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Biomedical subjects

R Herd

Publications and source records attributed to R Herd.

At least 19 recordsLinked to original sources

Insulin-like growth factor-I and bone mineral density.

To assess the relationship between insulin-like growth factor-I (IGF-I) and bone mineral density (BMD) 201 healthy postmenopausal women (age 41-68 years) within 10 years of menopause were studied. In all subjects, BMD at the lumbar spine and left hip were measured using dual-energy X-ray absorptiometry and blood samples were obtained. In all subjects, serum IGF-I and parathyroid hormone (PTH) were measured. In a subgroup of these subjects serum concentrations of IGF-binding protein-3 (IGFBP-3), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), tartrate-resistant acid phosphatase (TRAP), and carboxyterminal propeptide of type I procollagen (PICP) were also measured. Serum IGF-I correlated significantly with age (r = -0.159, p = 0.0241), serum OC (r = 0.226, p = 0.0131), BALP (r = 0.259, p < 0.0001), and TRAP (r = 0.261, p < 0.0015), but not with PICP, PTH, or BMD at any site. Although there was a strong correlation between IGF-I and IGFBP-3 (r = 0.559, p < 0.0001), there was no correlation between IGFBP-3 and any of the markers of bone turnover (OC, BALP, TRAP, or PICP) nor with PTH or BMD at any site. We conclude that IGF-I and markers of bone turnover are related, but there is no relationship between IGF-I and BMD.

Absorptiometry, Photon

Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I alpha 1 gene.

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and increased fracture risk. Current evidence suggests that the inheritance of bone mass is under polygenic control but the genes responsible are poorly defined. Type I collagen is the major protein of bone encoded by the COLIA1 and COLIA2 genes. While these are strong candidates for the genetic regulation of bone mass, no abnormality of either gene has so far been defined in osteoporosis. In this study, we describe a novel G-->T polymorphism in a regulatory region of COLIA1 at a recognition site for the transcription factor Sp1(7) that is significantly related to bone mass and osteoporotic fracture. G/T heterozygotes at the polymorphic Sp1 site (Ss) had significantly lower bone mineral density (BMD) than G/G homozygotes (SS) in two populations of British women and BMD was lower still in T/T homozygotes (ss). The unfavourable Ss and ss genotypes were over-represented in patients with severe osteoporosis and vertebral fractures (54%), as compared with controls (27%), equivalent to a relative risk of 2.97 (95% confidence interval 1.63-9.56) for vertebral fracture in individuals who carry the 's' allele. While the mechanisms that underlie this association remain to be defined, the COLIA1 Sp1 polymorphism appears to be an important marker for low bone mass and vertebral fracture, raising the possibility that genotyping at this site may be of value in identifying women who are at risk of osteoporosis.

Binding Sites

Distribution of bone mineral density in the lumbar spine in health and osteoporosis.

The significance of variability in bone mineral density (BMD) between lumbar vertebrae L1 to L4 in the same individual was investigated by dual-energy X-ray absorptiometry in 1000 normal women aged 40-60 years (average 52 years) and 145 women aged 45-80 years (average 65 years) with vertebral osteoporosis. The mean BMD increased from L1 to L4 in normal women from 0.841 g/cm2 to 1.017 g/cm2, and in osteoporotics from 0.562 g/cm2 to 0.709 g/cm2. Z scores for osteoporotic women (Z = osteoporotic BMD - age-normal BMD/normal SD) were significantly lower for individual vertebrae compared with L1-4 and at L4 compared with L1, L2 and L3 (p < 0.001). The mean difference between Z scores for the highest and lowest vertebrae in an individual was 0.70 for normals (SD = 0.40) and 0.64 for osteoporotics (SD = 0.36). The mean Z score difference between the L1-4 Z score and the lowest individual vertebral Z score was 0.36 for normals (SD = 0.23) and 0.06 for osteoporotics (SD = 0.31). However, receiver operating analysis (ROC) curves showed that the lowest Z score for any individual vertebra did not provide improved discrimination between normals and osteoporotics when compared with the L1-4 Z score. The area under the ROC curve for L1-4 was significantly greater than for individual vertebrae (p < 0.05) and that for L4 was significantly smaller than for L1, L2 or L3 (p < 0.001). In conclusion, L1-4 BMD gives greater diagnostic sensitivity for osteoporosis than individual vertebrae, and L1, L2 and L3 are better than L4.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Post-menopausal vertebral osteoporosis: can dual energy X-ray absorptiometry forearm bone density substitute for axial measurements?

This study compared measurements of BMD using dual energy X-ray absorptiometry (DXA) at three sites in the nondominant forearm (ultradistal, distal one-third and a mid-region between these two), the lumbar spine (L1-L4) and the proximal femur (femoral neck, trochanter and Ward's triangle) for the evaluation of vertebral osteoporosis. Studies were performed on 100 normal women aged 29-69 yr (average 52 yr) and 63 osteoporotic women age 48-75 yr (average 66 yr) using the Hologic QDR-1000. Precision values of < 1% were obtained in both normal and osteoporotic women at both forearm and axial sites. Z-scores for the osteoporotics [Z = (mean BMD normal--mean abnormal)/S.D.] were--2.02 lumbar spine, -1.96 femoral neck, -1.79 ultradistal forearm, -1.73 mid region and -1.66 distal one-third forearm. Receiver operating characteristic curves showed that the lumbar spine and femoral neck equally discriminated between normals and osteoporotics with a 95% area under each curve, significantly greater values than those for the forearm which were 87% ultradistal, 89% mid forearm and 86% distal one-third forearm. Fracture thresholds, defined as the 90th centile of BMD for osteoporotic patients, were 1 S.D. below the normal mean for lumbar spine and femoral neck but equal to the mean for ultradistal, 0.6 S.D. below mean for mid region and 0.3 S.D. below mean for distal one-third region. We conclude that for the discrimination of normals and osteoporotic women the three forearm sites are comparable. However, both lumbar spine and proximal femur BMD are superior to all forearm sites.

Absorptiometry, Photon

Spine and femur BMD by DXA in patients with varying severity spinal osteoporosis.

Bone mineral density (BMD) at the lumbar spine, femoral neck, trochanteric region, and Ward's triangle was measured using dual-energy X-ray absorptiometry (DXA) in 118 women with osteoporotic vertebral collapse (average age 65 years), divided into four groups according to numbers and SD of vertebral deformation below norms: group 1: -3SD deformations only; group 2: one -4SD deformation; group 3: two-four -4SD deformations; and group 4: 5 or more -4SD deformations. There were no significant differences between the groups. Results were compared with those from 80 premenopausal (average age 32 years, range 20-40 years) and 109 postmenopausal normal women (average age 64, range 60-70 years). Mean BMD in osteoporotic group 1 was lower than premenopausal normal women by 32% at the lumbar spine, 31% femoral neck, 30% trochanteric region, and 44% at Ward's triangle, and postmenopausal controls by 17% lumbar spine, 16% femoral neck, 17% trochanter, and 14% Ward's triangle. There was a clear trend to reduction in mean BMD between osteoporotic groups 1 and 4 at all four measured sites with significant differences at the spine of 0.102 g/cm2 (P < 0.01) and Ward's triangle 0.059 g/cm2 (P < 0.01). When compared with premenopausal controls, there was a reduction in mean BMD between osteoporotic groups 1 and 4 of 10% at the lumbar spine, 7% femoral neck, 8% trochanteric region, and 13% Ward's triangle. Receiver operating characteristic analysis showed no significant differences in diagnostic sensitivities among the four measured sites for vertebral fractures. We conclude from this cross-sectional data that the majority of bone loss in spinal osteoporosis occurs before the onset of fractures.

Absorptiometry, Photon

Research recommendations.

Delegates met on the final morning to identify areas where information is lacking and to highlight priority areas for future research. Five principal topics were discussed: veterinary usage, methodology, invertebrate populations, agricultural impact and integrated pest management.

Animals

A study of respiratory infections in a healthy adult population during the 1987 Australian winter.

During the 1987 Australian winter, respiratory illness patterns were studied in a population of 454 healthy adults, aged 18-59, over a period of 45 days. These patterns were matched with data obtained from laboratory diagnoses for respiratory viruses, Mycoplasma pneumoniae and bacteria. Influenza B/1/86 was by far the most prevalent pathogen but other viruses including influenza A, paramyxoviruses, respiratory syncytial virus and coronavirus OC-43 were also present, either alone or in combination during the sampling period. Overall, 92 males and 101 females experienced one episode, 12 males and 22 females experienced two episodes and four females experienced three episodes. However, there were only 52 instances of viral or M. pneumoniae infections, of which 37 had a defined aetiology, while the remainder were clinically silent. No bacterial pathogens could be detected from throat swabs taken from 15 of 37 volunteers in whom a viral infection was detected, or from 43 of 70 volunteers who did not experience such infections. The study indicates that major deficiencies in our understanding of the aetiology of respiratory viral illness are probably due to methodological problems in obtaining laboratory diagnoses for many respiratory viruses, and that great difficulties exist in establishing an aetiology for respiratory infections based upon clinical symptoms alone.

Adolescent

Laboratory diagnosis of Mycoplasma pneumoniae infection. 4. Antigen capture and PCR-gene amplification for detection of the Mycoplasma: problems of clinical correlation.

Direct detection assays for Mycoplasma pneumoniae were established by PCR amplification of short sequences within the foot protein/adhesin (P1) gene and the 16S ribosomal RNA gene. Specificity and sensitivity was excellent, no hybridization was observed with M. genitalium and other human Mycoplasma species. In nose and throat washings from subjects with respiratory infection a pattern of high counts (c.f.u./ml) of M. pneumoniae (deduced from the amount of amplified PCR product), and a positive antigen capture assay, was found in 83% of subjects with serological evidence of current infection with M. pneumoniae. A small proportion of subjects with serological patterns suggesting infection in the more distant past had positive PCR assays. This was considered to represent either persistence of the organism from a previous infection or perhaps transient carriage during a reinfection, without substantial change in antibody response. PCR-based assay of M. pneumoniae offers a powerful, rapid, and sensitive substitute for culture of the mycoplasma. Antigen capture, while less sensitive than PCR, offers the advantage that it is more often positive with samples from current infection and requires less stringent laboratory organization to contain false positive results. We conclude however that the laboratory diagnosis of a chosen clinical episode should not rest on the PCR or Ag-EIA assays alone, but must also include antibody assays to confirm whether infection is current or represents persistence from past exposure.

Antigens, Bacterial

The natural history of dilated cardiomyopathy--a community study.

The incidence, clinical features and natural history of dilated cardiomyopathy within a clearly defined population of Scotland was studied retrospectively. From 1982 to 1986, 57 cases were recorded in a population of 145,00, representing an annual incidence of 7.9 per 100,000 per year. This incidence rate is higher than that reported from other centres, and the overall survival rates were poorer.

Aged

Improved colorimetric assay for detecting influenza B virus neutralizing antibody responses to vaccination and infection.

An automated neutralization test for influenza B virus is described in which antibody titers are determined according to the release of neutral red from infected or uninfected cells of the Madin-Darby canine kidney line. Endpoints are determined in a standard enzyme-linked immunosorbent assay reader. The test requires no expensive immunologic reagents and was used to evaluate responses to both vaccination and natural infection against influenza B virus. Overall responses to vaccination were comparable with those obtained by hemagglutination inhibition, using Tween-ether-split influenza B/Ann Arbor/1/86 virus as the antigen (the HI-TE test). The sensitivities of neutralization responses compared with those obtained by the HI-TE test for two vaccines were 88 and 89%; the specificities were lower at 61 and 60%, respectively. Responses to vaccination, measured by hemagglutination inhibition, were significantly higher with split virus compared with whole virus. However, seroconversion by both the HI-TE and neutralization tests was observed in 5 of 10 individuals from whom virus was detected by either culture of nasal or throat washings or the presence of antigen from immunofluorescence in cells from nasal washings.

Animals

A study of intranasally administered interferon A (rIFN-alpha 2A) for the seasonal prophylaxis of natural viral infections of the upper respiratory tract in healthy volunteers.

The efficacy of interferon A (rIFN-alpha 2A), an Escherichia coli-derived interferon, in the prophylaxis of acute upper respiratory tract infection, was evaluated in a community-based double-blind placebo-controlled study in the Australian winter of 1985. The trial population of 412 healthy volunteers (190 males and 222 females, aged 18-65 years) self-administered 1.5, 3.0 and 6.0 megaunits (MU) of interferon A per day or a placebo, intranasally for 28 days. The period of study coincided with an outbreak of H3N2 influenza A (detected in 35 of the 107 acute specimens) as well as substantial numbers of respiratory syncytial virus and adenovirus infections. Rhinoviruses were isolated from only three specimens. In many cases, subjects had laboratory and clinical evidence of having had more than one respiratory tract infection during the period of the study. Viruses were detected in 54 or 107 acute specimens (49%). No statistically significant differences were noted between the various treatment groups in the incidence of laboratory-proven viral infection (virus isolation and/or antibody response). Analysis of reported symptoms indicated that blood-tinged mucus and nasal stuffiness occurred more frequently with higher doses of interferon. There appeared to be no clinical benefit from the use of interferon A in the amelioration of symptoms.

Administration, Intranasal

The clinical features of diabetes with coexisting autoimmune thyroid disease.

A study was made of the clinical features of diabetics with coexisting Graves' disease (n = 117) or primary hypothyroidism (n = 98). Those with Graves' disease developed thyroid dysfunction and diabetes at an earlier age than patients with primary hypothyroidism. There was, however, no difference between the two groups in respect of sex ratio nor proportion of subjects requiring insulin treatment. In contrast to the general diabetic population, 87% of diabetics with thyroid disease were female, 56% required insulin treatment and of patients requiring insulin from diagnosis, the median age at diagnosis of diabetes was 36 years. A strong correlation was observed between age at diagnosis of diabetes and that of hyperthyroidism (r = 0.71, p less than 0.001) or hypothyroidism (r = 0.65, p less than 0.001). With increasing age at diagnosis of diabetes the interval between diagnosis of diabetes and thyroid disease diminished. The mean +/- SEM interval between diagnosis of diabetes and that of thyroid dysfunction was longer in hypothyroid (6.7 +/- 1.2 years) than in hyperthyroid diabetics (-2.4 +/- 1.2 years). Neither insulin-dependent nor non-insulin dependent diabetics with associated thyroid disease exhibited a significant seasonal variation in diagnosis or symptomatic onset of diabetes. It is conceivable that where diabetes accompanies autoimmune thyroid disease in the same patient, both conditions may share a common and coincident pathogenesis which is unrelated to acute environmental influences.

Adolescent

Serum alpha 2-macroglobulin levels in diabetes.

Serum alpha 2-macroglobulin levels have been determined in diabetic patients by quantitative radial immunodiffusion and compared with those observed in age- and sex-matched controls. In addition, the results in diabetics have been analysed with respect to such variables as the age and sex of the patient, the duration of disease, treatment, control, and the occurrence of retinopathy or nephropathy. The alpha 2-macroglobulin levels in diabetic patients were found to be significantly higher than in age- and sex-matched controls, thus confirming previous observations. However, these differences were most apparent in the more extreme age groups. Multiple regression analysis also revealed that the only variables contributing significantly to the regression apart from age and sex were control and retinopathy.

Adolescent