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Biomedical subjects

S C Jones

Publications and source records attributed to S C Jones.

At least 19 recordsLinked to original sources

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

Isovolumic hemodilution with dextran 40 in the rat: effect on the development of peripheral edema and various physiologic parameters.

Low molecular weight dextran 40 (D40), 40,000 daltons, is a potential therapeutic agent for cerebral ischemia because it increases local cerebral blood flow. However, the evaluation of D40 in the rat has been difficult due to systemic effects. We evaluated the effects of isovolumic hemodilution with D40 on the development of peripheral edema, mean arterial pressure, hematocrit (Hct) and total blood volume in 18 rats, during 30 min or 4 hr i.v. infusions, in animals with and without previous challenge with D40. Reduction of Hct without peripheral edema to a mean of approximately 31% was only achieved in the animals challenged with i.p. D40 24 hr before hemodilution and who received D40 over a period of 4 hr. Infusion of D40 over a period of 30 min was associated with shorter survival time, compared to the 4-hr infusion group (P less than .005). In the pretreated, rapidly infused group, total blood volume per body weight decreased significantly over time (P less than .005) and the mean arterial blood pressure dropped, but not significantly (P less than .07), whereas no change in Hct was detected and there was a trend toward increased peripheral edema, relative to the slowly infused groups. We conclude that reduction of Hct can be achieved successfully with i.p. administration of D40 24 hr before the study combined with infusion of the agent during a 4-hr period, without significant peripheral edema and early hypotension. This procedure should be used to avoid allergic reactions when evaluating hemodilution with D40 in rats.

Animals

Abdominal migraine: does it exist?

Abdominal migraine is well recognised in children, but in spite of anecdotal reports migraine is not well established as a cause of abdominal pain in adults. Functional abdominal pain is usually classified as either irritable bowel syndrome or nonulcer dyspepsia, but some patients have intermittent abdominal pain associated with headache or other migraine accompaniments and, in these, a diagnosis of abdominal migraine should be considered. It is possible that some patients with functional abdominal pain have migraine presenting with few or even no migraine accompaniments. There is no nonclinical objective standard for diagnosing migraine, and research in this area is therefore very difficult. Nevertheless, some patients with functional abdominal pain may respond to antimigraine medication and, if their symptoms are suggestive, a trial of therapy may be desirable.

Abdominal Pain

Optimal design of a thermistor probe for surface measurement of cerebral blood flow.

Microthermistors are put on the surface of cerebral cortex to monitor local cerebral blood flow (CBF) continuously with minimal tissue damage and disturbance to the normal physiological state. Using a distributed, dynamic model of the measurement system, we simulated the effects of this flow measurement method under isothermal and adiabatic boundary conditions. Numerical results show that the adiabatic boundary condition can provide maximal sensitivity to perfusion changes at physiological perfusion levels. The constant power and constant temperature operating modes are compared in terms of output relation, sensitivity, and frequency response through analytical and numerical solutions. While the steady-state relations between thermistor measurements and perfusion for the two modes do not differ significantly, the constant temperature mode has better frequency response. Analytical results show that the relative sensitivity is the same for the two modes and is approximately proportional to the radius of thermistor. If there is an unperfused layer surrounding the thermistor, the sensitivity will decrease as the thickness of the layer increases. Simulations predict that the thermal measurement has a low-pass frequency response and the cutoff frequency is inversely proportional to the probe surface area. The results provide a theoretical foundation to the optimal design of thermistor probe for continuous CBF measurement from tissue surface.

Cerebrovascular Circulation

Epidermal growth factor binding and action on tympanic membranes.

A significant percentage of tympanic membrane (TM) perforations require some form of therapy to heal. Topical application of epidermal growth factor (EGF), a potent mitogen for epidermal and mesodermal cells, promotes healing of injuries in tissues histologically similar to TM, such as cornea and skin. We evaluated TM as a target tissue for EGF action. Specific, high affinity receptors for EGF were detected in TM (Kd = 3.1 nM, 150 fmol receptor/mg protein). Autoradiography of iodine 125-EGF binding to intact TMs revealed that EGF receptors were present on cells in the stratified squamous epithelial layer and in the stromal/mucoepithelial layer. Repetitive treatment of perforated cat TMs with 20 micrograms of EGF formulated in saline induced substantial hyperplasia of epithelial and stromal layers compared to paired TMs treated with saline. A single treatment of perforated cat TMs with 50 micrograms of EGF formulated in a hydrogel or in shredded Gelfoam produced significantly (p less than .05) smaller perforations at 6 days following the operation compared to paired TMs treated with vehicles. These results demonstrate that TM is a target tissue for EGF and that topical treatment with EGF stimulates healing of TM perforations.

Animals

Vascular pressures and cortical blood flow in cavernous angioma of the brain.

This study was designed to investigate the hemodynamic characteristics of cavernous angiomas of the brain. Five adult patients with a cavernous angioma underwent local cortical blood flow studies and vascular pressure measurements during surgery for the excision of the cavernous angioma. Clinical presentation included headache in four patients, seizures in four patients, and recurring diplopia in one patient. Magnetic resonance imaging demonstrated the cavernous angiomas in all patients and revealed an associated small hematoma in two. Four patients with a cerebral cavernous angioma were operated on in the supine position and the remaining patient, whose lesion involved the brain stem, was operated on in the sitting position. Mean local cortical blood flow (+/- standard error of the mean) in the cerebral cortex adjacent to the lesion was 60.5 +/- 8.3 ml/100 gm/min at a mean PaCO2 of 35.0 +/- 0.6 torr. Mean CO2 reactivity was 1.1 +/- 0.2 ml/100 gm/min/torr. The local cortical blood flow results were similar to established normal control findings. Mean pressure within the lesion in the patients undergoing surgery while supine was 38.2 +/- 0.5 mm Hg; a slight decline in cavernous angioma pressure occurred with a drop in mean systemic arterial blood pressure and PaCO2. Mean pressure in the cavernous angioma in the patient operated on in the sitting position was 7 mm Hg. Jugular compression resulted in a 9-mm Hg rise in cavernous angioma pressure in one supine patient but no change in the patient in the sitting position. Direct microscopic observation revealed slow circulation within the lesions. The hemodynamic features demonstrated in this study indicate that cavernous angiomas are relatively passive vascular anomalies that are unlikely to produce ischemia in adjacent brain. Frank hemorrhage would be expected to be self-limiting because of relatively low driving pressures.

Adult

Bimodal treatment with nimodipine and low-molecular-weight dextran for focal cerebral ischemia in the rat.

We compared the effects of intravenous treatment with combined low-molecular-weight dextran and nimodipine (n = 9), or placebo (n = 10), on local cerebral blood flow after occlusion of the left middle cerebral and common carotid artery in the rat. Treatment for a total of 4 hours with low-molecular-weight dextran (5 mg/kg/min) and nimodipine (0.25 microgram/kg/min) produced a decrease in hematocrit from 46 +/- 1 to 33 +/- 1% at the end of the study and a statistically significant increase in local cerebral blood flow, when compared to the control group, in 6 regions of interest: the territories of the right middle (p = 0.01), right anterior (p = 0.007), and left anterior cerebral arteries (p = 0.001); the superior (p = 0.03) and inferior border zone (p = 0.003); and white matter in the right hemisphere (p = 0.04). The ischemic volume, defined as brain volume with a cerebral blood flow of less than the critical level of 25 ml/min/100 gm was determined as a percentage of total brain volume for the control and treatment groups. The group treated with low-molecular-weight dextran and nimodipine showed a 31% decrease in ischemic volume (p = 0.03). These results indicate that a bimodal approach with low-molecular-weight dextran and nimodipine can be safely used in a model of acute stroke and has a beneficial effect on local cerebral blood flow and ischemic volume when compared with control subjects. After 4 hours, the potential exists that this treatment is therapeutic, assuming that the ischemic volume progresses to infarction.

Animals