Zopiclone, a current drug of misuse.
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Azabicyclo Compounds↗
Biomedical subjects
S Rooney
Publications and source records attributed to S Rooney.
Analysis of the RET proto-oncogene in sporadic parathyroid adenomas.
Missense germline mutations of the RET proto-oncogene have recently been identified in the hereditary cancer syndromes MEN2A, MEN2B, and FMTC, all characterized by medullary carcinoma, but also including phaeochromocytoma in MEN2A and MEN2B and parathyroid disease in MEN2A. In addition, somatic RET proto-oncogene mutations have been identified in a subset of sporadic medullary carcinomas and phaeochromocytomas. This study investigated the possibility that RET plays a role in sporadic parathyroid neoplasia. Firstly, normal and neoplastic parathyroid tissues were screened for expression of the RET proto-oncogene, using an RT-PCR approach on autopsy material. Secondly, 20 archival parathyroid adenomas were screened for somatic mutations in the transmembrane region of RET, the region associated with germline mutations in MEN2A and hence parathyroid disease, using a PCR-solid phase direct sequencing approach. RET expression was identified in all the parathyroid tissues analysed. However, no mutations were identified in any of the 20 adenomas, suggesting either that other mechanisms of RET activation occur, such as translocation, or that RET plays a more minor role in the growth control of the parathyroid cells than in C cells or phaeochromocytes.
Adenoma↗
RET activation in adult and childhood papillary thyroid carcinoma using a reverse transcriptase-n-polymerase chain reaction approach on archival-nested material.
Activation of the RET tyrosine kinase domain occurs in a proportion of thyroid papillary carcinomas. Three chromosomal rearrangements have been described, of which PTC1 is the commonest. Wide differences (2.5-25%) in frequency of PTC1 in different populations have been reported; it is not clear whether these are due to environmental factors, racial differences or technical reasons. We have developed a simple and rapid reverse transcriptase nested polymerase chain reaction (RT-nPCR) method enabling the detection of gene expression from single 5 microns sections of formalin-fixed paraffin wax-embedded archival material. We have applied this approach to detect expression of the RET tyrosine kinase domain, allowing identification of RET activation resulting from any rearrangement, whether characterised or not, or from overexpression. A retrospective study was performed on 22 adult and 21 childhood papillary carcinomas. Thirteen of 22 (59%) adult and 10 of 21 (48%) childhood carcinomas showed evidence of RET activation, demonstrating a major role for the RET oncogene in UK thyroid papillary carcinogenesis. This study also shows a similar frequency of RET activation in both children and adults. The use of a technique that allows reliable amplification of RNA from archival material, using primers chosen in different exons so that amplified products are readily distinguished from genomic DNA, will allow correlation of translocations and chromosomal rearrangements with a variety of specific tumour types.
Actins↗
Suture loop restriction of the medtronic hall valve: late presentation of a rare complication.
Restriction of movement of the occluder of a single disc prosthetic valve is a serious and potentially fatal complication. We present a case in which the movement of the disc of a Medtronic Hall aortic valve was restricted by a loop of aortotomy closing suture inadvertently passed around the central guide of the valve.
Aged↗
Mucolytic activity of azelastine in mice and rats.
The mucolytic activity of azelastine, an antiallergic/antiasthmatic drug, in mice and rats was investigated. The oral administration of test compounds 30 min before phenol red i.p. injection stimulated dye secretion in the trachea of mice. The resulting oral ED50's (mg/kg) were: azelastine, 0.16; salbutamol, 2.5; N-acetylcysteine, 61.8; S-Carboxymethyl-l-cysteine, < 100; bromhexine, > 100; and potassium iodide, approximately 200. In rats, several drugs stimulated secretion of fluorescein sodium (FINa) in the tracheobronchial lumen. The resulting oral ED50's (mg/kg) were: azelastine, 0.33; terbutaline, 0.3; salbutamol, 0.89; and S-carboxymethyl-l-cysteine, 56.8. Terfenadine and diphenhydramine (1-10 mg/kg, p.o.) did not stimulate tracheal secretion in rats and mice. The mucolytic activity of azelastine may contribute to its overall effectiveness, including antitussive activity in asthmatics. Finally, this activity seems to be dissociated from its H1-histamine receptor blocking activity.
Acetylcysteine↗
Anti-IL-5 monoclonal antibody inhibits allergic late phase bronchial eosinophilia in guinea pigs: a therapeutic approach.
In this study the effect of purified rat anti-mouse IL-5 monoclonal antibody on aeroallergen-induced infiltration of eosinophils in the bronchoalveolar lavage fluid of guinea pigs was studied. The i.p. injection of anti-IL-5 antibody 4 h after aeroallergen challenge inhibited eosinophil infiltration in a dose-dependent fashion. The resulting ED50 was 10 (3.4-32.8) micrograms/kg. The clinical therapeutic usefulness of anti-IL-5 or anti-IL-5-producing cells in asthma/allergy treatment remains to be an intriguing possibility.
Animals↗
Reactivity of P-glycoprotein monoclonal antibodies in childhood cancers.
P-Glycoprotein (P-gp), the product of the mdr-1 gene, is implicated in the development of chemoresistance in a variety of, mostly adult, cancers. Its role in paediatric tumours, most of which are non-epithelial in origin, has yet to be fully elucidated. A study was undertaken to investigate reactivity of two P-gp monoclonal antibodies (MAbs), JBS-1 and MRK16, recognising cytoplasmic and surface epitopes, respectively, of the P-gp molecule, in a variety of newly diagnosed and relapsed childhood cancers. P-gp was not expressed in any of 36 tumours examined (neuroblastoma 13, nephroblastoma 12, rhabdomyosarcoma 6, lymphoma 3, teratoma 1, Ewings 1), 14 of whom had chemoresistant disease. Reactivity to both MAbs was also investigated in patients with acute leukaemia. Out of 10 diagnostic acute lymphoblastic leukaemia (ALL) samples, a positive reaction with JSB-1 was observed in 1 patient who failed to remit on standard induction therapy and in 3 of 6 patients in ALL relapse, only 1 of whom showed low grade positivity with MRK16. Both MAbs reacted positively in 1 patient with acute non-lymphocytic leukaemia (ANLL) at diagnosis who achieved remission with teniposide and cytosine arabinoside, but relapsed 7 months later and was again positive with both Mabs. JSB-1 also showed varying degrees of positivity in 4 out of 4 other patients in ANLL relapse. It would therefore appear that P-gp is unlikely to mediate chemoresistance in most solid tumours of childhood, but may well play a major role in the development of chemoresistance in acute leukaemia.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
A randomized comparison of infrared photocoagulation with bipolar diathermy for the outpatient treatment of hemorrhoids.
One hundred two patients with symptomatic hemorrhoids were randomized to receive treatment with either infrared photocoagulation (IRPC) or a bipolar diathermy probe (BD). There was no significant difference in complications, number of treatments required (IRPC 1.7 [0.9], BD 1.6 [0.8]). Third-degree hemorrhoids required more treatments than smaller piles. BD has some practical advantages over IRPC but results are similar.
Ambulatory Surgical Procedures↗
The management of hemorrhoids.
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Hemorrhoids↗
Structural studies on adenosine deaminase from calf intestinal mucosa.
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Alkylation↗
Prevalence of abnormal thyroid function tests in a Down's syndrome population.
As thyroid function has been documented to be of a higher prevalence in individuals with Down's syndrome, a study was set up to assess the thyroid status of these individuals. Thyroid function tests (T.F.T.s) were initially reviewed on 100 individuals with Down's syndrome in the community and on 36 individuals who were residentially based. Abnormal T.F.T.s were then reviewed 3 yr later. In total sample of 136, initially 13 percent [n = 18] of individuals with Down's syndrome had abnormal T.F.T.s, 5 percent [n = 7] were established cases of thyroid disease and 8 percent [n = 11] were newly identified cases who had abnormal T.F.T.s. Three yr later 6.5 percent [n = 9] of the group who had had abnormal T.F.T.s continued to have abnormal T.F.T.s, 5 percent [n = 7] had thyroid disease and 1.5 percent [n = 2] still had biochemical evidence of thyroid dysfunction. There was a statistically significant increase in abnormal T.F.T.s in the residential sample compared to the community sample on both occasions. The incidence of thyroid dysfunction has been found to increase with age, particularly over the age of 40, however in this study the majority were under the age of 40 with an age range between 28.3 yr and 33.8 yr. The results in this study, coupled with the variability of T.F.T.s over time, highlights the need for regular monitoring of the thyroid status of individuals with Down's syndrome.
Adolescent↗