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Biomedical subjects

Martin Smith

Publications and source records attributed to Martin Smith.

At least 19 recordsLinked to original sources
PubMed2006

High rates of HIV in surgical patients in Soweto, South Africa: impact on resource utilisation and recommendations for HIV testing.

Interactions between HIV and surgical diseases are relatively poorly described in high HIV prevalence settings. We report HIV prevalence and its associations in a prospective study of adults admitted to surgical units in Soweto, South Africa. Voluntary counselling and testing (VCT) for HIV was offered to surgical inpatients. Research nurses interviewed participants at enrolment and doctors reviewed records after discharge. In HIV-infected participants, CD4 counts and viral loads were ascertained. Of 1000 participants, 537 consented to VCT, of whom 176 (32.8%, 95% CI 28.8-36.9%) tested HIV positive. A history of tuberculosis (adjusted odds ratio (AOR) 3.0, 95% CI 1.5-6.2) or sexually transmitted infection (AOR 2.7, 95% CI 1.8-4.2) was associated with HIV infection. Diagnoses of cutaneous abscesses (OR 3.4, 95% CI 1.4-8.1) and anorectal sepsis (OR 3.1, 95% CI 1.1-9.0) were associated with HIV and indicated advanced disease. There were no differences in rates of operative procedures, wound sepsis, investigations or length of stay by HIV status. Hospital-acquired pneumonia was more common in HIV-infected participants (P=0.028). In conclusion, in this high HIV prevalence setting, resource utilisation is similar between HIV-infected and uninfected patients in surgical wards where high rates of HIV in young adults support routine HIV testing. WHO clinical staging of HIV should include anal sepsis as an indicator of advanced HIV disease.

Adult↗
PubMed2006

Changes in cerebral oxygenation and haemodynamics during postural blood pressure changes in patients with autonomic failure.

Patients with autonomic failure suffer severe postural hypotension that may be associated with symptoms of cerebral hypoperfusion. This study utilized near-infrared spectroscopy (NIRS) to measure changes in cerebral oxygenation and haemodynamics during the head-up tilt table test in 18 patients with autonomic failure and 10 healthy age-matched volunteers. Heart rate, blood pressure (MAP), oxygen saturation, cerebral tissue oxygen index (TOI) and total cerebral haemoglobin concentration [HbT] were measured continuously. In patients with autonomic failure there was a mean (SD) reduction in MAP of 46.7 (26.5) mmHg (p < 0.005) associated with a reduction in TOI of 8.6 (6.2)% (p < 0.005) during the head-up tilt table test. In healthy volunteers mean (SD) MAP rose by 12.3 (8.0) mmHg (p < 0.005) and TOI fell by 2.6 (3.2)% (p < 0.05). There was a mean (SD) reduction in [HbT] of 3.09 (2.82) micromol l(-1) (p < 0.005) in patients, equivalent to a decrease in cerebral blood volume of 0.2 (0.18) ml/100 g. There were no changes in [HbT] in the healthy volunteers. Postural hypotension in patients with autonomic failure is associated with a substantial decrease in absolute cerebral oxygenation measured by NIRS and this might reflect a critical reduction in cerebral oxygen delivery.

Adult↗
PubMed2006

Measurement of the absolute optical properties and cerebral blood volume of the adult human head with hybrid differential and spatially resolved spectroscopy.

A hybrid differential and spatially resolved spectroscopy (SRS) technique has been developed to measure absolute absorption coefficient (mu(a)), reduced scattering coefficient (mu'(s)) and cerebral blood volume (CBV) in the adult human head. A spectrometer with both differential and SRS capabilities has been used to carry out measurements in 12 subjects. Two versions of the calculation have been considered using the hybrid technique, with one considering water as a chromophore as well as oxy- and deoxy-haemoglobin, and one ignoring water. The CBV has also been measured using a previously described technique based on changing the arterial saturation (SaO(2)) measured separately by a pulse oximeter, resulting in mean +/- SD CBV(a) (intra-individual coefficient of variation) = 2.22 +/- 1.06 ml/100 g (29.9%). (The superscript on CBV indicates the different calculation basis.) Using the hybrid technique with water ignored, CBV(0) = 3.18 +/- 0.73 ml/100 g (10.0%), mu(0)(a)(813 nm) = 0.010 +/- 0.003 mm(-1) and mu'(0)(s)(813 nm) = 1.19 +/- 0.55 mm(-1) (data quoted at 813 nm). With water considered, CBV(w) = 3.05 +/- 0.77 ml/100 g (10.5%), mu(w)(a)(813 nm) = 0.010 +/- 0.003 mm(-1) and mu'(w)(s)(813 nm) = 1.28 +/- 0.56 mm(-1). The mean biases between CBV(0)/CBV(w), CBV(0)/CBV(a) and CBV(w)/CBV(a) are 0.14 +/- 0.09, 0.79 +/- 1.22 and 0.65 +/- 1.24 ml/100 g. The mean biases between mu(0)(a)(813 nm)/mu(w)(a)(813 nm) and mu'(0)(s)(813 nm)/mu'(w)(s)(813 nm) are (5.9 +/- 10.0) x 10(-4) mm(-1) and -0.084 +/- 0.266 mm(-1), respectively. The method we describe extends the functionality of the current SRS instrumentation.

Adult↗
PubMed2006

Early identification of secondary brain damage in subarachnoid hemorrhage: a role for glial fibrillary acidic protein.

Secondary ischaemic deficit adversely affects outcome in patients with subarachnoid hemorrhage (SAH). Astrocytes are vulnerable to ischemia, releasing glial fibrillary acidic protein (GFAP) when challenged. In this study, we followed nine patients with SAH who underwent extra-ventricular drainage for the management of secondary hydrocephalus. Cerebrospinal fluid (CSF) was collected daily for up to 14 days. CSF GFAP was quantified using a standard ELISA. In the patients, we found that the CSF GFAP values were pathologically elevated in 83/89 (93%) of the CSF samples. The levels were highest on day 1 (median = 47.64 ng/mL) and decreased to 11.19 ng/mL on day 3, leveling out at approximately 1 ng/mL after 10 days. In non-survivors, a secondary rise of GFAP levels became significant during the high-risk period for vasospasm, with median levels of 21.76 ng/mL compared to 2.62 ng/mL in the survivors (p = 0.037) on day 6. This study suggests that CSF GFAP levels are of prognostic value in SAH. Additionally, the difference in the slope of GFAP levels between survivors (rapid wash-out) and non-survivors (secondary peaks) may allow difierentiation between primary brain injury from secondary brain damage due to delayed cerebral ischaemia.

Aged↗
PubMed2006

Disturbances of sodium in critically ill adult neurologic patients: a clinical review.

Disorders of sodium and water balance are common in critically ill adult neurologic patients. Normal aspects of sodium and water regulation are reviewed. The etiology of possible causes of sodium disturbance is discussed in both the general inpatient and the neurologic populations. Areas of importance are highlighted with regard to the differential diagnosis of sodium disturbance in neurologic patients, and management strategies are discussed. Specific discussions of the etiology, diagnosis, and management of cerebral salt wasting syndrome, the syndrome of inappropriate antidiuretic hormone secretion, and central diabetes insipidus are presented, as well as the problems of overtreatment. The importance of diagnosis at an early stage of these diseases is stressed, with a recommendation for conservative management of milder cases.

Animals↗
PubMed2005

Extracellular N-acetylaspartate depletion in traumatic brain injury.

N-Acetylaspartate (NAA) is almost exclusively localized in neurons in the adult brain and is present in high concentration in the CNS. It can be measured by proton magnetic resonance spectroscopy and is seen as a marker of neuronal damage and death. NMR spectroscopy and animal models have shown NAA depletion to occur in various types of chronic and acute brain injury. We investigated 19 patients with traumatic brain injury (TBI). Microdialysis was utilized to recover NAA, lactate, pyruvate, glycerol and glutamate, at 12-h intervals. These markers were correlated with survival and a 6-month Glasgow Outcome Score. Eleven patients died and eight survived. A linear mixed model analysis showed a significant effect of outcome and of the interaction between time of injury and outcome on NAA levels (p = 0.009 and p = 0.004, respectively). Overall, extracellular NAA was 34% lower in non-survivors. A significant non-recoverable fall was observed in this group from day 4 onwards, with a concomitant rise in lactate-pyruvate ratio and glycerol. These results suggest that mitochondrial dysfunction is a significant contributor to poor outcome following TBI and propose extracellular NAA as a potential marker for monitoring interventions aimed at preserving mitochondrial function.

Adult↗
PubMed2005

Rate of change in cerebral oxygenation and blood pressure in response to passive changes in posture: a comparison between pure autonomic failure patients and controls.

The cardiovascular and cerebrovascular responses to head-up postural change are compromised in pure autonomic failure (PAF) patients because of sympathetic denervation. The aim of this study was to characterize the rate of change of systemic mean blood pressure (MBP) and cerebral haemodynamics in response to passive posture changes. Nine PAF patients and 9 age-matched controls took part in this study. MBP and oxy- (O2Hb), deoxy-haemoglobin (HHb), and tissue oxygenation index (TOI) on the forehead were continuously monitored non-invasively using the Portapres and near-infrared spectroscopy (NIRS), respectively. From visual inspection of the haemoglobin difference signal (Hb(diff) = O2Hb-HHb), seven distinct phases were marked (1: supine, 2: start passive tilt, 3: head up to 60 degrees degrees, 4: end of tilt, 5: tilt reversal, 6: return to supine, 7: rest); the same time points were used for all of the other signals. For each phase, the slope was calculated using a linear regression algorithm. Significant differences were found between PAF patients and controls in the Hb(diff) slope magnitudes for phases 3 (P < .05) and 5 (P = .01), and the duration of phase 2 (P < .05). MBP slope magnitudes showed significant differences for phases 2 (P < .01) and 5 (P < .01). These differences in the rate of change suggest differences in blood vessel resistance related to sympathetic activation.

Aged↗
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↗
PubMed2005

Best evidence topic report. How to immobilise after shoulder dislocation?

A short cut review was carried out to establish the best way to immobilise dislocated shoulders after reduction. A total of 47 papers were identified using the reported search, of which four represent 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. For patients with a first anterior shoulder dislocation immobilisation in external rotation may be of more benefit than immobilisation in internal rotation.

Humans↗
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↗