Laboratory screening method for selection of healthy volunteers

The aim of laboratory screening in Phase I is to exclude subjects with subclinical illness, who might be at increased risk in the study, and who might also adversely influence interpretation of the results. A new method for laboratory screening, based on Bayesian probability theory, is proposed, which consists of: 1. Drawing up a list of diseases to be excluded. 2. Defining for each disease, the maximum acceptable risk that an included subject could be affected by it. 3. Identifying one test for each disease. 4. Using a contingency table to calculate the specificity of the test and integrating the estimated prevalence of the disease from epidemiological data. 5. Applying the percentage obtained by the calculation of specificity to the previously determined distribution of values in the volunteer population to identify the threshold value for inclusion. Use of this deductive method in screening volunteers for Phase I trials affords increased security of selection, while reducing the number of non-pertinent exclusions because of laboratory findings.     

The callous elbow and aging of the upper arm

The author describes his surgical approach to the problems of the aging upper arm and elbow region. Surgery at an appropriate age can prevent the progressive wrinkling of the elbow which is further aggravated by aging of the upper arm. The author's operation is aimed at correcting both portions of the arm anatomy at the same time.     

日本血吸虫尾蚴至童虫期超微结构变化与生理适应的关系

本文应用透射电镜观察比较日本血吸虫尾蚴和皮肤型童虫的体壁、腺体和消化道的超微结构。结果表明,从尾蚴至皮肤型童虫转变过程,其体壁和钻腺的超微结构发生明显改变,但头腺及消化道则未见明显变化。这些变化与其相应的微环境密切相关。     

Immunohistochemistry of glial reaction after injury in the rat: Double stainings and markers of cell proliferation

The astrocytic reaction in the rat after brain injury has been studied immunohistochemically for intermediate filaments (GFAP and vimentin), also with double staining procedures, and for markers of proliferation (BrdU and PCNA). GFAP-positive reactive astrocytes appeared around the lesion, where they were vimentin-positive and at a distance. BrdU and PCNA showed a high labelling index around the wound at day 2 and scattered positive nuclei were also found at a distance in the ipsilateral side. BrdU-positive astrocytes represented a minor fraction of GFAP- and vimentin-positive astrocytes. The expression of vimentin persisted at least 15 days after the lesion. Our results could suggest that distant reactive astrocytes originate through hypertrophy while those close to lesion arise by hyperplasia from mature or immature glial cells. The hypothesis is formulated that cells of the periventricular matrix contribute to the post-traumatic proliferative activity.     

Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Flow cytometry analysis of platelet antibodies

We have devised assays to detect both circulating alloantibodies to platelets (indirect assay) and platelet-association IgG and IgM (direct assay) using a flow cytometric technique. A variety of patients with immune thrombocytopenia were studied. Employment of a confocal lens in the flow cytometer increased the discrimination power of the instrument. Patients with autoimmune thrombocytopenia (idiopathic thrombocytic purpura [ITP], systemic lupus erythematosus (SLE), lymphoma, leukemia, and drug-induced thrombocytopenia showed a significant increase in platelet-associated antibody. Circulating antibodies to platelets (alloantibodies) were demonstrated in cases of platelet refractoriness and neonatal isoimmune purpura. Day-today precision of the assays ranged from 3% to 6% (coefficient of variation). No interference was shown in the presence of hemoglobin (5 g/L), triglycerides (10 g/L), or polyclonal and monoclonal immunoglobulinemia (50 g/L: IgG, IgA, IgM). The sensitivity of the direct assay was 500 attograms of IgG or IgM platelet.     

Carbon dioxide recruitment threshold as a predictor of successful weaning in chronic obstructive pulmonary disease patients: A pilot study

Abstract Several methods have been used to predict successful weaning and extubation among chronic obstructive pulmonary disease (COPD) patients. The objective of this study is to determine whether carbon dioxide recruitment threshold (PCO₂RT) can be used as adjunct to conventional weaning parameters to predict early weaning and successful extubation. Twelve COPD patients who were ready to be extubated based on conventional weaning parameters were divided into group A ( n = 7) and group B ( n = 5). Group A were those patients with better weaning parameters and hence a higher probability of successful extubation as compared to group B. Carbon dioxide apnoeic threshold (PCO₂AT) was obtained by hyperventilating the patient using an increment of two breaths per min until apnoea occurs. At this point, the PCO₂AT or the PaCO₂ during said apnoeic period was recorded. A dead space of 150 cc is then added to the circuit until the patient starts to breathe as evidenced by the sensitivity trigger indicator. The PCO₂ obtained at this period is termed PCO₂RT. After weaning for 30 min on a T-tube, another arterial blood gas is determined and this is called the PCO₂SB or the CO₂ level after 30 min on spontaneous breathing. If the PCO₂SB-PCO₂RT difference is high with a sensitivity of 85.71% and specificity of 100% vs sensitivity of 57.14% and specificity of 60% using the conventional weaning parameters. Thus an increase in PCO₂SB at 30 min T-tube is indicative of impending respiratory pump failure and that other causes of failure to wean must be investigated.     

Local health services: some lessons from their evolution in Bolivia

Summary For a decade, numerous projects in Bolivia have tried to put in practice the concept of local health systems. But, so far, no significant changes have been made and local health services still are the 'poor relation' of the system. The main components of the project—expansion of health facilities, training of health personnel and institutional decentralization—were not designed to respond to the complexity of the problems encountered. Decentralization was implemented at the level of health districts but not accompanied by redefinition of functions at the central level, and challenged by civil servants' attempts to save their jobs. While training activities did introduce new methods and subjects, they were too often reduced to short workshops or seminars. Health facilities were built without regard for their significance beyond health care. A strategic approach is needed to adapt the planning process to the degree of liberty allowed by society.     

An analysis of the deep social structure preventing the development of a national policy for children and families in the United States

The United States is one of the few economically developed nations without a national policy supporting children and their families. This paper suggests that the United States has a unique national ideology, based on the “Calvinistic Ethic,” which results in opposition to not only social programs for children and families, but to all government supported welfare programs. Such an ethic is not found in European countries. Finally, since the United States does not have a national family policy, millions of children and their families go without health care, lack social services, and suffer from inadequate economic supports.