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Biomedical subjects

S C Jones

Publications and source records attributed to S C Jones.

At least 55 records · Page 3Linked to original sources

Validation of continuous thermal measurement of cerebral blood flow by arterial pressure change.

A thermal measurement system to monitor cerebral blood flow (CBF) continuously from the cortical surface is evaluated in vivo. It has a temperature resolution of better than 0.001 degrees C (1 m degrees C) and can compensate for baseline temperature fluctuations in the brain tissue. A new approach has been developed to test the capability of monitoring dynamic CBF response. Transient CBF changes associated with changes in mean arterial blood pressure (MABP) caused by repeated bolus norepinephrine injections are used to examine the response of the measurement system in both the heated mode, sensitive to flow, and the unheated mode, sensitive only to temperature. Experiments on 13 rats demonstrate that changes in the MABP are closely correlated with those of temperature difference in the heated mode. Regression analysis shows a mean slope of 0.9 m degrees C/mm Hg in the heated mode, which is significantly different from zero (p < 0.002) and from the mean slope in the unheated mode (p < 0.002). This indicates that flow signal in the system output can be distinguished from the baseline thermal fluctuations. Thus, the system can be used to detect and study dynamic perfusion changes from the brain surface with minimal tissue damage. Furthermore, analysis of the data shows that the transient flow signal before autoregulation is linearly correlated with changes in MABP.

Animals↗

A patient knowledge questionnaire in inflammatory bowel disease.

A multiple choice knowledge questionnaire was developed for patients with inflammatory bowel disease (IBD). Initially, 20 questionnaires were piloted, and then questions of poor discriminatory ability (> 75% patients giving a correct response) were eliminated. A second pilot study proved the internal consistency (coefficient alpha = 0.84) and the stability of the questionnaire using a test-retest method (Spearman R = 0.86, p = 0.002). The questionnaire was then completed by 60 randomly selected patients attending colitis clinic. The mean score was 13 of a total of 36 (range 2-29). Eighty percent of patients wished to know more about their disease. Knowledge score was higher in patients who were members of the National Association of Crohn's Disease and Colitis (NACC) (p < 0.005) and in patients with Crohn's disease (CD) rather than ulcerative colitis (UC) (p < 0.005). Knowledge score correlated with the number of years spent in full-time education (R = 0.48, p < 0.001) and inversely with age (R = -0.33, p < 0.02) but did not correlate with disease duration. The study demonstrated some misunderstandings about IBD although most patients would have liked more information. The questionnaire could be used as a tool to evaluate patient education programs.

Colitis, Ulcerative↗

Expression of interleukin-6 by intestinal enterocytes.

AIMS: To investigate the cellular source of the cytokine interleukin-6 (IL-6) in the small and large intestines of patients with inflammatory bowel disease, coeliac disease, and in controls. METHODS: IL-6 was detected in frozen sections of bowel by single and double label indirect immunofluorescence using rabbit polyclonal and murine monoclonal anti-IL-6 antibodies. The murine monoclonal antibodies RFDR1 (anti-MHC class II) and UCHT1 (anti-CD3) were used to localise macrophages and T lymphocytes, respectively. Lipopolysaccharide stimulated peripheral blood monocytes were used as positive control cells for IL-6 protein. RESULTS: IL-6 was demonstrated in the small and large intestine of patients with inflammatory bowel disease, coeliac disease, and in controls. The protein was present predominantly in enterocytes and colocytes in normal and inflamed mucosa, but not in the infiltrating inflammatory cells of the lamina propria. There were no discernable differences between patients with inflammatory bowel disease or coeliac disease and controls, nor between small and large bowel mucosa. Incubation of antibody with recombinant human IL-6 protein abolished the labelling. IL-6 protein was also present in lipopolysaccharide stimulated peripheral blood monocytes. CONCLUSIONS: The data suggest that enterocytes and colocytes may play an active part in the immune response of the gut. The presence of IL-6 in both inflamed and non-inflamed small and large intestine requires further investigation into the function of this cytokine in the gut.

Celiac Disease↗

Evidence that heterogeneity of cerebral blood flow does not involve vascular recruitment.

Recent studies indicate that blood flow to cerebral cortex is not homogeneous but may vary both spatially and temporally. In addition, some investigators have reported that capillaries and arterioles can be recruited to increase cerebral blood flow, an issue that is extremely controversial. The goal of this study was to determine whether recruitment of cerebral blood vessels is an important mechanism in spatial and temporal heterogeneity of cerebral blood flow. In seven anesthetized ventilated rats, different fluorescent tracers were injected 45 and 10 s before decapitation. In addition, [14C]iodoantipyrine also was injected 10 s before decapitation. After the brains were sectioned, fields in the cerebral cortex were examined microscopically for fluorescence and processed for measurement of cerebral blood flow with techniques of quantitative autoradiography and image analysis. With examination of 24 +/- 2 (SE) points in cerebral cortex of each rat, similar numbers of small blood vessels (< or = 10 microns) were counted that contained fluorescent tracers injected 45 and 10 s before decapitation (346 +/- 48 and 355 +/- 42 vessels/mm2, respectively; P > 0.05). Large blood vessels (20-60 microns; 73 +/- 6 vessels in each rat) contained both fluorescent tracers. In addition, adjacent regions of high and low blood flow contained similar numbers of small and large vessels. Our findings indicate that vascular recruitment is not an important mechanism in temporal or spatial heterogeneity of cerebral blood flow.

Animals↗

Cardiovascular changes during focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: Recent studies have suggested that cerebral infarction influences autonomic activity and may contribute to sudden death. The goal of this study was to examine effects of focal cerebral infarction on mean arterial pressure and heart rate. METHODS: Halothane-anesthetized rats were assigned to two groups: stroke (n = 10), in which the middle cerebral artery or an adjacent vessel was embolized with a silicone cylinder, and sham (n = 8), in which rats were sham embolized (saline). Arterial pressure and heart rate were measured for 90 minutes and again 24 hours after vascular occlusion. A change in electroencephalographic amplitude of -45% after embolization was used to determine if a significant degree of infarction was present. RESULTS: Vascular occlusion produced a significant increase in mean arterial pressure at 10, 60, and 90 minutes (p < 0.05). Changes in heart rate were significantly greater (p < 0.05) than in sham-treated rats at 10 and 30 minutes after embolization. In contrast, mean arterial pressure and heart rate measured 24 hours after embolization were similar in both groups. Anatomic analysis of the infarcted areas demonstrated that either insular cortex or amygdala was affected in all embolized rats. CONCLUSIONS: This study indicates that cerebral infarction produces a transient elevation of mean arterial pressure and heart rate. However, within 24 hours both parameters returned to preinfarcted levels. Our findings are consistent with clinical reports that indicate that mean arterial pressure and heart rate of stroke patients are similar to those of other groups when they are admitted to the hospital, although other cardiovascular parameters are greatly altered.

Amygdala↗

Transcranial Doppler assessment of cerebral perfusion reserve in patients with carotid occlusive disease and no evidence of cerebral infarction.

Using transcranial Doppler ultrasound (TCD), we measured bilateral middle cerebral artery mean blood flow velocities (MCAVs) before and 10 minutes after intravenous infusion of 1 gram of acetazolamide in 20 patients without cerebral infarction. Seven patients had normal carotid arteries (group 1), seven had unilateral internal carotid artery (ICA) stenosis > or = 75% (group 2), and six had unilateral ICA occlusion (group 3). Before acetazolamide infusion, side-to-side differences in MCAV were 0.06 cm/sec in group 1 (p = 0.98), 4.3 cm/sec in group 2 (p = 0.36), and 15.0 cm/sec in group 3 (p = 0.02). Bilateral MCAV increased in all three groups after acetazolamide infusion, and the side-to-side differences in MCAV were 3.2 cm/sec in group 1 (p = 0.40), 11.4 cm/sec in group 2 (p = 0.04), and 27.6 cm/sec in group 3 (p = 0.03). Patients with carotid stenosis or occlusion and ipsilateral transient ischemic attacks (TIAs) had higher side-to-side differences in MCAV before (p = 0.03) and after (p = 0.01) acetazolamide than did asymptomatic patients with carotid disease. The association of impaired cerebral perfusion reserve and TIAs suggests that the TCD-acetazolamide test may enable identification of a subgroup of patients with carotid occlusive disease who are at higher risk for stroke.

Acetazolamide↗

Evaluation of a cognitive behavioural programme for rehabilitating patients with chronic pain.

The aim of this prospective longitudinal study was to evaluate an inpatient cognitive behavioural pain management programme for patients with chronic pain. A physical and psychological assessment of patients was carried out before and after treatment, and at one and six months follow up. A total of 212 patients with disabling chronic pain of mean duration 10.5 years, for whom no further medical or psychiatric treatment was appropriate or available, were admitted; their mean age was 50 years and 65% were women. The four week programme was delivered by a multidisciplinary team of two psychologists, a physiotherapist, nurse, occupational therapist and anaesthetist. The main components of therapy included: education, teaching behavioural and cognitive skills, a stretch and exercise programme, medication reduction, goal setting and pacing, and relaxation training. Outcome measures assessed quality of life, physical performance (for example walking speed), pain intensity and distress, depression severity and confidence. Assessment immediately after treatment revealed significant improvements on all measures. Improvements were well maintained at six month follow up. Cognitive behavioural treatment can be of value in improving the day-to-day functioning and quality of life of patients with chronic pain for whom conventional medical treatments have apparently failed.

Adult↗

Familial visceral myopathy. A family with involvement of four generations.

A family with the autosomal dominant form of familial visceral myopathy is described involving four generations. The members illustrate several different clinical presentations including severe constipation, diarrhea, alternating constipation and diarrhea, volvulus, urinary tract infection, and retention of urine. One patient's history suggested that the uterus may have been involved. Diagnosis of this rare disease requires an awareness of the variable presentation and a careful histological examination of full-thickness sections of bowel. The potential pitfalls in both histological and clinical diagnosis of this condition are demonstrated in this family's history. The extensive involvement of small and large bowel in at least two family members is unusual in the autosomal dominant form of the disease, but their course has so far been favorable, lending further evidence to the impression that prognosis is good. This is of importance for genetic counseling of families who have this very rare disease.

Adult↗

Plasma viscosity in inflammatory bowel disease.

AIMS: To assess the relation of plasma viscosity to disease activity in patients with inflammatory bowel disease. METHODS: Crohn's disease (n = 60) and ulcerative colitis (n = 71) were diagnosed on the basis of typical histological or radiological features. Active Crohn's disease was defined as a Crohn's disease activity index of 150 or over. Active ulcerative colitis was defined as a liquid stool passed three times a day or more with blood. Blood samples were assessed for haemoglobin concentration, total white cell count, platelets, plasma viscosity, erythrocyte sedimentation rate, serum albumin, and C-reactive protein. RESULTS: Plasma viscosity was higher in those with active Crohn's disease compared with those with inactive Crohn's disease or active ulcerative colitis. Plasma viscosity correlated significantly with erythrocyte sedimentation rate, C-reactive protein, and platelet count in patients with Crohn's disease. In ulcerative colitis plasma viscosity correlated only with serum C-reactive protein. Plasma viscosity showed a low sensitivity for detecting active Crohn's disease, with 48% of those with active disease having a plasma viscosity within the laboratory reference range. CONCLUSIONS: Plasma viscosity is related to disease activity in Crohn's disease, but is insufficiently sensitive for it to replace erythrocyte sedimentation rate as a measure of the acute phase response in Crohn's disease.

Blood Sedimentation↗

Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats.

BACKGROUND AND PURPOSE: We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. METHODS: Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. RESULTS: The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. CONCLUSIONS: These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.

Animals↗

Neurologic complications related to cardiac surgery.

Neurologic complications are a major cause of morbidity, complicating open heart surgery, cardiac catheterization, and interventional techniques. Global or focal brain ischemia related to embolism or hypoperfusion predominates. Breakthrough cerebral hemorrhage and infection can complicate cardiac transplantation. Identifying individuals at risk for cerebrovascular complications may lead to more effective preventative and treatment measures.

Brain Damage, Chronic↗

Effect of topical recombinant TGF-beta on healing of partial thickness injuries.

Peptide growth factors produced by platelets, macrophages, epidermal, and dermal cells may play key roles in regulating healing of partial-thickness skin wounds. We examined the effects of recombinant transforming growth factor beta (TGF-beta) on cultures of epidermal and dermal cells in vitro and on healing of partial-thickness injuries in vivo. Increasing concentrations of TGF-beta (0.1, 1, and 10 ng/ml) progressively inhibited serum-stimulated DNA synthesis by up to 95% in cultures of adult human keratinocytes during 48 hr of exposure to TGF-beta. In contrast, TGF-beta (10 and 100 ng/ml) in serum-free media stimulated DNA synthesis by up to 80% compared to serum-free control cultures of adult human dermal fibroblasts. To evaluate the effects of TGF-beta on healing of partial-thickness injuries in vivo, wounds (20 x 20 x 0.6 mm) were created on the dorsal thoracolumbar region of adult pigs by an electrokeratome and were treated daily for 5 days after injury with vehicle or vehicle containing 0.1 or 1 microgram/ml TGF-beta and covered with occlusive dressing. Computerized planimetry of wound photographs demonstrated that TGF-beta treatment stimulated statistically significantly increases in the area of regenerated epidermis compared to wounds treated with saline vehicle on Days 3, 4, 5, and 7 after injury probably due to TGF-beta increasing the rate of epidermal cell migration. In addition, morphometry of biopsy specimens showed that TGF-beta treatment stimulated statistically significant increases in the cross-sectional depths of regenerated dermis compared to wounds treated with saline or Silvadene vehicles on Days 5, 6, and 8 after injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The role of unemployment in parasuicide.

Sixty-four in-patient cases of deliberate non-fatal self-poisoning were compared for psychosocial problems in a case-control study with a similar number of individually matched community controls. A strongly significant association was found between unemployment and self-poisoning. Further analysis revealed no firm evidence to support the hypotheses that unemployment was causally related to self-poisoning in an indirect manner or that it increased the vulnerability of individuals who self-poison to other stressful life events and difficulties. It is concluded that a possible explanation is that some third factor independently increases the risk of both unemployment and self-poisoning, giving rise to a non-causal relationship between these last two variables.

Adaptation, Psychological↗

Cerebral blood flow with the indicator fractionation of [14C]iodoantipyrine: effect of PaCO2 on cerebral venous appearance time.

The indicator fractionation technique using a diffusible indicator as a tracer for the determination of CBF has been used for numerous investigations of the cerebral circulation and its pathophysiology. The diffusible tracer is "trapped" in the brain based on the proper delay between tracer injection and cessation of the cerebral circulation by decapitation before the appearance of the tracer in the cerebral venous circulation. If this delay is too long, the quantitative assumption of the indicator fractionation technique will not be met, and CBF values will be underestimated. In 13 Sprague-Dawley rats anesthetized with pentobarbital, the appearance of [14C]iodoantipyrine at the torcular was assessed as a function of PaCO2. An inverse linear relationship between PaCO2 (in millimeters of mercury) and cerebral venous appearance, Ta (in seconds), was established with the regression equation Ta = -0.0842.PaCO2 + 12.3 (R2 = 0.70, slope significantly different from zero, p less than 0.001). Ta varied between 5 and 12 s and PaCO2 varied between 84 and 18 mm Hg, respectively. Thus, in low-flow states, the decapitation time may be lengthened to 12 s, whereas in high-flow states, the time must be 5 s to eliminate the possibility of backflux of tracer out of the brain.

Animals↗

Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom.

Increasing use of assays for TSH with improved sensitivity as a first-line test of thyroid function has raised questions regarding prevalence and clinical significance of abnormal results, especially values below normal. We have assessed the thyroid status of 1210 patients aged over 60 registered with a single general practice by measurement of serum TSH using a sensitive assay. High TSH values were more common in females (11.6%) than males (2.9%). TSH values below normal were present in 6.3% of females and 5.5% of males, with values below the limit of detection of the assay present in 1.5% of females and 1.4% of males. Anti-thyroid antibodies were found in 60% of those with high TSH but only 5.6% of those with subnormal TSH. Eighteen patients were hypothyroid (high TSH, low free thyroxine) and one thyrotoxic (low TSH, raised free thyroxine) at initial testing. Seventy-three patients with elevated TSH but normal free T4 were followed for 12 months; 13 (17.8%) developed low free T4 levels and commenced thyroxine, TSH returned to normal in four (5.5%) and 56 (76.7%) continued to have high TSH values. Sixty-six patients with TSH results below normal were followed. Of the 50 subjects with low but detectable TSH at initial testing, 38 (76%) returned to normal at 12 months; of those 16 with undetectable TSH followed, 14 (87.5%) remained low at 12 months. Only one subject (who had an undetectable TSH) developed thyrotoxicosis. In view of the marked prevalence of thyroid dysfunction in the elderly, we suggest that screening of all patients over 60 should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Importance of freezing time when iodoantipyrine is used for measurement of cerebral blood flow.

The goal of the present study was to determine effects of delay of freezing of the brain on distribution of [14C]iodoantipyrine in the brain. Blood flow to parietal cerebral cortex (CBF) and choroid plexus was measured with the indicator fractionation technique and quantitative autoradiography. After injection of iodoantipyrine, each rat was decapitated, and the head was immersed in chlorodifluoromethane (-40 degrees C). The brain was removed from the skull after it was frozen. In some rats, heads were immersed immediately after decapitation, and CBF was markedly heterogeneous. In another group, heads were frozen 3 min after decapitation. In this case, CBF was uniform in its distribution. Average CBF was similar in groups with immediate and delayed freezing (90-104 ml.min-1 x 100 g-1). In contrast, delays in freezing decreased blood flow to choroid plexus from 551 +/- 115 to 261 +/- 48 ml.min-1 x 100 g-1. Our findings indicate that immediate freezing of the brain after decapitation is necessary to prevent diffusion of iodoantipyrine from regions of high blood flow to regions of lower blood flow and underestimations of blood flow in regions with high blood flow.

Animals↗

Vascular responses of choroid plexus during hypercapnia in rats.

The response of blood flow to choroid plexus (CPBF) during hypercapnia is controversial. The goal of this study was to determine the effect of hypercapnia on CPBF in unanesthetized rats. Rats breathed air or a mixture of 5-8% CO2 in air, and CPBF was measured with [14C]isopropyliodoamphetamine and quantitative autoradiography. In hypercapnic rats [arterial PCO2 61.6 +/- 1.6 (SE) mmHg; n = 7] CPBF was similar to that of normocapnic control rats (525 +/- 39 ml.min-1.100 g-1; arterial PCO2 42.7 +/- 0.6 mmHg; n = 5). In contrast, blood flow to cerebral cortex increased 67% during hypercapnia. CPBF in normocapnic rats that were treated with phentolamine was similar to untreated normocapnic and hypercapnic rat CPBF. However, during hypercapnia, CPBF in phentolamine-treated rats increased 29%. Responses were similar in blood flow to choroid plexus of lateral, third, and fourth ventricles. Our findings indicate that hypercapnia has no effect on CPBF when alpha-adrenergic receptors are intact. In contrast, after blockade of alpha-adrenergic receptors, hypercapnia increases CPBF. These findings suggest that, during hypercapnia, levels of sympathetic activity or blood-borne catecholamines are increased that prevent increases in CPBF.

Amphetamines↗