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Biomedical subjects

J Ireland

Publications and source records attributed to J Ireland.

At least 19 recordsLinked to original sources
PubMed2004

A clinical method for locating the femoral head centre during total knee arthroplasty.

Localisation of the femoral head centre (FHC) during total knee arthroplasty (TKA) is necessary when assessing the overall alignment of the leg using an extramedullary guide for the femur. On-table radiographs for this purpose are time consuming and inconvenient. We describe a clinical method for estimating the FHC: it is marked 1.5 cm lateral to the point where the femoral artery crosses the line joining the pubic tubercle and the anterior superior iliac spine. Using this method the estimated FHC was within 15 mm of the anatomic centre in 84% of cases, and within 24 mm in 99%. This translates into possible knee alignment errors of 2 degrees and 3 degrees, respectively. As alignment error of up to +/-3 degrees is compatible with satisfactory clinical results of TKA, our method provides useful approximation of the FHC. For greater accuracy however, an on-table radiograph is recommended.

Arthroplasty, Replacement, Knee↗
PubMed2003

Evaluations of unformulated and formulated dendrimer-based microbicide candidates in mouse and guinea pig models of genital herpes.

Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

Animals↗
PubMed2002

Gait adaptations in patients with chronic posterior instability of the knee.

OBJECTIVE: A retrospective analysis was performed to assess gait in individuals with a long history of posterior knee instability. DESIGN: Descriptive study. BACKGROUND: There are few studies in the literature concerning evaluation of the biomechanics of the knee in patients with knee posterior instability. METHODS: Nine individuals with posterior knee instability and a matched control group of uninjured subjects were tested in regards to knee kinematics and kinetics while walking and ascending and descending stairs. The mean follow up time for the individuals with posterior instability was 11.1 years. Individual satisfaction with the knee was measured by having participants complete the Flandry (also known as Hughston Clinic) self-assessment questionnaire. RESULTS: It was found that patients with knee posterior instability who indicated a higher level of satisfaction on the Flandry score walked in a manner that demonstrated greater peak knee extensor torque during stance phase, while less satisfied patients with knee posterior instability demonstrated lower peak knee extensor torque. There was a significant correlation between the self-assessment score and the peak knee extensor torque during level walking (P=0.003). During stair ascent and descent, patients with posterior instability averaged lower knee extensor torque and power than the control subjects, but those differences were only statistically significant in power while descending stairs (P=0.048). CONCLUSIONS: Individuals with chronic knee posterior instability modify their gait, and the adaptation can be predicted based upon the individuals self-assessment of their knee using the Flandry questionnaire. RELEVANCE: These data suggest that gait retraining may be a valuable addition to the traditional muscle strengthening programs, which are commonly used during conservative management of knee posterior instability.

Adaptation, Physiological↗
PubMed2002

Improvement of comparability of dietary intake assessment using currently available individual food consumption surveys.

BACKGROUND: Food consumption data are used for monitoring dietary indicators of health. In this context, there is a need for comparable (individual) data at the European level. The preference is to perform a pan-European survey able to generate data collected on the same basis. Until this can be realized, the existing data have to be made as comparable as possible. OBJECTIVE: To identify solutions; to make existing food consumption data from nationally representative databases more comparable. METHODS: General guidelines for the comparison of food intake data using currently available data were discussed and agreed upon in the EFCOSUM project team. RESULTS AND CONCLUSIONS: Criteria were assessed with regard to the population involved, age of the survey, method of data collection, duration of the survey, the food classification system and the food composition tbl Based on these criteria, a maximum of 15 countries could provide food consumption data that can be made comparable at the individual level for the adult population. It is recommended to make data comparable at the food level, starting with vegetables (excluding potatoes), fruits (excluding fruit juices), fish (including shellfish) and bread. Comparability of foods is only possible at the 'raw edible' ingredient level. To achieve this, a large amount of work has to be undertaken. The approach of the EFG (Euro Food Groups) system is considered to be the best compromise between the different classification systems. Comparability at the nutrient level has to wait for the availability of a European Nutrient Database, like the one that is being developed within the EPIC context.

Adolescent↗
PubMed2002

Selection of a food classification system and a food composition database for future food consumption surveys.

OBJECTIVE: To harmonize food classification and food composition databases, allowing comparability of consumption at both food and nutrient levels in Europe. DESIGN: To establish the level of comparability at the food level, the EFCOSUM group benefited from the work already carried out within other European projects, which established a Euro Food Groups (EFG) classification system. Four food groups, ie bread, vegetables (excluding potatoes), fruits (excluding fruit juice) and fish and seafood, were judged on their applicability for making food consumption data comparable across countries at the food level. CONCLUSIONS: It was concluded that the EFG system could be used but that still much work has to be done. For food consumption data to be collected in the future, the software that will be used should enable conversion of foods 'as consumed' to foods at the 'raw edible' level. With respect to comparability of nutrient intake estimations, EFCOSUM advises waiting for the European Nutrient Composition Database (ENDB) currently being prepared by the EPIC group. Until this is available, comparison of consumption data at the nutrient level cannot be carried out between countries.

Databases, Factual↗
PubMed2001

Linkage disequilibrium in the human genome.

With the availability of a dense genome-wide map of single nucleotide polymorphisms (SNPs), a central issue in human genetics is whether it is now possible to use linkage disequilibrium (LD) to map genes that cause disease. LD refers to correlations among neighbouring alleles, reflecting 'haplotypes' descended from single, ancestral chromosomes. The size of LD blocks has been the subject of considerable debate. Computer simulations and empirical data have suggested that LD extends only a few kilobases (kb) around common SNPs, whereas other data have suggested that it can extend much further, in some cases greater than 100 kb. It has been difficult to obtain a systematic picture of LD because past studies have been based on only a few (1-3) loci and different populations. Here, we report a large-scale experiment using a uniform protocol to examine 19 randomly selected genomic regions. LD in a United States population of north-European descent typically extends 60 kb from common alleles, implying that LD mapping is likely to be practical in this population. By contrast, LD in a Nigerian population extends markedly less far. The results illuminate human history, suggesting that LD in northern Europeans is shaped by a marked demographic event about 27,000-53,000 years ago.

Alleles↗
PubMed2001

Tibial tunnel enlargement following anterior cruciate reconstruction: does post-operative immobilisation make a difference?

The aetiology of tunnel enlargement following anterior cruciate reconstruction is still not fully understood. We studied, with particular reference to the tibial tunnel appearances, a group of 28 patients 1 year from anterior cruciate reconstruction by a four-strand hamstring technique. Fourteen underwent accelerated rehabilitation and 14 were immobilised post-operatively for 2 weeks following reconstruction. Tunnel enlargement was significantly greater in the immobilised group. There was no significant correlation between tunnel enlargement and the clinical result at 1-year post-reconstruction.

Adult↗
PubMed2001

Pseudo-aneurysm of the anterior tibial artery complicating high tibial osteotomy--a case report.

The anterior recurrent branch of the anterior tibial artery is vulnerable during high tibial osteotomy. It may be injured during subperiosteal elevation of soft tissue from the lateral tibia--necessary for visualisation of the osteotomy or for placing the fixation device; or during excision of the infero-medial aspect of the fibular head--necessary to facilitate closure of the osteotomy. Recurrent bleeding from the operation site should draw attention to the possibility of a pseudo-aneurysm. Angiography helps in making an accurate diagnosis. Ligation of the feeding vessels provides effective treatment.

Aneurysm, False↗
PubMed2000

Pathogenesis of acyclovir-resistant herpes simplex type 2 isolates in animal models of genital herpes: models for antiviral evaluations.

Our understanding of the pathogenesis of acyclovir (ACV)-resistant herpes simplex virus (HSV) is limited, especially with regard to reactivation and recurrent disease. To further explore the pathogenesis of ACV-resistant HSV-2 viruses, we used the guinea pig model of genital HSV-2 infection to evaluate several ACV-resistant isolates of both thymidine kinase (Tk)-altered and Tk-deficient phenotypes obtained from HIV-infected patients. Two plaque-purified workpools from each isolate were initially evaluated. Each produced acute disease and at least one clinical recurrence. The two strains that produced the most severe primary disease and most recurrences, one Tk-deficient virus and one Tk-altered virus, were further evaluated and shown to produce acute and recurrent genital disease similar to that seen with wild-type viruses. Furthermore, the reactivated virus producing recurrent lesions could be a pure population with minimal Tk activity. Finally, we showed that topical foscarnet treatment could alter disease and vaginal virus replication following vaginal inoculation with these two ACV-resistant strains. Using the guinea pig model of genital HSV-2 infection, we found that recurrent disease following infection with markedly Tk-deficient viruses was more common than expected, especially in select isolates. Furthermore, this model should be useful in evaluating potential new therapies for ACV-resistant HSV strains.

Acyclovir↗
PubMed2000

Cord-care practice in Scotland.

OBJECTIVE: To identify the range of policies, practices and rationale for umbilical-cord stump care in the NHS in Scotland. DESIGN: A postal questionnaire survey completed in two stages. The first stage elicited the views of Heads of Midwifery/Senior Midwives, and the second stage the views of midwives, enrolled nurses and nursery nurses. SETTING: NHS units in Scotland providing intrapartum care. They were separated into large and small units with small units having < or = 1000 deliveries per year (n = 178), and large units > 1000 deliveries per year (n = 300). PARTICIPANTS: The Heads of Midwifery/Senior Midwives from the 51 units were invited to participate in the study and 49 (96.1%) replied. In stage two 512 maternity unit employees were sent questionnaires and 390 (76.2%) replied. These were six enrolled nurses, 20 nursery nurses and 360 midwives and four respondents of unspecified occupation. MEASUREMENTS: The existence of cord-care policies and their rationale. FINDINGS: About half of the units that responded had a written policy. Large units were four times more likely than small units to have a written policy. Both managers and staff reported that the most common policy/agreed practice was no specific care (cord observed and only cleaned if soiled). Where a written policy existed, less than one-half of the Heads of Midwifery/Senior Midwives and less than one third of the staff reported that the basis for this policy was research. KEY CONCLUSIONS: Units with a written policy are in the minority and small units are far less likely to have such a policy. Wide variation exists in policy, practice and rationale. Diversity within and between units creates anxiety and disillusionment for practitioners. It may also cause confusion for patients who are exposed to different cord-care practices either as these change over time or because they use different units. IMPLICATIONS FOR PRACTICE: The midwifery profession must examine this area of practice and determine how to address this lack of evidence. Further research is required to determine the most effective method of cord care and how best to put the findings into practice. Outstanding questions which beg further investigation are: How do cords heal and separate and what bacteria are naturally involved in this process? What constitutes an infected cord as opposed to a colonised cord?

Clinical Competence↗
PubMed2000

The influence of salinity and temperature change on the functioning of the urinary bladder in the early larval stages of the atlantic herring Clupea harengus L.

Major changes in the morphology of the urinary bladder were observed during the transition from yolk-sac to feeding larval stages of herring, in particular bladder volume increased almost sixfold. Initially, the urine flowed into the hindgut, but within days of hatching a separate urinary duct, leading to the exterior, had formed. Micturation was intermittent but quite regular. The period between micturations increased from 1.6 to 4 min in the progression between the two larval stages. The discharge volume was approximately 50 % of the full bladder volume in all stages studied. Urine flow rate (UFR) in sea water rose slightly from 1 to 1.7 nl mg(-)(1 )h(-)(1) during early larval development. Exposure to low salinities significantly reduced UFR in yolk-sac larvae, but in the later stages UFR increased significantly in hypo-osmotic salinities, so that UFR in 4 salinity was 2.5 times that in 34 salinity. The main variable influencing UFR was discharge frequency. Cardiac output was not influenced by salinity and was considered not to be a controlling factor in the UFR response to salinity change. UFR increased with temperature with Q(10) of 2.3 in stage 1 larvae and 1. 5 in stage 2 larvae, over 7-15 degrees C.

Animals↗
PubMed1999

Elevated immunoglobulin E (IgE) levels in children with exposure to environmental lead.

Lead has been reported to be an immunosuppressive agent in animal systems at levels far below those recognized as overtly toxic. Little data exist on lead's effects on the human immune system, especially in young children who are at greatest risk for exposure to this environmental hazard. The effects of environmental lead exposure on the human immune system were examined in a population of young children, age 9 months-6 years, from the urban population of Springfield-Greene County, Missouri. Reported here are data from 279 children with blood lead levels ranging from 1 to 45 microg/dl. White blood cell populations have been enumerated and examined for cell surface expression of activation markers. Serum has been analyzed for IgE, specific titers to Rubella vaccine, sCD25 (the soluble form of the IL2 receptor), sCD27 (the soluble form of the lymphocyte specific member of the tumor necrosis factor receptor family), and IL4 (the cytokine interleukin 4). Variation of these assays with age of the child was considered in statistical analysis of data. A statistically significant relationship of IgE and blood lead level was found in this population; as blood lead (PbB) level increases, IgE level increases. No other statistically significant differences between risk categories or other associations with blood lead level were found. The exact mechanism for this apparent stimulus of IgE-producing B cells remains to be elucidated. The development of allergic symptoms is often preceded by an increase in IgE. These data indicate that ingested lead could play a role in this process by stimulating IgE production.

Age Factors↗
PubMed1999

Effect of undecylenic acid as a topical microbicide against genital herpes infection in mice and guinea pigs.

There is increasing interest in the use of topical microbicides to help prevent the spread of sexually transmitted diseases (STD). Undecylenic acid (UA), a monosaturated fatty acid, is the active ingredient in a number of over-the-counter (OTC) antifungal spray powders, that also exhibits in vitro antibacterial and antiviral activity, including herpes simplex virus (HSV) activity. We, therefore, evaluated UA as a topical microbicide against genital HSV infection using the murine and guinea pig models of genital herpes. Mice were administered a 20% solution of UA in polyethylene glycol (PEG) vehicle, vehicle alone or phosphate buffered saline (PBS) intravaginally immediately prior to vaginal challenge with HSV-2. Pre-treatment with UA decreased the number of mice that became infected (P < 0.001 vs. PBS or vehicle control), developed symptoms (P <0.001) or died (P <0.001). However, when treatment was extended to either 5 min prior to or after viral inoculation, protection was lost. Similar findings were found using the guinea pig model, where UA treatment completely prevented HSV-2 vaginal infection when given immediately prior to HSV-2 inoculation (P<0.001 vs. PBS or vehicle control). Thus, UA, an approved OTC medication, provided significant protection against HSV disease and infection only when applied immediately before viral inoculation, indicating that better formulations were needed to extend the duration of protection.

Administration, Topical↗
PubMed1999

Allograft reconstruction of the extensor mechanism for progressive extensor lag after total knee arthroplasty and previous patellectomy: a 3-year follow-up.

Major extensor lag after total knee arthroplasty may follow operative damage to the patellar tendon or its insertion. It may also occur in a late progressive form postoperatively. A successful allograft reconstruction of the extensor mechanism for progressive extensor lag after total knee arthroplasty is described. Patellectomy had been carried out earlier on the same knee for patellofemoral osteoarthritis.

Aged↗
PubMed1999

Characterization of single-nucleotide polymorphisms in coding regions of human genes.

A major goal in human genetics is to understand the role of common genetic variants in susceptibility to common diseases. This will require characterizing the nature of gene variation in human populations, assembling an extensive catalogue of single-nucleotide polymorphisms (SNPs) in candidate genes and performing association studies for particular diseases. At present, our knowledge of human gene variation remains rudimentary. Here we describe a systematic survey of SNPs in the coding regions of human genes. We identified SNPs in 106 genes relevant to cardiovascular disease, endocrinology and neuropsychiatry by screening an average of 114 independent alleles using 2 independent screening methods. To ensure high accuracy, all reported SNPs were confirmed by DNA sequencing. We identified 560 SNPs, including 392 coding-region SNPs (cSNPs) divided roughly equally between those causing synonymous and non-synonymous changes. We observed different rates of polymorphism among classes of sites within genes (non-coding, degenerate and non-degenerate) as well as between genes. The cSNPs most likely to influence disease, those that alter the amino acid sequence of the encoded protein, are found at a lower rate and with lower allele frequencies than silent substitutions. This likely reflects selection acting against deleterious alleles during human evolution. The lower allele frequency of missense cSNPs has implications for the compilation of a comprehensive catalogue, as well as for the subsequent application to disease association.

Alleles↗
PubMed1999

Failed adoptive immunity transfer: reactivation or reinfection?

A 26-year-old female bone marrow transplant (BMT) recipient was hepatitis B surface antigen (HBsAg) and hepatitis B e antibody (HBeAb) positive. The donor, her human leucocyte antigen (HLA)-compatible sister, was HBsAg negative but hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) positive. Twelve weeks post-BMT the patient became HBsAg negative, as determined using a monoclonal antibody-based assay. At 16 weeks post-BMT, HBsAg became undetectable by monoclonal and polyclonal immunoassay with seroconversion to HBsAb; however, at 24 weeks post-BMT the patient again became HBsAg positive. Both the recipient and the donor were retrospectively tested by hepatitis B virus (HBV) polymerase chain reaction (PCR) and found to be positive. The recipient displayed variants at amino acids 4 and 47 of the surface (S) gene prior to BMT. These mutations were not detected 32 weeks post-BMT when the S gene sequence was identical to that of an adr prototype. The donor was found to have four unique amino acid substitutions at positions 30, 98, 101 and 210 of the S gene. However, in vitro-expressed HBsAg from the donor was detected by commercial kits and an immunofluorescence assay, indicating that antigenic alteration did not explain HBsAg negativity. This donor highlights the value of PCR as the gold standard test for current HBV infection. It also demonstrates that discordance between two commercial HBsAg assays may not always be caused by antigenic variants. The second episode of hepatitis may theoretically have been caused by reactivation, selection of an escape mutant by HBsAb, reinfection or recombination. We suggest it was reactivation because none of the donor variants was seen in the recipient post-BMT.

Adoptive Transfer↗