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Biomedical subjects

P Kirkpatrick

Publications and source records attributed to P Kirkpatrick.

At least 19 recordsLinked to original sources

Conventional digital subtraction x-ray angiography versus magnetic resonance angiography in the evaluation of carotid disease: patient satisfaction and preferences.

AIM: To compare conventional digital subtraction x-ray angiography (DSA) and contrast-enhanced magnetic resonance angiography (MRA) of the carotid arteries in terms of patient satisfaction and preferences. METHODS: One hundred and sixty-seven patients with symptomatic carotid artery disease, who underwent both DSA and MRA, were prospectively recruited in this study. Patients' perceptions of each method were assessed by the use of a questionnaire after each procedure. Main outcome measures were anxiety, pain, satisfaction rate and patient preferences. RESULTS: DSA generated more anxiety and pain during the procedure, but the severity of these ill-effects was mild. Satisfaction rates for each method were similar. More patients were, however, willing to have a repeat MRA compared with DSA (67 versus 41%). The majority of patients (62%) preferred MRA over DSA (31%). The shorter MRA imaging time was found to be a significant factor in patients' acceptance of the technique. The main reasons cited by patients for their dislike of a particular procedure was noise and claustrophobia for MRA and invasiveness, pain and post-procedural bed rest for DSA. CONCLUSIONS: MRA is the method that is preferred by the majority of patients, although the actual disutility of DSA may be small. Assuming equal diagnostic accuracy, our data supports replacement of DSA by MRA for routine carotid imaging.

Adult↗

Staphylococcal species in the oral cavity from patients in a regional burns unit.

The aim of this study was to perform a quantitative and qualitative analysis of oral carriage of staphylococci in a range of oral specimens from patients admitted to a regional burns unit. The study recruited 28 patients and reasons for admittance were: burns (46%), skin grafting (39%), lacerations (7%), scalding (4%) and necrotizing fasciitis (4%). No patient had smoke inhalation injuries or trauma to the oro-pharynx. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in oral specimens. For three patients only the wound and oral specimens were positive for MRSA. In one patient only the oral specimens were positive for MRSA. There were five patients from whom methicillin-sensitive S. aureus (MRSA) could be detected in the oral specimens. In one patient only the oral specimens were positive for MSSA. Staphylococci could be recovered from the dental plaque, denture and toothbrush specimens with a mean count of 1.1 x 10(4)cfu/mL (range 20-5.3 x 10(4)), 5.4 x 10(3) (range 40-2.1 x 10(4)) and 264 cfu/mL (range 20-500), respectively. Both MSSA and MRSA could be recovered from these specimen types. In one patient only the toothbrush was positive for MRSA and all other oral specimens were negative. This study suggests that staphylococci are not infrequent colonizers of the oral cavity, and that this site may serve as a potential reservoir for transmission to other body sites.

Adolescent↗

The ACE I allele is associated with increased risk for ruptured intracranial aneurysms.

Genetic and environmental factors play roles in the aetiology of ruptured intracranial aneurysms. Hypertension has been reported as a risk factor for intracranial aneurysm haemorrhage. We have tested if genotypes at the angiotensin converting enzyme (ACE) gene locus are associated with ruptured intracranial aneurysms. The insertion/deletion polymorphism in the ACE gene was genotyped in 258 subjects presenting in East Anglia with ruptured intracranial aneurysms (confirmed at surgery or angiographically) and 299 controls from the same region. ACE allele frequencies were significantly different in the cases and the controls (alleles chi(2)(1)=4.67, p=0.03). The I allele was associated with aneurysm risk (odds ratio for I allele v D allele = 1.3 (95% CI=1.02-1-65); odds ratio for II v DD genotype = 1.67 (95% CI=1.04-2.66)). The I allele at the ACE locus is over-represented in subjects with ruptured intracranial aneurysms. These data are supported by non-significant trends in the same direction in two previous smaller studies. Thus, this allele may be associated with risk for ruptured intracranial aneurysms.

Adult↗

Identification of mutations in the repeated part of the autosomal dominant polycystic kidney disease type 1 gene, PKD1, by long-range PCR.

We have used long-range PCR to identify mutations in the duplicated part of the PKD1 gene. By means of a PKD1-specific primer in intron 1, an approximately 13.6-kb PCR product that includes exons 2-15 of the PKD1 gene has been used to search for mutations, by direct sequence analysis. This region contains the majority of the predicted extracellular domains of the PKD1-gene product, polycystin, including the 16 novel PKD domains that have similarity to immunoglobulin-like domains found in many cell-adhesion molecules and cell-surface receptors. Direct sequence analysis of exons encoding all the 16 PKD domains was performed on PCR products from a group of 24 unrelated patients with autosomal dominant polycystic kidney disease (ADPKD [MIM 173900]). Seven novel mutations were found in a screening of 42% of the PKD1-coding region in each patient, representing a 29% detection rate; these mutations included two deletions (one of 3 kb and the other of 28 bp), one single-base insertion, and four nucleotide substitutions (one splice site, one nonsense, and two missense). Five of these mutations would be predicted to cause a prematurely truncated protein. Two coding and 18 silent polymorphisms were also found. When, for the PKD1 gene, this method is coupled with existing mutation-detection methods, virtually the whole of this large, complex gene can now be screened for mutations.

Base Sequence↗

Continuous monitoring of cerebrovascular pressure-reactivity in head injury.

OBJECTIVE: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or concentration of carbon dioxide in blood. We have investigated whether slow waves in ABP and ICP may be used to derive an index which reflects reactivity of vessels to changes in arterial blood pressure. METHODS: A method for the continuous monitoring of the association between slow spontaneous waves in ICP and AP has been adopted in a group of 98 head injured patients. ABP, ICP and transcranial Doppler blood flow velocity (FV) in the middle cerebral artery was recorded daily (20 to 120 minutes time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged over 5 seconds. A moving correlation coefficient between spontaneous fluctuations of mean FV and CPP (Mx), which was previously reported to describe cerebral blood flow autoregulation, was also calculated. In an additional 25 patients, PRx was calculated and recorded continuously along with mean ICP, ABP and parameters describing ICP waveform. RESULTS: A positive PRx correlated with high ICP (r = 0.366; p < 0.001), low admission GCS (r = 0.29; p < 0.01), and poor outcome at 6 months after injury (r = 0.48; p < 0.00001). During the first two days following injury, PRx was positive (p < 0.05) in patients with unfavourable outcome. The correlation between PRx and Mx (r = 0.63) was highly significant (p < 0.000001). Continuous recordings demonstrated that PRx was able to indicate individual thresholds of vascular reactivity for CPP, ICP, and ventilation parameters. CONCLUSION: Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

Adolescent↗

Assessment of cerebrovascular reactivity in patients with carotid artery disease using near-infrared spectroscopy.

The aim of this study was to assess Near-infrared spectroscopy (NIRS) as a tool for testing CO2 reactivity in patients with carotid occlusive disease. One hundred sixty patients were examined (age range 44 to 85 years). Monitored parameters included transcranial Doppler flow velocity (FV), changes in concentration of oxy-(HbO2) and deoxy (Hb) haemoglobin, cutaneous Laser Doppler blood flow (LDF), endtidal CO2, ABP, and SaO2. Hypercapnia was induced using a 5% CO2 air mixture for inhalation. To estimate the skin flow contribution to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in LDF recorded. FV and HbO2 derived reactivity values were related to the severity of the stenosis (p = 0.0001 and 0.021 respectively). The correlation between the two modalities was significant (r = 0.47, p < 0.000001). The average estimated skin contribution to NIRS changes was 16.5%. Reproducibility of HbO2-reactivity was similar but worse than FV reactivity (19.1% and 13.8% variation respectively). The clinical correlations improved when our method of correction for skin influence was used. NIRS shows potential as an alternative technique for testing CO2 reactivity in patients with carotid disease provided the conditions are carefully controlled and the contribution from extracranial tissue is taken into account.

Adult↗

A computing system for the clinical and experimental investigation of cerebrovascular reactivity.

We present a computing system for the recording and on-line analysis of analogue signals derived from bedside cerebrovascular monitors in different pathophysiological conditions. These include arterial blood pressure and oxygen saturation, end-tidal carbon dioxide concentration, cerebral blood flow velocities using transcranial Doppler ultrasonography, and concentration changes in cerebral oxy- and deoxyhaemoglobin from near infrared spectroscopy. Configuration and analysis adopts arithmetic expressions of different signal processing functions, various statistical properties for each signal, frequency spectrum analysis using fast Fourier transformation, and correlation/cross-correlation. The software offers off-line analysis of non-invasive tests of cerebrovascular reactivity. Several examples of clinical assessment of cerebrovascular reactivity are presented, including cerebral haemodynamic stress tests which employ carbon dioxide, acetazolamide, the breath holding test, leg cuff inflation and deflation, and transient carotid artery compression. Application within the experimental setting with induced haemorrhagic hypotension can also be used.

Cardiovascular Diseases↗

Continuous assessment of the cerebral vasomotor reactivity in head injury.

OBJECTIVE: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or the concentration of carbon dioxide in blood. We investigated whether slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) may be used to derive an index that reflects the reactivity of vessels to changes in ABP. METHODS: A method for the continuous monitoring of the association between slow spontaneous waves in ICP and arterial pressure was adopted in a group of 82 patients with head injuries. ABP, ICP, and transcranial doppler blood flow velocity in the middle cerebral artery was recorded daily (20- to 120-min time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged for a period of 5 seconds. A moving correlation coefficient (Mean Index) between spontaneous fluctuations of mean flow velocity and cerebral perfusion pressure, which was previously reported to describe cerebral blood flow autoregulation, was also calculated. RESULTS: A positive PRx correlated with high ICP (r = 0.366; P < 0.001), low admission Glasgow Coma Scale score (r = 0.29; P < 0.01), and poor outcome at 6 months after injury (r = 0.48; P < 0.00001). During the first 2 days after injury, PRx was positive (P < 0.05), although only in patients with unfavorable outcomes. The correlation between PRx and Mean index (r = 0.63) was highly significant (P < 0.000001). CONCLUSION: Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

Adolescent↗

Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation.

OBJECTIVES: Cerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate which of the indices, that can be derived using transcranial Doppler ultrasonography and trends of intracranial pressure and blood pressure, are useful in clinical tests of autoregulatory reserve. METHODS: Time dependent interactions between pressure, flow, and volume of cerebral blood and CSF were modelled using a set of non-linear differential equations. The model simulates changes in arterial blood inflow and storage, arteriolar and capillary blood flow controlled by cerebral autoregulation, venous blood storage and venous outflow modulated by changes in ICP, and CSF storage and reabsorption. The model was used to simulate patterns of blood flow during either short or longlasting decreases in cerebral perfusion pressure. These simulations can be considered as clinically equivalent to a short compression of the common carotid artery, systemic hypotension, and intracranial hypertension. Simulations were performed in autoregulating and non-autoregulating systems and compared with recordings obtained in patients. RESULTS: After brief compression of the common carotid artery, a subsequent transient hyperaemia can be interpreted as evidence of intact autoregulation. During longlasting sustained hypoperfusion, a gradual increase in the systolic value of the blood flow velocity waveform along with a decrease in the diastolic value is specific for an autoregulating cerebrovascular system. CONCLUSION: Modelling studies help to interpret both clinical and experimental cerebral haemodynamic phenomena and their dependence on the state of autoregulation.

Blood Flow Velocity↗

Clinical evaluation of near-infrared spectroscopy for testing cerebrovascular reactivity in patients with carotid artery disease.

BACKGROUND AND PURPOSE: Near-infrared spectroscopy (NIRS) derives information about the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) from measurements of light attenuation caused by these chromosphores. The aim of this study was to assess NIRS as a tool for testing CO2 reactivity in patients with carotid artery disease. METHODS: One hundred patients with symptomatic carotid occlusive disease were examined (age range, 44 to 83 years). The severity of stenosis ranged from 30% to 100% (median, 80%) on the ipsilateral side and 0% to 100% (median, 30%) on the contralateral side. Monitored parameters included transcranial Doppler flow velocity, changes in concentration of HbO2 and Hb, cutaneous laser-Doppler blood flow, endtidal CO2, arterial blood pressure, and arterial oxygen saturation. Hypercapnia was induced with the use of a 5% CO2/air mixture for inhalation. To estimate the contribution of skin flow to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in laser-Doppler blood flow were recorded. Finally, reproducibility of reactivity testing was assessed in 10 patients who were subjected to repeated examinations over 3 days. RESULTS: Flow velocity- and HbO2-derived reactivity values were related to the severity of the stenosis (P = .0001 and P = .017, respectively). The correlation between the two reactivity modalities was significant (r = .49, P < .000001). The median estimated contribution of skin flow to NIRS changes was 15.8%. Another variable affecting HbO2 signal changes during the CO2 challenge was arterial blood pressure (P = .025). Reproducibility of HbO2 reactivity was similar to flow velocity reactivity (14.3% and 18.6% variation, respectively). CONCLUSIONS: NIRS shows potential as an alternative technique for testing CO2 reactivity in patients with carotid disease provided that conditions are carefully controlled. Marked changes in arterial blood pressure may render the NIRS reactivity indices unreliable, and the contribution from extracranial tissue must be taken into account when significant.

Adult↗

Evaluation of the transient hyperemic response test in head-injured patients.

The transient hyperemic response test has been shown to provide an index of cerebral autoregulation in healthy individuals and in patients who have suffered a subarachnoid hemorrhage. In this study, the test was applied to patients who had received a severe head injury, and the value of the test was assessed by comparing its result with the individual's clinical condition (Glasgow Coma Scale [GCS] score), cerebral perfusion pressure (CPP), transcranial Doppler wave form-derived index for cerebral autoregulation (relationship between the CPP and the middle cerebral artery flow velocity), and outcome (Glasgow Outcome Scale [GOS] score). Forty-seven patients, aged 16 to 63 years, with head injuries were included in the study. Signals of intracranial pressure, arterial blood pressure, flow velocity, and cortical microcirculatory flux were digitized and recorded for a period of 30 minutes using special computer software. Two carotid compressions were performed at the beginning of each recording. The transient hyperemic response ratio (THRR: the ratio of the hyperemic flow velocity recorded after carotid release and the precompression baseline flow velocity) was calculated, as was the correlation coefficient Sx used to describe the relationship between slow fluctuations in the systolic flow velocity and CPP throughout the period of recording. No significant changes in CPP were found during compression. There was a significant correlation between the THRR and the Sx (r = 0.49, p < 0.0001). The hyperemic response proved to be lower in patients who exhibited a poor clinical grade at presentation (GCS scores < 6, p = 0.01) and lower in patients achieving a poor outcome (GOS scores of 3, 4, and 5, p = 0.003). Loss of postcompression hyperemia occurred when the CPP fell below 50 mm Hg. The carotid compression test provides a simple index of cerebral autoregulation that is relevant to the clinical condition and outcome of the severely head injured patient.

Adolescent↗

Significance of intracranial pressure waveform analysis after head injury.

The authors have investigated the relationships between the amplitude of the ICP pulse wave, the mean values of ICP and CPP, and the outcome of 56 head injured ventilated patients. The ICP was monitored continuously using a Camino transducer (35 patients) or subdural catheter (21 patients). The mean Glasgow Coma Score was 6 (range 3-13; 5 patients had a GCS > 8 after resuscitation). Patients were grouped according to their Glasgow Outcome Score assessed at 12 months after injury. The amplitude of ICP pulse waveform was assessed using the fundamental harmonic of the pulse waveform (AMP) to avoid distortion caused by different frequency responses of the pressure transducers used in the study. Statistical analysis revealed that in patients with fatal outcome the ICP pulse amplitude increased when the mean ICP increased to 25 mmHg and then began to decrease. The upper breakpoint of the AMP-ICP relationship was not present in patients with good/moderate outcome. The moving correlation coefficient between the fundamental harmonic of ICP pulse wave and the mean ICP (RAP: R-symbol of correlation between A-amplitude and P-pressure) was introduced to describe the time-dependent changes in correlation between amplitude and mean ICP. The RAP was significantly lower in patients who died or remained in the vegetative state. In 7 patients who died from uncontrollable intracranial hypertension RAP was oscillating or decreased to 0 or negative values well before brain-stem herniation. The combination of an ICP above 20 mmHg for a period longer than 6 hours with low correlation between the amplitude and pressure (RAP < 0.5) was described as an predictive index of an unfavourable outcome.

Adolescent↗

Egg-sharing in assisted conception: ethical and practical considerations.

The present acute shortage of eggs for donation cannot be overcome unless adequate guidelines are set to alleviate the anxieties regarding payments, in cash or kind, to donors. The current Human Fertilisation and Embryology Authority (HFEA) guidelines do not allow direct payment to donors but accept the provision of lower cost or free in vitro fertilization (IVF) treatment to women in recognition of oocyte donation to anonymous recipients. Egg-sharing achieved in this way enables two infertile couples to benefit from a single surgical procedure. However, the practical guidelines related to this approach are ill-defined at the present time leading to some justifiable uncertainty. A pilot study was therefore undertaken in order to establish the place of egg-sharing in an assisted conception programme. The current HFEA guidelines on medical screening of patients, counselling, age and rigid anonymity between the donor and recipient were followed. The study involved 55 women (25 donors and 30 recipients) in 73 treatment cycles involving fresh and frozen-thawed embryos. Donors were previous IVF patients who, regardless of their ability to pay, shared their eggs equally with matched anonymous recipients. They paid only for their consultations and tests right up to the point of being matched with a recipient. The sole recipient paid the cost applicable in egg donation of a single egg collection, although both received embryo transfers. The results indicate that although the recipients were older than the donors (41.4 +/- 0.9 versus 31.6 +/- 0.5 years), and there was no difference in the mean number of eggs allocated, the percentage fertilization rates, or the mean number of embryos transferred, there were more births per patient amongst recipients than amongst donors (30 versus 20%). We conclude that providing the donors are selected carefully, this scheme whereby a sub-fertile donor helps a sub-fertile recipient is a very constructive way of solving the problem of the shortage of eggs for donation. There are also the advantages of including a group of women who would otherwise be denied treatment. Problems related to 'patient coercion' can, in our view, be fully overcome by the application of strict common-sense safeguards. The ideal of pure altruism is not without its medical and moral risk. The success of egg-sharing depends on shared interests and a degree of altruism between the donor, the recipient and the centre. The current HFEA guidelines should be applauded for enabling a highly effective concept of mutual help to develop.

Adult↗

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↗

Assessment of cerebral autoregulation using carotid artery compression.

BACKGROUND AND PURPOSE: A simple method of testing cerebral autoregulation by observing transcranial Doppler changes in middle cerebral artery flow velocity (FV) during a brief ipsilateral carotid artery compression (the transient hyperemic response test) was studied in 11 normal healthy volunteers. The aim of this study was to assess the reliability of the method and to compare derived autoregulatory indices with those of a standard noninvasive test of autoregulation, Aaslid's leg-cuff test. METHODS: Volunteers were subjected to repeated carotid compressions and leg-cuff tests at different levels of CO2. Hypercapnia was induced using inhalation of a mixture of 5% CO2 in air. Hypocapnia was induced by moderate hyperventilation. To assess the influence of the duration of carotid compression, a series of carotid compressions lasting 3, 4, 5, 7, and 9 seconds were performed in random sequence. Monitored parameters included ipsilateral FV, end-tidal CO2, and arterial blood pressure. The transient hyperemic response ratio (THRR), calculated as the maximum increase of FV divided by baseline values after release of the carotid compression, was taken as the autoregulation index. This index was compared with the rate of autoregulation index derived from the leg-cuff test. RESULTS: Both tests were significantly associated with end-tidal CO2 (ANOVA, P < .000001 for both carotid compression and cuff test). There was a linear correlation between THRR and autoregulation index (r = .86). However, the reproducibility of the THRR was more consistent than for the autoregulation index from single tests (13% versus 46%, respectively; P < .0001). Although the influence of the duration of carotid compression on THRR values was significant for carotid compressions lasting up to 5 seconds, there was no relation to the relative magnitude of FV drop during the compression. CONCLUSIONS: Brief (> 5 seconds) carotid artery compression provides an index of cerebral autoregulation that is reproducible and is affected by CO2 tension in a fashion similar to autoregulatory indices derived from a standard leg-cuff test. The simplicity of the method provides a potentially useful addition to other noninvasive autoregulation tests for clinical assessments, particularly when repeated measurements are required.

Adaptation, Physiological↗