Academics: why has everyone left?
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Academic Medical Centers↗
Biomedical subjects
S Cunningham
Publications and source records attributed to S Cunningham.
Stratification of foot ulcer risk in patients with diabetes: a population-based study.
This trial assessed whether a simple clinical tool can be used to stratify patients with diabetes, according to risk of developing foot ulceration. This was a prospective, observational follow-up study of 3526 patients with diabetes (91% type 2 diabetes) attending for routine diabetes care. Mean age was 64.7 (range 15-101) years and duration of diabetes was 8.8 (+/-1.5 SD) years. Patients were categorised into 'low' (64%), 'moderate' (23%) or 'high' (13%) risk of developing foot ulcers by trained staff using five clinical criteria during routine patient care. During follow-up (1.7 years), 166 (4.7%) patients developed an ulcer. Foot ulceration was 83 times more common in high risk and six times more in moderate risk, compared with low-risk patients. The negative predictive value of a 'low-risk score' was 99.6% (99.5-99.7%; 95% confidence interval). This clinical tool accurately predicted foot ulceration in routine practice and could be used direct scarce podiatry resources towards those at greatest need.
Adolescent↗
Low oxygen exposure does not cause pulmonary injury in the newborn rat.
BACKGROUND: Two recent studies have suggested that low levels of supplemental inspired oxygen may cause lung injury in preterm infants. AIMS: To assess lung injury of newborn rats exposed to 14 days of low-level variation of oxygen. STUDY DESIGN: Four groups were compared with 12 animals per group and 4 lung sections per animal. These were, a control group raised in room air and three groups raised in levels of inspired oxygen fluctuating around the following mean values: group Lo (mean FiO(2) 0.179), group N (mean FiO(2) 0.213), and group Hi (mean FiO(2) 0.247). The degree of oxygen variability was identical for each group. Lungs were inflated at 20 cm H(2)O, fixed and stained with H and E and Millers Elastin. SUBJECTS: Sprague Dawley albino newborn rats. OUTCOME MEASURES: Random alveolar areas were studied and analysed using imaging software to assess total amount of tissue and elastin, number of secondary septa, and mean linear intercept. RESULTS: There were no significant differences between the three experimental oxygen groups and the control group in terms of lung/body weight ratio and the measured markers of lung development. CONCLUSION: We conclude that low-level oxygen supplementation during early lung development does not affect alveolar development in the newborn rat.
Animals↗
Perceptions of facial aesthetics in two and three dimensions.
The aims of this study were to investigate whether the preferred facial relationship chosen by professionals and the general public is Class I and to ascertain whether viewing two-dimensional (2D) or three-dimensional (3D) images had any effect on the ranking of facial attractiveness. Orthodontists (n = 47), maxillofacial surgeons (n = 25) and members of the general public (n = 78) assessed 2D and 3D facial scans of two males and two females that had been morphed to produce five images reflecting different skeletal patterns: Class I, mild and moderate Class II, and mild and moderate Class III. Each assessor placed the images in rank order of preference, after viewing alternate 2D and 3D image formats for each face. The data were analysed using logistic regression. In 2D, professionals (orthodontists and maxillofacial surgeons) chose Class I as the preferred facial image more frequently than the general public for only one of the four faces. However, in 3D format they chose Class I as the preferred facial image for some subject faces more, and others less, frequently when compared with the general public. The gender of the assessor was not significant when assessing the preferred facial relationship for Class I images in either 2D or 3D formats. The oldest assessors (56+ years) were significantly less likely than the younger age groups to select Class I as the preferred facial relationship in both 2D and 3D. In summary, there was too great a degree of variation to say that a difference between 2D and 3D facial images was evident.
Adolescent↗
IFNG polymorphisms are associated with gender differences in susceptibility to multiple sclerosis.
Interferon-gamma (IFNgamma) treatment is deleterious in multiple sclerosis (MS). MS occurs twice as frequently in women as in men. IFNgamma expression varies by gender. We studied a population-based sample of US MS patients and ethnicity-matched controls and independent Northern Irish and Belgian hospital-based patients and controls for association with MS, stratified by gender, of an intron 1 microsatellite [I1(761)*CAn], a single nucleotide polymorphism 3' of IFNG [3'(325)*G --> A] and three flanking microsatellite markers spanning a 118 kb region around IFNG. Men carriers of the 3'(325)*A allele have increased susceptibility to MS compared to noncarriers in the USA (P=0.044; OR: 2.58, 95% CI: 0.97-8.08) and Northern Ireland (P=0.019; OR: 2.37, 95% CI: 1.10-5.13). There is a nonsignificant trend in the same direction in Belgian men (P=0.299; OR: 1.50, 95% CI: 0.71-3.26). Men carriers of I1(761)*CA13, which is in strong linkage disequilibrium with the 3'(325)*A, have increased susceptibility (P=0.050; OR: 2.22, 95% CI: 0.98-5.40), while men carriers of I1(761)*CA12 have decreased susceptibility (P=0.022; OR: 0.46, 95% CI: 0.23-0.90) to MS in the USA. Similar associations were reported in Sardinia between the I1(761)*CA12 allele and reduced risk of MS in men. Flanking markers were not associated with MS susceptibility. Polymorphisms of IFNG may contribute to differences in susceptibility to MS between men and women.
3' Flanking Region↗
Haplotype analysis of the preprotachykinin-1 (TAC1) gene in multiple sclerosis.
The potential relevance of chromosome 7q21-22 in susceptibility to multiple sclerosis (MS) has been highlighted in genome-wide linkage screens as well as in association studies of 7q-specific polymorphic microsatellites. Especially, recent, independently performed studies have provided evidence for significant association of the markers D7S554 and D7S3126 with MS in Sardinian, Northern Irish and Spanish-American cohorts. The gene most closely located to these markers is the neuropeptide preprotachykinin-1 (TAC1) gene. Both its position and the array of biological functions exerted by its expression products make it a logical primary choice for further scrutiny as the putative chromosome 7q21-22 MS susceptibility gene. We report identification of eight polymorphisms in this gene by means of a sequencing approach. A Northern Irish case-control was typed for six of these polymorphisms. One of these, an intron 1 single-nucleotide polymorphism (SNP), showed significant association with MS (P=0.009). Two-marker haplotypes composed of allelic combinations of TAC1 promoter-intron 1 SNPs were highly significantly associated with MS and more so with the relapsing-remitting form of this disease. While independent reproduction of these data in other data sets is indicated, our work is suggestive for a role of the TAC1 gene in MS. Genes and Immunity (2005) 6, 265-270. doi:10.1038/sj.gene.6364175 Published online 24 February 2005.
Genetic Predisposition to Disease↗
Contact allergy to peanuts in bird feed.
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Animal Feed↗
Two imaging techniques to find too flexible an airway: looking for malacia.
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Bronchial Diseases↗
Breath condensate ammonium is lower in children with chronic asthma.
Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children. The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.5 yrs) compared with 47 healthy controls (median age 10 yrs); and 2) longitudinal assessment of eight children (mean age 8.5 yrs) admitted with asthma exacerbation. Condensate pH and ammonium were compared with clinical observations. In the cross-sectional part of the study, lower per cent forced expiratory volume in one second was associated with more symptoms and treatment. There was no significant difference between median pH in children with stable asthma (6.05) compared with controls (5.90). Ammonium was significantly lower in children with asthma (median 258 microM) compared with controls (median 428 microM). No association was found between ammonium or pH and lung function or symptom-free days. In the longitudinal study, significant improvements in oxygen saturation and respiratory rate with treatment of an acute exacerbation were not reflected by changes in pH or ammonium. In conclusion, pH does not appear to reflect disease or severity in children with asthma. Ammonium was significantly lower in children with asthma when compared with controls.
Adolescent↗
Detection of vancomycin-resistant enterococci before and after antimicrobial therapy: use of conventional culture and polymerase chain reaction.
Antimicrobial therapy can increase the colonization density of gastrointestinal vancomycin-resistant enterococci (VRE). Among previously VRE-colonized patients, we evaluated VRE colonization before and after initiation of antimicrobial therapy by means of polymerase chain reaction (PCR) and culture. Perianal swab samples were obtained at admission to the hospital and after receipt of antimicrobial therapy. At admission, 12 (21%) of 56 patients were culture positive, and 17 (30%) had vanA or vanB genes detected by PCR. Culture results showed that 25 (86%) of 29 culture-negative patients from whom a second swab sample was obtained remained culture negative, 2 (6.9%) had a relapse of colonization with a strain related to the previously colonizing strain type (2 and 6 days after admission), and 2 (6.9%) tested positive for a previously undetected strain type (16 and 19 days after admission). PCR at admission detected VRE in 1 of the 2 patients who later relapsed. Patients with negative results of culture of the initial swab sample and of PCR were unlikely to relapse after receipt of antimicrobial therapy.
Adult↗
Polymorphisms in the interferon-gamma/interleukin-26 gene region contribute to sex bias in susceptibility to rheumatoid arthritis.
OBJECTIVE: To determine whether polymorphisms in the interferon-gamma (IFNgamma)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA). METHODS: Four microsatellite markers, located in a 118-kb interval that contains both the IFNgamma and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction-based fragment analysis. RESULTS: Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [P(corr)] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32-0.78; P = 0.002, P(corr) = 0.03) but not in men with RA. CONCLUSION: Our results demonstrate that common polymorphisms in the IFNgamma/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.
Adult↗
Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012).
OBJECTIVE: To examine the emergence and fading of NVP resistance (NVP(R)) mutations in HIV-1-infected Ugandan women and infants who received single dose NVP to prevent HIV-1 vertical transmission. DESIGN: We examined NVP(R) in women and infants who received NVP in the HIVNET 012 clinical trial, including 41 out of 48 women with infected infants, 70 randomly-selected women with uninfected infants, and 33 out of 49 infected infants. METHODS: Plasma HIV-1 was analyzed using the Applied Biosystems ViroSeq HIV-1 Genotyping System. RESULTS: NVP(R) mutations were detected in 21 out of 111 (19%) women tested 6-8 weeks after delivery. The rate of NVP(R) was similar among women whose infants were or were not HIV-1 infected. K103N was the most common mutation detected. NVP(R) mutations faded from detection within 12-24 months in all 11 evaluable women. High baseline viral load and low baseline CD4 cell count were associated with development of NVP(R). NVP(R) mutations were detected in 11 out of 24 (46%) evaluable infants who were infected by 6-8 weeks of age. The most common NVP(R) mutation detected in infants was Y181C. Those mutations faded from detection by 12 months of age in all seven evaluable infants. Of nine evaluable infants with late HIV-1 infection, only one had evidence of NVP(R). CONCLUSIONS: NVP(R) was detected more frequently in infants than women following NVP prophylaxis, and different patterns of NVP(R) mutations were detected in women versus infants. NVP(R) was detected infrequently in infants with late HIV-1 infection. NVP-resistant HIV-1 faded from detection in women and infants over time.
Anti-HIV Agents↗
Impact of human immunodeficiency virus type 1 (hiv-1) subtype on women receiving single-dose nevirapine prophylaxis to prevent hiv-1 vertical transmission (hiv network for prevention trials 012 study).
In Uganda, the HIV Network for Prevention Trials (HIVNET) 012 study recently demonstrated that single-dose nevirapine (Nvp) prophylaxis is effective for preventing mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1). This exploratory study examines the relationship between HIV-1 subtype, MTCT, and the development of Nvp resistance (Nvp(R)) in women enrolled in HIVNET 012. For 102 women (32 whose infants were HIV-1 infected by age 6-8 weeks and 70 whose infants were uninfected), HIV-1 subtypes included 50 (49%) subtype A, 35 (34%) subtype D, 4 (4%) subtype C, 12 (12%) recombinant subtype, and 1 unclassified. There was no apparent difference in the rate of MTCT among women with subtype A versus D (adjusted odds ratio [OR], 1.24; 95% confidence interval [CI], 0.45-3.43). Nvp(R) mutations were detected more frequently at 6-8 weeks postpartum in women with subtype D than in women with subtype A (adjusted OR, 4.94; 95% CI, 1.21-20.22). Additional studies are needed to further define the relationship between HIV-1 subtype and Nvp(R) among women receiving Nvp prophylaxis.
Anti-HIV Agents↗
Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377).
In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance mutations were assessed before study treatment (baseline) and at virologic failure. Zdv, ddI, and ddC mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp and 3TC mutations were detected frequently at virologic failure, and Nvp mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp and 3TC mutations plus Rtv and Nfv mutations. However, Rtv and Nfv mutations were detected at unexpectedly low rates.
Adolescent↗
Myocardial ischaemia in normal patients undergoing elective Caesarean section: a peripartum assessment.
Incidence rates of electrocardiographic changes during Caesarean section vary from 25 to 60%. To date, no investigator has identified myocardial ischaemia resulting from these changes. We investigated patients undergoing elective Caesarean section using peripartum Holter monitoring and serum analysis of cardiac troponin I (cTnI). Twenty-six patients presenting for elective Caesarean section were studied. Peroperative Holter monitoring continued for 12 h postoperatively, at which time blood samples for cTnI levels were taken. Significant ST changes were recorded in 42% of patients peroperatively and 38.5% of patients postoperatively. Forty-two per cent of patients experienced peroperative chest pain requiring opioid analgesia. Chest pain was significantly associated with abnormal electrocardiogram (ECG) findings. Ischaemic levels of cTnI were recorded in two patients. This study reports, for the first time, myocardial ischaemia (7.69% of patients) arising in conjunction with the ECG changes seen during elective Caesarean section. We also report episodes of significant postoperative ST-segment changes.
Adult↗
What's new in respiratory allergy?
The past 10 years have seen important advances in our understanding of allergic respiratory disease and the targets for potential therapies. Sensitisation and triggering of allergic reactions now appear to be better understood at a clinical and molecular level. Environmental intervention studies are underway attempting to reduce the sensitisation and the triggering of symptoms. Therapeutic intervention studies targeting key pathways in the allergic cascade are also taking place. This paper will assess both of these aspects of respiratory allergy, updating readers on the new evidence in our quest to understand how and when sensitisation occurs and also how we might be able to control triggered reactions using targeted therapeutics against specific elements of the allergic cascade.
Child↗
Performance of Applied Biosystems ViroSeq HIV-1 Genotyping System for sequence-based analysis of non-subtype B human immunodeficiency virus type 1 from Uganda.
The Applied Biosystems ViroSeq HIV-1 Genotyping System is a commercially available, integrated system for sequence-based analysis of drug resistance mutations in human immunodeficiency virus type 1 (HIV-1) protease and reverse transcriptase (RT). We evaluated the performance of this system for analysis of non-subtype B HIV-1 by analyzing plasma samples from Ugandan women and infants. Plasma samples were obtained from 105 women and 25 infants enrolled in a Ugandan clinical trial. HIV-1 analysis was performed with the ViroSeq system according to the manufacturer's instructions, except that the volume of plasma used for analysis was less than the recommended 0.5 ml for some samples. Viral loads ranged from 2,313 to 2,336,400 copies/ml. PCR products suitable for sequencing were amplified from all samples tested. Complete sequences for protease (amino acids 1 to 99) and RT (amino acids 1 to 320) were obtained for 102 of 105 (97%) of the maternal samples tested and all 25 of the infant samples tested. Complete double-stranded sequences were obtained for 90 of 105 (86%) of the maternal samples tested and 22 of 25 (88%) of the infant samples tested. The sequences obtained with this system were used for HIV-1 subtyping. The subtypes identified were A, C, D, and A/D recombinant HIV-1. The performances of the seven sequencing primers were similar for the subtypes examined. The ViroSeq system performs well for analysis of Ugandan plasma samples with subtypes A, C, D, and A/D recombinant HIV-1. The availability of this genotyping system should facilitate studies of HIV-1 drug resistance in countries where these subtypes are prevalent.
Anti-HIV Agents↗
Performance of the applied biosystems ViroSeq human immunodeficiency virus type 1 (HIV-1) genotyping system for sequence-based analysis of HIV-1 in pediatric plasma samples.
The ViroSeq HIV-1 Genotyping System is a commercially available, integrated sequence-based system for analysis of human immunodeficiency virus type 1 (HIV-1) drug resistance. We evaluated the performance of this system by analyzing HIV-1 in pediatric plasma samples. Plasma samples from children 4 months to 17 years of age were obtained from a clinical trial protocol (PACTG 377). Children in PACTG 377 were randomized to four treatment arms, including different combinations of antiretroviral drugs. HIV-1 genotyping was performed using samples collected prior to antiretroviral therapy (baseline) and at the time of virologic failure. Performance of the genotyping system was compared in three university laboratories. A total of 196 samples were analyzed, including 135 baseline and 61 failure samples. Plasma volumes ranged from 0.05 to 0.5 ml, and viral loads ranged from 1,084 to 3,484,991 copies/ml. PCR products suitable for sequencing were obtained for 192 of the 196 samples. Complete sequences for protease and reverse transcriptase were obtained for all of these 192 samples. For 180 samples, data were obtained from both DNA strands for the entire region analyzed. There was no evidence of sample cross-contamination based on phylogenetic analysis of HIV-1 sequences. Performance of the genotyping system was similar in three laboratories. This genotyping system performs well for analysis of HIV-1 in pediatric plasma samples, including those with low volume and low viral load. The availability of this system should facilitate studies of HIV-1 drug resistance.
Adolescent↗