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A Middleton

Publications and source records attributed to A Middleton.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence and surgical significance of a high-origin anterior tibial artery.

PURPOSE: To assess the prevalence of proximal high-origin anterior tibial artery and its surgical significance. METHODS: 100 knees were prospectively studied using colour Doppler ultrasonography. No patient had a history of lower-limb arterial pathology or previous knee surgery. All ultrasound images were assessed by a single experienced vascular technician to eliminate inter-observer variability. RESULTS: The mean age of the patients was 56 years (range, 21-96 years). Prevalence of the high-origin anterior tibial arterial pattern was 6%, greater than that reported by previous angiographic or cadaveric studies. In all patients with high-origin anterior tibial artery, the artery was in direct contact with the posterior cortex of the tibia. CONCLUSION: This highlights the danger of using sharp instruments in knee procedures that involve extension of osteotomy to the posterior tibial cortex, particularly high-tibial osteotomy and total knee replacement. Knowledge of the anatomical variations in the branching of the popliteal artery is important because damage to its branches can be limb- or life-threatening.

Adult↗
PubMed2006

Achieving 2003 European lipid goals with rosuvastatin and comparator statins in 6743 patients in real-life clinical practice: DISCOVERY meta-analysis.

BACKGROUND: There is an increasing body of evidence to support the benefits of reducing low-density lipoprotein cholesterol (LDL-C) levels and this has been reflected in a lowering of LDL-C goals recommended by international guidelines. Therefore, there is a growing need for effective lipid-modifying therapies to optimise the achievement of these more stringent LDL-C goals. OBJECTIVE: A meta-analysis of data pooled from five studies participating in the DISCOVERY (DIrect Statin COmparison of LDL-C Values: an Evaluation of Rosuvastatin therapY) Programme was performed to compare the effect of rosuvastatin treatment with other statins in real-life clinical practice. RESULTS: These studies included 6743 patients with hypercholesterolaemia from different ethnicities, countries and cultural environments. The meta-analysis showed that significantly more patients receiving rosuvastatin 10 mg achieved the 2003 European LDL-C goals compared with those who received atorvastatin 10 mg or simvastatin 20 mg (p < 0.001 for both comparisons). A significantly greater proportion of patients receiving rosuvastatin 10 mg also achieved the 2003 European total cholesterol goal compared with those on atorvastatin 10 mg (p < 0.001). CONCLUSIONS: The meta-analysis showed that rosuvastatin was more effective than comparator statins at lowering LDL-C levels and enabling patients to achieve lipid goals at recommended start doses. In addition, all statins studied were well tolerated and confirmed that rosuvastatin had a similar safety profile to other statins.

Aged↗
PubMed2003

An anatomical database of carpal bone measurements for intercarpal arthrodesis.

During limited intercarpal fusion it is sometimes difficult to determine correct screw length and staple size. This is because of overlap, and the shape and orientation of the carpal bones on radiography. One hundred complete sets of dry cadaver carpal bones were measured to provide an anatomical database of carpal bone measurements. This should help prevent inadvertent overpenetration of fixation devices during surgery.

Adult↗
PubMed2002

Continuous versus non-nightly use of zolpidem in chronic insomnia: results of a large-scale, double-blind, randomized, outpatient study.

New treatment strategies are encouraged in insomnia and, in particular, discontinuous treatment. The aim of this double-blind study was to compare, in a large primary care population of chronic insomniacs (> 4 weeks duration) the efficacy and safety of zolpidem 10 mg 5 nights/week and placebo 2 nights/week, to that of nightly zolpidem. Seven hundred and eighty-nine drug-free insomniacs, with a Total Sleep Time (TST) of 3-6 h/night were enrolled in seven European countries. After a placebo run-in period, treatment lasted 14 days. The primary criterion was the Clinical Global Impression improvement score (CGI-II) which showed that 65.2% of patients in the continuous and 58.6% in the discontinuous groups were rated 'much' or 'very much' improved. Even though the non-inferiority test did not show the equivalence of both regimens, the difference of 7% in responder rates does not appear to be clinically relevant. Other sleep parameters such as TST, number of nocturnal awakenings and Quality of Life scales showed marked, not significantly different, improvements in both groups. Both regimens were well tolerated and no adverse event which could be related to non-treatment nights was reported in the discontinuous group. Non-nightly zolpidem appears to be a feasible and safe additional option for the management of chronic insomnia.

Adolescent↗
PubMed2001

Modulation by cellular cholesterol of gene transcription via the cyclic AMP response element.

The effect of rapid changes in cellular cholesterol content on adenosine 3',5'-cyclic monophosphate (cAMP) response element-mediated gene transcription was investigated. The study was carried out in Chinese hamster ovary (CHO-K1) cells permanently expressing the human beta(2)-adrenoceptor. Gene transcription was quantified using a reporter gene (secreted placental alkaline phosphatase) under the transcriptional control of cAMP response element (CRE) sequences. Cellular cholesterol was reduced by 42% or elevated by 47% by incubating cells for 1 hr with methyl-beta-cyclodextrin alone or methyl-beta-cyclodextrin complexed with cholesterol, respectively. There was a significant negative correlation between the free cholesterol content of the cells and CRE-mediated gene expression in response to 10(-6) M isoprenaline (slope = -4.57 +/- 0.73, P < 0.001), indicating that beta(2)-adrenoceptor-mediated activation of the CRE is inhibited by cholesterol. Cyclic AMP accumulation in response to isoprenaline (10(-12) to 10(-5) M) was also inhibited in cholesterol-enriched cells and enhanced in cholesterol-depleted cells compared to controls (P < 0.05, two-way ANOVA). Cholesterol also inhibited serum-mediated enhancement of CRE-driven gene expression, and we present data suggesting that the pathway activated by serum and inhibited by cholesterol could be independent of adrenoceptor activation and protein kinase A. We conclude that in CHO-K1 cells cholesterol inhibits at least two processes that can stimulate CRE-mediated gene expression. One is isoprenaline activation of cAMP synthesis, the other is activated by serum. These findings demonstrate that activation of gene transcription by extracellular stimuli could be influenced by cellular cholesterol content.

Adrenergic beta-Agonists↗
PubMed2001

Comparison of once- and twice-daily clarithromycin in the treatment of adults with severe acute lower respiratory tract infections.

BACKGROUND: Although the modified-release (MR) formulation of clarithromycin has demonstrated bioequivalence to the immediate-release (IR) formulation and thus can be prescribed for lower respiratory tract infections (LRTIs), a MEDLINE search from 1995 through 1998 and information on file with the manufacturer indicate that no data are available on the effectiveness of this new formulation in the treatment of severe LRTIs such as community-acquired pneumonia. OBJECTIVE: This study was designed to compare clinical success rates (percentage of patients with clinical cure or improvement) with once- and twice-daily regimens of clarithromycin in the treatment of patients with severe, acute LRTIs requiring oral antibiotic therapy. METHODS: In this multicenter, investigator-blinded, randomized, parallel-group study, adult patients with clinical evidence suggesting severe, acute LRTI were recruited from 22 general practices in the United Kingdom. Patients were randomly allocated to receive either clarithromycin 500 mg BID (IR tablets) or clarithromycin 1 g OD (two 500-mg MR tablets) for 7 to 14 days. The outcome measures were resolution of or improvement in clinical signs and symptoms (including resolution of cough), unscheduled visits for the same symptom, days to resumption of normal activities, and improvements in quality of life (assessed using the EQ-5D version of the EuroQoL questionnaire). Clinical, microbiologic, and serologic assessments were performed before, during, and after treatment. Efficacy and safety data were analyzed on an intent-to-treat basis. RESULTS: One hundred sixty men (n = 83) and women (n = 77) between the ages of 19 and 88 years took part in the study, 78 receiving clarithromycin 500 mg BID and 82 receiving clarithromycin 1 g OD. At 4 weeks after the start of treatment, the high clinical success rates were comparable between groups: 84.6% with clarithromycin 500 mg BID and 90.2% with clarithromycin 1 g OD. No significant differences in outcome measures were noted between the 2 regimens. Both treatments were well tolerated, with taste disturbance being the most commonly reported adverse event (10.6% vs 6.1% with clarithromycin 500 mg BID and 1 g OD, respectively). CONCLUSIONS: The 2 clarithromycin regimens were equally efficacious and well tolerated in the treatment of severe, acute LRTIs. However, caution should be exercised in applying these results to the general population, because the study excluded certain categories of patients who would normally be treated. In addition, the small sample size may have obscured clinically significant differences between the 2 regimens.

Administration, Oral↗
PubMed2001

Prenatal diagnosis for inherited deafness--what is the potential demand?

Genetic testing for inherited deafness is now available within some genetics centres. This study used a structured questionnaire to assess the potential uptake of prenatal diagnosis (PND) for inherited deafness, and document the opinions of deaf and hearing individuals toward PND and termination of pregnancy (TOP) for hearing status. Participants were self-selected from the whole of the UK, of whom 644 were deaf, 143 were hard of hearing or deafened, and 527 were hearing individuals who had either a deaf parent or child. The results showed that 21% of deaf, 39% of hard of hearing and deafened, and 49% of hearing participants said they would consider PND for deafness. Six percent of deaf, 11% of hard of hearing and deafened, and 16% of hearing participants said they would consider a TOP if the fetus was found to be deaf. Two percent of deaf participants said they would prefer to have deaf children and would consider a TOP if the fetus was found to be hearing.

Abortion, Eugenic↗
PubMed2001

Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study.

This randomized, double-blind, parallel-group study compared the efficacy and tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute oral treatment of up to six moderate-to-severe migraine attacks. The intention to treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan 2.5 mg (2671 attacks), 514 with zolmitriptan 5 mg (2744 attacks) and 508 with sumatriptan 50 mg (2693 attacks). Overall, the 2-h headache response rates in these groups were 62.9, 65.7 and 66.6%, respectively. There were no statistically significant differences between sumatriptan 50 mg and zolmitriptan 2.5 mg (P = 0.12) or 5 mg (P = 0.80). Approximately 40% of patients in each group reported a 2-h headache response in > or = 80% of attacks. There were no statistically significant differences between the groups in the rates of headache response at 1 h (zolmitriptan 2.5 mg 36.9%, zolmitriptan 5 mg 39.5% and sumatriptan 50 mg 38.0%) or 4 h (70.3, 72.9 and 72.2%, respectively) or in the rates of meaningful migraine relief at 1, 2 or 4 h or sustained (24-h) pain relief. All treatments were well tolerated. In conclusion, zolmitriptan (2.5 or 5 mg) proved similarly efficacious compared with sumatriptan (50 mg), both in terms of response rates and consistency across attacks.

Administration, Oral↗
PubMed2001

Foot problems in patients with systemic sclerosis.

OBJECTIVES: To assess the nature of the foot problems experienced in patients with systemic sclerosis (SSc) and patient awareness of such problems. METHODS: Fifty unselected patients (42 females, eight males) with SSc were assessed by means of examination by a senior podiatrist, completion of a questionnaire detailing past and present foot problems, determination of random plasma glucose, plain X-rays of the feet, and measurement of the ankle/brachial index and of digital pulses by Doppler ultrasound. RESULTS: Eighty-six per cent of patients reported colour changes in their feet in response to temperature changes, 82% reported pain usually related to cold, 26% had suffered foot ulceration and 8% had a history of foot surgery. Podiatry assessment confirmed the presence of significant abnormalities, including ulcerations in 10%, pre-ulcerative lesions in 34%, toenail changes in 62%, callus formation in 80% and calcinosis in 18%. Forty per cent of the patients had problems with the fitting of shoes, and 19% had been provided with footwear from the hospital. Plain films of the feet demonstrated the presence of erosions in 6%, soft-tissue calcification in 17%, osteopenia in 26% and degenerative changes in 60% of cases. Ten per cent of the patients had an abnormal ankle brachial index (less than 1.0). Only 21% of the 47 patients in whom digital pulses were examined had normal pulses in all toes, and in 26% all toe pulses were absent. CONCLUSION: Although problems with the hands are well recognized in SSc, foot problems also occur in the majority of patients, and can be a cause of major disability. Care of the feet is therefore an important part of the management of SSC.

Adult↗
PubMed2000

In-hospital delay in the diagnosis of breast cancer.

BACKGROUND: There is evidence that delay in the diagnosis of breast cancer may prejudice survival. The aim of this study was to determine the incidence, time trends and causes of delay in a dedicated breast clinic. METHODS: The interval between first breast clinic visit and a definitive diagnosis was recorded in all patients with invasive breast cancer between 1988 and 1997. In all patients with a delay of 3 months or more, the case notes were reviewed for evidence of a triple assessment (clinical examination, imaging and needle biopsy). The principal cause of delay was identified. RESULTS: Of 1004 patients with invasive breast cancer, there was a delay in diagnosis of 3 months or more in 42 patients between 1988 and 1997, an incidence of 4.2 per cent. The median delay was 6 months and the median age at diagnosis was 53 (range 27-89) years. Triple assessment was undertaken in 30 patients; ten did not have a needle biopsy performed and three patients had no mammography. The principal cause of delay was: false-negative or inadequate fine-needle aspiration cytology (FNAC) in 19 patients, failure of follow-up in eight, clinical signs did not impress in five, FNAC not carried out in four, false-negative mammogram in three, failure of needle localization in two and one patient did not accept clinical advice. The annual incidence of delay in diagnosis did not change significantly over the 10-year interval. CONCLUSION: Triple assessment is not sufficiently sensitive to detect every breast cancer and a small incidence of diagnostic delay is therefore inevitable with current techniques.

Adult↗
PubMed1999

Congenital non-syndromal sensorineural hearing impairment due to connexin 26 gene mutations--molecular and audiological findings.

We screened DNA from 72 sibships and 138 sporadically affected individuals with congenital non-syndromal sensorineural hearing impairment (NSSNHI) for mutations in the 26 (CX26) gene. A total of 20 (27.8%) of the sibships and 11 (7.9%) of the sporadically affected individuals were homozygous or compound heterozygotes for CX26 mutations. A total of 11 (17.2%) of 64 individuals with severe and 30 (30%) of 100 with profound NSSNHI compared to eight (8.7%) of 92 persons with moderate and none (0%) of 19 individuals with mild hearing impairment were homozygous or compound heterozygotes for CX26 mutations (chi2 test, 3 df, P = 0.000). CX26 mutation status bad no effect on the symmetry of the hearing impairment or configuration of the audiogram. In addition, serial audiograms showed no evidence of progression of the hearing impairment or differences in the severity of the hearing impairment in affected siblings in persons whether or not due to CX26 mutations. Sporadically affected individuals with congenital NSSNHI should be routinely tested for mutations in CX26, especially if the hearing impairment is severe or profound in severity, since identification of a mutation in CX26 allows use of Mendelian recurrence risks.

Audiometry, Pure-Tone↗
PubMed1998

Differential roles of extracellular signal-regulated kinase-1/2 and p38(MAPK) in interleukin-1beta- and tumor necrosis factor-alpha-induced low density lipoprotein receptor expression in HepG2 cells.

The inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF), elevated in inflammatory, malignant, and infectious diseases, induce low density lipoprotein (LDL) receptor transcription in HepG2 cells, and such an induction can account for hypocholesterolemia associated with these states. However, the signaling mechanisms of cytokine-mediated LDL receptor induction are largely unexplored. In the present studies, we examined the potential involvement of different mitogen-activated protein kinase (MAPK) pathways. Northern analysis demonstrated that IL-1beta or TNF significantly increased LDL receptor transcript in HepG2 cells, whereas expression of another tightly regulated sterol-responsive squalene synthase gene was unaffected. IL-1beta treatment resulted in transient activation of three MAPK cascades, namely p46/54(JNK), p38(MAPK), and ERK-1/2, with maximal activation of 20-, 25-, and 3-fold, respectively, occurring 15-30 min after cytokine addition. PD98059, a specific inhibitor of MAPK kinase activity, inhibited IL-1beta-induced LDL receptor expression. In contrast, SB202190, a specific inhibitor of p38(MAPK), enhanced IL-1beta-induced LDL receptor expression, with a concomitant increase in ERK-1/2 activity. Similarly, TNF induced LDL receptor expression also required ERK-1/2 activation. Finally, sterols repressed IL-1beta induced receptor expression, without affecting ERK-1/2 activation. These results show that IL-1beta- or TNF-induced LDL receptor expression requires ERK-1/2 activation, that the p38(MAPK) pathway negatively regulates LDL receptor expression, and that sterols inhibit induction at a point downstream of ERK-1/2 in HepG2 cells.

Animals↗
PubMed1998

Elevation of cyclic AMP by iloprost and prostaglandin E1 increases cholesterol efflux and the binding capacity for high-density lipoproteins in human fibroblasts.

Elevation of cAMP concurrently enhances cholesterol efflux and binding of HDL3 in human skin fibroblasts. These effects were observed regardless of the route by which cAMP levels were increased. Cholesterol efflux and HDL3 binding were stimulated by the cAMP analogue CPT-cAMP, the adenylate cyclase activator forskolin, and by iloprost and prostaglandin E1 (PGE1) (which elevate cAMP via receptor-mediated processes). Dideoxyforskolin and PGF2alpha, which do not elevate cAMP, altered neither cholesterol efflux nor binding of HDL3. Inhibition of protein kinase A with H89 abolished the stimulatory effects of CPT-cAMP and iloprost, suggesting protein kinase A involvement in enhancing cholesterol efflux and HDL3 binding. Enhancement of HDL3 binding by iloprost was due to increased maximal capacity of the cells to bind HDL3, i.e., a greater number of HDL3 binding sites. A positive correlation was demonstrated between changes in HDL3 binding and changes in [3H]cholesterol efflux. The data are compatible with a model in which cholesterol efflux is partially dependent upon HDL binding to the cells. A short exposure to iloprost was sufficient to stimulate cAMP synthesis, triggering a chain of events leading to increased HDL3 binding and [3H]cholesterol efflux 20-24 h later. We conclude that both cholesterol efflux and the maximal capacity for HDL3 binding are enhanced by elevation of cellular cAMP. Cyclic AMP-elevating prostanoids could initiate these responses in vivo.

Alprostadil↗
PubMed1998

Attitudes of deaf adults toward genetic testing for hereditary deafness.

Recent advances within molecular genetics to identify the genes for deafness mean that it is now possible for genetic-counseling services to offer genetic testing for deafness to certain families. The purpose of this study is to document the attitudes of deaf adults toward genetic testing for deafness. A structured, self-completion questionnaire was given to delegates at an international conference on the "Deaf Nation," held at the University of Central Lancashire in 1997. The conference was aimed at well-educated people, with an emphasis on Deaf culture issues. Eighty-seven deaf delegates from the United Kingdom returned completed questionnaires. The questionnaire had been designed to quantitatively assess attitudes toward genetics, interest in prenatal diagnosis (PND) for deafness, and preference for having deaf or hearing children. The results from this study provide evidence of a predominantly negative attitude toward genetics and its impact on deaf people, in a population for whom genetic-counseling services are relevant. Fifty-five percent of the sample thought that genetic testing would do more harm than good, 46% thought that its potential use devalued deaf people, and 49% were concerned about new discoveries in genetics. When asked about testing in pregnancy, 16% of participants said that they would consider having PND, and, of these, 29% said that they would prefer to have deaf children. Geneticists need to appreciate that some deaf persons may prefer to have deaf children and may consider the use of genetic technology to achieve this. Any genetic-counseling service set up for families with deafness can only be effective and appropriate if clinicians and counselors take into consideration the beliefs and values of the deaf community at large.

Congresses as Topic↗
PubMed1997

Prelingual deafness: high prevalence of a 30delG mutation in the connexin 26 gene.

Prelingual non-syndromic (isolated) deafness is the most frequent hereditary sensory defect. In >80% of the cases, the mode of transmission is autosomal recessive. To date, 14 loci have been identified for the recessive forms (DFNB loci). For two of them, DFNB1 and DFNB2, the genes responsible have been characterized; they encode connexin 26 and myosin VIIA, respectively. In order to evaluate the extent to which the connexin 26 gene (Cx26) contributes to prelingual deafness, we searched for mutations in this gene in 65 affected Caucasian families originating from various countries, mainly tunisia, France, New Zealand and the UK. Six of these families are consanguineous, and deafness was shown to be linked to the DFNB1 locus, 10 are small non consanguineous families in which the segregation of the trait has been found to be compatible with the involvement of DFNB1, and in the remaining 49 families no linkage analysis has been performed. A total of 62 mutant alleles in 39 families were identified. Therefore, mutations in Cx26 represent a major cause of recessively inherited prelingual deafness since according to the present results they would underlie approximately half of the cases. In addition, one specific mutation, 30delG, accounts for the majority (approximately 70%) of the Cx26 mutant alleles. It is therefore one of the most frequent disease mutations so far identified. Several lines of evidence indicate that the high prevalence of the 30delG mutation arises from a mutation hot spot rather than from a founder effect. Genetic counseling for prelingual deafness has been so far considerably impaired by the difficulty in distinguishing genetic and non genetic deafness in families presenting with a single deaf child. Based on the results presented here, the development of a simple molecular test could be designed which should be of considerable help.

Australia↗
PubMed1996

Elevation of cyclic AMP in human skin fibroblasts results in increased capacity for HDL binding.

Pre-incubation of cultured human skin fibroblasts, lung fibroblasts and vascular smooth muscle cells, for 24 h with cAMP-elevating agents resulted in a significant increase (40-60%) of the cells' capacity to bind HDL. The increase was due to enhancement of the maximal binding capacity of a high affinity saturable site which binds HDL in preference to LDL. The effect was dependent upon the concentration of the cAMP-elevating agents and required more than 4 h to become evident. Cyclic AMP-mediated elevation of HDL binding occurred in cells with access to an exogenous source of cholesterol, which could be the physiological donor LDL or non-lipoprotein in origin. The observed effects were not subsequent to changes in cellular balance of cholesterol to cholesterol ester and were not due to inhibition of cellular proliferation.

Cells, Cultured↗