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Biomedical subjects

R Hall

Publications and source records attributed to R Hall.

At least 127 records · Page 7Linked to original sources

Arterial hypertension causing leg ulcers.

We report clinical and histological features of 16 consecutive patients with hypertensive leg ulcers. The lumen/wall ratio in arterioles at the edges of these hypertensive leg ulcers was compared with that in other types of chronic leg ulcers and was found to be significantly reduced (P < 0.001). Additional conditions such as venous hypertension or main vessel arterial disease contributed. Nineteen of 22 ulcers were completely healed after a mean of 4.9 months. Recognition of this condition enables correct treatment choice, which usually involves excision and grafting, and early healing.

Aged↗

The status of bladder-preserving therapeutic strategies in the management of patients with muscle-invasive bladder cancer.

The recommended treatment for medically fit patients with muscle-invading bladder cancer is usually radical cystectomy. However, transurethral resection of the tumor, partial cystectomy, irradiation and systemic chemotherapy are each effective in some patients. These latter treatments allow bladder preservation and cure as an alternative to radical cystectomy although when used unselectively the survival rates are inferior to those of radical cystectomy. The updated results of conservative surgery, radiation therapy and systemic chemotherapy as monotherapy, as well as strategies of combined modality treatment were reviewed. Based on this review many areas of consensus were reached which include: 1. The primary goal of any treatment for a patient with muscle-invading bladder cancer is survival; bladder preservation in the interest of quality of life is a secondary objective. 2. Only a small proportion of carefully selected patients may be cured by transurethral surgery alone, or by partial cystectomy alone. 3. Radiation therapy is currently the standard bladder-preserving therapy against which all other bladder-preserving methods must be compared. 4. Systemic chemotherapy as monotherapy is inadequate and cannot be recommended. 5. The addition of cisplatin-containing systemic chemotherapy to radiation therapy or conservative surgery appears to improve local control. While no multi-modality therapeutic regimen has yet been shown to be clearly optimal with regard to local efficacy and minimizing toxicity, monotherapy for bladder preservation is probably not desirable as a routine approach. 6. Deferring the patient from immediate cystectomy does not appear to compromise survival, nor does the addition of primary systemic chemotherapy appear to significantly increase the morbidity of cystectomy or radiotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Combined Modality Therapy↗

A population-based survey of immunisation coverage in two-year-old children.

A cross-sectional, population-based, cluster-sample survey of 187 children was conducted in the Newcastle area to assess the proportion of two-year-old children who were fully immunised, to ascertain whether administration of these vaccines was age-appropriate and to look for factors predicting incomplete immunisation. Parents or guardians were interviewed at their homes and the immunisation status of the children was verified either by the parent-held record or by the immunisation-provider-held record. Levels of full immunisation were 77 per cent at the time of interview and 72 per cent at the second birthday if Haemophilus influenzae type b (Hib) vaccine was excluded. If it was included, the full immunisation level was 51 per cent. Coverage was highest for oral polio vaccine and lowest for Hib vaccine. Twenty-nine per cent of all immunisations were given early, 44 per cent were given on time and 20 per cent were given late. Doses of vaccines due at older ages were more likely to be given late or not at all. Factors predicting incomplete immunisation were: the principal caregiver being aged under 25 years, being born outside Australia, having post-secondary qualifications, being female and having more than one child in the household. Immunisation coverage levels were not high enough to protect against outbreaks of pertussis and measles and cases of Haemophilus influenzae type b. Immunisation providers should aim to increase coverage to protect the population against all vaccine preventable diseases, and aiming at high-risk groups could more effectively do this.

Adult↗

Linkage analysis of a large pedigree with hereditary sideroblastic anaemia.

A large pedigree showing a history of pyridoxine responsive X linked sideroblastic anaemia was screened with several polymorphic DNA markers from the X chromosome. Linkage analysis between each marker and disease status was performed, giving a maximum two point lod score of 3.64 at zero recombination with the microsatellite marker PGK1P1 at Xq11.2-12. Close linkage to PGK at Xq13.3, one of the candidate regions for X linked sideroblastic anaemia, was excluded. Linkage to DNA markers distal to PGK and at Xp21 was also excluded. Multipoint linkage analysis was performed with markers located between Xq11.2-21. The maximum map specific lod score obtained was 3.56 at PGK1P1 (Xq11.2-12). Linkage remained significant over the interval 20 cM proximal to PGK1P1 and 5 cM distal to PGK1P1, with definite exclusion around the PGK locus. The most likely location of the gene involved in sideroblastic anaemia in this pedigree is therefore within the pericentromeric region of the X chromosome. This region includes the erythroid 5-aminolaevulinate synthetase gene of the haem synthesis pathway, which is a candidate gene for X linked sideroblastic anaemia located at Xp11.21.

Alleles↗

Mathematical model of oxygen transport: a teaching aid for normal physiology adaptable to extracorporeal oxygenation circuits.

The ultimate aim of most intensive care therapies is to improve tissue oxygen delivery; consequently, a detailed knowledge of this area of physiology is important to a wide range of Critical Care Staff. We describe a simple mathematical model of oxygen transport that was initially written as a training aid for extracorporeal oxygenation training. The model has subsequently proved useful for explaining the determinants of oxygen transport to a broader audience. It is based on simple linear equations and is easily displayed with a standard computer spreadsheet. Apart from its teaching value, the model can also generate a graph of oxygen saturation vs. inspired oxygen fraction for different degrees of pulmonary shunt. This provides a noninvasive method for determining the magnitude of pulmonary venous admixture and may also prove to have some clinical value.

Biological Transport, Active↗

Thyroid peroxidase autoantibody fingerprints. II. A longitudinal study in postpartum thyroiditis.

It is not known whether epitopes recognized by autoantibodies in an individual remain constant or change over time, especially during perturbations of the humoral immune response. To address this question, we studied the epitopic profile ("fingerprint") of autoantibodies to thyroid peroxidase (TPO) in the sera of 19 women during the postpartum period. Fingerprints were determined in competition studies using 4 recombinant F(ab). At delivery and at 3 time intervals over the subsequent 9-12 months, the pool of F(ab) inhibited autoantibody binding to TPO by 80-100%, consistent with the definition by these F(ab) of a TPO immunodominant region (A1, A2, B1, and B2 domains). Despite a wide spectrum among individuals, the TPO epitopic fingerprints for all 19 women were relatively unchanged throughout the postpartum period. Fingerprint constancy occurred regardless of fluctuations in serum TPO autoantibody levels. When assessed numerically as a ratio of inhibition by the A domain F(ab) to inhibition by the B domain F(ab), the A/B domain ratios in individual women ranged from 0.2 (predominantly B domain) to more than 3.0 (predominantly A domain). However, for each individual woman, the A/B epitopic ratio was conserved throughout the study interval. Our TPO autoantibody epitopic fingerprint data have potential implications for understanding the humoral autoimmune response in man. First, the present study indicates a remarkable lack of spreading of B cell epitopes during a state of perturbation of the immune system over a period of 1 yr. Second, and perhaps more important, despite marked variations in TPO epitopic profiles among different individuals, their constancy over time suggests that TPO autoantibody fingerprints may be inherited.

Autoantibodies↗

Role of complement in the pathogenesis of postpartum thyroiditis: relationship between complement activation and disease presentation and progression.

The aim of this study was to assess whether the presentation and progression of autoimmune postpartum thyroiditis (PPT) was related to the degree of thyroid peroxidase autoantibody (TPO-ab)-mediated activation of the complement cascade. One hundred and forty-eight thyroid autoantibody-positive women have been followed during their postpartum year. Seventy-five women remained euthyroid during this time whilst the remaining 73 showed one or more episodes of thyroid dysfunction. Fourteen women showed hyperthyroid PPT, 23 showed a biphasic PPT and the remaining 36 showed hypothyroid PPT. Hyperthyroid PPT was always transient but 29 of the 59 women with hypothyroidism remained hypothyroid or still required thyroxine replacement therapy at the conclusion of the study. Thyroid autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), free triiodothyronine and free thyroxine by the Amerlex M methods and thyrotrophin by the Amerlite TSH (monoclonal) assay. Complement component C3b, immobilized as a result of classical complement pathway activation in the presence of TPO/TPO-ab complexes in vitro, was measured by ELISA. Bioactive TPO-ab were calculated as the product of the C3 index and TPO-ab level. Basal levels of complement C3 activation were seen in the euthyroid TPO-ab-positive women (C3 index 0.06 at delivery rising to 0.36 at 12 months postpartum; bioactive TPO-ab activity 0.4 kIU/l at delivery rising to 10.4 kIU/l at 12 months' postpartum (N = 75). These parameters were elevated progressively as the severity of the clinical syndrome increased. In 14 hyperthyroid PPT women the C3 index was 0.47 at 8 months' postpartum (bioactive TPO-ab activity = 20 kIU/I; p vs euthyroid group, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Promoting tobacco control policies in northwest Indian tribes.

A culturally sensitive consultative process to facilitate adoption by tribal councils of more effective tobacco control policies was developed and evaluated. Thirty-nine Northwest Indian tribes were randomized to early intervention or late intervention conditions. Early intervention tribes received a policy workbook and consultation by means of meetings and telephone calls. Late intervention tribes were assessed but received no assistance or encouragement regarding tobacco use policies. The stringency of the policies was assessed via telephone at baseline and after intervention. At postintervention, there were consistent, and generally statistically significant, differences in adoption of more stringent and comprehensive smoking policies for early intervention tribes compared with late intervention tribes. The intervention could be used in other Indian settings.

Cultural Characteristics↗

Package seals. Causes and avoidance of defects.

Defective heat sealing can result in leakage, packs that are difficult to open, or contamination of the contents. This article comments on materials, machinery, and maintenance to provide an understanding of the causes of sealing problems.

Consumer Behavior↗

Changes to recommended immunisation procedures.

The fifth edition of the Australian Immunisation Procedures Handbook updates what has become an important reference and practical guide to immunisation practice in Australia. A number of significant changes have been incorporated into this edition. The purpose of this paper is to alert and remind general practitioners of these changes.

Adolescent↗

[Recommendations for prevention of thromboembolism in heart valve diseases. Working Group on Valvular Heart Disease, European Society of Cardiology].

Thromboembolic events are still a major cause of morbidity and mortality in patients with native valvular heart disease and in patients with prosthetic heart valves. Although the introduction of oral anticoagulation reduced this risk, thromboembolism and anticoagulation-related hemorrhages still represent significant problems in the management of these patients. In this article the guidelines developed by the Working Group on Valvular Heart Disease of the European Society of Cardiology for the management of antithrombotic therapy in heart valve disease are thoroughly discussed. The indication for and intensity of anticoagulation in various clinical situations, the concept of risk factor-adjusted intensity of anticoagulation, and the concept of control of oral anticoagulation with the International Normalized Ratio are presented.

Administration, Oral↗

Effect of vitamin C upon gastric mucosal O6-alkyltransferase activity and on gastric vitamin C levels.

The repair enzyme O6-alkyltransferase will repair O6-methylguanine adducts in human DNA. In gastric mucosal DNA these adducts may be formed as a result of exposure to nitrosamines within the gastric lumen. The formation of these nitrosamines may be inhibited by vitamin C. We have examined the effect of oral vitamin C supplementation upon intragastric vitamin C levels and gastric mucosal O6-alkyltransferase levels in 48 patients. Intragastric vitamin C levels were significantly elevated in those patients with normal gastric mucosal histology after treatment, although a variable response in intragastric vitamin C to supplementation was seen in the presence of chronic atrophic gastritis. Gastric mucosal O6-alkyltransferase activities ranged from 100 to 950 fmol/mg protein before vitamin C administration. The range of enzyme activity was similar after the course of vitamin C (62-1137 fmol/mg) but O6-alkyltransferase activities were found to be higher in 33 of the 48 patients following treatment (P < 0.01). Once again this effect was more pronounced in patients with normal gastric mucosa than those displaying evidence of chronic atrophic gastritis. We speculate that inhibition of intragastric nitrosation by vitamin C results in decreased formation of O6-methylguanine-DNA. In consequence, less O6-alkyltransferase is consumed in repairing these adducts resulting in higher tissue levels of this enzyme.

Ascorbic Acid↗

Conducting clinical research in the new NHS: the model of cancer. United Kingdom Coordinating Committee on Cancer Research.

The United Kingdom Coordinating Committee on Cancer Research represents the major organizations funding cancer research in the United Kingdom. The deliberations of a working party convened by the committee to evaluate recently expressed concerns that the changes in the NHS threaten research, especially clinical trials to evaluate new treatments, are reported. A survey of contributors to trials coordinated by the committee showed that half are now experiencing difficulties in continuing to participate in clinical trials. The two major problems identified were lack of time and of staff, especially for NHS staff in non-teaching hospitals. Recent changes in junior doctors' hours and proposed reductions in the length of time for training will exacerbate this. It is possible to identify the direct and indirect excess costs of conducting research in the NHS, but currently the mechanism does not exist to designate funds specifically for this purpose. Consultation with the regional directors of research and development confirmed that the service increment for teaching and research is not the solution for this. Proposals are made to secure future clinical research in the NHS, including finance, indemnity, the licensing of new drugs, the greater use of nurse counsellors, and the value of cancer registries.

Clinical Trials as Topic↗

DNA damage as measured by 32P-postlabelling in normal and pre-malignant gastric mucosa.

DNA was extracted from the gastric mucosa of 69 patients and analysed for the presence of DNA adducts by 32P-postlabelling. Adduct levels found in patients with histologically normal gastric mucosa were compared with levels found in patients displaying evidence of chronic atrophic gastritis or intestinal metaplasia, both of which may be considered pre-malignant conditions. Adduct patterns were the same for all patients, but the highest adduct levels were found in the latter two groups. Mean adduct levels were also higher in patients with abnormal gastric mucosa, but there was no statistically significant difference in adduct levels between the normal and pre-malignant groups (P > 0.05, Mann-Whitney U test). Thus DNA adduct levels do not correlate with the presence of histological abnormalities in the stomach and are not useful as a marker of malignant potential.

Adult↗

Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group.

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

Aged↗

Polymorphism of SPAG-1, a candidate antigen for inclusion in a sub-unit vaccine against Theileria annulata.

SPAG-1, a Theileria annulata sporozoite surface antigen, is a vaccine candidate. Data is presented, based on the clonal segregation of SPAG-1 associated RFLPs, showing that this antigen is encoded by a single copy gene. We have cloned and sequenced a full-length genomic copy of the SPAG-1 gene and a comparison of this with a previously published SPAG-1 cDNA sequence demonstrates a high degree of polymorphism. We infer that these sequences represent two distinct allelic SPAG-1 variants. The deduced polypeptides show an overall identity of 92% with the most variable stretch (60% identity) occurring towards the middle of the molecule. The N and C termini are more conserved with identities of 92% and 97% respectively. The elastin receptor ligand, VGVAPG, present 3 times in the protein sequence derived from the cDNA is not found in that deduced from the genomic copy. Evidence for 2 further SPAG-1 alleles was obtained from PCR based sequences using macroschizont clones containing different SPAG-1 associated RFLPs. In summary we have shown the existence of at least 4 highly polymorphic SPAG-1 alleles. The implications of such polymorphism between and within distinct geographical isolates for the development of a SPAG-1 based subunit vaccine is discussed.

Alleles↗

Molecular mimicry.

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Amino Acid Sequence↗