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Biomedical subjects

A Wood

Publications and source records attributed to A Wood.

At least 91 records · Page 5Linked to original sources

The effect of anticholinergic bronchodilator therapy on cough during upper respiratory tract infections.

1. Oxitropium bromide (Oxivent), an anticholinergic bronchodilator, inhibits coughing induced by hypotonic aerosols in both asthmatic and non-asthmatic individuals. We have now extended this work to investigate whether this antitussive activity is reproducible in cough associated with viral infection. 2. The effect of oxitropium bromide (200 micrograms three times daily) on cough and pulmonary function has been studied in 56 non-asthmatic volunteers with upper respiratory tract infections (URTI) in a double-blind, randomised, parallel group, placebo controlled study over 10 days. 3. Lung function, symptom questionnaire and cough response to ultrasonically nebulised distilled water (UNDW) inhalation were initially recorded within 72 h of development of cough and again after the 10 day treatment period. By use of a diary card at home, frequency and severity of cough, nocturnal symptoms and general malaise were assessed daily throughout the treatment period using 5 cm visual analogue scales (VAS). Peak expiratory flow rate (PEFR) was recorded thrice daily before treatment over this 10 day period. 4. VAS scores of symptoms and UNDW-induced cough frequency all decreased over the 10 days of observation whether oxitropium bromide or placebo was administered. The mean PEFR showed a statistically significant fall in morning values during the early stages of infection which lessened with recovery but no effect of treatment with oxitropium bromide was observed (P > 0.05). 5. Oxitropium bromide, which inhibits the cough response to UNDW, does not offer an effective therapy for cough associated with an upper respiratory tract viral infection.

Adolescent↗

Psychodynamic group therapy for older adults: the life experiences group.

1. Psychodynamically oriented group psychotherapy is an effective treatment mode for older adults. The common denominator of members of the Life Experiences Group is lifelong difficulties in relationships. 2. Group goals of the Life Experiences Group are twofold: To improve interpersonal relationships through increased self-awareness and group feedback; and to enhance self-perception and attitude, and relieve symptoms through a focus on wellness within long-term illness. 3. Elders are not as vulnerable as portrayed in ageist stereotypes; they can deal with painful issues when provided with the opportunity, and they can benefit from the experience in terms of enhanced relationships and improved self-esteem.

Adaptation, Psychological↗

Efficacy of urgent thoracotomy for trauma in patients attended by a helicopter emergency medical service.

Over a 12-month period the Helicopter Emergency Medical Service underwent 1084 missions attending casualties in the London area. Sixteen patients required an emergency thoracotomy for resuscitation, nine of which were performed at the scene and seven in the emergency department. The median injury severity score of these patients was 29.9 (SIR 11.8) of which 11 had suffered blunt injuries. Medical attention at scene was administered 16.2 min (SIR 4.0) following the London ambulance service receiving the emergency call. Significantly longer time was spent attending patients who had a scene thoracotomy (35.1 min SIR 16.4) compared with those in whom the thoracotomy was performed in the casualty department. No patient in this series survived resuscitative thoracotomy. It is suggested that scene thoracotomy be abandoned and emphasis placed upon the rapid transport of patients to an emergency facility. This enables other resuscitative measures in addition to thoracotomy to be applied effectively and concentrated over a brief period by a multidisciplinary team.

Adolescent↗

Relationship between cell adherence and proteoglycan synthesis in cultures of human peripheral blood mononuclear cells: effects of concanavalin A.

Human, blood-derived mononuclear cells (MC), stimulated with Concanavalin A (Con A), synthesized a chondroitin sulfate (CS) proteoglycan (PG), which was elaborated largely by T-cells. Following Con A stimulation, the majority of MC adhered to the culture dish by day 2, but as incubation progressed to day 10 the proportion of non-adherent (NAd) MC increased in a fashion which approximately paralleled the accumulation of PG in the medium. Cell kinetic studies suggest that, following Con A stimulation, there was an inverse relationship between the amount of newly synthesized cellular PG and adherence, which appears to be related to a reciprocal effect on PG synthesis of the declining adherent (Ad) cell density with time of culture. In the stimulated cultures, NAd cells contained much more newly synthesized CS/cell than Ad cells up to day 6 of incubation. Cell type analysis, using monoclonal antibodies against specific cell surface markers, suggested that the higher PG synthesis in the NAd population may, at least in part, be due to a greater proportion of T-helper cells.

Cell Adhesion↗

Pharmacotherapy of bulimia nervosa--experience with fluoxetine.

A number of compounds having an effect on serotonergic transmission have been shown to have a beneficial therapeutic action in patients with bulimia nervosa. Many previous studies, however, have suffered from methodological shortcomings, in particular small population sizes. This article reviews present data which suggest that fluoxetine is effective in the treatment of bulimia nervosa. Two trials of unprecedented size (n = 387 and 398, respectively) have recently been reported. These two studies show that fluoxetine, 60 mg daily, has a clear beneficial effect on behavioural and other (attitudinal) measures of bulimic symptomatology, and that this dose of fluoxetine is well tolerated in patients with bulimia nervosa. The role of pharmacotherapy in the long-term treatment of this disorder and the relative roles of pharmacotherapy and psychotherapy in treating bulimia nervosa are also discussed.

Adult↗

Pharmacotherapy of obsessive compulsive disorder--experience with fluoxetine.

Recent epidemiological data have shown that obsessive compulsive disorder (OCD) has a lifetime prevalence of 2.5-3.0%. Compounds having an effect on serotonergic neurotransmission have demonstrated a reproducible therapeutic effect in OCD. Most recent attention has been focused on the specific serotonin re-uptake inhibitor (SSRI) class of compounds. The pooled data from two recently completed placebo-controlled studies of the SSRI, fluoxetine, have demonstrated clear evidence of a clinically valuable therapeutic effect in patients with OCD. Combined efficacy and safety data suggest that fluoxetine, 20 mg/day, will be effective in many patients. The therapeutic response emerges slowly and increases gradually. Data from extension studies suggest that, in some patients, an optimal response may only be achieved with higher daily doses of fluoxetine. Clinical response has been shown to be sustained over periods of 9 months of treatment and following withdrawal in an open-label trial. Fluoxetine is safe and well tolerated in this group of patients.

Clinical Trials as Topic↗

The management of renal cell carcinoma with inferior vena-caval involvement.

Seven patients with renal cell carcinoma involving the inferior vena cava underwent surgical resection between 1975 and 1991. Pre-operative staging defined five patients with stage T3bNoMo disease, one patient with stage T3bN1Mo, and one patient with stage T3bNoM1 disease. At operation one patient had tumour thrombus filling the right atrium. Two patients had tumour thrombus within the intrahepatic vena cava and four infrahepatic tumour thrombus. The mean follow-up is 34.4 months (median 40 months). Four patients have been followed for over 4 years. Three of these patients are survivors, two have remained disease-free since their initial surgery. The other patient had a liver resection at 49 months for a solitary metastases; he is currently disease free. One patient died at 38 months from a gastrointestinal haemorrhage. Three patients are 12 months or less postoperation. Operative mortality was zero. The mean postoperative hospital stay was 14.7 days. Data suggests that 3-10% of renal cell carcinomas will involve the inferior vena cava. The small number of patients in this series suggests that many patients with renal cell carcinoma involving the inferior vena cava are not referred for surgical assessment. These patients are potential surgical candidates. Their survival after surgical resection, excluding the group with extension of tumour thrombus into the hepatic cava or above, is not reduced when compared with other patients with renal carcinoma.

Adult↗

Specific induction of intracellular calcium oscillations by complement membrane attack on oligodendroglia.

Oligodendroglia (ODG) are unique among glial cell types in their capacity to activate complement in the absence of antibody, causing insertion of the potentially damaging membrane attack complex (MAC) into the plasma membrane. Using microfluorimetry of indo-1 fluorescence we have detected a complex oscillatory [Ca2+]i response in ODG following exposure to sublethal dilutions of serum-derived complement. Oscillations were transitory and preceded complete and stable return to resting [Ca2+]i levels, whereas nonoscillating ODG underwent rapid lysis. Depletion of the terminal complement component C9 from serum removed the oscillatory stimulus, which could be restored by reconstitution with purified C9. Exposure to the C9-homologous peptide melittin produced [Ca2+]i oscillations similar in pattern to those induced by whole serum. However, this type of response could not be reproduced by Ca2+ ionophores or mechanical wounding, suggesting that oscillations cannot be provoked by Ca2+ influx alone and depend on the presence of the MAC or a pore-forming lesion. Oscillations were not prevented in the continuous presence of caffeine, demonstrating independence from caffeine-releasable intracellular stores. Inhibition of the endoplasmic reticular Ca(2+)-ATPase with thapsigargin produced an abrupt elevation in [Ca2+]i but did not alter the latency between exposure to serum and the initial complement-induced transient. However, the slope of this initial transient was considerably reduced and oscillations suppressed, demonstrating dependence of the oscillatory mechanism on functional endoplasmic reticular Ca2+ stores. The coincidence of ODG recovery with oscillating [Ca2+]i suggests that the complex calcium signal that follows MAC attack may stimulate repair or protective mechanisms.

Animals↗

Segregation and early dispersal of neural crest cells in the embryonic zebrafish.

We have exploited our ability to visualize and follow individual cells in situ, in the living embryo, to study the development of trunk neural crest in the embryonic zebrafish. In most respects, the development of zebrafish trunk neural crest is similar to the development of trunk neural crest in other species: zebrafish trunk neural crest cells segregate from the dorsal neural keel in a rostrocaudal sequence, migrate ventrally along two pathways, and give rise to neurons of the peripheral nervous system, Schwann cells, and pigment cells. However, some aspects of the development of zebrafish trunk neural crest differ from those of other vertebrates: zebrafish trunk neural crest cells are significantly larger and fewer in number than those in avian embryos and the locations of their migratory pathways are slightly different. This initial description of neural crest development in the zebrafish embryo provides the foundation for future experimental studies.

Animals↗

Differential effects of concanavalin A, serum and cytokines on proteoglycan elaboration and DNA synthesis by mononuclear cells from human peripheral blood.

Human blood derived mononuclear cell (MC) cultures required concanavalin A (Con A) stimulation to synthesize and secrete into the medium high levels of a protease-resistant proteoglycan (PG) containing predominantly chondroitin sulfate (CS), which was elaborated largely by T-cells in culture. PG and DNA synthesis were studied in MC cultures in the absence and presence of Con A as well as serum and some biologically active polypeptide factors. In the presence of Con A, stimulation of PG synthesis was substantially greater in T-cell enriched cultures than in B-cell enriched cultures. DNA synthesis was also stimulated in the presence of Con A. This stimulation was concentration-dependent, but required the presence of serum for additional responses. DNA and cell proliferation were stimulated by interleukin-2 (IL-2), but PG production was not stimulated by conditioned media, IL-1, IL-2, IL-3, or transforming growth factor-beta (TGF-beta). Our results indicate that the elaboration of PG from T-cells of human MC is independent of the effects of regulatory peptides on cell proliferation and DNA synthesis.

B-Lymphocytes↗

A synthetic peptide corresponding to a sequence in the GTPase activating protein inhibits p21ras stimulation and promotes guanine nucleotide exchange.

Amino acid sequence homology between the GTPase Activating Protein (GAP) and the GTP-binding regulatory protein, Gs alpha, suggests that a specific region of GAP primary structure (residues 891-898) may be involved in its stimulation of p21ras GTP hydrolytic activity (McCormick, F. [1989] Nature 340, 678-679). A peptide, designated p891, corresponding to GAP residues 891-906 (M891RTRVVSGFVFLRLIC906) was synthesized and tested for its ability to inhibit GAP-stimulated p21ras GTPase activity. At a concentration of 25 microM, p891 inhibited GAP activity approximately 50%. Unexpectedly, p891 also stimulated GTP binding to p21N-ras independent of GAP. This stimulation correlated with an enhancement of p21N-ras.GDP dissociation; an approximate 15-fold increase in the presence of 10 microM p891. In contrast, dissociation of the p21N-ras.GTP gamma S complex was unaffected by 10 microM p891. The p21N-ras.GDP complex was unresponsive to 100 microM mastoparan, a peptide toxin shown previously to accelerate GDP dissociation from the guanine nucleotide regulatory proteins, Gi and Go. p21H-ras, as well as the two p21H-ras effector mutants, Ala-38, and Ala-35, Leu-36, also exhibited increased rates of GDP dissociation in the presence of p891. Also tested were three ras-related GTP-binding proteins; rap, G25K and rac. The rap.-GDP complex was unaffected by 10 microM p891. Dissociation of the G25K- and rac.GDP complexes were enhanced slightly; approximately 1.3- and 1.8-fold over control, respectively. Thus, the inhibitory effect of p891 on GAP stimulation of p21ras suggests that amino acids within the region 891-906 of GAP may be essential for interaction with p21ras. In addition, p891 independently affects the nucleotide exchange properties of p21ras.

Amino Acid Sequence↗

The transient expression of type II collagen at tissue interfaces during mammalian craniofacial development.

Using immunocytochemical techniques, the spatiotemporal distribution of the major collagen isoform of cartilage, type II collagen, has been investigated during early craniofacial development in the mouse embryo. Early and transient expression was associated with the otic and optic vesicles, the ventrolateral surfaces of the developing brain, olfactory conchi, endocardial and mesocardial tissues, the lateral and basal surfaces of the pharyngeal endoderm and beneath the ectoderm of the branchial arches. A number of these locations are sites of epithelial-mesenchymal tissue interaction believed to generate the component parts of the chondrocranium; here, type II collagen appears transiently in advance of overt chondrogenesis in the mesenchyme. At such sites, immunofluorescence is typically localised along the basal surface of the epithelial partner, with the strongest reaction detected between the basal aspects of the otic and rhombencephalic epithelia. Immunoelectron microscopy, using pre-embedding immunostaining and a protein G-gold technique, reveals that the type II collagen is adjacent to, but not integral with, the basal laminae. Gold particles are clearly associated with 10-15 nm fibrils of the extracellular matrix in the reticulate lamina region. The pattern of type II collagen expression in the mouse closely correlates with that demonstrated previously in the quail, indicating a high degree of phylogenetic conservation between these two vertebrate species. These findings are consistent with the hypothesis that the pattern of epithelial secretion of type II collagen, or a coexpressed matrix molecule, constitutes a morphogenetic signal, realised as a matrix-mediated tissue interaction, and specifying the form of the vertebrate chondrocranium. Three-dimensional reconstruction of early type II collagen distribution, and of the subsequent chondrocranial cartilages, reveals that chondrocranial form can be derived from a 'pre-pattern' of epithelially derived type II collagen expressed at epithelial-mesenchymal tissue interfaces.

Animals↗

Recurrent symptoms after ventricular pacing in unexplained syncope.

We report clinical and hemodynamic data in two cases of recurrent syncope. Both patients received permanent demand ventricular pacing (VVI) for unexplained syncope. Both patients experienced recurrent syncope after pacemaker implantation. They later underwent 60 degrees head-up tilt testing, initially noninvasively and then with hemodynamic profile. A vasovagal response to tilt occurred with bradycardia and was complicated by the onset of ventricular pacing and retrograde atrioventricular conduction (RAVC) with hemodynamic deterioration and rapid reproduction of syncope. Limited intracardiac electrophysiological study (EPS) excluded atrioventricular (AV) conduction disease, sinus node disease, and carotid sinus syndrome, and confirmed RAVC. Both patients were upgraded to dual chamber pacing, DDI mode, with 50/80 rate hysteresis. One patient was asymptomatic at repeat tilt testing; the other experienced continued symptoms due to the vasodepressor component of vasovagal syncope. Cardiac pacing alone is ineffective treatment for this phenomenon, and no proven therapy is presently available. Ventricular pacing applied to patients with unexplained syncope may lead to an increase in or continuation of symptoms rather than an amelioration. There is a need for full investigation of such patients, which must include tilt testing, to allow for the most accurate diagnosis possible and guide the most appropriate therapy.

Aged↗