit hip arthroplasty without HA coating: a clinicoradiologic study.

Sixty-one consecutive patients (68 hips) with an average age of 49.7 years (range, 21-72 years) had the Freeman uncemented hip arthroplasty without HA coating performed in the Southern General Hospital between 1987 and 1990. These patients were reviewed retrospectively for a mean duration of 66 months (range, 3-103 months). A high incidence of significant thigh pain (40.4%) at 5 to 8 years was noted in this series. The average 5- to 8-year femoral subsidence was 5.4 mm (range, 0-16.1 mm) in 45 hips. Seventeen hips (29.3%) required revision at the time of analysis. Nine hips (15.5%) were revised for aseptic loosening at an average duration of 54 months after the index operation. The conclusion drawn from this series is that the Freeman press-fit hip produced unsatisfactory medium-term results.

Aged↗

Testing of adult and paediatric ventilators for use in a magnetic resonance imaging unit.

We have assessed the performance of a series of ventilators (modified versions of the ventiPAC, paraPAC and babyPAC ventilators; SIMS pneuPAC Ltd, Luton, UK) in a magnetic resonance imaging (MRI) scanning environment, with MR safety and compatibility issues being addressed. Following initial modifications to remove ferromagnetic components and replace them with MR-safe materials, all three ventilators performed well in a series of tests in static magnetic fields up to 2 T. Ventilator performance was unaffected by static fields, switching gradients or radio frequency fields within the MR suite. Furthermore, the devices produced no degradation of image quality when used during MR scanning. We discuss management strategies for the care of critically ill ventilated patients during MR procedures.

Adult↗

Infusion pump performance in an MR environment.

Concerns about life support equipment accompanying the critically ill patient have to date made magnetic resonance imaging (MRI) studies of this patient group the exception. We present here a series of tests performed on an IVAC P3000 infusion pump to investigate its suitability for the magnetic resonance imaging environment. We investigate safety, pump performance and image quality issues. The pump was housed at the end of the patient couch to prevent motion towards the scanner. Gravimetric tests found the pump to work within acceptable parameters at a static field of 10 mT. Image interference issues were addressed.

Artifacts↗

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non-spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid-dorsolateral and mid-ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non-spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a 'spatial span' task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood-flow was observed in the right mid-ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid-dorsolateral frontal-lobe region. By contrast, during a '2-back' task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid-ventrolateral and mid-dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid-dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid-dorsolateral and mid-ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Adult↗

Measuring brain tissue oxygenation compared with jugular venous oxygen saturation for monitoring cerebral oxygenation after traumatic brain injury.

UNLABELLED: Jugular bulb oximetry is the most widely used method of monitoring cerebral oxygenation. More recently, measurement of brain tissue oxygenation has been reported in head-injured patients. We compared the changes in brain tissue oxygen partial pressure (PbO2) with changes in jugular venous oxygen saturation (SjVO2) in response to hyperventilation in areas of brain with and without focal pathology. Thirteen patients with severe head injuries were studied. A multiparameter sensor was inserted into areas of brain with focal pathology in five patients and outside areas of focal pathology in eight patients. A fiberoptic catheter was inserted into the right jugular bulb. Patients were hyperventilated in a stepwise manner from a PaCO2 of approximately 35 mm Hg to a PaCO2 of 22 mm Hg. There was no significant change in cerebral perfusion pressure or arterial partial pressure of oxygen with hyperventilation. In areas without focal pathology, there was a good correlation between changes in SjVO2 and PbO2 (deltaSjVO2 and deltaPbO2; r2 = 0.69, P < 0.0001). In areas with focal pathology, there was no correlation between deltaSjVO, and APbO2 (r2 =0.07, P = 0.23). In this study, we demonstrated that measurement of local tissue oxygenation can highlight focal differences in regional cerebral oxygenation that are disguised when measuring SjVO2. Thus, monitoring of PbO2 is a useful addition to multimodal monitoring of patients with traumatic head injury. IMPLICATIONS: Brain oxygenation is currently monitored by using jugular bulb oximetry, which attracts a number of potential artifacts and may not reflect regional changes in oxygenation. We compared this method with measurement of brain tissue oxygenation using a multiparameter sensor inserted into brain tissue. The brain tissue monitor seemed to reflect regional brain oxygenation better than jugular bulb oximetry.

Adult↗

Cerebrovascular cytokine responses during coronary artery bypass surgery: specific production of interleukin-8 and its attenuation by hypothermic cardiopulmonary bypass.

UNLABELLED: Brain dysfunction after cardiopulmonary bypass (CPB) is common, and it has been hypothesized that this injury might be due partly to activation of inflammatory processes in the brain. We measured juguloarterial gradients for interleukin-1beta, interleukin-6, and interleukin-8 (IL-8) as indices of local proinflammatory cytokine production in the brain and studied the effect of temperature during CPB on these changes. Twelve patients undergoing coronary artery bypass graft surgery (normothermic CPB n = 6, hypothermic CPB n = 6) were studied. Cytokine levels were measured in paired arterial and jugular bulb samples obtained before, during, and after CPB. Although systemic levels of all three cytokines increased during and after CPB, increases in juguloarterial cytokine gradients were observed only for IL-8. Juguloarterial IL-8 gradients started to increase 1 h post-CPB and were significantly elevated 6 h post-CPB (P < 0.05). At this time point, the median (interquartile range) juguloarterial IL-8 gradients were significantly larger in the normothermic CPB group (25.81 [24.49-39.51] pg/mL) compared with the hypothermic CPB group (6.69 [-0.04 to 15.47] pg/mL; P < 0.05). These data imply specific and significant IL-8 production in the cerebrovascular bed during CPB and suggest that these changes may be suppressed by hypothermia during CPB. IMPLICATIONS: Using juguloarterial gradients to measure cerebrovascular cytokine production is novel in the setting of cardiopulmonary bypass and implicates the cerebral activation of inflammatory processes, which may contribute to brain dysfunction. Hypothermia during cardiopulmonary bypass may significantly attenuate this response.

Aged↗

Magnetic resonance imaging compatibility testing of intracranial pressure probes. Technical note.

There is increasing recognition that magnetic resonance (MR) imaging and spectroscopy may provide important information in the assessment of patients with acute brain injury. However, optimum care of the acutely head injured patient requires monitoring of intracranial pressure (ICP). Although many monitoring modalities have been integrated into commercially available MR-compatible systems, there have been no reports of commonly used intraparenchymal ICP sensors in an MR environment. The authors describe the use of an ICP micromanometer probe in an MR environment, with a fiberoptic connection that interfaces the probe with a commercially available MR-compatible monitoring system. Phantom studies were performed to demonstrate the safety and compatibility of the modified MR system at 0.5 tesla. The safety of the device was assessed in relation to its interaction with the static, gradient, and radiofrequency fields used in MR imaging. The MR compatibility was documented by demonstrating that its performance was unaffected by the operation of imaging sequences and by showing that there was no degradation of the diagnostic quality of imaging data obtained during ICP monitoring.

Equipment Design↗

Cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability in isolated pig hearts after ischaemia and reperfusion.

Isolated pig hearts, subsequently perfused with pig or human blood, were prepared for the cytochemical demonstration of sites of hydrogen peroxide generation and increased vascular permeability. Oxidant stress was associated with ultrastructural changes commonly seen following myocardial reperfusion. In addition, the precipitation of cerium perhydroxide following perfusion with physiological saline containing cerium chloride suggested the vascular endothelium and leukocytes as sources of oxidants. This was associated with rapid penetration of horseradish peroxidase through the intercellular clefts of the vascular endothelium into the interstitial space, suggesting increased vascular leakiness at these sites. The rapid penetration of horseradish peroxidase was observed at all monitored periods of reperfusion with pig or human blood. This indicates that the increased permeability occurred during the ischaemic period and continued during reperfusion. Morphological damage was greatest in pig hearts reperfused with whole human blood and this was attenuated if the blood was preabsorbed to remove antibodies prior to reperfusion. We conclude that oxidant stress was initiated during ischaemia and continued during reperfusion in this model.

Animals↗

The intensive care of severe head injury: a survey of non-neurosurgical centres in the United Kingdom.

Few data exist regarding the management of severe head injury in non-neurosurgical centres within the UK. We aimed to discover the number of intensive care units admitting head injury patients, the number of patients admitted annually, and the monitoring and treatment methods followed. Questionnaires were sent to the senior nurse and consultant in 263 intensive care units within non-neurosurgical hospitals. The response rate was 78.8%, with at least one response received from 93.2% of hospitals. The severely head injured were routinely admitted in 56.7% of units. Approximately 2100 patients are admitted annually, a mean of 15 per unit. Intracranial pressure monitoring is routine in only 9% of units and 7% are without 24-h facilities for CT, a cause for concern. More encouragingly, 63% of hospitals have access to rehabilitation facilities. Distribution of guidelines to all intensive care units participating in the care of head injury may improve management and outcome.

Critical Care↗

Antioxidant effects of propofol in human hepatic microsomes: concentration effects and clinical relevance.

Propofol is known to possess antioxidant properties. There is controversy regarding the mechanisms by which the drug produces its antioxidant effects and the significance of these effects in relation to plasma concentrations of propofol in clinical practice. We studied the effects of increasing concentrations of Intralipid, propofol, butylated hydroxytoluene (BHT) and a vitamin E analogue (Trolox C) in 0.9% saline on non-enzymic and enzymic lipid peroxidation in human hepatic microsomes, and on concentrations of antioxidant enzymes in a Hep G2 cell line. Propofol showed significant inhibition of lipid peroxidation, but was less potent than BHT or Trolox C. IC50 values for non-enzymic and enzymic lipid peroxidation were mean 9.47 (SD 0.86) and 7.39 (0.84) mumol litre-1 for propofol, 1.30 (0.57) and 0.32 (0.02) mumol litre-1 for BHT and 2.34 (0.68) and 0.35 (0.04) mumol litre-1 for Trolox C, respectively. The antioxidant activities of propofol were substantially retained in the presence of up to 30 g litre-1 of human serum albumin. Propofol at concentrations of up to 100 mumol litre-1 had no significant effect on the activities of antioxidant enzymes. Clinically relevant concentrations of propofol produced significant inhibition of both enzymic and non-enzymic lipid peroxidation in hepatic microsomal preparations, possibly as a result of accumulation in lipophilic environments. Measurement of antioxidant effects of drugs in aqueous media may have little relevance to their effects in protecting against lipid peroxidation in biological systems.

Anesthetics, Intravenous↗

Propofol preserves the viability of isolated rat hepatocyte suspensions under an oxidant stress.

UNLABELLED: The purpose of this study was to investigate whether propofol protects rat hepatocyte suspensions against an oxidant attack by a free radical generator 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Rat hepatocyte suspensions (2 x 10(6) cells/mL) were prepared using Seglen's collagenase perfusion technique. Suspensions were treated with AAPH (50 mM) alone, propofol (28 microM) plus AAPH, or, in a separate experiment, with either AAPH alone or 10% intralipid (0.5 microL/mL) plus AAPH. Each experiment had untreated control suspensions. Cell viability was measured at 1, 2, and 3 h using the trypan blue exclusion test and expressed as a percentage of the initial number of viable cells. Cells taken from control at time 0 h and each experimental group at 1 h from five separate hepatocyte preparations were examined by electron microscopy. Control cell viability decreased with time. The addition of AAPH significantly reduced viability compared with control (P < 0.0001); pretreatment with propofol significantly attenuated this effect at 1 h (P = 0.0008), but 10% intralipid had no effect. Electron microscopy revealed structural changes in cell membranes that could have accounted for the inability to exclude trypan blue. In conclusion, a 28-microM concentration of propofol protects rat hepatocytes from an oxidant stress sufficient to cause cell death at 1 h. IMPLICATIONS: Oxidants contribute to tissue injury in a variety of situations. We have shown that the anesthetic propofol improves survival of liver cells exposed to oxidant injury at blood concentrations achieved in anesthetized patients. These effects may be relevant during transplantation and critical illness.

Anesthetics, Intravenous↗

Neuroprotection (including hypothermia).

There have been over 2000 publications in the last year addressing the topic of neuroprotection. Novel and emerging therapeutic targets that have been explored include cerebral inflammation, hypothermia, neural transplantation and repair and gene therapy. Unfortunately, with few exceptions, the successes of experimental neuroprotection have not been translated into clinical practice. The possible reasons for the discrepancy between experimental success and clinical benefit are explored.

Journal Article↗

Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study.

The objective of this study was to analyse the temporal course of the jugular venous-arterial gradient of S-100B protein after severe head injury and the correlation between the absolute concentrations of serum S-100B protein and outcome, CT findings, and clinical variables. Fifteen patients were included in this pilot study. All patients were treated according to a standard therapy protocol targeted to maintain cerebral perfusion pressure. The serum concentration of S-100 protein was measured daily for five consecutive days after injury by a monoclonal two site immunoluminometric assay. Nine patients showed favourable and six unfavourable outcome after 6 months with a mortality rate of 33% (five patients). The mean gradient between jugular venous and arterial blood was 8.2% (p<0.05). Patients showing an unfavourable outcome had significantly higher jugular venous or arterial S-100 values compared with those with a favourable outcome (jugular venous S-100B 2.78 microg/l v 1.22 microg/l, p<0.05; arterial S-100B 2.48 microg/l v 1.19 microg/l, p<0.05). All patients with an initial or secondary increase in S-100B value of >2 microg/l were found to have an unfavourable outcome. S-100B was found to be an independent predictor of outcome after severe head injury. The persisting increase of S-100B for three to five days even in patients with favourable outcome and no signs of secondary insults might reflect continuing damage to the blood-brain barrier or ongoing glial cell death.

Adolescent↗

Propofol neuroprotection in a rat model of ischaemia reperfusion injury.

This study was designed to test the hypothesis that propofol, which possesses antioxidant properties, would produce greater protection than isoflurane in cerebral ischaemia reperfusion injury, at dose levels that produced similar affects on brain electrical activity. Twenty Sprague-Dawley rats were anaesthetized using isoflurane 1.5% in air/oxygen, and mechanically ventilated to a PaCO2 of 4.5 kPa. Following 90 min of middle cerebral artery occlusion using an intraluminal filament, rats were given, in random order, either propofol 1 mg kg-1 min-1 or isoflurane 3% (both of which have been shown to reliably produce EEG burst suppression). After a further 30 min, reperfusion was induced by withdrawing the filament. Animals were killed following 240 min of reperfusion. Rats in the propofol group showed a 21% reduction in mean hemispheric infarct volume when compared with the isoflurane group (P < 0.0001). These data suggest that propofol may act by mechanisms in addition to CMRO2 depression, and provide a basis for further studies of propofol neuroprotection.

Anesthesia↗