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Biomedical subjects

R A Davies

Publications and source records attributed to R A Davies.

At least 19 recordsLinked to original sources
PubMed2003

Herpes simplex encephalitis. A study of seven patients and their immunological response prior to routine acyclovir treatment.

OBJECTIVES: A retrospective study on cerebrospinal fluid (CSF) samples was made possible by access to a large CSF bank, which has been supplemented by the well characterised prior collection of CSF from patients with Herpes simplex encephalitis (including serial samples from some patients and kindly donated by Professor Maurice Longson, Manchester). These samples are of particular interest because they were collected prior to the routine administration of acyclovir. METHODS: Although an earlier study had shown that there was indeed a correlation between higher titres of antibody and a better outcome, the data did not emerge with statistical significance. The current study was based upon an improved method, which demonstrates the antigen-specific clonality of the immune response. RESULTS: The primitive polyclonal anamnestic response was contrasted with the strong antigen-specific response, which was manifested by a monoclonal pattern in some patients. A clear distinction emerged between two sub-groups of patients on the basis of these findings, which showed a statistically significant (P<0.03) correlation with outcome. CONCLUSIONS: This has allowed us to further support the hypothesis that a strong immunological response has positive prognostic value during the course of the disease.

Acyclovir↗
PubMed2003

Menstrual cycle effects on hypothalamic dopamine receptor function in women with a history of puerperal bipolar disorder.

Neuroendocrine challenge tests of hypothalamic dopamine receptor function in the early postpartum period suggest that the sensitivity of these receptors is increased in women with a history of bipolar disorder after childbirth. We tested the hypothesis that, in women predisposed to bipolar disorder in the puerperium, hypothalamic dopamine receptor function is more sensitive to changes in circulating ovarian hormone concentrations than in women without such histories. Eight fully recovered and drug-free women who had had at least one episode of bipolar illness following childbirth were compared with nine normal controls. Growth hormone (GH) responses to apomorphine (APO 0.005 mg s.c.) were measured in the early follicular phase, when plasma concentrations of ovarian hormones are low, and in the mid-luteal phase, when they are relatively high. The recovered bipolar subjects and the controls did not differ from each other in their follicular and midluteal oestrogen and progesterone concentrations. In the midluteal phase, both groups had increased oestrogen and progesterone levels. The recovered bipolar subjects did not differ from controls in baseline concentrations of GH in either of the menstrual phases. The APO-GH responses of the two groups did not differ in the follicular phase, but in the midluteal phase, when female sex steroids are relatively increased, the recovered group had significantly enhanced APO-GH responses [MANOVA for repeated measures: (i) area under the curve, group by phase effect: p < 0.04; (ii) GH peak rise after APO, group by phase effect: p < 0.056] and the responses were not related to concurrent measures of mood. The results of this small study of women predisposed to bipolar disorder in the puerperium shows an increased dopaminergic receptor sensitivity in the luteal phase of the menstrual cycle. It suggests that their dopaminergic systems have increased sensitivity to changes in circulating female sex steroids. This may be aetiologically relevant to the pathogenesis of puerperal bipolar disorder.

Adult↗
PubMed2002

The use of ultrasound to demonstrate small bowel polyps in a patient with Peutz-Jeghers syndrome.

A 21-year-old woman presented to the accident and emergency department with a 2-day history of lower abdominal pain. Her lips had the stigma of melanosis. Previously, she had received a diagnosis of Peutz-Jeghers syndrome, although no polyps had been detected in small and large bowel barium studies performed approximately 8 years before. Clinically, the patient had mild deep lower abdominal tenderness, and a mass was palpable in the suprapubic region. Urgent ultrasound showed ileoileal intussusception and small polyps in the lumen of the small bowel. At laparotomy, ileoileal intussusception was confirmed. It was not possible to reduce it because of nonviable small bowel, so 20 cm of the ileum, including the intussusception, was excised. After this, intraoperative enteroscopy was performed, showing further polyps in the small bowel distal and proximal to the intussusception, which were excised locally. Only a few reports in the literature describe ultrasound used to diagnose to condition. Intraoperative enteroscopy has been recommended as the treatment of choice because it allows identification of polyps that previously would have been missed.

Adult↗
PubMed2002

Positional down beating nystagmus in 50 patients: cerebellar disorders and possible anterior semicircular canalithiasis.

OBJECTIVES: To clarify the clinical significance of positional down beat nystagmus (pDBN). METHODS: A discussion of the neuro-otological findings in 50 consecutive patients with pDBN. RESULTS: In 38 patients there was evidence of CNS disease (central group) but in 12 there was not (idiopathic group). In the CNS group, presenting symptoms were gait, speech, and autonomic dysfunction whereas in the idiopathic group patients mostly reported positional vertigo. The main neurological and oculomotor signs in the CNS group were explained by cerebellar dysfunction, including 13 patients with multiple system atrophy. In patients with multiple system atrophy with a prominent extrapyramidal component, the presence of pDBN was helpful in the differential diagnosis of atypical parkinsonism. No patient with pDBN had the Arnold-Chiari malformation, a common cause of constant down beat nystagmus (DBN). In the idiopathic group, the pDBN had characteristics which suggested a peripheral labyrinthine disorder: vertigo, adaptation, and habituation. In six patients an additional torsional component was found (concurrently with the pDBN in three). Features unusual for peripheral disorder were: bilateral positive Dix-Hallpike manoeuvre in nine of 12 patients and selective provocation by the straight head-hanging manoeuvre in two. CONCLUSION: It is argued that some patients with idiopathic pDBN have benign paroxysmal positional vertigo (BPPV) with lithiasis of the anterior canal. The torsional component may be weak, because of the predominantly sagittal orientation of the anterior canal, and may not be readily seen clinically. Nystagmus provocation by bilateral Dix-Hallpike and straight head-hanging may be explained by the vertical upwards orientation of the ampullary segment of the anterior canal in the normal upright head position. Such orientation makes right-left specificity with the Dix-Hallpike manoeuvre less important than for posterior canal BPPV. This orientation requires a further downwards movement of the head, often achieved with the straight head-hanging position, to provoke migration of the canaliths. The straight head-hanging manoeuvre should be carried out in all patients with a history of positional vertigo and a negative Dix-Hallpike manoeuvre.

Adult↗
PubMed2000

Interatrial conduction of atrial tachycardia in heart transplant recipients: potential pathophysiology.

Surgical suture lines formed at the site of anastamosis have been considered to be electrically inert and thus present a line of block to conduction. However, a number of reports have suggested that conduction is occasionally possible across suture lines. Most of these cases have reported conduction between donor and recipient atria following cardiac transplantation. We report an illustrative case successfully treated with radiofrequency ablation, and present pathology findings that may give insight into the pathophysiology.

Adult↗
PubMed2000

Symptoms, disability and handicap in unilateral peripheral vestibular disorders. Effects of early presentation and initiation of balance exercises.

The aim of this study was to obtain a profile of disability and handicap in patients with unilateral peripheral vestibular disorders presenting to a specialist tertiary care unit. Two validated questionnaires were sent to patients who had a unilateral peripheral vestibular disorder as defined by strict criteria. Some patients still suffered moderate handicap and disability 5 years after the initial symptoms related to a unilateral vestibular disorder, although the duration of symptoms (onset to questionnaire completion) did not correlate with severity of disability and handicap, as judged by questionnaire scores. However, patients presenting to the unit within 6 months of onset of vertigo commenced balance exercises significantly earlier and had significantly lower disability scores than patients presenting later. A high proportion of non-compliance with, and delay in initiation of, vestibular rehabilitation exercises was noted in the total patient sample, while compliance with, and early initiation of, Cooksey Cawthorne exercises were significantly correlated with low disability and questionnaire scores. These findings suggest that early referral to a specialist balance unit for patients with persistent dizziness is associated with better outcome.

Adolescent↗
PubMed2000

Evaluation of brain damage resulting from penetrating and non-penetrating captive bolt stunning using lambs.

OBJECTIVE: To compare the brain damage in sheep resulting from penetrating and non-penetrating captive bolt stunning. DESIGN: The unrestrained heads of anaesthetised lambs were impacted in the temporal region with penetrating and non-penetrating captive bolt pistols (humane stunners) using a constant charge. Two hours after head impact, brains were perfusion-fixed with 4% paraformaldehyde. Coronal sections were stained with haematoxylin and eosin and immunohistochemically for amyloid precursor protein, a sensitive marker of axonal and neuronal reaction in brains after trauma. Pathological changes in these brains were then quantified by morphometric analysis. RESULTS: The skull was fractured in 50% of lambs after a non-penetrating head impact and in all animals after a penetrating head wound. Impact contusions were present in 80% of lambs receiving a non-penetrating head injury and in all of those with a penetrating wound. Total contusion area was similar in both groups. Amyloid precursor protein-positive axons and neurons, and haemorrhage, were widely distributed in the brain after both head impact types, but there was no statistically significant difference between the two groups. Multifocal necrosis of the cerebellar granular layer was found in all lambs with non-penetrating head injury, but in none with a penetrating injury. CONCLUSIONS: The structural brain damage, a mixture of focal and diffuse injury, produced by penetrating and non-penetrating captive bolt pistols was overall similar and of sufficient severity to suggest that both types of weapon are acceptable for euthanasia.

Animal Welfare↗
PubMed1999

Discoordinate modulation of natriuretic peptides during acute cardiac allograft rejection in humans.

BACKGROUND: Increased circulating levels of the cardiac polypeptide hormones atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) may be observed after orthotopic cardiac transplantation. Both the hypertrophic and inflammatory processes in the allograft may contribute to this increase, but no mechanistic explanation has been suggested for this observation. METHODS AND RESULTS: Plasma immunoreactive ANF and BNP determinations were performed in 10 consecutive transplant patients. These were correlated with degree of rejection as reflected by histopathological findings at serial endomyocardial biopsies. Three patients had associated hemodynamic measurements and blood samples 24 hours before and after transplantation. All rejection episodes that received treatment were accompanied by a marked increase in BNP plasma levels to > approximately 400 pg/mL. Steadily increasing BNP levels preceded overt rejection as assessed by histopathological criteria. The increase in plasma BNP was not always accompanied by an increase in ANF, which suggests the specific upregulation of BNP gene expression during acute rejection episodes. Treatment of the acute rejection episodes led to a substantial decrease of BNP plasma levels. CONCLUSIONS: The significant selective increase in plasma BNP levels found in the present study has not been previously described. This finding provides a new insight into the mechanism of allograft rejection and the modulation of natriuretic peptide synthesis and release. Furthermore, although preliminary, the data suggest that BNP plasma levels could form the basis for a new, noninvasive screening test to predict acute cardiac allograft rejection. Because treatment with the antilymphocyte monoclonal antibody OKT3 (murine monoclonal antibody to the CD3 antigen of the human T-cell) decreased BNP plasma levels, cytokine production by T-cells may mediate the selective increase in circulating BNP.

Adult↗
PubMed1999

The effect of severity of unilateral vestibular dysfunction on symptoms, disabilities and handicap in vertiginous patients.

This study compares the symptoms, disabilities and handicap, as assessed by means of a questionnaire, in two groups of patients with a unilateral peripheral vestibular disorder: those with a total canal paresis and those with a partial canal paresis, as judged by the duration parameter using the Fitzgerald Hallpike caloric test in the absence of optic fixation. The results of the study indicate that the severity of dizziness, the Dizziness Index (severity x frequency) and the overall level of disabilities related to visual vertigo are less severe in unilateral profound or total loss of vestibular function than in unilateral mild vestibular loss.

Case-Control Studies↗
PubMed1999

Circulatory support for cardiogenic shock due to acute myocardial infarction: a Canadian experience.

BACKGROUND: Cardiogenic shock due to acute myocardial infarction (AMI) is associated with high mortality. Circulatory support devices may be used to assist these patients while they await cardiac transplantation. METHODS AND RESULTS: From 1986 to 1997, 25 patients in cardiogenic shock complicating AMI within 3.6+/-0.7 days of the event were supported with artificial hearts. Of the 25 patients, 21 were men with a mean age of 48.4 +/- 1.8 years. The age range was 26 to 62 years. Patients were considered for a device when the following criteria were met: cardiac index less than 1.8 L/min/m2, wedge pressure greater than 20 mmHg despite one or two inotropes and/or intra-aortic balloon support. They received either a CardioWest total artificial heart (n=13), a Thoratec biventricular assist device (n=6) or left ventricular assist device (LVAD) (n=6). Three patients were not considered transplant candidates and died while on the devices (two with multiorgan failure and one found to have a bronchogenic carcinoma after implant), with 22 undergoing cardiac transplantation within 8.6+/-2.2 days of device implant. Six patients died in hospital after the transplants (27.3% mortality). Complications included bleeding or tamponade in seven (28%), pneumonia in six (24%) and right ventricular failure in three LVAD patients (12%). Post-transplant actuarial one-, two- and five-year survival rates were 71.4%, 71.4% and 51%, respectively. CONCLUSIONS: Circulatory support devices offer a means to maintain organ perfusion in patients who develop cardiogenic shock due to AMI. Patients can then undergo transplantation with a reasonable expectation for survival when the alternative is death. Eventually the availability of permanent support devices may obviate the need for transplant in these patients.

Acute Disease↗
PubMed1999

Stenting of an unprotected left main coronary artery stenosis in a cardiac transplant patient.

Cardiac allograft vasculopathy is the leading cause of death in cardiac transplant patients who survive the first year. Retransplantation is limited by shortage of donors and reduced survival rates compared with the initial transplant. Recent reports of successful stenting in these patients may offer some hope, although randomized trials are lacking. Successful stenting of an 'unprotected' left main coronary artery stenosis under cardiopulmonary support is presented in a cardiac transplant patient. A 16-month follow-up angiogram demonstrated a patent stent without restenosis and no interim clinical events.

Coronary Angiography↗
PubMed1998

Catecholamines and heart function in heart transplant patients: effects of beta1- versus nonselective beta-blockade.

OBJECTIVES: To evaluate cardiac responses to norepinephrine and epinephrine in heart transplant patients compared with patients with mild essential hypertension and to evaluate the contribution of beta2-receptors versus beta1-receptors to the cardiac responses by assessing the effects of the 2 agonists after treatment with placebo compared with the beta1-selective blocker atenolol and the nonselective blocker nadolol. METHODS: A double-blind, randomized crossover design was used to study patients after administration of placebo, atenolol, or nadolol for 2 weeks. Infusion of norepinephrine was performed at incremental rates of 12.5, 25, 50, and 100 ng/kg/min and of epinephrine at rates of 20, 40, 80, and 120 ng/kg/min. Blood pressure, heart rate, left ventricular function (by echocardiogram), and venous plasma concentrations were assessed at rest and at the end of each infusion rate. RESULTS: Infusion of epinephrine and norepinephrine was associated with 3-fold and 2-fold higher increases, respectively, in plasma concentrations in the transplant patients versus patients with hypertension. Enhanced blood pressure responses to either agonist were found in the transplant patients, but not when venous plasma concentrations were considered. Norepinephrine decreased heart rate and cardiac index in patients with hypertension receiving placebo and more markedly when receiving atenolol and nadolol. In contrast, heart transplant patients showed increases in heart rate, ejection fraction, and cardiac index, which largely were blocked (but not reversed into decreases) by atenolol and nadolol. In patients with hypertension receiving placebo, epinephrine increased heart rate, ejection fraction, and cardiac index. These responses were enhanced in transplant patients, also relative to plasma concentrations. Atenolol had only minor effects on these cardiac responses. On nadolol epinephrine decreased heart rate, stroke volume, and cardiac index in the patients with hypertension, whereas the transplant patients receiving nadolol showed no longer increases in cardiac function by epinephrine. CONCLUSIONS: Both absence of parasympathetic buffering and diminished systemic clearance contributed to the enhanced cardiac responses to infusion of norepinephrine and epinephrine in heart transplant patients compared with patients with essential hypertension. Cardiac beta2-receptors mediate most of the chronotropic and inotropic responses to epinephrine in both patients with hypertension and heart transplant patients.

Adrenergic beta-1 Receptor Antagonists↗
PubMed1998

Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon.

OBJECTIVES: The frequency of pathologically reduced click thresholds for vestibular activation was explored in patients with the Tullio phenomenon (sound induced vestibular activation). METHODS: Seven patients (eight affected ears) with symptoms of oscillopsia and unsteadiness in response to loud external sounds or to the patient's own voice were examined. In all but one patient, vestibular hypersensitivity to sound was confirmed by the fact that eye movements could be produced by pure tones of 110 dB intensity or less. Conventional diagnostic imaging was normal in all cases and three of the patients had normal middle ears at surgical exploration. Thresholds for click evoked vestibulocollic reflexes were compared with those of a group of normal subjects. Galvanic stimulation was used as a complementary method of examining the excitability of vestibular reflexes. RESULTS: All the patients showed a reduced threshold for click activation of vestibulocollic reflexes arising from the affected ear. Short latency EMG responses to clicks were also present in posterior neck and leg muscles, suggesting that these muscles receive vestibular projections. Galvanic stimulation produced a normal pattern of body sway in four of the five patients tested. CONCLUSIONS: A pathologically reduced threshold to click activation (< or = 70 dB NHL (average normal hearing level)) seems to be a consistent feature of the Tullio phenomenon and a useful diagnostic criterion. This in turn is most likely to be due to an increased effectiveness of the transmission of sound energy to saccular receptors. Activation of these receptors probably contributed to the vestibular symptoms experienced by the patients.

Acoustic Stimulation↗
PubMed1997

Pilot study of multiple chemotherapy resistance modulators plus epirubicin in the treatment of resistant malignancies.

We studied the toxicity and efficacy of adding to epirubicin five resistance modulators in the treatment of resistant solid tumors. Additional drugs were added in successive cohorts of patients, such that cohort 1 patients received two drugs along with their epirubicin, while cohort 4 patients received five modulators along with their epirubicin. Metronidazole, tamoxifen (cohort 1), dipyridamole (cohort 2), ketoconazole (cohort 3) and cyclosporin (cohort 4) were administered with epirubicin. A total of 22 patients were treated. Nausea and vomiting was usually mild to moderate. There was an unexpectedly high incidence of possible cardiac toxicity associated with treatment, although in some patients it was uncertain whether or not observed cardiac events were related to treatment. Granulocytopenia was significant in all four cohorts, but it was unclear whether it was increased by the modulators. There were two febrile neutropenic events in cohorts 1 and 2 successfully treated with antibiotics, and three septic deaths (one in each of cohorts 1, 2 and 4). It was elected to discontinue enrollment on the study prematurely in light of cardiac and other toxicity seen in the first two patients accrued in cohort 4. A single response was observed. While this approach is feasible, the observed toxicity and the difficulty patients experienced in ingesting the large number of prescribed pills will make further exploration of this approach difficult.

Adjuvants, Pharmaceutic↗
PubMed1997

Migraine-associated vertigo.

A retrospective analysis was performed on a consecutive series of 363 patients presenting with vertigo; 32% had migraine. Of the 224 patients with no pathology other than migraine or vestibular dysfunction, migraineurs had a significantly higher prevalence of normal, central, and combined central and peripheral vestibular dysfunction compared to non-migraineurs. The combination of central and peripheral vestibular signs was a feature of migraine with aura. The results support the hypothesis that migraine-associated vertigo is a diagnostic entity.

Adult↗
PubMed1996

The growth hormone response to apomorphine at 4 days postpartum in women with a history of major depression.

We have examined the responsiveness of dopamine sensitive neurones in the postpartum period in woman with a history of major depression who are at high risk of experiencing a recurrence of illness in the postpartum period. Fourteen women were assessed at 36 weeks of pregnancy and during the 3 months following delivery, using the Schedule for Affective Disorders and Schizophrenia, including its change version. They were not depressed at initial assessment. Five of the 14 women went on to experience a postpartum relapse (2 major depressive disorder, 2 generalised anxiety disorder, 1 panic disorder). On the fourth day postpartum, i.e., before relapse, the growth hormone response to the dopamine agonist apomorphine was measured as an index of the functional state of hypothalamic dopamine D2 receptors. Women who subsequently relapsed had a significantly greater growth hormone response to apomorphine than those who remained well. This was particularly marked in women with anxiety/panic. The development of increased sensitivity of hypothalamic dopamine D2 receptors in the postpartum period appears to predict the onset of depressive and anxiety disorders.

Anxiety Disorders↗