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Biomedical subjects

A Bowman

Publications and source records attributed to A Bowman.

At least 55 records · Page 3Linked to original sources
PubMed1988

Ifosfamide in previously untreated disseminated neuroblastoma. Results of Study 3A of the European Neuroblastoma Study Group.

A prospective study of the effectiveness of ifosfamide as a single agent in the management of previously untreated patients with Evans stage IV neuroblastoma was undertaken. Eighteen children aged more than 1 year were treated with ifosfamide (IFX) 3 g/m2 daily for 2 days immediately after diagnosis and 3 weeks later. Treatment was continued with combination chemotherapy using vincristine, cyclophosphamide, cisplatinum and etoposide (OPEC) or a variant. Mesna (2-mercaptoethane sulphonate) was given to all patients during IFX treatment to prevent urotoxicity. Eight of the 18 patients (44%) responded to IFX. Nine had greater than 66% reduction in baseline tumor volume. Of 15 evaluable patients with raised pre-treatment urinary catecholamine excretion, six (40%) achieved greater than 50% reduction in pretreatment levels. Two of 10 patients evaluable for bone marrow response had complete clearance. Toxicity was mild in all patients. Upon completing 'first line' therapy, only four patients (22%) achieved a good partial remission (GPR) or complete response (CR). Median survival was 11 months. There was a lower rate of attaining GPR and shortened median survival in patients receiving phase II IFX before OPEC or variant, compared to patients with similar pre-treatment characteristics treated with OPEC from diagnosis in an earlier study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

The accuracy of the clinical histories given by mothers of seriously ill African children.

The mothers of 87 Gambian children with a potentially fatal illness were interviewed at the time that their children were admitted to hospital and attempts were made to establish a diagnosis using the mothers' history alone. In 66 cases (76%) initial diagnoses corresponded to the diagnoses established finally by clinical and laboratory investigations. Diagnoses established at second interviews held with 51 mothers 1 month after their children had left hospital were accurate in 88% of cases. Gambian mothers can describe accurately a serious illness in their children and they can, therefore, be relied upon to give accurate information about an illness from which a child has died.

Adult↗
PubMed1987

Intensive consolidation chemotherapy for acute lymphoblastic leukaemia (UKALL X pilot study).

Eighty two children with acute lymphoblastic leukaemia presenting at this hospital received one or two modules of intensive chemotherapy to consolidate remission. Modules were given after four and roughly 19 weeks on treatment. Each included two doses of daunorubicin (45 mg/m2/day), cytosine arabinoside (100 mg/m2 twice daily X 5), etoposide (100 mg/m2/day X 5), and 6-thioguanine (80 mg/m2/day X 5). A total of 132 courses were given. This study included all new patients except girls aged 1-14 years with presenting leucocyte count less than 20 X 10(9)/l. Twenty patients with recurrent disease were also included. The first 32 patients were given cytosine as a 24 hour infusion, but combined with the other agents this was associated with severe intestinal toxicity, which necessitated a change to a less toxic 12 hourly bolus regimen. The complications of the module are reviewed in terms of myelosuppression, enterotoxicity, infection, and other clinical problems encountered. All patients became profoundly neutropenic and thrombocytopenic. The latter was significantly more severe after cytosine infusion. Overall, 64% received platelet transfusions and 85% were re-admitted with fevers requiring intravenous antibiotics for between four and 56 days. Gastrointestinal toxicity with the modified module occurred in 38% of patients and was severe in 13%. This intensification module has been adopted by the Medical Research Council Working Party on Childhood Leukaemia for use in a multicentre study (UKALL X) and the details of the problems encountered in the pilot study may be of value to other centres now using this protocol.

Adolescent↗
PubMed1986

A comparison of the action of the endothelium-derived relaxant factor and the inhibitory factor from the bovine retractor penis on rabbit aortic smooth muscle.

The dependence of relaxation of rabbit aortic strips by carbachol and by the inhibitory factor from the bovine retractor penis (BRP) on the presence of endothelium has been compared. Carbachol-induced relaxation is abolished by removing the endothelium, inhibitory factor-induced relaxation is unimpaired. The inhibitory factor, therefore, does not act by releasing an endothelium-derived relaxing factor (EDRF). The effect of inhibitors of eicosanoid metabolism on relaxation was examined. Quinacrine and nordihydroguaiaretic acid abolished the relaxant effect of carbachol and flurbiprofen had no effect. The relaxation produced by the inhibitory factor was unaffected by quinacrine and flurbiprofen while nordihydroguaiaretic acid potentiated the response. No eicosanoid appears, therefore, to be involved in the relaxant effect of the inhibitory factor from the BRP. Methylene blue, a drug reported to inhibit guanylate cyclase, in a concentration of 10 microM selectively abolished the relaxation produced by carbachol. However, at the higher concentration of 30 microM it abolished almost completely the response to inhibitory factor from the BRP and reduced inhibition by sodium nitroprusside. It is not possible from these results to exclude the possibility that the EDRF and the inhibitory factor from the BRP are chemically related.

Animals↗
PubMed1985

A phase II study of ifosfamide in children with recurrent solid tumours.

Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.

Adolescent↗
PubMed1985

The effect of hypoxia on neuroeffector transmission in the bovine retractor penis and rat anococcygeus muscles.

The effects of reducing the PO2 of the bathing fluid were studied on non-adrenergic non-cholinergic (NANC) transmission in isolated preparations of the bovine retractor penis muscle, the rat anococcygeus muscle, the guinea-pig taenia caeci and the guinea-pig urinary bladder. Hypoxia rapidly and reversibly impaired NANC transmission in the bovine retractor penis and rat anococcygeus muscles but did not affect transmission in the guinea-pig taenia caeci or bladder, suggesting that different NANC mechanisms are involved. Although neurally-evoked relaxation of the bovine retractor penis was impaired by hypoxia, relaxations produced by vasoactive intestinal peptide, prostaglandin E1, sodium nitroprusside or an inhibitory factor isolated from the bovine retractor penis were unaffected. Since the inhibitory factor is similar to, and may actually be the NANC transmitter, the results suggest that the site of action of hypoxia in impairing transmission is prejunctional at the inhibitory nerve endings.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1984

Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle.

Field stimulation of the non-adrenergic, non-cholinergic inhibitory nerves to the bovine isolated retractor penis muscle evoked a relaxation that was preceded by a rise in the tissue content of cyclic GMP. There was no change in the content of cyclic AMP. The selective cyclic GMP phosphodiesterase inhibitor, 2-o- propoxyphenyl -8- azapurin -6-one (M&B 22948), elevated the tissue's cyclic GMP content, and potentiated both the relaxation and the rise in cyclic GMP produced by inhibitory nerve stimulation. Sodium nitroprusside and an inhibitory factor extracted from the bovine retractor penis muscle mimicked the effects of inhibitory nerve stimulation in that they each produced relaxation associated with a selective rise in cyclic GMP concentration. Haemoglobin (in the form of erythrocyte haemolysate) and N- methylhydroxylamine , which are known to block guanylate cyclase, blocked the relaxation and the rise in cyclic GMP content produced by inhibitory nerve stimulation, inhibitory factor and sodium nitroprusside. Haemoglobin itself caused a rise in muscle tone and at the same time reduced the cyclic GMP content of the tissue. 8-Bromocyclic GMP, a permeant derivative of cyclic GMP, produced a relaxation of the muscle that, as expected, was not blocked by haemoglobin. Vasoactive intestinal polypeptide, prostaglandin E1 and forskolin each produced relaxation associated with a selective rise in cyclic AMP content. Their effects were not blocked by haemoglobin or N- methylhydroxylamine . It is concluded that inhibitory nerve stimulation in the bovine retractor penis muscle produces a relaxation that is mediated by cyclic GMP, although some substances relax the muscle without affecting cyclic GMP levels. The results are also compatible with the view that the extracts of muscle contain the inhibitory neurotransmitter.

Animals↗
PubMed1983

Neurogenic vasodilatation in isolated bovine and canine penile arteries.

Field stimulation of isolated, perfused bovine or canine penile arteries produced dilatation, after the adrenergic motor component of the response had been blocked with guanethidine and the vessels had developed a background tone. The vasodilatation was blocked by tetrodotoxin but not by atropine. The vasodilator responses to field stimulation were compared with those produced by ATP, by vasoactive intestinal peptide (VIP), and by the inhibitory factor extracted from the bovine retractor penis muscle. Of the three putative transmitters, the inhibitory factor produced responses that most closely resembled those to field stimulation. Haemoglobin, which blocks non-adrenergic, non-cholinergic inhibitory transmission in the bovine and canine retractor penis muscles, did not impair the vasodilatations produced by ATP or VIP, but slowly reduced or abolished those produced by field stimulation or by the inhibitory factor. Haemoglobin itself produced a powerful constriction of the isolated penile arteries. The results are compatable with the possibility that the inhibitory factor from the bovine retractor penis muscle (which may be the inhibitory transmitter in that muscle) is, or closely resembles, the transmitter of non-adrenergic, non-cholinergic vasodilator fibres in the penile arteries of dog and ox.

Adenosine Triphosphate↗
PubMed1982

Block of some non-adrenergic inhibitory responses of smooth muscle by a substance from haemolysed erythrocytes.

1. A preparation of haemolysed rat erythrocytes (the haemolysate) blocked the relaxations of both the bovine retractor penis and the rat anococcygeus muscles in response to field stimulation of their non-adrenergic inhibitory nerves. The effective concentration range was 5-20 mul./ml. of haemolysate, equivalent to 0.25-1.0 mul./ml. of blood. The active principle in the haemolysate was a non-dialysable, heat-labile material of molecular weight between 50,000 and 100,000 daltons. If, as appeared probable, the active component of the haemolysate was oxyhaemoglobin, its effective blocking concentration was 0.5-2 muM.2. Haemolysate (5-20 mul./ml.) also blocked the relaxation of both the bovine retractor penis and the rat anococcygeus to the inhibitory factor extracted from the bovine retractor penis, an observation supporting the possibility that this inhibitory factor may be the transmitter released by the inhibitory nerves in these tissues. In the bovine retractor penis, haemolysate was also effective in blocking relaxations in response to sodium nitroprusside, but relaxations produced by prostaglandin E(1) or isobutylmethylxanthine were unchanged or only slightly reduced.3. In contrast, in the taenia of the guinea-pig caecum, haemolysate did not block the non-adrenergic inhibitory response to field stimulation, nor the relaxation produced by ATP, although it did block the relaxation produced by the inhibitory factor.4. In spiral strips of isolated rabbit aorta, haemolysate (10 mul./ml.) increased the contraction produced by noradrenaline and blocked the relaxation produced by the inhibitory factor. These were shown to be independent effects.5. Apamin, which blocked the relaxation of the taenia of the guinea-pig caecum elicited by either ATP or field stimulation of its non-adrenergic nerves, was without effect on relaxations of the bovine retractor penis or rat anococcygeus muscles in response to field stimulation of inhibitory nerves or to inhibitory factor.6. These differences in the blocking effects of apamin and haemolysate suggest either that the transmitter in the bovine retractor penis and rat anococcygeus differs from that in the guinea-pig taenia, or, if the transmitter is the same, then its mechanism of action differs.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Actions on the cardiovascular system of an inhibitory material extracted from the bovine retractor penis.

1 A partially purified material has been isolated from methanol extracts of the bovine retractor penis muscle. This material exerts biological activity only after treatment with acid and subsequent neutralisation. The active principle in this extract, which appears to be no known autacoid, mimics the response to stimulation of the non-adrenergic, non-cholinergic nerves in the bovine isolated retractor penis muscle. 2 This inhibitory extract did not alter the heart rate or blood pressure of the anaesthetized rat when administered either by intravenous or intra-arterial injection, nor did it have any obvious effect on isolated cardiac muscle. 4 The extract produced relaxation of spiral strips of various arteries isolated from ox, cat, rabbit or rat, in which tone was induced by noradrenaline, K+ of Ba2+. 5 The extract also produced dilatation of the resistance vessels of the rat isolated mesenteric circulation and the rat hindquarters perfused with Krebs solution; tone was induced in these vessels by adrenaline or noradrenaline. 6 Lack of vasodilator activity of the extract in the whole animal appeared to be due to rapid inactivation in the blood, probably by binding to the erythrocytes.

Anesthesia↗
PubMed1979

The inhibitory material in extracts from the bovine retractor penis muscle is not an adenine nucleotide.

Methods are described for the removal of adenosine or purine nucleotides from extracts of bovine retractor penis muscle (BRP). These methods did not interfere with the biological test preparations. Removal of adenosine and purine nucleotides by these methods did not modify the inhibitory action of the extract on the BRP. The effect of the extract on the BRP resembles that of inhibitory nerve stimulation. If the inhibitory substance present in the extract is the inhibitory transmitter, then the results indicate that, in this tissue, the transmitter is neither adenosine nor a purine nucleotide.

Adenine Nucleotides↗
PubMed1969

Mechanism and factors influencing the veronal inhibition of bacterial spore germination.

The inhibitory effect of sodium 5,5-diethyl barbiturate (Veronal) on the L-alanine-induced initiation of germination of Bacillus subtilis spores was examined. Veronal reversibly inhibited the initiation of germination by a noncompetitive mechanism. The inhibition was time-independent and it took place whether L-alanine was or was not allowed to permeate the spore before the addition of the inhibitor. The concentration of the inhibitor and the pH of the initiation system were important factors determining the effectiveness of Veronal as an inhibitor. The magnitude of the inhibition increased linearly with decreasing pH at constant concentration and with increasing concentration at constant pH. These results suggest that the inhibition involves a permeability phenomenon related to the access of drug to the active sites in the spore and that the entry of Veronal into the spores is regulated by the concentration of undissociated molecule. At the physiologically important pH of 7.4, initiation with alanine in phosphate buffer at high spore densities (about 10(9) spores per ml) was 50% inhibited by 4 mM Veronal, and 8mM Veronal inhibited initiation completely. L-Alanine initiation in tris(hydroxymethyl)amino-methane-hydrochloride buffer was completely inhibited by 5 mM Veronal. The inhibition could be partially reversed by the combined addition of D-fructose, D-glucose, and K(+). Possible reasons for the failure of otherwise inhibitory concentrations of Veronal to inhibit completely the L-alanine-induced initiation when a combination of fructose, glucose, and K(+) was present and a suggested relationship to two functional roles of L-alanine in the initiation of germination are discussed.

Alanine↗