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Biomedical subjects

P Townsend

Publications and source records attributed to P Townsend.

At least 19 recordsLinked to original sources

A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens.

C57Bl6 mice sensitized to Dermatophagoides pteronyssinus and challenged with D. pteronyssinus allergen extract given intranasally followed by treatment with intranasal applications of a 60-kDa truncated, trimeric recombinant form of human SP-D (rfhSP-D) showed a significant reduction in serum IgE, IgG1, peripheral blood eosinophilia and airway hyperresponsiveness compared to saline or bovine serum albumin-treated controls. Intracellular cytokine staining of lung and spleen homogenates showed increases in interleukin (IL)-12 production in lung tissue and normalization of IL-12 and interferon (IFN)-gamma in spleen tissue. In previous studies we demonstrated the effectiveness of native SP-D and rfhSP-D in down-regulating allergic responses to allergens of Aspergillus fumigatus. The results reported here indicate that rfhSP-D can suppress the development of allergic symptoms in sensitized mice challenged with allergens of the common house dust mite.

Animals↗

Radiofrequency thermal balloon angioplasty in an experimental model of peripheral arterial stenosis.

RATIONALE: To assess the effect of thermal balloon angioplasty on surgically created peripheral arterial stenoses. METHODS: Unilateral femoral arterial stenoses were created in 17 neonatal lambs (Dorset X Suffolk/Mule), using absorbable sutures. Six to 8 weeks later, the stenoses were dilated using either a standard (N=5), or thermal balloon angioplasty (N=9). Immediate angiography, flow and pressure gradient measurements were made to assess the acute result following either procedure. The survivors were followed up for a further period of 4 to 6 weeks, and a terminal angiographic study performed. The thermally treated segments of vessels were removed for qualitative histologic analysis. RESULTS: Thermal angioplasty appeared to be acutely successful in eight of nine animals, compared with one of five successful procedures following standard angioplasty. Higher therapeutic temperatures (> or = 80 degrees C) were associated with vascular complications. At the terminal study, stenoses had recurred in four of six survivors successfully treated with thermal angioplasty. Histologic studies demonstrated non-uniform effects of thermal dilation on the vessel wall, with variable changes ranging from partial or full-thickness tears, fibroblastic or myocyte proliferation, and disorganization of the vessel wall layers. CONCLUSION: Thermal angioplasty appears to be acutely more beneficial compared with standard angioplasty. However there is a significant recurrence of stenoses, and non-uniform changes in the vessel wall.

Angioplasty, Balloon↗

Ventricular flutter in a neonate--severe electrolyte imbalance caused by urinary tract infection in the presence of urinary tract malformation.

Male infants under the age of 3 months presenting with pyelonephritis in the presence of urinary tract malformation (UTM) are prone to transient pseudohypoaldosteronism. This may resemble congenital adrenal hyperplasia (CAH). Hyponatremia, hyperkalemia, dehydration, and metabolic acidosis are the primary findings that permit the diagnosis of CAH. We report a case of transient pseudohypoaldosteronism resulting from pyelonephritis and vesicouretric reflux. The 17-day-old boy presented with a salt-losing episode simulating adrenal insufficiency. An initial diagnosis of CAH was made. The severe metabolic imbalance resulted in ventricular flutter that resolved after correction of the metabolic acidosis and the electrolyte and volume depletion. Early diagnosis is essential because both conditions are potentially fatal and treatment differs significantly. Differential diagnosis may be achieved by urinalysis and abdominal ultrasound scan.

Acidosis↗

Nodal rhythm and bradycardia during inhalation induction with sevoflurane in infants: a comparison of incremental and high-concentration techniques.

We studied heart rate and rhythm changes during sevoflurane inhalation induction in 60 healthy, unpremedicated infants. Patients were allocated randomly to receive an incremental (2% sevoflurane, increased every four to six breaths by 2% increments, to 8%) or high-concentration induction technique (8% sevoflurane from the outset). The ECG was recorded for 330 s (30 s pre- and 300 s postinduction) using a mini-Holter device (Recollect Dual Channel, Hertford Medical) and later analysed by an independent observer. Twelve patients developed nodal rhythm (six in each group), but no other dysrhythmias were recorded. The onset of nodal rhythm was associated with bradycardia (< 80 bpm) in seven out of 12 cases, and occurred significantly earlier in the high-concentration group (median 123 (range 99-139) s versus 164 (127-138) s). Its duration was similar in both groups (62 (2-84) s versus 90 (20-167) s). These findings highlight the importance of using continuous ECG analysis when studying volatile anaesthetic agents in young children.

Anesthesia, Inhalation↗

Why is the patient still hypoxic despite being ventilated?

The passage of oxygen from the atmosphere to the mitochondria is a complex process. Pathological conditions may affect this transfer at any step. The patient on the intensive care unit is particularly likely to be affected by disease or iatrogenic intervention. Hypoxia may be caused by an abnormal supply of oxygen, abnormalities of gas exchange, deficient transport in the blood or alterations in localized tissue utilization. An understanding of the principles involved will enable effective interpretation and subsequent management of the hypoxic patient.

Critical Care↗

Gliomatosis cerebri. Results with radiation therapy.

BACKGROUND: This review was undertaken to determine the outcome for patients diagnosed in the modern era and treated with radiation therapy. METHODS: Using the tumor registries of six institutions in a large metropolitan area, cases of gliomatosis were identified and retrospectively reviewed. RESULTS: The clinical course for each patient was unique. Deterioration during treatment, brief stabilization, and reversal of the clinical signs and symptoms with stability and high quality of life at 16 months from diagnosis characterized Patients 1, 2, and 3, respectively. CONCLUSIONS: Radiotherapy for gliomatosis appears to stabilize or improve neurologic function in some patients. Its impact on survival will await additional reports and longer follow-up.

Adult↗

Widening inequality of health in northern England, 1981-91.

OBJECTIVE: To identify relative and absolute changes in mortality in the Northern region of England between 1981 and 1991. DESIGN: 1981 and 1991 census data were used to rank 678 wards on an index of material deprivation composed of four variables (unemployment, car ownership, housing tenure, household overcrowding). Standardised mortality ratios (all causes) were calculated for various periods between 1981 and 1991 and for different age categories. SETTING: Counties of Cleveland, Cumbria, Durham, Northumberland, and Tyne and Wear. RESULTS: During 1981-91 mortality differentials widened between the most affluent and deprived fifths of wards in all age categories under 75 years. The decline in the relative position of the poorest areas was particularly great, and there was no narrowing of inequalities across the remainder of the socioeconomic spectrum. In absolute terms, there were improvements in mortality in all age categories in the most affluent areas. In the poorest areas improvements in the 55-64 age group were balanced by increased mortality among men aged 15-44, a slight rise among women aged 65-74, and static rates among men aged 45-54. CONCLUSIONS: These results re-emphasise the case for linking mortality patterns with material conditions rather than individual behaviour.

Adolescent↗

Long term bradycardia by electrical pacing: a new method for studying heart rate reduction.

OBJECTIVE: The aim was to develop a method of inducing bradycardia on a chronic basis by electrical pacing and to study its effect upon myocardial capillarity in pigs. METHODS: Farm pigs were instrumented with Medtronic dual chamber telemetric pacemakers and two leads, either both atrial or one atrial and one ventricular. Bradycardia was achieved by linking pacing stimuli to endogenous atrial or ventricular events for the different electrode positions respectively, and monitored postoperatively for 4-5 weeks by implanted telemetric ECG devices. Myocardial capillary supply (lectin staining) and myocyte cross sectional areas were then estimated in sections of the left ventricle. RESULTS: Heart rates were reduced by 40-50 beats.min-1 at operation from a resting rate of 110(SEM 3) beats.min-1 in eight animals and bradycardia maintained upon recovery from anaesthesia for up to five weeks, with no obvious limitations for the animals. After this time, heart rates measured under anaesthesia were found to remain low for up to 2 h after pacing had been switched off. There was no evidence of myocyte hypertrophy, yet mean capillary density.mm-2 was significantly increased by pacing, from 1470(50) to 1734(82), p < 0.02. CONCLUSIONS: It is possible to produce primary heart rate reduction in the pig by a novel means of pacing on a chronic basis, leading to increased myocardial capillary supply without myocyte hypertrophy. This method can provide a basis for future investigations of the beneficial effects of heart rate reduction in the vascularly compromised heart.

Animals↗

New materials for rectus muscle tendon extension in strabismus surgery.

Conventional strabismus surgery has both limitations and complications. Some of these have been overcome by the use of 'hang-back' sutures. Here we describe a new technique using Mersilene and Teflon as extraocular muscle implants for large muscle recessions. Results of initial studies in rabbits are presented and discussed. Mersilene implants evoked a marked fibroblastic reaction which limits their usefulness. Results with Teflon were more encouraging and suggest that it would be a useful spacer material in tendon extensions.

Animals↗

Control of cyclic AMP levels in primary cultures of human tracheal smooth muscle cells.

1. [3H]-adenosine 3':5'-cyclic monophosphate ([3H]-cyclic AMP) responses were studied in primary cultures of human tracheal smooth muscle cells derived from explants of human trachealis muscle and in short term cultures of acutely dissociated trachealis cells. 2. Isoprenaline induced concentration-dependent [3H]-cyclic AMP formation with an EC50 of 0.2 microM. The response to 10 microM isoprenaline reached a maximum after 5-10 min stimulation and remained stable for periods of up to 1 h. After 10 min stimulation, 1 microM isoprenaline produced a 9.5 fold increase over basal [3H]-cyclic AMP levels. The response to isoprenaline was inhibited by ICI 118551 (10 nM), (apparent KA 1.9 x 10(9) M-1) indicating the probable involvement of a beta 2-adrenoceptor in this response in human cultured tracheal smooth muscle cells. However, with 50 nM ICI 118551 there was a reduction in the maximum response to isoprenaline. Prostaglandin E2 also produced concentration-dependent [3H]-cyclic AMP formation (EC50 0.7 microM, response to 1 microM PGE2 6.4 fold over basal). 3. Forskolin (1 nM - 100 microM) induced concentration-dependent [3H]-cyclic AMP formation in these cells. A 1.6 fold (over basal) response was also observed following stimulation with NaF (10 mM). 4. The nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) (0.1 mM) and the type IV, cyclic AMP selective, phosphodiesterase inhibitor rolipram (0.1 mM) both elevated basal [3H]-cyclic AMP levels by 1.8 and 1.5 fold respectively. IBMX (1-100 microM) and low concentrations of rolipram (< 10 microM), also potentiated the response to 1 microM isoprenaline. Inhibitors of the type III phosphodiesterase isoenzyme (SK&F 94120 and SK&F 94836) were without effect upon basal or isoprenaline-stimulated cyclic AMP responses in these cells.5. Carbachol (1 nM-I 00 microM) produced concentration-dependent inhibition of the [3H]-cyclic AMP response to 1 microM isoprenaline in human cultured tracheal smooth muscle cells (IC50 0.24 JM). Carbachol(1 JM) inhibited the [3H]-cyclic AMP response to 1 JM isoprenaline by 60%. This effect of carbachol was itself inhibited by atropine (50 nM) (KA 2.3 x 109 M-') indicating the involvement of a muscarinic receptor.6. These results show that primary cultures of human tracheal smooth muscle cells demonstrate cyclic AMP responses to direct receptor stimulation, adenylyl cyclase activation and inhibition with nonselective and type IV-selective cyclic AMP phosphodiesterase isoenzyme inhibitors, and that the cyclic AMP response to isoprenaline can be inhibited by muscarinic receptor stimulation.

1-Methyl-3-isobutylxanthine↗

Tumour necrosis factor alpha secretion in leporine endotoxaemia: role of the liver and effects of hepatic ischaemia.

A leporine model to investigate tumour necrosis factor alpha (TNF alpha) secretion after peripheral vein or mesenteric vein lipopolysaccharide injection was devised. Mesenteric vein injection provoked lower arterial concentrations after 90 minutes (median (range), 2.81, (0.75-11.96) ng/ml) than peripheral vein injection (7.00 (4.27-14.95) ng/ml (p less than 0.05)). Mesenteric vein injection after 10 minutes' warm hepatic ischaemia, which impairs hepatic clearance, provoked higher median arterial TNF alpha values at 90 minutes (7.98 (2.85-21.48) ng/ml) than in normal animals (p less than 0.05). Portal vein endotoxaemia induced less TNF alpha production than systemic endotoxaemia unless hepatic clearance was impaired, thus the major source of TNF alpha in systemic endotoxaemia is probably extrahepatic.

Animals↗