FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.     

用于筛选天然产物中脲酶抑制剂的脲酶活性测试方法的建立

抑制幽门螺杆菌产生的脲酶具有治疗胃炎和消化性溃疡的作用。用酚红指示剂和Ｂｅｒｔｈｅｌｏｔ试剂在９６孔培养板上检测重组脲酶活性，其灵敏度指标酚红法每ｍｇ酶蛋白引起的每分钟吸光度变化。△Ａ为６．９，而Ｂｅｒｔｈｅｌｏｔ法每ｍｇ酶蛋白引起的每分钟吸光度比值变化△Ａ为３１３。结果表明用Ｂｅｒｔｈｅｌｏｔ试剂检测重组脲酶活性适宜在９６孔培养板上大规模筛选天然产物中的脲酶抑制剂。     

The use and cost of HIV service provision in England in 1996. National Prospective Monitoring System (NPMS) Steering Group and NPMS Working Party on Costs.

OBJECTIVE: The aim of the study was to measure the use and estimate the cost of HIV service provision in England. DESIGN AND SETTING: Standardised activity and case-severity data were collected prospectively in 10 English HIV clinics (5 London and 5 non-London sites) for the periods 1 January 1996 to 30 June 1996 and 1 July 1996 to 31 December 1996 and linked to unit cost data. In total, 5440 patients with HIV infection attended during the first 6 months and 5708 during the second 6 months in 1996. MAIN OUTCOME MEASURES AND RESULTS: The mean number of inpatient days per patient-year for patients with AIDS was 19.7 [95% confidence interval (CI): 13.7 to 25.7] for January to June and 20.8 (95% CI: 15.3 to 26.4) for July to December 1996. The mean number of outpatient visits for asymptomatic patients with HIV infection was 14.8 (95% CI: 11.9 to 17.6) and 13.3 (95% CI: 10.8 to 15.7) for the respective periods and 16.1 (95% CI: 13.21 to 18.97) and 15.7 (95% CI: 11.2 to 20.2), respectively, for patients with symptomatic non-AIDS (i.e. symptomatic patients with HIV infection but without AIDS-defining conditions). Substantial centre-to-centre variation was observed, suggesting that many clinics can continue the shift from an inpatient- to an outpatient-based service. Cost estimates per patient-year for HIV service provision for 1996 varied from 4695 Pounds (95% CI: 3769 Pounds to 5648 Pounds) for asymptomatic patients, to 7605 Pounds (95% CI: 6273 Pounds to 8909 Pounds) for symptomatic non-AIDS patients to 20,358 Pounds (95% CI: 17,681 Pounds to 23,206 Pounds) for patients with AIDS. CONCLUSIONS: Different combinations of antiretroviral therapy affect the cost estimates of HIV service provision differently. Anticipated reduction in inpatient-related activity through the increased use of combination antiretroviral therapy will further shift service provision from an inpatient- to outpatient-based service and reduce costs per patient-year. The extent and duration of such effects are currently unknown. The long term effects of combination treatment on the morbidity and mortality patterns of individuals infected with HIV are also currently unknown, as are their implications on the use and cost of HIV service provision. Multicentre databases like the National Prospective Monitoring System (NPMS) will provide healthcare professionals with information to improve existing services and anticipate the impact of new developments.     

Identification of non-amplifying CYP21 genes when using PCR-based diagnosis of 21-hydroxylase deficiency in congenital adrenal hyperplasia (CAH) affected pedigrees

Steroid 21-hydroxylase deficiency is among the most common inborn errors of metabolism in man. Characterization of mutations in the 21- hydroxylase gene (CYP21) has permitted genetic diagnosis, facilitated by the polymerase chain reaction (PCR). The most common mutation is conversion of an A or C at nt656 to a G in the second intron causing aberrant splicing of mRNA. Homozygosity for nt656G is associated with profoundly deficient adrenal cortisol and aldosterone synthesis, secondary hypersecretion of adrenal androgens, and a severe form of congenital adrenal hyperplasia (CAH) characterized by ambiguous genitalia and/or sodium wasting in newborns. During the course of genetic analysis of CYP21 mutations in CAH families, we and others have noticed a number of relatives genotyped as nt656G homozygotes, yet showing no clinical signs of disease. A number of lines of evidence have led us to propose that the putative asymptomatic nt656G/G individuals are incorrectly typed due to dropout of one haplotype during PCR amplification of CYP21. For prenatal diagnosis, we recommend that microsatellite typing be used as a supplement to CYP21 genotyping in order to resolve ambiguities at nt656.      

Enzyme immunoassay for Q fever: comparison with complement fixation and immunofluorescence tests and dot immunoblotting.

Enzyme-linked immunosorbent assays (ELISA) for the detection of specific immunoglobulin G (IgG) and IgM antibodies were developed by using purified Coxiella burnetii cells. Variables, including type of microtiter plate, blocking agent, incubation conditions, antigen stability, and substrate type, were examined to achieve optimal ELISA performance. The reliabilities of the assay systems were compared with those of complement fixation (CF) and enhanced immunofluorescence (EIF) tests with 600 human serum samples from defined clinical cases of Q fever, routine samples, and serum specimens from farmers. ELISA and EIF test results agreed in all cases. Dot immunoblotting was also used to test some of these sera and gave a rapid, qualitative result, which agreed with ELISA and EIF test results in all cases. No instances were found in which both ELISA and EIF test results were negative and the CF test results was positive. However approximately 5% of the sera were positive by ELISA and the EIF test while the CF test result was either negative or unreadable because of serum anticomplementary activity. We conclude that dot immunoblotting is a useful screening test, whereas ELISA and the EIF test are both rapid and sensitive tests when used for the serodiagnosis of Q fever and should be considered to be replacements for the CF test.     

Behavioural factors associated with symptom outcomes in a primary care-based depression prevention intervention trial

BACKGROUND: A randomized trial of a primary care-based intervention to prevent depression relapse resulted in improved adherence to long-term antidepressant medication and depression outcomes. We evaluated the effects of this intervention on behavioural processes and identified process predictors of improved depressive symptoms. METHOD: Patients at high risk for depression recurrence or relapse following successful acute phase treatment (N=386) were randomly assigned to receive a low intensity 12-month intervention or continued usual care. The intervention combined education about depression, shared decision-making regarding use of maintenance pharmacotherapy and cognitive-behavioural strategies to promote self-management. Baseline, 3, 6, 9 and 12-month interviews assessed patients' self-care practices, self-efficacy for managing depression and depressive symptoms. RESULTS: Intervention patients had significantly greater self-efficacy for managing depression (P<0.01) and were more likely to keep track of depressive symptoms (P<0.0001), monitor early warning signs (P<0.0001), and plan for coping with high risk situations (P<0.0001) at all time points compared to usual care control patients. Self-efficacy for managing depression (P<0.0001), keeping track of depressive symptoms (P=0.05), monitoring for early warning signs (P=0.01), engaging in pleasant activities (P<0.0001) and engaging in social activities (P<0.0001) positively predicted improvements in depression symptom scores. CONCLUSIONS: A brief intervention designed to target cognitive-behavioural factors and promote adherence to pharmacotherapy in order to prevent depression relapse was highly successful in changing several behaviours related to controlling depression. Improvements in self-efficacy and several self-management behaviours that were targets of the intervention were significantly related to improvements in depression outcome.