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Biomedical subjects

A Ford

Publications and source records attributed to A Ford.

At least 19 recordsLinked to original sources

Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients.

BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. OBJECTIVES: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects. SEARCH STRATEGY: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2003 were hand-searched. SELECTION CRITERIA: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards. DATA COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects. MAIN RESULTS: 60 trials were eligible. Data extraction was not possible in 7 trials, and 53 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (27 trials 2509 patients, RR = 0.20; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (10 trials, 1029 patients, RR = 0.28; 95% CI 0.18, 0.43). REVIEWERS' CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Adult↗

Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients.

BACKGROUND: Peptic ulcer disease is the cause for dyspepsia in about 10% of patients. 95% of duodenal and 70% of gastric ulcers are associated with Helicobacter pylori. Eradication of H pylori reduces the relapse rate of ulcers but the magnitude of this effect is uncertain. OBJECTIVES: The primary outcomes were the proportion of peptic ulcers healed initially and proportion of patients free from relapse following successful healing. Eradication therapy was compared to placebo or pharmacological therapies in H. pylori positive patients. Secondary aims included symptom relief and adverse effects. SEARCH STRATEGY: A search was undertaken according to the Cochrane Upper Gastrointestinal and Pancreatic Diseases Review Group module using CCTR, MEDLINE, EMBASE and CINAHL databases. Experts in the field and pharmaceutical companies were contacted. Abstract books between 1994 and 2002 were hand-searched. SELECTION CRITERIA: Randomised controlled trials of short and long-term treatment of peptic ulcer disease in H. pylori positive adults were analysed. Patients received at least one week of H pylori eradication compared with ulcer healing drug, placebo or not treatment. Trials were included if they reported assessment from 2 weeks onwards. DATA COLLECTION AND ANALYSIS: Data were collected on ulcer healing, recurrence, relief of symptoms and adverse effects. MAIN RESULTS: 59 trials were eligible. Data extraction was not possible in 7 trials, and 52 trials were included. In duodenal ulcer healing, eradication therapy was superior to ulcer healing drug (UHD) (34 trials, 3910 patients, relative risk [RR] of ulcer persisting = 0.66; 95% confidence interval [CI] = 0.58, 0.76) and no treatment (2 trials, 207 patients, RR = 0.37; 95% CI 0.26, 0.53). In gastric ulcer healing, no significant differences were detected between eradication therapy and UHD (13 trials, 1469 patients, RR = 1.32; 95% CI = 0.92, 1.90). In preventing duodenal ulcer recurrence no significant differences were detected between eradication therapy and maintenance therapy with UHD (4 trials, 319 patients, relative risk [RR] of ulcer recurring = 0.73; 95% CI = 0.42, 1.25), but eradication therapy was superior to no treatment (26 trials 2434 patients, RR = 0.19; 95% CI = 0.15, 0.26). In preventing gastric ulcer recurrence, eradication therapy was superior to no treatment (9 trials, 774 patients, RR = 0.31; 95% CI 0.19, 0.48). REVIEWER'S CONCLUSIONS: A 1 to 2 weeks course of H. pylori eradication therapy is an effective treatment for H. pylori positive peptic ulcer disease.

Adult↗

Congenital bowel perforation in twin-to-twin transfusion syndrome.

Two unrelated survivors of twin-to-twin transfusion syndrome (TTTS) presented with intestinal perforation at birth. Both were localised perforations without any suggestion of widespread ischaemic disease to the splanchnic bed. Histopathology from the perforation site showed evidence of focal ischaemic necrosis, presumably from a vascular accident. One infant later died of multiple organ failure with major brain damage, but the other survived without long-term sequelae. These two cases appear to represent an unreported variation of the ischaemic intestinal complications of TTTS.

Female↗

Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder.

OBJECTIVES: To determine the presence, distribution and molecular forms of the vanilloid receptor VR1, and confirm the presence and distribution of the ATP-gated ion channel P2X3 in the human urinary bladder. Materials and methods Normal urinary bladder tissues were obtained at postmortem from four subjects. Eight urinary bladder biopsies were also taken from patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin. The specimens were studied using affinity-purified specific antibodies to VR1 and P2X3 by Western blotting and immunocytochemistry, and compared with immunostaining using antibodies to the pan-neuronal marker PGP 9.5 and Schwann cell marker S-100. RESULTS: VR1- and P2X3-immunoreactive fine nerve fibres were scattered throughout the suburothelium of the normal bladder and cystoscopic biopsies, and traversed the muscle layer. They had a similar distribution to PGP 9.5-immunoreactive fibres, but there were fewer, suggesting localization in subsets of axons. Western blot studies showed an expected 100-kDa VR1 protein and a P2X3-immunoreactive 66-kDa protein. Conclusion VR1 and P2X3 are present in the human urinary bladder and may contribute to distinct pathophysiological states of bladder overactivity, in accord with their differential expression in sensory neurones. Intravesical vanilloids act via VR1 and are effective in the treatment of detrusor hyper-reflexia. P2X3 may represent a selective therapeutic target for other causes of overactive bladder.

Adenosine Triphosphate↗

Functionalized carbosilane dendritic species as soluble supports in organic synthesis.

A new methodology, which is compatible with the use of reactive organometallic reagents, has been developed for the use of carbosilane dendrimers as soluble supports in organic synthesis. Hydroxy-functionalized dendritic carbosilanes Si[CH2CH2CH2SiMe2(C6H4CH(R)OH)]4 (G0-OH, R = H or (S)-Me) and Si[CH2CH2CH2Si[CH2CH2CH2SiMe2(C6H4CH(R)OH)]3]4 (G1-OH, R = H or (S)-Me) were prepared and subsequently converted into the esters Si[CH2CH2CH2SiMe2(C6H4CH(R)OC(O)CH2Ph)]4 (R = H or (S)-Me) and Si[CH2CH2CH2Si[CH2CH2CH2SiMe2(C6H4CH(R)OC(O)CH2C6H4 R')]3]4 (R = H and R' = H or R = (S)-Me and R' = H or R = H and R' = Br). As an example the latter compound was functionalized under Suzuki conditions. The functionalized carboxylic acid was obtained in high yield after cleavage from the dendritic support. Moreover, the ester functionalized dendrimers were converted to the corresponding zinc enolates followed by a condensation reaction with an imine to a beta-lactam in excellent yield and purity. Furthermore, it was demonstrated that a small combinatorial library of beta-lactams could be prepared starting from a carbosilane dendrimer functionalized with different ester moieties. These results show that carbosilane dendrimers can be applied as soluble substrate carriers for the generation of low molecular weight organic molecules. In combination with nanofiltration techniques, separation and recycling of the dendrimers can be realized.

Lactams↗

Enantioselective reduction of prochiral ketones by catecholborane catalysed by chiral group 13 complexes

LiGaH4, in combination with the S,O-chelate 2-hydroxy-2'-mercapto-1,1'-binaphthyl (MTBH2), forms an active catalyst for the asymmetric reduction of prochiral ketones, with catecholborane as the hydride source. Enantioface differentiation is on the basis of the steric requirements of the ketone substituents. Aryl/ n-alkyl ketones are reduced in 90-93% ee and RC(O)Me (e.g. R = iPr, cycloC6H11, tBu) in 60-72% ee. Other borane sources and alternative catalyst structures based on indium do not form enantioselective catalysts.

Journal Article↗

Rapid detection of BCR/ABL and PML/RARA using fluorescence in situ hybridization in cytospin preparations.

Fluorescence in situ hybridization (FISH) is increasingly used as an adjunct to conventional cytogenetic analysis in the diagnosis of haematological malignancies and in monitoring minimal residual disease. FISH, however, is generally performed on slides prepared after short-term sample incubation and therefore, whilst faster than conventional cytogenetics, still requires a minimum of 2 days for a result to be obtained. A simplification of the FISH procedure is reported using uncultured cytospin preparations of bone marrow or peripheral blood for the rapid diagnosis of the BCR-ABL and PML-RARa gene rearrangements. It demonstrates that culturing has no effect on the ratio of normal to abnormal cells in the nondividing population. Data is presented from an analysis of 24 cases in whom unequivocal results were obtained in less than 12 h and in complete concordance with results obtained by conventional cytogenetics and/or interphase FISH.

Bone Marrow↗

Localization of ATP-gated P2X2 and P2X3 receptor immunoreactive nerves in rat taste buds.

P2X receptors have been suggested to play a role in the transduction of sensory signals such as pain and sound. In the present study, polyclonal antibodies against P2X1 to P2X6 receptors were used to localize P2X receptors in circumvallate and fungiform papillae of rats. Nerve fibres innervating the taste buds stained intensely with P2X3 receptor antibodies. P2X3 receptor-positive nerves were observed in the intra- and subgemmal regions. The nerve fibres were also stained with P2X2 receptor antibodies, but the intensity was much lower. The distribution of P2X2 receptor immunoreactivity overlaps with that of P2X3. These results suggest that ATP might be a neurotransmitter in taste reception cells in the taste buds, where it transducts the taste signals to the afferent taste nerves by activating P2X receptors at the synapses. This is the first experiment indicating such a role for ATP, although supplementary functional studies are required.

Adenosine Triphosphate↗

Self-assessment of morbidity following radical hysterectomy for cervical cancer.

The aim of this study was to assess the magnitude of the morbidity following radical surgery for early stage cervical cancer. We performed a retrospective survey of all women who had undergone a radical hysterectomy and lymphadenectomy between the months of July 1995 and December 1996 inclusive at either the Royal Marsden or St George's Hospital (n =38), using a detailed questionnaire on bladder, ano-rectal and sexual function, both before and after treatment. Sixteen women (44.4%) received adjuvant radiotherapy. The mean interval between surgery and inquiry was 16.4% months (range 8-25 months). The mean age at the time of surgery was 40.5 years. Thirty-six out of 38 women contacted responded (94.7%). Overall 33 women (91.7%) reported new bladder, ano-rectal or sexual symptoms. Complaints of urinary incontinence, particularly of urge incontinence, and of voiding difficulties increased significantly after surgery (P <0.05). However, only 5.3% of women had sought treatment. Tenesmus increased significantly (P <0.05), while increases in diarrhoea and faecal incontinence were not statistically significant (P =0.051). Although 12.9% of women stated an improvement in their sex lives, 54.8% thought that their sex life was worse after treatment, and 12.9% of women had ceased sexual activity altogether. Of women of childbearing age 53.8% felt adversely affected by their loss of fertility. Bladder, ano-rectal and sexual symptoms are very common following radical hysterectomy for cervical cancer, with adverse effect on quality of life, and persist into the second year after treatment.

Journal Article↗

HTLV-I induced intestinal lymphoma.

We document an unusual case of HTLV-I positive adult T-cell leukaemia lymphoma (ATLL) in a 25 year old Chilean patient who presented with primary small intestinal involvement and during evolution developed a leukaemic phase. Duodenal biopsy showed infiltration by pleomorphic lymphoid cells with a CD45RO+ CD20- phenotype. Circulating lymphocytes had a convoluted nucleus and displayed a mature T-cell phenotype: CD2+, CD3+, CD4+, CD8-, CD25+, HLA-Dr+. HTLV-I serology was positive and HTLV-I retroviral sequences were demonstrated by PCR in the tissue. The patient was treated with chlorambucil and is well, disease free five years from diagnosis. Intestinal lymphoma as initial manifestation of ATLL is extremely uncommon, but when a T-cell lymphoma is detected in this localisation, in patients from a HTLV-I endemic area, retroviral studies are recommended in order to exclude an association with this retrovirus.

Adult↗

Localization of ATP-gated P2X2 receptor immunoreactivity in the rat hypothalamus.

Previous pharmacological studies have indicated that ATP receptors may be involved in the regulation of physiological functions in hypothalamus. In the present study, the distribution of P2X2 receptor in the rat hypothalamus was studied with immunohistochemistry. It was shown that P2X2 immunoreactivity-positive neurons and nerve fibres were localized in many hypothalamic nuclei. Intense labelling of both neuronal cell bodies and nerve fibres was observed in the paraventricular nucleus, arcuate nucleus, retrochiasmatic area, periventricular nucleus, and the ventral part of tuber cinereum area. In supraoptic, circular, and ventral tuberomammillary nuclei the neuronal cell bodies were strongly positive, but few nerve fibres were positive. Axons with strong P2X2 immunoreactivity were found in the organum vasculosum of the lamina terminalis and median eminence. Some scattered positive neurons and nerve fibres were found in many hypothalamic nuclei including preoptic nucleus. The results of the present study demonstrated the existence of P2X receptors in hypothalamus, as a basis for detailed studies of the roles of P2X receptors in the regulation of hypothalamic functions.

Adenosine Triphosphate↗

Aspergillus fumigatus conidia induce a Th1-type cytokine response.

The response of human peripheral blood mononuclear cells (MNC) to Aspergillus fumigatus in vitro was evaluated. In studies of the proliferative response of MNC from 18 healthy donors to heat-killed A. fumigatus conidia, 15 displayed a significant response, with a stimulation index (SI) between 4 and 193. In contrast, all donors displayed a positive response to Candida albicans blastoconidia (SI ranged from 10 to 224). Despite the variability in reactivity to A. fumigatus conidia, the response of a particular individual was stable when retested over periods of 1-2 weeks. Supernatant from cocultures of A. fumigatus conidia with MNC contained increased levels of interferon-gamma, granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-alpha, and interleukin (IL)-2, compared with unstimulated cells, but not IL-10 or IL-4. In addition, A. fumigatus induced lymphocyte surface expression of adhesion/activation-associated molecules. These results suggest that lymphocytes may contribute to host defense against Aspergillus by generating a Th1-type response.

Antigens, CD↗