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Biomedical subjects

B Venkatesh

Publications and source records attributed to B Venkatesh.

At least 19 recordsLinked to original sources
PubMed2006

Active-site properties of Phrixotrix railroad worm green and red bioluminescence-eliciting luciferases.

The luciferases of the railroad worm Phrixotrix (Coleoptera: Phengodidae) are the only beetle luciferases that naturally produce true red bioluminescence. Previously, we cloned the green- (PxGR) and red-emitting (PxRE) luciferases of railroad worms Phrixotrix viviani and P. hirtus[OLE1]. These luciferases were expressed and purified, and their active-site properties were determined. The red-emitting PxRE luciferase displays flash-like kinetics, whereas PxGR luciferase displays slow-type kinetics. The substrate affinities and catalytic efficiency of PxRE luciferase are also higher than those of PxGR luciferase. Fluorescence studies with 8-anilino-1-naphthalene sulfonic acid and 6-p-toluidino-2-naphthalene sulfonic acid showed that the PxRE luciferase luciferin-binding site is more polar than that of PxGR luciferase, and it is sensitive to guanidine. Mutagenesis and modelling studies suggest that several invariant residues in the putative luciferin-binding site of PxRE luciferase cannot interact with excited oxyluciferin. These results suggest that one portion of the luciferin-binding site of the red-emitting luciferase is tighter than that of PxGR luciferase, whereas the other portion could be more open and polar.

Animals↗
PubMed2006

Uneven evolutionary rates of bradykinin B1 and B2 receptors in vertebrate lineages.

Bradykinin acts through two receptor subtypes in mammals and generates a variety of responses including pain, inflammation and hypotension. The evolutionary history of the bradykinin system has been unclear due to shortage of information outside mammals. We describe here two receptor subtypes and the bradykinin precursor in three species of bony fish (the zebrafish Danio rerio, the Japanese pufferfish Takifugu rubripes, and the green spotted pufferfish Tetraodon nigroviridis) and chicken and analyze the relationships to mammals by a combination of phylogeny, conserved synteny and exon-intron organization. All of these species have two receptor genes located close to each other in a tandem formation, with the B2 gene 5' to the B1 gene, in chromosomal regions displaying conserved synteny between the species (albeit conservation of synteny in zebrafish is still unclear due to poor genome assembly). The evolutionary rate differs between the two genes as well as between lineages leading to differing pharmacological properties for both B1 and B2 across vertebrate classes. Also the bradykinin precursor gene was identified in all of these species in a chromosome region with conserved synteny. The tissue distribution of mRNA in T. rubripes is similar for B1 and B2, suggesting more similar regulation for the two genes than in mammals. In conclusion, the receptor tandem duplication predates the divergence of ray-finned fish and tetrapods and no additional duplicates of the receptors or bradykinin seem to have survived the ray-finned fish tetraploidization.

Animals↗
PubMed2006

B-type natriuretic peptide concentrations and myocardial dysfunction in critical illness.

B-type natriuretic peptide (BNP) is the first biomarker of proven value in screening for left ventricular dysfunction. The availability of point-of-care testing has escalated clinical interest and the resultant research is defining a role for BNP in the investigation and treatment of critically ill patients. This review was undertaken with the aim of collecting and assimilating current evidence regarding the use of BNP assay in the evaluation of myocardial dysfunction in critically ill humans. The information is presented in a format based upon organ system and disease category. BNP assay has been studied in a spectrum of clinical conditions ranging from acute dyspnoea to subarachnoid haemorrhage. Its role in diagnosis, assessment of disease severity, risk stratification and prognostic evaluation of cardiac dysfunction appears promising, but requires further elaboration. The heterogeneity of the critically ill population appears to warrant a range of cut-off values. Research addressing progressive changes in BNP concentration is hindered by infrequent assay and appears unlikely to reflect the critically ill patient's rapidly changing haemodynamics. Multi-marker strategies may prove valuable in prognostication and evaluation of therapy in a greater variety of illnesses. Scant data exist regarding the use of BNP assay to alter therapy or outcome. It appears that BNP assay offers complementary information to conventional approaches for the evaluation of cardiac dysfunction. Continued research should augment the validity of BNP assay in the evaluation of myocardial function in patients with life-threatening illness.

Biomarkers↗
PubMed2006

The imaginary line method is not reliable for identification of prosthetic heart valves on AP chest radiographs.

OBJECTIVE: To examine the utility of four criteria for distinguishing aortic from mitral valve prostheses on supine anteroposterior (AP) chest x rays in critically ill patients. MATERIALS AND METHODS: Two reviewers independently examined the post operative chest X-rays (CXR) of all patients undergoing either an aortic or mitral valve replacement over a 32 month period, in a blinded fashion. They applied four criteria to each film. For each criterion a sensitivity and specificity of differentiating the valve positions correctly was calculated for each reviewer, as well as a kappa statistic for inter-observer agreement between the two reviewers. RESULTS: Two hundred and twenty seven CXR's were evaluated by each of the reviewers. There were 174 aortic and 53 mitral valve replacements. There was a high level of inter-observer agreement for all four criteria applied (kappa values 0.785 to 0.966). Criterion one (imaginary line method) could be applied by both reviewers to less than 50% of CXR's, and when applied was specific but not sensitive. The other three criteria could be applied by both reviewers to approximately 80% of films. Criterion 2 (orientation method) was sensitive but not specific. Criteria 3 (valve orifice method) and 4 (perceived direction of blood flow method) were both highly sensitive and specific and are therefore the best methods. CONCLUSIONS: The well known imaginary line method is of limited value when identifying prosthetic valve positions on supine AP CXR's. We advocate the use of the "valve orifice" method or the "perceived direction of blood flow" method to gain valuable information regarding the presence and position of prosthetic heart valves.

Aortic Valve↗
PubMed2005

Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study.

It is unclear whether a random plasma cortisol measurement and the corticotropin (ACTH) test adequately reflect glucocorticoid secretory capacity in critical illness. This study aimed to determine whether these tests provide information representative of the 24 hour period. Plasma cortisol was measured hourly for 24 hours in 21 critically ill septic patients followed by a corticotropin test with 1 microg dose administered intravenously. Serum and urine were analysed for ACTH and free cortisol respectively. Marked hourly variability in plasma cortisol was evident (coefficient of variation 8-30%) with no demonstrable circadian rhythm. The individual mean plasma cortisol concentrations ranged from 286 +/- 59 nmol/l to 796 +/- 83 nmol/l. The 24 hour mean plasma cortisol was strongly correlated with both random plasma cortisol (r2 0.9, P < 0.0001) and the cortisol response to corticotropin (r2 0.72, P < 0.001). Only nine percent of patients increased their plasma cortisol by 250 nmol/l after corticotropin (euadrenal response). However, 35% of non-responders had spontaneous hourly rises > 250 nmol/l thus highlighting the limitations of a single point corticotropin test. Urinary free cortisol was elevated (865 +/- 937 nmol) in both corticotropin responders and non-responders suggesting elevated plasma free cortisol. No significant relationship was demonstrable between plasma cortisol and ACTH. We conclude that although random cortisol measurements and the low dose corticotropin tests reliably reflect the 24 hour mean cortisol in critical illness, they do not take into account the pulsatile nature of cortisol secretion. Consequently, there is the potential for erroneous conclusions about adrenal function based on a single measurement. We suggest that caution be exercised when drawing conclusions on the adequacy of adrenal function based on a single random plasma cortisol or the corticotropin test.

APACHE↗
PubMed2005

Experiences of anticholinesterase pesticide poisonings in an Australian tertiary hospital.

There is limited information regarding the management and outcomes of patients presenting with anticholinesterase pesticide poisoning in Australia. Patients presenting to a tertiary referral hospital with anticholinesterase exposures were identified by discharge coding. The medical records of each patient were retrospectively reviewed. Based on clinical outcome, patients were classified as severe or non-severe poisonings. Forty-one presentations were noted between 1990 and 2003. Eight patients (20%) had severe poisoning of which tachycardia, fasciculations with weakness and metabolic acidosis were common manifestations. The diagnosis was delayed in four patients due to the absence of a clear history, which did not influence patient outcomes or put hospital staff at risk of nosocomial poisoning. The median length of hospital stay was prolonged in severe poisonings (20 days) compared to 12 hours in other patients. Two cases of intermediate syndrome were attributed to fenthion and diazinon, and one case of delayed polyneuropathy to trichlorfon. Cholinesterase activities were performed in only 49% of presentations. The overall mortality was 2.4% (1 death) and the mortality in patients with severe poisoning was 12.5%. The incidence of anticholinesterase poisoning in Australia is low. These outcomes were favourable and comparable with other published data. Measures to enhance the knowledge of medical staff supplemented by validated treatment protocols should be developed. For less significant exposures, an emphasis on adequate documentation of cholinergic signs and cholinesterase activities is necessary for rapid triage and may also have potential forensic implications if not performed.

Adolescent↗
PubMed2005

Monitoring cerebral perfusion and oxygenation: an elusive goal.

The impetus for cerebral hemodynamic monitoring in neurotrauma first arose from the original "talk and die" studies which described the group of head injured patients "who talk and then subsequently died". At necropsy, hypoxic or ischaemic brain damage was observed in a variable proportion of patients raising the possibility that systemic or cerebral hypoxia post trauma may have contributed to the poor neurological outcome. Improved understanding of the pathophysiology of neurotrauma influenced clinical practice in two ways: a) there was a plethora of monitoring modalities developed for evaluating cerebral hemodynamics and oxygenation and b) squeezing oxygenated blood through a swollen brain became the cornerstone of therapy in patients with head injury. Whilst there appears to be some agreement on the principles of management of neurotrauma, opinion still remains divided on what provides the best assessment of cerebral perfusion and oxygenation. Although initial monitoring was largely confined to global indices of brain oxygenation, refinement in technology has made the measurement of oxygen tensions further down in the oxygen cascade at the level of the tissue possible and applicable by the bedside. Metabolic monitoring of the brain is now possible with the use of a variety of biochemical indices and with the availability of microdialysis. The purpose of this review is to examine the various modes of monitoring cerebral oxygenation, critically review the literature concerning their use in day to day intensive care practice, outline their limitations and define possible indications for their use.

Journal Article↗
PubMed2004

Indices to quantify changes in intracranial and cerebral perfusion pressure by assessing agreement between hourly and semi-continuous recordings.

OBJECTIVES: Little published data exists on whether nurse-recorded end-hour values of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) are representative of continuous monitoring during the hour. There is also no standard method of quantifying the observed perturbations in cerebral hemodynamics. This study compared the level of agreement between end-hour values and computer downloaded observations of ICP and CPP at 15-min intervals. We also developed the intracranial hypertension index and the cerebral hypoperfusion index to quantify perturbations in cerebral hemodynamics. Each of these indices relates the number of abnormal observations to the total number of observations taken. METHODS: Prospective, non-interventional study. RESULTS: The bias and precision between the two methods for ICP and CPP were -0.002+/-2.6 mmHg and -1.1+/-6.2 mmHg, respectively. A strong correlation existed between the hourly mean calculated from the 15-min and the end-hour values for both ICP ( r(2)=0.95, p<0.0001) and CPP ( r(2)=0.78, p<0.001). The intracranial hypertension index was 40% from the 15-min measurements and 41% from the hourly observations ( p= NS). The cerebral hypoperfusion indices were 13.4% and 13.1% with the 15-min and end-hour values, respectively ( p= NS). CONCLUSIONS: The end-hour values of ICP and CPP are as accurate as more frequent measurements during the hour and are adequate for purposes of epidemiological research and medico-legal audit. The intracranial hypertension and cerebral hypoperfusion indices may be useful in describing cerebral hemodynamics for future interventional studies and for assessing quality in the delivery of neuro-critical care.

Brain Injuries↗
PubMed2004

Fractal characterization of bpn weights evolution.

Training methodology of the Back Propagation Network (BPN) is well documented. One aspect of BPN that requires investigation is whether or not the BPN would get trained for a given training data set and architecture. In this paper the behavior of the BPN is analyzed during its training phase considering convergent and divergent training data sets. Evolution of the weights during the training phase was monitored for the purpose of analysis. The evolution of weights was plotted as return map and was characterized by means of fractal dimension. This fractal dimensional analysis of the weight evolution trajectories is used to provide a new insight to understand the behavior of BPN and dynamics in the evolution of weights.

Algorithms↗
PubMed2004

Mapping of three translocation breakpoints associated with orofacial clefting within 6p24 and identification of new transcripts within the region.

Orofacial clefting (OFC) is a common congenital malformation. Here we report the refinement of three translocation breakpoints of patients exhibiting OFC within the 6p24 region, and the isolation and characterisation of novel genes, one of which is directly disrupted by the translocation breakpoint of a patient. The gene has been characterized and orthologues identified in bovine, murine and pufferfish.

Animals↗
PubMed2004

Serum procalcitonin and C-reactive protein as markers of sepsis and outcome in patients with neurotrauma and subarachnoid haemorrhage.

This prospective study evaluated serum procalcitonin (PCT) and C-reactive protein (CRP) as markers for systemic inflammatory response syndrome (SIRS)/sepsis and mortality in patients with traumatic brain injury and subarachnoid haemorrhage. Sixty-two patients were followed for 7 days. Serum PCT and CRP were measured on days 0, 1, 4, 5, 6 and 7. Seventy-seven per cent of patients with traumatic brain injury and 83% with subarachnoid haemorrhage developed SIRS or sepsis (P=0.75). Baseline PCT and CRP were elevated in 35% and 55% of patients respectively (P=0.03). There was a statistically non-significant step-wise increase in serum PCT levels from no SIRS (0.4+/-0.6 ng/ml) to SIRS (3.05+/-9.3 ng/ml) to sepsis (5.5+/-12.5 ng/ml). A similar trend was noted in baseline PCT in patients with mild (0.06+/-0.9 ng/ml), moderate (0.8+/-0.7 ng/ml) and severe head injury (1.2+/-1.9 ng/ml). Such a gradation was not observed with serum CRP There was a non-significant trend towards baseline PCT being a better marker of hospital mortality compared with baseline CRP (ROC-AUC 0.56 vs 0.31 respectively). This is the first prospective study to document the high incidence of SIRS in neurosurgical patients. In our study, serum PCT appeared to correlate with severity of traumatic brain injury and mortality. However, it could not reliably distinguish between SIRS and sepsis in this cohort. This is in part because baseline PCT elevation seemed to correlate with severity of injury. Only a small proportion of patients developed sepsis, thus necessitating a larger sample size to demonstrate the diagnostic usefulness of serum PCT as a marker of sepsis. Further clinical trials with larger sample sizes are required to confirm any potential role of PCT as a sepsis and outcome indicator in patients with head injuries or subarachnoid haemorrhage.

APACHE↗
PubMed2004

Assessment of adrenocortical function in the critically ill.

OBJECTIVE: To review current concepts in the diagnosis of adrenocortical disease in the critically ill patient. DATA SOURCES: A review of articles reported on adrenocortical insufficiency in the acutely ill patient. SUMMARY OF REVIEW: The contribution of adrenal insufficiency to the morbidity of critically ill patients is currently under renewed scrutiny. The debate continues about the role of steroids in sepsis and essentially the question remains unanswered. Central to this debate is the issue of whether adrenal insufficiency is common in the critically ill patient. What is incontrovertible is that adrenocortical function is essential for host survival during critical illness, but what constitutes adrenocortical insufficiency in critically ill patients is not clear. Absolute adrenocortical insufficiency (diagnosed by very low plasma cortisol concentrations) is uncommon in the intensive care population. The diagnosis of relative adrenocortical insufficiency (elevated basal plasma cortisol with a subnormal increase in plasma concentrations following an ACTH stimulus) continues to generate debate. The controversy surrounding the role of steroids in sepsis and the confusion over the criteria for diagnosing adrenal insufficiency in the critically ill are reviewed. CONCLUSIONS: We suggest that the following caveats be borne in mind when diagnosing adrenal insufficiency in the critically ill patient. Firstly, the gold standard for the diagnosis has not been established. Secondly, caution must be exercised when interpreting a single plasma cortisol value. In the event of a single result indicating adrenal hypofunction, we suggest repeating the measurements after a 6 to 12 hour interval. The clinician must also be aware of variations in cortisol concentrations induced by the assay. Thirdly, the clinician must be aware of the potential limitations of the conventional high dose corticotrophin test. We also suggest that plasma free cortisol is more relevant than total plasma cortisol in the assessment of adrenal function in critical illness and that the low dose corticotrophin test is more sensitive than the conventional high dose test. These areas should be the subject of further investigations.

Journal Article↗
PubMed2003

Neurone-specific expression and regulation of the pufferfish isotocin and vasotocin genes in transgenic mice.

We used comparative genetics to investigate the location, structure and evolution of the oxytocin and vasopressin gene regulatory regions. The pufferfish, Fugu rubripes, is an attractive vertebrate model for comparison because of its maximal evolutionary distance from mammals and short intergenic regions. To determine whether regulatory DNA is conserved between oxytocin and vasopressin, and their Fugu homologs, isotocin and vasotocin, we generated transgenic mice bearing overlapping Fugu cosmids that contained the isotocin and/or vasotocin genes as well as short isotocin (5 kb) and vasotocin (9 kb) constructs. Our study shows that the Fugu isotocin and vasotocin genes express specifically in the mouse oxytocinergic and vasopressinergic neurones, respectively, and that the cis-regulatory elements which mediate neurone-specific expression are located within the short transgene constructs tested. Thus, the neurone-specific expression of the oxytocin and vasopressin gene families, and the mechanisms mediating the cell-specificity, evolved before the divergence of the fish and mammalian lineages. Salt-loading of transgenic mice induced an increase in abundance of isotocin, but not vasotocin mRNA in the cognate neurones. It appears that either the vasotocin gene does not respond to osmotic perturbations or the vasotocin transgene construct tested lacks osmotic response elements. Comparisons of homologous flanking sequences of the Fugu and mouse genes identified several short matching sequences, which are candidate regulatory elements.

Animals↗
PubMed2003

Designing 'balanced' crystalloids.

OBJECTIVE: To present a rationale for the design of balanced resuscitation and renal replacement crystalloids based on Stewart's physical chemical approach to acid-base. DATA SOURCES: Articles and published abstracts on acid-base physiology, crystalloid infusions and renal replacement therapy. SUMMARY OF REVIEW: Although it is uncertain that crystalloid-induced metabolic acidosis causes significant harm, Stewart's approach assists in designing balanced fluids without this side effect. In his analysis, the three independent variables determining acid-base balance are PCO2, the total concentration of non-volatile weak acid (A(TOT)) and the strong ion difference (SID). Raising and lowering A(TOT) while holding SID constant cause a metabolic acidosis and alkalosis respectively. Lowering and raising plasma SID while clamping A(TOT) cause a metabolic acidosis and alkalosis respectively. The SID of a crystalloid is its [HCO3-], or that part of an organic bicarbonate surrogate which is metabolised on infusion. Rapid infusion alters plasma SID towards crystalloid SID, but also lowers A(TOT) by haemodilution. We have shown that the SID of a balanced infusion crystalloid is 24 mEq/L. This generates a fall in plasma SID precisely counteracting the A(TOT) dilutional alkalosis. In contrast, a balanced renal replacement crystalloid must generate a higher plasma SID appropriate for the existing A(TOT), since there is no dilution. If A(TOT) is low, as in hypoalbuminaemia, the balanced dialysis SID falls correspondingly. A further SID reduction is needed to counteract Donnan effects within the filter. CONCLUSIONS: A crystalloid SID of 24 mEq/L is 'balanced' for rapid intravenous administration. The 'balanced' SID of renal replacement fluids is likely to be significantly higher, although less than the normal plasma SID of 42 mEq/L.

Journal Article↗
PubMed2003

Interpreting CSF lactic acidosis: effect of erythrocytes and air exposure.

OBJECTIVE: Elevated cerebrospinal fluid (CSF) lactate concentrations in neurotrauma and sub-arachnoid haemorrhage are associated with a poor prognosis. However, in blood-stained CSF, elevated lactate levels may arise from red cell metabolism, even without ischaemia, potentially reducing specificity. This study was undertaken to quantify the erythrocyte contribution to CSF lactate measurements, with and without, exposure to room air. METHODS: Blood was added to CSF to achieve three different red cell concentrations. The CSF was then exposed at 37 degrees C to either room air or 5% CO2 and 95% oxygen. Vancomycin and gentamycin were added to inhibit bacterial growth. Lactate concentrations and red cell concentrations were measured prior to the addition of blood and 10 minutes, 6 hours and 24 hours later. CSF without the addition of blood was used as a control. RESULTS: In the control specimens there were no increases in CSF lactate concentrations over time, either in air or CO2, whereas all specimens with blood added demonstrated significant increases in lactate at 6 and 24 hours (P < 0.01). The lactate increases in both air and CO2 were correlated directly with red cell counts (R2 = 0.62 to 0.87). At all red cell concentrations, the mean lactate increase was greater in air. CONCLUSIONS: Red cells in CSF cause significant increases in lactate concentrations, more so when exposed to air. This should be considered when interpreting lactate in blood stained CSF. Blood-stained CSF specimens for lactate assay should be collected directly from an external ventricular drain rather than a reservoir bag.

Journal Article↗
PubMed2002

Outcome of stroke patients admitted to intensive care: experience from an Australian teaching hospital.

The objective of this study was to determine the mortality rate and the functional outcomes of stroke patients admitted to the intensive care unit (ICU) and to identify predictors of poor outcome in this population. The records of all patients admitted to the ICU with the diagnosis of stroke between January 1994 and December 1999 were reviewed. Patients with subarachnoid haemorrhage were excluded. Data were collected on clinical and biological variables, risk factors for stroke and the presence of comorbidities. Mortality (ICU, in-hospital and three-month) and functional outcome were used as end-points. In the six-year-period, 61 patients were admitted to the ICU with either haemorrhagic or ischaemic stroke. Medical records were available for only 58 patients. There were 23 ischaemic and 35 haemorrhagic strokes. The ICU, in-hospital and three-month mortality rates were 36%, 47% and 52% respectively. There were no significant differences in the prevalence of premorbid risk factors between survivors and non-survivors. The mean Barthel score was significantly different between the independent and dependent survivors (94+/-6 vs 45+/-26, P<0.001). A substantial number of patients with good functional outcomes had lower Rankin scores (92% vs 11%, P<0.001). Only 46% of those who were alive at three months were functionally independent. Intensive care admission was associated with a high mortality rate and a high likelihood of dependent lifestyle after hospital discharge. Haemorrhagic stroke, fixed dilated pupil(s) and GCS <10 during assessment were associated with increased mortality and poor functional outcome.

Activities of Daily Living↗
PubMed2002

Monitoring tissue gas tensions in critical illness.

OBJECTIVE: To review the technology and the role of monitoring tissue oxygenation in critical illness. DATA SOURCES: Articles and published peer review abstracts on monitoring tissue oxygenation. SUMMARY OF REVIEW: Miniaturised optodes and electrode systems are the commonly used technology for measurement of tissue gas tensions. Reductions in tissue perfusion frequently leads to a decrease in tissue PO2 and an increase in tissue PCO2 which has been confirmed in a number of animal and human trials in hypovolaemic shock. Monitoring tissue oxygenation has also enabled the delineation of cytopathic hypoxia, which is one of the important pathophysiological mechanisms of sepsis. Although these devices have improved our understanding of pathophysiological mechanisms of critical illness, at a clinical level titrating oxygen therapy to tissue oxygen tensions has only been shown to be useful in patients with impaired wound healing. A number of questions remain unanswered in relation to the monitoring of tissue oxygenation in critical illness. These include establishing normal values of PO2 and PCO2 in humans at the various tissue beds, establishing dysoxic thresholds for the various tissues, identifying optimal sites for monitoring and improving measurement accuracy. Furthermore, the nature of microcirculatory blood flow and tissue gas exchange in critical illness is complex and incompletely understood, limiting our ability to interpret changes from the baseline. Knowing critical tissue PO2 thresholds will provide the clinician with practical resuscitation endpoints in hypoxia and shock, and may even modify the practice of 'permissive hypoxia' in severe respiratory failure. These questions need answers in the years to come. CONCLUSIONS: Monitoring of tissue oxygenation is largely a research tool. For its application in the critically ill patient there needs to be a greater understanding of normal values of PO2 and PCO2 at the various tissue beds, dysoxic thresholds for the various tissues and optimal sites for monitoring.

Journal Article↗