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Biomedical subjects

Martin Smith

Publications and source records attributed to Martin Smith.

17 recordsLinked to original sources
PubMed2005

Best evidence topic report. Intranasal midazolam in patients with fits.

A short cut review was carried out to establish whether intranasal midazolam was effective for stopping fits. Altogether 36 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Administration, Intranasal↗
PubMed2004

Consensus meeting on microdialysis in neurointensive care.

BACKGROUND: Microdialysis is used in many European neurointensive care units to monitor brain chemistry in patients suffering subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). DISCUSSION: We present a consensus agreement achieved at a meeting in Stockholm by a group of experienced users of microdialysis in neurointensive care, defining the use of microdialysis, placement of catheters, unreliable values, chemical markers, and clinical use in SAH and in TBI. CONCLUSIONS: As microdialysis is maturing into a clinically useful technique for early detection of cerebral ischemia and secondary brain damage, there is a need to following such definition regarding when and how to use microdialysis after SAH and TBI.

Brain Injuries↗
PubMed2004

Nuclear factor-kappaB is constitutively activated in prostate cancer in vitro and is overexpressed in prostatic intraepithelial neoplasia and adenocarcinoma of the prostate.

PURPOSE: The transcription factor nuclear factor-kappaB (NF-kappaB) promotes the production of angiogenic, antiapoptotic, and prometastatic factors that are involved in carcinogenesis. EXPERIMENTAL DESIGN: Electromobility gel shift assays were used to evaluate NF-kappaB DNA binding in vitro. The functional relevance of NF-kappaB DNA binding was assessed by both cDNA array analyses and proliferation assays of prostate cancer cells with and without exposure to an NF-kappaB inhibitor, parthenolide. Immunohistochemistry staining for the p65 NF-kappaB subunit was used to determine the frequency and location of NF-kappaB in 97 prostatectomy specimens. The amount of staining was quantified on a 0-3+ scale. RESULTS: An electromobility gel shift assay confirmed the presence of NFkappaB DNA binding in all four prostate cancer cell lines tested. The binding was inhibited by parthenolide, and this agent also decreased multiple gene transcripts under the control of NF-kappaB and inhibited proliferation of prostate cancer cells. The staining results revealed overexpression of p65 in the prostatic intraepithelial neoplasia and cancer compared with the benign epithelium. Specifically, there was a predominance of 1+ and 2+ with no 3+ staining in benign epithelium, whereas there was only 2+ and 3+ staining (30 and 70%, respectively) in the cancerous areas. These differences were statistically different. There was no correlation with tumor grade or stage. CONCLUSIONS: NF-kappaB is constitutively activated in prostate cancer and functionally relevant in vitro. Immunohistochemistry of human prostatectomy specimens demonstrated overexpression of the active subunit of NF-kappaB, p65, and that this occurs at an early stage in the genesis of prostate cancer. This work supports the rationale for targeting NF-kappaB for the prevention and/or treatment of prostate cancer.

Adenocarcinoma↗
PubMed2004

Physiologic changes during brain stem death--lessons for management of the organ donor.

The widespread physiologic changes that follow brain stem death lead to a high incidence of complications in the donor and jeopardize vital organ function. Strategies for the management of organ donors exist whereby the rapid physiologic decline seen after brain stem death can be stabilized by active donor resuscitation so that the functional integrity of potentially transplantable organs is maintained. Understanding the complex physiologic changes that occur after brain stem death is crucial to the development of effective donor management strategies. This article reviews the pathophysiologic changes that occur after brain stem death and discusses controversies in donor management.

Brain Death↗
PubMed2004

Investigation of cerebral haemodynamics by near-infrared spectroscopy in young healthy volunteers reveals posture-dependent spontaneous oscillations.

Autonomic reflexes enable the cardiovascular system to respond to gravitational displacement of blood during changes in posture. Spontaneous oscillations present in the cerebral and systemic circulation of healthy subjects have demonstrated a regulatory role. This study assessed the dynamic responses of the cerebral and systemic circulation upon standing up and the posture dependence of spontaneous oscillations. In ten young healthy volunteers, blood pressure and cerebral haemodynamics were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. Oscillatory changes in the cerebral NIRS signals and the diastolic blood pressure (DBP) signal have been identified by the fast Fourier analysis. Blood pressure increased during standing and returned to basal level when volunteers sat on a chair. The mean value of cerebral tissue oxygen index (TOI) as measured by NIRS did not demonstrate any significant changes. Oscillatory changes in DBP, oxyhaemoglobin concentration [O2Hb] and TOI showed a significant increase when subjects were standing. Investigation of the low frequency component (approximately 0.1 Hz) of these fluctuations revealed posture dependence associated with activation of autonomic reflexes. Systemic and cerebral changes appeared to preserve adequate blood flow and cerebral perfusion during standing in healthy volunteers. Oscillatory changes in [O2Hb] and TOI, which may be related to the degree of cerebral sympathetic stimulation, are posture dependent in healthy subjects.

Adolescent↗
PubMed2004

Medical management of severe traumatic brain injury.

This article reviews the current guidelines for the management of patients with severe traumatic brain injury from presentation in the accident and emergency department, through transfer, to specialist treatment in a neurocritical care unit.

Brain Injuries↗
PubMed2003

Long-term plasticity of endocannabinoid signaling induced by developmental febrile seizures.

Febrile (fever-induced) seizures are the most common form of childhood seizures, affecting 3%-5% of infants and young children. Here we show that the activity-dependent, retrograde inhibition of GABA release by endogenous cannabinoids is persistently enhanced in the rat hippocampus following a single episode of experimental prolonged febrile seizures during early postnatal development. The potentiation of endocannabinoid signaling results from an increase in the number of presynaptic cannabinoid type 1 receptors associated with cholecystokinin-containing perisomatic inhibitory inputs, without an effect on the endocannabinoid-mediated inhibition of glutamate release. These results demonstrate a selective, long-term increase in the gain of endocannabinoid-mediated retrograde signaling at GABAergic synapses in a model of a human neurological disease.

Action Potentials↗
PubMed2003

Measuring cerebral oxygenation during normobaric hyperoxia: a comparison of tissue microprobes, near-infrared spectroscopy, and jugular venous oximetry in head injury.

We measured simultaneous changes in jugular venous oxygen saturation, brain tissue oxygen tension, and cerebral tissue oxygen index by using near-infrared spectroscopy during normobaric hyperoxygenation in eight severely brain-injured patients. Patients were ventilated at their baseline fraction of inspired oxygen (FIO(2)), followed by stepped changes in FIO(2) to 1.0, 0.6, and 0.02-0.05 less than baseline. There was an increase (P < 0.01) in jugular venous saturation (mean +/- SD) from a baseline value of 79% +/- 7% to 89% +/- 6% and 84% +/- 8% at an FIO(2) of 1.0 and 0.6, respectively. The changes in brain tissue oxygen tension were from a baseline of 30 +/- 5 mm Hg to 147 +/- 36 mm Hg and 63 +/- 6 mm Hg at an FIO(2) of 1.0 and 0.6, respectively (P < 0.01). The baseline tissue oxygen index was 78% +/- 3%, and this increased to 83% +/- 5% and 80% +/- 4% at an FIO(2) of 1.0 and 0.6, respectively. There was a reduction (P < 0.05) in tissue oxygen index to 76.2% +/- 3.0% when the FIO(2) was reduced to less than baseline. The changes in the three variables followed similar patterns but varied in their degree and speed of response. During brain injury, FIO(2) affects measured variables of cerebral oxygenation.

Adult↗
PubMed2002

Role of serum S100B as an early predictor of high intracranial pressure and mortality in brain injury: a pilot study.

OBJECTIVE: To investigate whether serum S100B is suitable as a sensitive biomarker for early prediction of increased intracranial pressure and mortality rates after brain injury. DESIGN: A prospective, longitudinal study. SETTING: Neurosurgical intensive care unit. PATIENTS: Twenty-one patients with acute brain injury and 13 healthy controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed Glasgow Coma Scale score and pupil reaction on admission and quantified serum S100B (in-house enzyme-linked immunosorbent assay) and intracranial pressure on admission and the subsequent 6 days. Serum S100B concentrations on admission and day 1 were significantly higher in patients with fatal outcome (p <.05, p<.01, respectively), with a sensitivity of 100% and a specificity of 75-83%. Patients with high serum S100B on admission had an eight-fold and on day 1 a 12-fold increased relative risk of a fatal outcome. Subsequent serum S100B values predicted the development of high intracranial pressure in patients with traumatic brain injury (p <.01). Patients with high intracranial pressure on day 5 had an 11-fold and on day 6 a nine-fold increased risk of fatal outcome. CONCLUSIONS: Serum S100B is a sensitive biomarker for early prediction of the development of high intracranial pressure and fatal outcome following acute brain injury. Monitoring S100B concentrations could contribute to early detection of patients at risk of secondary increases in intracranial pressure and subsequent mortality. This would allow earlier targeting of therapy in selected patients.

Adult↗
PubMed2002

Noninvasive measurement of cerebral blood flow in adults using near-infrared spectroscopy and indocyanine green: a pilot study.

This pilot study was designed to determine the feasibility of measuring cerebral blood flow noninvasively after an intravenous bolus of indocyanine green using near-infrared spectroscopy and pulse dye-densitometry. Feasibility aside, this study did not attempt to validate the measured values of cerebral blood flow against an established method of measurement. Twelve healthy volunteers were investigated after peripheral intravenous injection of indocyanine green. Arterial and cerebral changes in indocyanine green concentration were measured using pulse dye-densitometry and near-infrared spectroscopy, respectively. Two methods of calculating cerebral blood flow were used, and a blood flow index was also estimated. Absolute cerebral blood flow was calculated using a modification of the Fick principle and a deconvolution algorithm to derive the impulse residue function. Mean (range) estimated cerebral blood flow for the Fick method was 8.2 mL/100 g/min (4.2-16.2 mL/100 g/min) and 8.3 mL/100 g/min (4.7-15.3 mL/100 g/min) for the impulse residue function method. The impulse residue function method provided a more precise intrasubject estimation of cerebral blood flow compared with the modified Fick principle, with a coefficient of variation of 10.1% versus 25.5%. The blood flow index was 8.6 mg/sec (range: 5.6-17.3 mg/sec) with an intrasubject coefficient of variation of 12.0%. Estimation of cerebral blood flow using near-infrared spectroscopy and pulse dye-densitometry can be made at the bedside after intravenous injection of indocyanine green, and the precision can be improved using a deconvolution algorithm. Notwithstanding the low values obtained for absolute cerebral blood flow, further investigation and validation of this bedside technique is warranted.

Adult↗