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Biomedical subjects

D K Menon

Publications and source records attributed to D K Menon.

At least 91 records · Page 5Linked to original sources

Non-invasive measurement of cerebral blood volume in volunteers.

Invasive techniques are used for conventional measurements of cerebral blood volume and there is a need for methods which are more readily applicable clinically. We studied 13 healthy volunteers using near infrared spectroscopy and transcranial Doppler sonography. Middle cerebral artery flow velocity (vmca) and changes in cerebral oxygenated haemoglobin (HbO2), deoxygenated Hb (Hb), HbO2 - Hb (Hbdiff) [corrected] and HbO2 + Hb (total haemoglobin; Hbt) were measured at baseline and during graded reduction in arterial oxygen saturation (Spo2) to 85% at hypo-, normo- and hypercapnia. Cerebral blood volume (CBV) values, calculated from regression lines of Hbdiff/SpO2 and HbO2/SpO2 were 5.38 and 4.03 ml 100 g-1 for the two methods, respectively. CBV varied directly with FE'CO2, with mean CBV reactivities of 1.25 and 1.06 ml 100 g-1 kPa-1, respectively. Changes in Hbt were not systematically related to changes in FE'CO2. An increase in vmca and reciprocal decrease in estimated cerebrovascular resistance were observed when oxygen saturation decreased to less than 90-93%. These results suggest that cerebral haemodynamics in individual subjects may be monitored non-invasively providing the methodology is modified to account for hypoxic vasodilatation.

Adult↗

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part I: Elimination from the head.

We describe the first human experiments to demonstrate wash-out of isoflurane using fluorine magnetic resonance spectroscopy. Using a surface receive coil, we found two-compartment kinetics within the head with decay half-times of 9.5 and 130 min, but the signal was too weak to localize the compartments. If the fast compartment is assumed to be the brain then our results match the predictions of the classical perfusion-limited pharmacokinetic model of inhalation anaesthesia.

Adult↗

Magnetic resonance spectroscopy of isoflurane kinetics in humans. Part II: Functional localization.

We describe the first experiments to relate the cerebral kinetics of isoflurane (determined by fluorine magnetic resonance spectroscopy) to cerebral function. Using a surface receive coil we found two-compartment kinetics within the head with equilibrium half-times of 3.5 min and approximately 1 h with respect to expired isoflurane concentrations. Using critical fusion flicker frequency as an objective measure of the cerebral effect of isoflurane, we found evidence to identify the fast component as the brain. Responsiveness to command was lost at a brain partial pressure of 0.3% isoflurane. We conclude that the measured cerebral kinetics of isoflurane exactly matched the predictions of the classical perfusion-limited model.

Anesthetics, Inhalation↗

Thresholds for hypoxic cerebral vasodilation in volunteers.

UNLABELLED: The effects of hypoxemia on the cerebral vasculature have been described in animal models, but data from human studies are limited and have often relied on invasive methodology. The ability to detect a threshold for hypoxic vasodilatation in humans may be clinically useful, particularly in patients with impaired intracranial compliance. Because physiology may differ among subjects, it would be advantageous to measure such thresholds using noninvasive bedside techniques that could be readily applied to individual patients. We have attempted to identify thresholds of hypoxic vasodilatation in volunteers using noninvasive methods of measurement. Thirteen healthy volunteers were studied using transcranial Doppler sonography. Time-averaged middle cerebral artery maximal flow velocity (MCA FVx), mean arterial blood pressure, peripheral oxygen saturation (Spo2), and partial pressure of endtidal CO2 were measured at baseline and during graded reduction in arterial Spo2 to 85%, at normocapnia. Flow velocity and estimated cerebrovascular resistance (CVRe) were indexed and plotted against Spo2. There was no significant change in mean arterial pressure during desaturation to 85%, although the mean heart rate increased from 65 to 82 bpm. An increase in MCA FVx and reciprocal decrease in CVRe were observed when Spo2 decreased to below 90%. These results suggest that hypoxemic cerebral vasodilatation may be measured noninvasively and that in normal human volunteers, the threshold is at an Spo2 of 90%, which is greater than that previously reported. IMPLICATIONS: The ability to detect the point at which cerebral blood vessels dilate using noninvasive techniques is clinically advantageous. We have attempted to do this using transcranial Doppler sonography in volunteers whose inspired oxygen concentrations were gradually decreased. Thresholds of cerebral vasodilatation were found to be higher than those previously reported. These thresholds are important with regard to adequate perfusion in various pathologic states.

Adult↗

Haemodynamic effects of intravenous nimodipine following aneurysmal subarachnoid haemorrhage: implications for monitoring.

Nimodipine is widely used in patients with aneurysmal subarachnoid haemorrhage for the prevention and treatment of delayed ischaemic neurological deficits. Intravenous nimodipine has significant vasodilatory properties and may compromise the achievement of haemodynamic targets in patients who receive hypertensive hypervolaemic haemodilution therapy. We have studied 22 patients who received postoperative therapy with intravenous nimodipine and show that in a substantial minority (29%) hypotension was not reversed by simple volume loading or low doses of inotropes. Formal haemodynamic assessment in these patients showed widely varying haemodynamic variables, with differences in the need for inotropic and vasopressor therapy. We conclude that optimal haemodynamic management in this subgroup of patients will require the use of pulmonary artery catheterisation.

Adult↗

Effects of level of socio-economic development on course of non-affective psychosis.

BACKGROUND: This study explored the relation of level of socio-economic development to the course of non-affective psychosis, by extending the analysis of urban/rural differences in course in Chandigarh, India. METHOD: The proportion of 'best outcome' cases between urban (n = 110) and rural (n = 50) catchment areas were compared at two-year follow-up, separately for CATEGOS+ and non-S+ schizophrenia. RESULTS: The proportion of subjects with 'best outcome' ratings at the urban and rural sites, respectively, was similar for CATEGOS+ schizophrenia (29 v. 29%), but significantly different for non-S+ psychosis (26 v. 47%). CONCLUSIONS: The fact that in rural Chandigarh, psychoses have a more favourable course than in the urban area may be explained in large part by psychoses distinct from 'nuclear' schizophrenia.

Cohort Studies↗

Survey of intensive care of severely head injured patients in the United Kingdom.

OBJECTIVES: To study practice in intensive care of patients with severe head injury in neurosurgical referral centres in United Kingdom. DESIGN: Structured telephone interview of senior nursing staff in intensive care unit of adult neurosurgical referral centre. SETTING: 39 intensive care units in hospitals that accepted acute head injuries for specialist neurosurgical management, identified from Medical Directory and information from professional bodies. MAIN OUTCOME MEASURES: Details of organisation and administration of intensive care and patterns of monitoring and treatment for patients admitted with severe head injury. RESULTS: Patients were managed in specialist neurosurgical intensive care units in 21 of the centres and in general intensive care units in 18. Their intensive care was coordinated by an anaesthetist in 25 units and by a neurosurgeon in 12. Annual case-load varied between units: 20 received > 100 patients, 12 received 50-100, and seven received 25-49. Monitoring and treatment varied considerably between centres. Invasive arterial pressure monitoring was used routinely in 36 units, but central venous pressure monitoring was routinely used in 24 and intracranial pressure was routinely monitored in only 19. Corticosteroids were used to treat intracranial hypertension in 19 units. Seventeen units routinely aimed for arterial carbon dioxide pressure of 3.3-4.0 kPa, and one unit still used severe hyperventilation to a pressure of < 3.3 kPa. CONCLUSION: The intensive care of patients with acute head injuries varied widely between the centres surveyed. Rationalisation of the intensive care of severe head injury with the production of widely accepted guidelines ought to improve the quality of care.

Adrenal Cortex Hormones↗

Plasma antioxidant potential in severe sepsis: a comparison of survivors and nonsurvivors.

OBJECTIVE: To determine the plasma antioxidant potential of patients in the intensive care unit (ICU) with severe sepsis and secondary organ dysfunction and relate these findings to outcome. DESIGN: A prospective, cohort study. SETTING: A nine-bed ICU in a university teaching hospital. PATIENTS: Fifteen consecutive patients, who were within 16 hrs of development of severe sepsis and secondary organ dysfunction. INTERVENTIONS: Plasma samples were obtained within 16 hrs of the onset of secondary organ dysfunction and subsequently on days 2, 3, 4, 6, 8, 10, and 15 until patients either left the ICU or died. Plasma antioxidant potential was determined by an ultraviolet spectrophotometric technique. MEASUREMENTS AND MAIN RESULTS: The mean initial plasma antioxidant potential was lower than our range for healthy volunteers (p < .05). Survivors had an initial plasma antioxidant potential that was greater than nonsurvivors (p < .01), and serial subset analysis demonstrated that survivors, despite having a low initial plasma antioxidant potential rapidly attained normal or supranormal values. While plasma antioxidant potential also increased in nonsurvivors over time, values in this subset never reached the normal range and remained below values in survivors at all time points studied (p < .05). CONCLUSIONS: Plasma antioxidant potential is initially decreased in patients with sepsis who develop organ dysfunction, and it increases over time. While we have no clear evidence to prove that this reduction has a causal relationship, failure to achieve a normal plasma antioxidant potential is strongly associated with an unfavorable outcome.

APACHE↗

The effects of hypoxaemia and recommendations for postoperative oxygen therapy.

Hypoxaemia following surgery is common and may be prolonged and severe. The thresholds for deleterious effects of hypoxaemia on the heart and central nervous system are reviewed and the problems of assessment of the adequacy of tissue oxygenation are outlined. Recommendations for postoperative oxygen therapy are made.

Brain↗

Plasma antioxidant consumption associated with ischemia/reperfusion during carotid endarterectomy.

BACKGROUND AND PURPOSE: Thirteen patients undergoing carotid endarterectomy were studied to correlate changes in jugular bulb venous oxygen saturation (SjO2) with indices of free radical production during cerebral ischemia/reperfusion. Levels of oxidant species were also monitored in arterial samples to determine any change across the cerebral circulation. METHODS: Blood was sampled from a venous catheter inserted in the ipsilateral jugular bulb and from an arterial catheter. Co-oximetry measurements were made to determine jugular bulb venous oxygenation saturation. To monitor changes in oxidant stress, a colorimetric assay was used to determine plasma antioxidant potential, and electron paramagnetic resonance spectroscopy was used to quantify free radical-spin trap adducts formed in a blood sample treated with the spin trap alpha-tert-butyl phenyl nitrone (PBN). RESULTS: SjO2 decreased significantly from 68 +/- 11% to 61 +/- 10% (P < .05) during clamping of the internal carotid artery and returned to baseline (65 +/- 11%) when the carotid clamp was removed. Jugular venous plasma antioxidant potential decreased significantly from 32.76 +/- 5.42% inhibition to 28.02 +/- 6.77% inhibition (P < .05). There was no concomitant change in arterial plasma antioxidant potential values, indicating a decrease in antioxidant capacity across the cerebral circulation. However, analysis of spin trap-free radical adducts did not provide conclusive evidence for free radical production. CONCLUSIONS: These results provide supportive evidence for oxidant production during cerebral ischemia/reperfusion in a clinical setting.

Aged↗

Monitoring of cerebral autoregulation in head-injured patients.

BACKGROUND AND PURPOSE: Disturbed cerebral autoregulation has been reported to correlate with an unfavorable outcome after head injury. Using transcranial Doppler ultrasonography, we investigated whether hemodynamic responses to spontaneous variations of cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve. METHODS: We studied 82 patients with head injury daily. Waveforms of intracranial pressure (ICP), arterial pressure, and transcranial Doppler flow velocity (FV) were captured during 2-hour periods. Time-averaged mean FV (FVm) and the FV during cardiac systole (FVs) were resolved. The correlation coefficient indices between FVm and CPP (Mx) and between FVs and CPP (Sx) during spontaneous fluctuations of CPP were calculated during 3-minute epochs and averaged for each investigation. RESULTS: Mx and Sx correlated with CPP (r = -.34, P = < .002; r = -.2, P = NS. respectively), with ICP (r = .46, P < .0001; r = .34, P < .003, respectively), with admission Glasgow Coma Scale score (r = -.34, P < .0025; r = -.38, P < .0008, respectively), and with outcome after head injury (r = .41, P < .0002; r = .48, P < .00009, respectively). In patients who died, cerebral autoregulation was severely disturbed during the first 2 days after injury. CONCLUSIONS: Indices derived from spontaneous fluctuations of FV waveform and CPP describe cerebral vascular pressure reactivity. They correlate with outcome after head injury and therefore may be used to guide autoregulation-oriented intensive therapy.

Adolescent↗

In vivo hepatic 31P magnetic resonance spectroscopy in chronic alcohol abusers.

BACKGROUND/AIMS: In vivo hepatic 31P magnetic resonance spectroscopy (MRS) can provide information on hepatic energy metabolism, phospholipid substrates, and hepatocyte lipid bilayers. The aim of this study was to ascertain the effects of alcohol ingestion on hepatic 31P spectral variables. METHODS: Twenty-six chronic alcohol abusers underwent hepatic 31P MRS 6-12 hours after their last alcoholic drink; studies were repeated in 17 individuals following abstinence from alcohol. The reference population comprised 16 healthy volunteers. Ratios of phosphomonoesters (PME), inorganic phosphate, and phosphodiesters (PDE) relative to beta-adenosine triphosphate (ATP) were measured. RESULTS: In patients with minimal liver injury, recent drinking was associated with a significant elevation in the mean PDE/ATP ratio (P < 0.0001) and an increase in mean PME/ATP, which was not significant; abstinence was associated with reductions in both metabolite ratios. In patients with alcoholic cirrhosis, recent drinking was associated with an elevation in mean PME/ATP (P < 0.05) and an increase in mean PDE/ATP, which was not significant; abstinence was associated with no significant change in PME/ATP but with a reduction in PDE/ATP. CONCLUSIONS: In the absence of significant liver injury, chronic alcohol abuse is associated with the elevation of PME/ATP, possibly reflecting changes in hepatic redox potential, and of PDE/ATP, most likely reflecting the induction of hepatocyte endoplasmic reticulum. In the presence of cirrhosis, these changes are attenuated and modified.

Adenosine Triphosphate↗

Visualisation of changes in regional cerebral blood flow (rCBF) produced by ketamine using long TE gradient-echo sequences: preliminary results.

Autoradiographic studies have shown that low dose ketamine produces increases in regional glucose utilisation and blood flow in the hippocampus, cerebral cortex, and olfactory lobe in the rat brain, probably due to antagonism at the NMDA receptor. Functional MRI using deoxyhaemoglobin contrast can be used to study changes in regional cerebral blood flow (rCBF). Long TE gradient-echo sequences were used to study changes in rCBF produced by low dose ketamine in rats anaesthetised with nitrous oxide, supplemented with either halothane (HAL) or fentanyl/fluanisone/midazolam (FFM) combination. Images from rats in the FFM group showed a 10-14% increase in signal intensity in the hippocampus, cerebral cortex, and olfactory lobe following either a single bolus or a low dose infusion of ketamine (p < .05). These changes were significantly reduced in the HAL group (p < .005). Halothane is known to attenuate the changes in regional glucose utilisation produced by the noncompetitive NMDA antagonist dizocilpine (MK-801), and its effects on ketamine-induced changes in rCBF seen in this study may be due to a similar effect. The potential use of functional MRI in studying the effect of pharmacological interventions on rCBF is discussed.

Anesthetics, Dissociative↗

Near-infrared spectroscopy use in patients with head injury.

A multimodality recording system was used in 14 ventilated patients with closed head injury to assess the potential use of near-infrared spectroscopy (NIRS) in the neurointensive care unit. Signals of intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, jugular venous saturation, and NIRS-derived changes in the chromophores of oxy- and deoxyhemoglobin were digitized and recorded. After a review of 886 hours of continuous monitoring, 376 hours were considered free from artifact and were entered for final analysis. In nine of the patients 38 events were recorded that demonstrated clear changes in cerebral perfusion pressure accompanied by hemodynamic changes in middle cerebral artery flow velocity (transcranial Doppler) and cortical perfusion (laser Doppler flowmetry). Near-infrared spectroscopy showed correlated changes in 37 events (97%) whereas jugular venous saturation monitoring registered only 20 (53%). There was associated peripheral oxygen desaturation in eight cases (21%), intracranial hypertension in 10 (26%), and cerebral hyperemia in eight (21%). The remaining 12 events (32%) appeared to be complex changes of uncertain origin. Iatrogenic factors were identified as causative in 14 cases (37%). The potential application of NIRS in adults and the importance of using multiple parameter recording systems in the interpretation of cerebral events are discussed.

Adolescent↗

Effect of functional grade and etiology on in vivo hepatic phosphorus-31 magnetic resonance spectroscopy in cirrhosis: biochemical basis of spectral appearances.

Hepatic phosphorus-31 magnetic resonance spectroscopy (31P MRS) was undertaken in 85 patients with histologically proven cirrhosis of varying etiologies and functional severity. Reference data were acquired from 16 healthy volunteers who had no history or evidence of liver disease or alcohol abuse. In vivo hepatic 31P MR spectra were acquired with pulse angle 45 degrees and repetition times (TR) of 5 and 0.5 seconds. Peak area ratios of phosphomonoesters (PME), inorganic phosphate (Pi), and phosphodiesters (PDE) relative to beta ATP, and of PME relative to PDE were calculated from spectra acquired at TR 5 seconds. Estimates of saturation effects for individual resonances were obtained by dividing the peak height at TR 5 seconds by that at TR 0.5 seconds to yield a T1-related signal height ratio (SHR). When compared with reference values, the patients with liver disease showed a significantly higher PME/ATP (P < .0001), PME/PDE (P < .0001), PME SHR (P < .001), and Pi SHR (P < .02), and a lower PDE/ATP (P < .001) and PDE SHR (P < .001). The magnitude of these changes increased significantly and progressively with increasing functional impairment. In patients with compensated cirrhosis spectral appearances varied with etiology; thus, patients with postviral cirrhosis showed a significantly higher Pi/ATP; those with alcoholic cirrhosis, a significantly lower PDE/ATP; and those with cirrhosis secondary to primary sclerosing cholangitis, a significantly lower Pi/ATP than the healthy volunteers or other etiological groups. However, spectral appearances did not vary with etiology in patients with decompensated disease. In vitro 31P MRS of perchloric extracts of samples of liver tissue obtained from 10 patients with cirrhosis at transplant hepatectomy showed increases in levels of the soluble PME metabolites, phosphorylcholine and phosphorylethanolamine, and reductions in the levels of the soluble PDE metabolites, glycerophosphorylcholine and glycerophosphorylethanolamine. These changes suggest regenerative activity in cirrhotic livers. The increases in soluble phosphomonoesters in the aqueous extracts accounted for the increased PME/ATP ratio seen in the in vivo spectra, and might account for the increase in PME SHR. The reduction in soluble phosphodiesters in the aqueous extracts did not entirely account for the reduction PDE/ATP ratio seen in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

New horizons in ICU sedation: exploring non-sedative effects of ICU sedation.

Sedative drugs are widely used in intensive care, primarily in ventilated patients. The common actions and side-effects of these agents are widely recognised. However, recent evidence suggests that opiates and other sedative agents that are used in this situation also have important, but not widely appreciated, effects on metabolism, physiological signalling and disease mechanisms. Some of these effects are an extension of their expected therapeutic actions; these are being elucidated as the biological consequences of stress, and its suppression is now being clarified. An example is the central effects of benzodiazepines and opioids on metabolism and immune function. In other instances these drugs have important peripheral actions, with immunomodulatory or metabolic roles. Furthermore, some drugs may modify disease processes--an example being the antioxidant effect of propofol. Finally, basic cellular mechanisms, such as immediate early gene expression and transcription factor activation, may involve processes that may be susceptible to modification by sedative agents. Such secondary effects of sedative agents need to be investigated for three reasons. First, they provide explanations for some phenomena observed during their use. Second, some of the undesirable side-effects may be avoided by judicious use of drugs in certain clinical situations. Finally, there is the prospect that we may be able to harness some actions for novel therapeutic purposes.

Adrenal Glands↗