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Biomedical subjects

G Savage

Publications and source records attributed to G Savage.

17 recordsLinked to original sources
PubMed2006

Novel and Mediterranean beta thalassemia mutations in the indigenous Northern Ireland population.

beta thalassemia is one of the most common genetic diseases worldwide resulting from aberrant beta-globin chain production. It is highly prevalent in regions with endemic malaria, but it is also present at low frequency in the indigenous populations of non-tropical areas such as Britain. Screening beta thalassemia trait individuals from Northern Ireland has detected 2 Mediterranean mutations, 39 (C --> T) and IVS-I-110 (G --> A); the previously reported IVS-II-850 (G --> A) mutation originally described in individuals of Scottish/English ancestry; and 2 novel mutations, initiation codon A --> C and 109 delG. Haplotype analysis indicates that the Mediterranean mutations are present on previously described haplotypes, suggesting that they have arisen due to migration. It remains to be established whether the novel mutations have arisen de novo in Northern Ireland.

Adolescent↗
PubMed2006

A sample distribution programme for erythropoietin.

A survey was sent to laboratories participating in the United Kingdom External Quality Assessment Service (UKNEQAS) Haematinics Scheme about the measurement of serum erythropoietin (EPO). Six laboratories, from a total of 120 that returned the survey, were measuring serum EPO concentrations by commercially available immunoassays on site in the United Kingdom. The workload of the laboratories varied from up to 100 specimens per month to more than 100 specimens analysed per week. All laboratories included control material in the assays and none of the laboratories was participating in an external quality assessment scheme for serum EPO. Four laboratories agreed to take part in the first sample distribution programme, with five and six laboratories participating in distributions 2 and 3 respectively. The results from eight kits were compared from the three distributions over a 2-year period. The serum EPO concentrations for the methods showed some variation across the range of 2.9-200 U/l when the serum EPO concentrations for each method were compared with the whole method mean. The results from this scheme have identified a role for an external quality assessment scheme for serum EPO measurements.

Benchmarking↗
PubMed2005

Recessive congenital methaemoglobinaemia: functional characterization of the novel D239G mutation in the NADH-binding lobe of cytochrome b5 reductase.

Type I recessive congenital methaemoglobinaemia (RCM), caused by the reduced form of nicotinamide adenine dinucleotide (NADH)-cytochrome b(5) reductase (cytb(5)r) deficiency, manifests clinically as cyanosis without neurological dysfunction. Two mutations, E255- and G291D, have been identified in the NADH-binding lobe of cytb(5)r in previously reported patients, and we have detected a further novel mutation, D239G, in this lobe in two unrelated Irish families. Although one family belongs to the genetically isolated Traveller Community, which separated from the general Irish population during the 1845-48 famine, the D239G mutation was present on the same haplotype in both families. Three known cytb(5)r mutations were also identified, including the R159- mutation, which causes loss of the entire NADH-binding lobe and had previously been reported in an individual with type II RCM. Characterization of the three NADH-binding lobe mutants using a heterologous expression system revealed that all three variants retained stoichiometric levels of flavin adenine dinucleotide with spectroscopic and thermodynamic properties comparable with those of native cytb(5)r. In contrast to the E255- and G291D variants, the novel D239G mutation had no adverse impact on protein thermostability. The D239G mutation perturbed substrate binding, causing both decreased specificity for NADH and increased specificity for NADPH. Thus cytb(5)r deficient patients who are heterozygous for an NADH-binding lobe mutation can exhibit the clinically less severe type I phenotype, even in association with heterozygous deletion of the NADH-binding lobe.

Adolescent↗
PubMed2004

Evidence of prostate cancer screening in a UK region.

OBJECTIVE: To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. SUBJECTS AND METHODS: Data were collected on all PSA tests in Northern Ireland between 1990 and 1999. Annual rates of PSA testing were calculated by age, GP Practice and year. RESULTS: In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. CONCLUSION: These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.

Adult↗
PubMed2001

Hemispheric and gender-related differences in the gross morphology of the anterior cingulate/paracingulate cortex in normal volunteers: an MRI morphometric study.

The sulci and gyri found within the anterior cingulate (AC), and across the cerebrum generally, have been found to vary in location and complexity from one individual to the next, making it difficult to analyze imaging data accurately and systematically. In this study, we examined the nature of morphometric variance in the AC of the left and right cerebral hemispheres using high-resolution structural magnetic resonance imaging (MRI) acquired from 176 healthy volunteers. Depending on the presence of a paracingulate sulcus (PCS) and its antero-posterior extent, three types of AC patterns were identified: 'prominent', 'present' and 'absent'. Hemispheric comparisons across the whole sample showed the PCS to be more commonly 'prominent' in the left hemisphere and more commonly 'absent' in the right hemisphere. There was a significant gender difference, such that males showed an asymmetric pattern characterized by increased fissurization of the left AC, while females showed greater symmetry, with less fissurization of the left AC. Overall cerebral morphology, namely hemispheric volume and hemispheric fissurization, were also measured and used as independent variables as well as covariates in the analyses in order to ascertain the specificity of the results regarding AC morphology. Results showed that cerebral volume for males was larger on the right than on the left while fissurization showed the reverse asymmetry of greater leftward fissurization. In contrast, females were symmetric in both respects. The findings regarding AC morphology could not be explained by differences in these overall cerebral measures or by differences in age and handedness within the population. The results suggest that in the normal male brain, there exist morphological asymmetries at both the global and local levels that are less apparent in the female brain. The findings have implications for future studies examining the organization, development and functional anatomy of the AC.

Adolescent↗
PubMed2001

Study of maternal influences on fetal iron status at term using cord blood transferrin receptors.

AIMS: To determine effects of maternal iron depletion and smoking on iron status of term babies using serum transferrin receptors (STfR) and their ratio to ferritin (TfR-F index) in cord blood. METHODS: Iron, ferritin, STfR, and haemoglobin (Hb) concentration were measured and TfR-F index calculated in 67 cord /maternal blood pairs. Twenty six mothers were iron depleted (ferritin <10 microg/l) and 28 were smokers. RESULTS: Maternal iron depletion was associated with decreased cord ferritin (113 v 171 microg/l) and Hb (156 v 168 g/l) but no change in STfR or TfR-F index. Smoking was associated with increased cord Hb (168 v 157 g/l) and TfR-F index (4.1 v 3.4), and decreased ferritin (123 v 190 microg/l). Cord TfR-F index and Hb were positively correlated (r = 0.48). CONCLUSIONS: Maternal iron depletion is associated with reduced fetal iron stores but no change in free iron availability. Smoking is associated with increased fetal iron requirements for erythropoiesis.

Anemia, Iron-Deficiency↗
PubMed1998

Initial experience with a physiologic morcellating resectoscope.

A new physiologic morcellating resectoscope allows operative hysteroscopy to be performed with a physiologic distention medium, thus reducing the risk of dilutional hyponatremia and cerebral edema secondary to excessive absorption of nonphysiologic fluid. To study this new technology, we gathered in vitro data with the SL resectoscope with dual-function electrode (FemRx, Sunnyvale, CA). Coupled to a standard monopolar electrosurgery unit and operating in normal saline or Ringer's lactate solution, extirpated uteri showed equivalent depth of tissue necrosis with this new physiologic morcellating resectoscope as with a conventional monopolar resectoscope used in an electrically nonconductive fluid.

Electrocoagulation↗
PubMed1997

The cost effectiveness of pneumococcal vaccination strategies.

Pneumonia and influenza, combined, are the sixth leading causes of death in the US. The age-adjusted mortality rate for these diseases increased by 20% between 1979 and 1993, perhaps as a result of the emergence of multi-drug-resistant and penicillin-resistant strains of bacteria that cause pneumonia. Of the approximately $US23 billion annual cost of community-acquired pneumonia, pneumococcal pneumonia is currently estimated to account for up to $US18 billion. Considering the clinical and economic consequences of pneumococcal disease, vaccination appears to be a valuable preventive strategy. However, despite Medicare coverage and the recommendations of the Advisory Committee on Immunisation Practices (ACIP), only 28% of elderly and high-risk patients received the pneumococcal vaccine in 1993. This article reviews the epidemiology and economic factors that determine the cost effectiveness of pneumococcal vaccination strategies. The strategies are taken from a review of 10 published economic analyses of the pneumococcal vaccine. Cost savings and favourable cost-effectiveness ratios are associated with key factors that increase vaccination programme benefits by maximising averted direct medical costs as well as reducing vaccination programme costs, such as through public vaccination campaigns.

Bacterial Vaccines↗
PubMed1990

Mortality and increasing drug use in Edinburgh: implications for HIV epidemic.

Mortality among a group of known drug users shows small numbers of deaths from AIDS so far but increasing deaths from overdose, especially in young women. Steadily rising numbers of drug injectors are observed. The need for a distinctly different educational approach in areas of very high seroprevalence is discussed and the requirement for close co-operation between prescribing sources identified.

Adult↗
PubMed1988

Predictive value of clinical, laboratory, pathologic, and treatment variables in steroid/immunosuppressive resistant lupus nephritis.

Twenty-seven patients with lupus nephritis and nephrotic syndrome had persistent disease activity despite an adequate trial of corticosteroids and immunosuppressive drugs; 30% were Asians, compared with 7% of our overall SLE population. Two years later, seven had a very good outcome and seven a poor outcome. Thirty clinical, pathological, laboratory, and treatment variables were analyzed in a good versus poor responder subset comparison in an effort to determine which factors were associated with favorable outcome. Administration of pulse steroids (P = .069) and a low biopsy chronicity index (P = .048) were associated with the good responder subset. Serum creatinine, biopsy class, blood pressure, complement, and anti-DNA values at entry as well as the choice of immunosuppressive drug were not helpful in predicting outcome. All seven good responders were plasmapheresed (P = .026). Patients with refractory lupus nephritis who have a low biopsy chronicity index may benefit from the use of pulse steroids or plasmapheresis, and controlled studies are suggested.

Adult↗