Prediction of human femoral bone strength using ultrasound velocity and BMD: an in vitro study.

The stiffness and strength of cancellous bone are important in the management of skeletal diseases such as osteoporosis. These properties are a function not only of bone density but also of bone architecture, some measure of which can be provided by quantitative ultrasound. The ability of quantitative ultrasound and bone mineral density (BMD) to predict stiffness and strength of human femoral heads removed from live subjects during hip replacement was assessed. Stiffness and strength were measured using a uniaxial compression test. Ultrasound velocity was measured using the pulse-submersion technique (McCue CUBAResearch) and BMD using DXA (Lunar DPX-L). Ultrasound velocity (quantitative ultrasound) and stiffness varied with the three orthogonal directions, the highest significance being between the proximo-distal (PD) and antero-posterior (AP) directions (p < 0.0001 for stiffness and p = 0.0003 for velocity). Ultrasound velocity was significantly correlated with compressive bone strength (r = 0.76, p < 0.0001) and stiffness (r = 0.79-0.83, p < 0.0001). BMD was also significantly correlated with compressive strength (r = 0.82, p < 0.0001) and stiffness (r = 0.66-0.81. p < 0.001). Using multiple regression analysis both BMD and velocity were significant predictors of strength (r = 0.88, p = 0.0004 and 0.0054 respectively) and stiffness (r = 0.92, p = 0.0001 and 0.0003 respectively). BMD and velocity were still independent significant predictors of both stiffness (r = 0.93, p < 0.0001 and 0.0001 respectively) and strength (r = 0.89, p < 0.0001 and 0.02) when they were combined as a product (BMDn*Vm). This suggests that BMD measured using DXA, if used in conjunction with ultrasound velocity, may be able to improve osteoporosis risk assessment. The information about femur anisotropy may also be important for hip prosthesis and in vivo modelling.

Unexplained hepatitis C virus antibody seroconversion in established blood donors.

BACKGROUND: Understanding of the epidemiology and natural history of hepatitis C virus (HCV) infection is incomplete without reference to the early phase of infection. The prevalence of HCV infection is well documented in numerous reports. The seroconversion pattern in previously antibody-negative blood donors provides a model for the study of the incidence and transmission of HCV infection. STUDY DESIGN AND METHODS: Records of HCV antibody tests at the West Midlands Blood Transfusion Centre were reviewed to determine the seroconversion rate in 1994 among previously anti-HCV-negative blood donors. Seroconverting donors were counseled to investigate the possible routes of infection. RESULTS: In 1994, blood donations (n = 256,935) were collected from 149,370 donors; 24 donors (0.016%; 1/6224) were positive in the screening enzyme-linked immunosorbent assay (ELISA) and the third-generation recombinant immunoblot assay (RIBA-3). Two donors previously negative for HCV antibody in ELISA were positive in both tests in 1994. Four donors positive in ELISA and indeterminate in RIBA-3 in 1993 reacted positively in both tests in 1994. One donor negative for HCV antibody on previous screening reacted positively in ELISA and was indeterminate in RIBA-3 in 1994 and has become positive in both tests in 1995. A further 43 donors negative for HCV antibody on previous screening reacted positively in ELISA and were indeterminate in RIBA-3 in 1994. CONCLUSION: Documented seroconversion can take place in the absence of exposure to recognizable risk factors for the infection. The index donation or the donation immediately preceding seroconversion may be positive for HCV RNA in the polymerase chain reaction.

Hepatitis C virus seroconversion by a third generation ELISA screening test in blood donors.

The significance of seroconversion as detected by an ELISA screening test for hepatitis C virus (HCV) antibody with a negative supplemental/confirmatory recombinant immunoblot assay (RIBA) result was investigated. Of 118,220 established West Midlands blood donors with at least one negative HCV antibody screen, 43 had seroconverted in 1994 according to the ELISA but had negative RIBA-3 results. The paired archive serum samples of the pre- and postseroconversion donations of 29 seroconverting donors were tested by nested polymerase chain reaction (PCR) for the detection of HCV RNA. All 58 samples were negative by PCR. The absence of detectable viraemia in all tested seroconverting donors suggests that HCV infection was not responsible for seroconversion by ELISA.

Management of blood donors whose donations are repeatedly falsely positive by the HIV antibody screening test.

Since 1985, over 1,800,000 donations have been screened by the West Midlands Regional Blood Transfusion Service for antibody to HIV. Twelve regular donors gave three or more donations that were alternatingly positive and negative in the screening test, but not confirmed to be HIV positive by supplementary testing. Extensive investigation of six of these donors, including the polymerase chain reaction (PCR), failed to confirm HIV infection. The donors were reassured but, nevertheless, retired to comply with the guidelines of the National Blood Transfusion Service. These findings indicate that, for UK donors, ambiguous serological findings are unlikely to reflect HIV infection. On the rare occasions where serological results are particularly ambiguous, PCR testing of donors' blood may be helpful.

Hepatitis C virus seroconversion rate in established blood donors.

The results of hepatitis C virus (HCV) antibody test of 237,813 blood donations collected from 143,815 donors by the West Midlands Blood Transfusion Centre in 1993 were analyzed retrospectively in order to determine the seroconversion rate among established previously anti-HCV negative donors. Three hundred sixteen (0.22%; 1 in 455) donors were positive by the enzyme linked immunosorbent assay (ELISA) screening test and 34 (0.024%; 1 in 4,230) donors were positive by ELISA and the Recombinant Immuno Blot Assay (RIBA). Three donors previously negative for HCV antibody reacted positively by both tests. The annual seroconversion rate was calculated as one in 35,937 donors. This figure argues against limitation of HCV antibody screening to new blood donors. A further 45 donors negative on previous screening reacted positively by ELISA and were indeterminate by RIBA. Unexpectedly, lapsed blood donors first tested for HCV antibody in 1993 had high positive reaction rates by ELISA and RIBA, which was significantly (P < 0.001) higher than those of new donors. RIBA-positive reaction rate among ELISA-positive donors was significantly higher amongst males than females (P < 0.001).

The sustained impact of a group and screen and maximum surgical blood ordering schedule policy on the transfusion practice in gynaecology and obstetrics.

A retrospective study was carried out to examine the durability of the impact of Group and Screen (GS) and Maximum Surgical Blood Ordering Schedule (MSBOS) policy on transfusion practices. The study involved the Gynaecology and Obstetrics wards of the three Aberdeen teaching hospitals, all of which are supplied with blood and services by the transfusion laboratory of Aberdeen and North East of Scotland Blood Transfusion Service. The transfusion laboratory and hospital records were examined and analysed for all transfusion events in Gynaecology and Obstetrics during the three periods of 6 months immediately before, immediately after and 2 1/2-3 years following the introduction of a GS and MSBOS policy in November 1986. The number of units of blood crossmatched and units transfused decreased consistently and progressively to half the pre-GS and MSBOS level in both Gynaecology wards and Obstetrics wards during the study periods. This reduction was not associated with a decrease in the clinical workload. However, the crossmatched/transfused ratio (CTR) showed an immediate but transient improvement (3.6 to 2.2 to 3.4) and only partial and delayed improvement (10.1 to 9.6 to 7.7) with regard to blood use in the Gynaecology wards and the Obstetrics wards (respectively) during the three periods of 6 months indicated above. We conclude that the introduction of a GS and MSBOS policy can have a significant and sustained impact in reducing unnecessary blood ordering. The CTR may not be as sensitive an indicator of the effect of the introduction of GS and MSBOS as the total blood usage and a more detailed examination of blood use is necessary to assess performance and long-term impact.

Hepatitis C virus infection in the asymptomatic British blood donor.

Blood donor screening for hepatitis C virus (HCV) antibodies is now routine. Most blood transfusion services recommend that seropositive donors are referred for further investigation. Southern European studies suggest that many asymptomatic seropositive donors have clinically significant liver disease. Seropositive donors in areas of high prevalence may not, however, be representative of British donors. We have prospectively examined the prevalence and severity of HCV infection in a British volunteer blood donor population. During a 14 month period, only 0.35% (999/287,332) of all donors in the West Midlands were anti-HCV (screening assay) positive. Only 5% (52/999) of these were confirmed true seropositive. Nearly 80% (41/52) of seropositive donors were referred to the Queen Elizabeth Hospital Liver Unit for further investigation. Most underwent complete investigation, including liver biopsy. Forty of forty-one donors had biochemical, histological, or virological evidence of persistent viral infection. Histological changes were generally mild and none was cirrhotic. Covertly infected patients had less severe disease than those with an overt risk factor for HCV exposure. In the British Midlands, the prevalence of blood donor seropositivity is low. In contrast with seropositive Southern European donors, the British donor is more likely to belong to an at-risk group for parenteral exposure and is less likely to have severe histological changes. This study highlights the importance of developing locally relevant guidelines for the counselling and investigation of anti-HCV-positive blood donors.

Blood exchanged in ritual ceremonies as a possible route for infection with hepatitis C virus.

Of 52 blood donors (25 men and 27 women) counselled because their donation tested positive for hepatitis C virus antibody, seven (13.5%) gave a history of practising the ritual of blood exchange in their childhood or early adult life. This practice can cause transmission of blood borne infections or alloimmunisation, or both.

Longitudinal study of circulating gastric antibodies in pernicious anaemia.

Temporal changes in gastric antibody response were investigated in 113 (51 men, 62 women) patients with confirmed pernicious anaemia. Their ages ranged from 31-92 years (mean (SD 13.2) 66). At diagnosis, parietal cell antibody and intrinsic factor antibody were detected in 90.9% and 39.1% of all patients, respectively. When the tests were repeated after a mean follow up of 70 months (range 14-137), parietal cell antibody and intrinsic factor antibody were positive in 82.8% and 58.7%, respectively. There was a definite but not significant trend for the organ specific parietal cell antibody to disappear; intrinsic factor antibody became more positive. These results may indicate that with progressive parietal cell destruction, the antigen is no longer available to sustain an immunological response. On the other hand, this hypothesis does not explain the increased prevalence of intrinsic factor antibody which is also a product of parietal cells.

A survey and critical evaluation of a dual isotope (Dicopac) vitamin B12 absorption test.

The results of all dual isotope tests (2142) carried out on 1989 patients, 807 males (40.6%) and 1182 females (59.4%), during a 10 year period (1976-1985 inclusive) in the Grampian Health Board Area (population 497,272) have been reviewed. Patient age ranged from 5-95 years with 45.5% over 60 years. The referring specialties were Gastroenterology (47.6%), Haematology (11.3%), Paediatrics (2.1%) and all others (39.0%). According to the manufacturer's recommended criteria, results were classified as normal in 1054 (49.2%), abnormal in 659 (30.8%), equivocal in 337 (15.7%) and unsatisfactory in 92 (4.3%) tests. Vitamin B12 malabsorption of ileal type was indicated in 544 tests (25.4%) and of gastric type in 115 (5.4%). Of the latter, 76 were related to pernicious anaemia, 10 to previous gastric surgery and 2 to gastric carcinoma. Of the 337 patients with equivocal results, 138 patients were reviewed and 115 (83.3%) found to have a documented cause for gastric malabsorption (96 pernicious anaemia and 19 previous gastric surgery). In 172 patients with proven pernicious anaemia the manufacturer's recommended criteria for gastric malabsorption were completely satisfied in only 76 (44.3%) but 167 (96.5%) had an excretion ratio greater than or equal to 1.3 and 127 (73.8%) a ratio greater than or equal to 1.7. Unsatisfactory tests were mainly due to incomplete urine collection (91.3%) or contamination with another isotope (5.4%).

Iron deficiency in pernicious anaemia: a neglected diagnosis.

In 114 patients (52 males and 62 females) with long-standing pernicious anaemia, hypoferritinaemia was found in 27 (23.7%) and hypochromic microcytic anaemia in 19 (16.6%). Our findings indicate that iron deficiency is a common yet neglected complication of long-standing pernicious anaemia and warrants greater diagnostic and therapeutic attention.

A proposed mechanism of action for ALG and ATG in severe acquired aplastic anaemia.

In this study we have shown that various batches of anti-lymphocyte globulin (ALG), anti-thymocyte globulin (ATG) and human intravenous immunoglobulin (IV Ig) all contain antibodies with the capacity to block lymphocyte receptors for the Fc region of IgG, i.e., Fc gamma receptors. These antibodies may exert an effect on Fc gamma receptor bearing suppressor T cell function in vivo. Since T cells have been implicated in the pathogenesis of acquired severe aplastic anaemia, it is conceivable that administration of Fc gamma receptor blocking antibodies in the form of ALG, ATG or IV Ig preparations may be important in the treatment of the disease. The level of Fc gamma receptor blocking produced by these IgG preparations was however found to vary from batch to batch and one lymphocyte donor to another. In vivo Fc gamma receptor modulation will therefore only occur when the "correct" batch of IgG is used, thus affording a possible explanation for the variable clinical response of patients to this type of therapy.

In vivo and in vitro blocking of human lymphocyte Fc gamma-receptors by intravenous gammaglobulin.

Lymphocyte subpopulations were measured in patients with idiopathic thrombocytopenic purpura before and immediately after high dose intravenous gammaglobulin (IV-IgG) therapy. A significant relative and absolute reduction in the Fc gamma-receptor bearing lymphocyte subpopulation was observed in 5 out of 7 patients tested. In vivo modulation of lymphocyte Fc gamma-receptors therefore probably occurs: an effect which may be attributable to the Fc gamma R-blocking anti-lymphocytic antibodies found in IV-IgG preparations. In vitro studies showed that IV-IgG preparations also contain antibodies with the capacity to block Fc gamma-receptors on human monocytes and polymorphs and that these antibodies can inhibit the T cell response to phytohaemagglutinin. These anti-lymphocyte antibodies may be important in the mode of action of high dose IV-IgG therapy.