Summary of a Food and Drug Administration workshop on nucleic acid testing to screen donations of blood and plasma for the hepatitis C virus.
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Biomedical subjects
Publications and source records attributed to M Y Yu.
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According to large-scale studies, oral contraceptive users become pregnant at rates that exceed ideal use failure rates. It is thought that a major cause is missed pills, but current research on consistent contraceptive pill taking is characterized by inadequate measures and a failure to investigate women's thinking about their own patterns of use. The purpose of this study was to gain some understanding about women's interpretations of consistency in their own pill taking through combining qualitative with quantitative data. The study was conducted in China, where contraception is free and widely available. Five urban and five rural oral contraceptive users were followed for up to three pill-taking cycles during 1996 for a total of 759 person-days. Consistency of pill taking was measured with electronic data obtained from a new blister package made by Anderson Clinical Technologies (Elmhurst, IL). Data from these devices were reviewed and interpreted by the study participants during in-depth private interviews. The users' reasons for missing pills included disruptions in their daily routines, their husband's absence, spotting, and trouble implementing the family planning program's instructions to take one pill per day for 22 days and start the next cycle on the fifth day of menses. One user gave these reasons for two cycles but denied missing numerous pills in her third cycle. Data from a series of four questionnaires showed that most demographic, psychosocial, and service system characteristics were not related to missed pills. However, results suggested that the daily routines of rural living may make consistent use more likely and that instructions for taking the pill may be associated with prolonged pill-free intervals and skipping pills during episodes of spotting. Three of the 10 women were at increased risk of pregnancy during the study period because of their pill-taking pattern. We concluded that the combination of qualitative with quantitative data enhances understanding of contraceptive use. Women themselves offer plausible reasons for their use behaviors. Listening to women could be useful in improving programs.
The modulational interaction of finite-amplitude high-frequency electrostatic waves propagating at an arbitrary angle to an external magnetic field with slow plasma motion is considered. A set of nonlinear evolution equations describing the interaction is obtained. New types of solitary waves propagating at near sonic speeds are found.
A self-consistent theory of ion-acoustic waves in dusty gas discharge plasmas is presented. The plasma is contaminated by fine dust particles with variable charge. The stationary state of the plasma and the dispersion and damping characteristics of the waves are investigated accounting for ionization, recombination, dust charge relaxation, and dissipation due to electron and ion elastic collisions with neutrals and dusts, as well as charging collisions with the dusts.
OBJECTIVE: This study compared laparoscopic sonography with surgical pathology in the evaluation of pelvic lymph nodes in women with cervical cancer. SUBJECTS AND METHODS: Intraoperative laparoscopic sonography of pelvic lymph nodes was performed in 31 women with biopsy-proven cervical cancer. A lymph node that was rounded (longitudinal-transverse axis ratio of <2) or showed absence of central hilum was defined as positive for metastasis. For comparison, lymph nodes from each hemipelvis were grouped anatomically into paraaortic, common, internal, and external iliac chains during evaluation on laparoscopic sonography and on surgical pathologic examination. RESULTS: Pelvic dissection in 31 women yielded 630 lymph nodes. There were 54 metastatic nodes in 12 women. Laparoscopic sonography revealed 32 (59%) of all pathologically metastatic lymph nodes. Sensitivity on laparoscopic sonography when comparing groups by hemipelves was 93.3% and by anatomic lymph node chains was 76.2%. Metastatic nodes were most commonly located in the common iliac region and were characteristically rounded, hypoechoic, showed absence of central hilum, and occasionally showed central necrosis. Nine (28%) of 32 metastatic lymph nodes revealed by laparoscopic sonography measured 1 cm or less. Six benign nodes in four patients were also visualized with laparoscopic sonography. CONCLUSION: Laparoscopic sonography achieved a sensitivity exceeding 90% in the detection of metastatic lymph nodes in the hemipelves of women with cervical cancer. Laparoscopic sonography is a feasible and promising technique for the evaluation of pelvic lymph nodes in women with cervical cancer and merits further evaluation.
Hepatocellular carcinoma (HCC) presenting as obstructive jaundice due to intrabile duct tumor growth is being reported with increasing frequency. We describe our clinical experiences and evaluate the results of different operative procedures for this disease. A retrospective study was undertaken to review 18 patients with obstructive jaundice by tumor emboli from HCC during a 15-year period of time. We reviewed clinical features, types of operative procedures, operative findings, and survival in the patients. All patients on initial examination had recurrent episodic jaundice or cholangitis. Types of surgical procedures were choledochotomy with T-tube drainage alone in nine patients, choledochotomy with T-tube drainage followed by hepatectomy in six, and T-tube drainage followed by transcatheter hepatic arterial chemoembolization in the remaining three patients. Liver cirrhosis was the associated disease in 15 (83.3%). There were three postoperative deaths (16.7%). The mean survival time for nine patients with external drainage alone was 4.5 months. For the three patients with T-tube drainage and transcatheter hepatic arterial chemoembolization, mean survival time was 11 months. Six patients who had undergone hepatectomy had a better postoperative survival time, with 1 surviving for more than 3 years and another alive for 70 months, without evidence of recurrence at the moment. Jaundice is not necessarily a harbinger of advanced disease and a contraindication for surgery. Managed properly, these patients will have satisfactory palliation and occasional cure.
OBJECTIVES: The objectives of this study were to evaluate the use of laparoscopic ultrasonography (USG) in combination with laparoscopic pelvic lymphadenectomy in the management of patients with cervical carcinoma. METHODS: A technique for detecting pelvic and para-aortic lymph node metastases through laparoscopic USG was developed. Laparoscopic USG was done prior to pelvic lymphadenectomy performed either laparoscopically or by laparotomy. Laparoscopic USG findings were compared with pathologic findings. RESULTS: The sensitivity and specificity of laparoscopic USG in detecting pelvic lymph node metastases were 91 and 100%, respectively. Metastatic pelvic lymph nodes could be completely removed through laparoscopes in 7 of 11 patients, with no complications. CONCLUSION: Laparoscopic USG is highly sensitive in detecting metastatic pelvic lymph nodes. Detection and removal of metastatic pelvic lymph nodes laparoscopically allow quick recovery from the operation and early commencement of radiotherapy.
BACKGROUND & AIMS: Plasmid DNA-based immunization has been shown to be an effective means of vaccination in animal models. In this study, the immune responses to various hepatitis C virus structural protein antigens were evaluated using this technique. METHODS: Six recombinant plasmids were constructed. These include, individually, the coding regions for the core protein (pC); E1 (pE1) and E2 (pE2); as well as core, E1, and E2 together (pCE1E2); E1 and E2 together (pE1E2); and finally an E2 construct from which the N-terminal hypervariable region had been deleted (pE2 deltaHVR). These plasmids were transfected into mammalian cells to test their protein expression and were injected into the quadriceps muscles of BALB/c mice to measure specific antibodies and cytotoxic T-lymphocyte responses. RESULTS: All the recombinant plasmids were shown to express specific antigens transiently in cells and elicited specific antibody responses to core, E1, and E2 in mice. Specific cytotoxic T lymphocyte responses were detected only in mice injected with plasmid constructs encoding the core. CONCLUSIONS: Genetic immunization can aid the development of hepatitis C virus vaccines by allowing for the rapid construction and evaluation of different expression plasmids as potential immunogens.
This paper examines the health status of women in China by reviewing levels and trends of female mortality at several phases of a woman's life cycle focusing on infancy girlhood, childbearing and old age. The mortality rates of Chinese women and men are compared for the period 1950-1990 as are comparisons with women in selected countries. The cause-specific death rate, expressed as a percentage of all deaths, and the burden of disease, measured in terms of the disability-adjusted life years (DALYs), are used to reflect the changing patterns of female diseases and causes of deaths. Significant improvement in the health status of Chinese women since 1950 is widely acknowledged as a major achievement for a developing country with the largest population in the world, but the differentials in women's health by region and urban/rural areas are considerable. The Physical Quality of Life Index (PQLI) indicates that the overall level of physical well-being of Chinese women has increased in recent decades, but disparity in health between men and women still exists. The Gender-Related Development Index (GDI) further reveals that China has achieved significant progress in women's health during the past four decades, but far less has been achieved with respect to gender equality overall. The final sections of the paper focus on the discussion of some health problems faced by the female population during the process of economic reform since the 1980 s. In order to promote gender equality between women and men, concerns on women's health care needs are highlighted.
There is increasing interest in both standardization and simplification of methods for enumeration of CD34+ hematopoietic progenitor cells (HPC) to facilitate cellular therapies and to improve interinstitutional comparison of clinical and laboratory results. We evaluated a novel method for CD34+ cell enumeration based on microvolume fluorimetry (MVF) compared with our laboratory's routine flow cytometric method on samples of peripheral blood and leukapheresis products. The MVF method is semiautomated and uses a 633-nm light from a helium-neon laser to scan fluorochrome-labeled cells held in stasis in a capillary known volume. The performance of the MVF assay for enumeration of CD34+ cells was found to be comparable to our routine flow cytometric assay in linearity and accuracy in the range of 5-1500 cells per microliter. Precision of MVF for replicate assays on the same instrument was demonstrated by coefficient of variation (CV) values of 8.4% at a CD34+ cell concentration of 284/microliters for a sample volume of 0.8 microliters, and 15.7% at 12/microliters for a sample volume of 3.2 microliter. Precision among three different instruments was demonstrated, using sample volumes of 1.6 microliters, by CV values of 44% at 6 cells/microliters and 4.6% at 733 cells/microliters. In a field sample evaluation, precision of the entire assay system for paired measurements on 0.8-microliter sample volumes was demonstrated by CV values of 50%, 31%, and 15% for peripheral blood samples with concentrations of 0-10, 10-20, and 20-100 CD34+ cells/microliters, respectively, and 6.3%, 8.1% and 6.5% for leukapheresis samples with concentrations of 0-100, 100-1,000, and 1,000-2,500 CD34+ cells/microliters, respectively. The MVF assay was easy to perform, required minimal technical training time, and had a turnaround time of 40 min, of which less than 10 min was actual technical time. These observations suggest that the MVF method for CD34+ cell enumeration may prove useful to clinical laboratories providing support for HPC collection, processing, and transplantation services that require relatively simple, rapid assays for product quality control or to guide real-time clinical decisions.
We report here a case of fatal Penicillium citrinum infection. The patient, who suffered from acute myeloid leukemia, developed signs and symptoms typical of fungal pneumonia and pericardial tamponade after undergoing standard induction chemotherapy. Despite attaining complete remission of her leukemia, the patient succumbed 8 weeks after presentation. At autopsy, multiple nodular cavitary pulmonary lesions with invasion by fungal hyphae were found. Pericardial and lung tissue obtained at autopsy grew P. citrinum, a fungus ubiquitous in the environment but seldom reported as a pathogen. The microbiological findings were consistent with the histopathological features and confirmed this as a case of true P. citrinum infection causing fatal pulmonary and pericardial complications in an immunocompromised host.
OBJECTIVE: To determine the risk of and risk factors for hepatitis C virus (HCV) infection among persons with immune deficiencies who had received intravenous immune globulin (IGIV) between March 1993 and February 1994. DESIGN: Retrospective cohort study. SETTING: An immunology program in a tertiary care hospital. PATIENTS: Of 341 persons who had received IGIV between March 1, 1993, and February 22, 1994, 278 (82%) were enrolled. The mean age for the enrolled persons was 9 years, and 99% had primary immune deficiencies. MAIN OUTCOME MEASURES: Evidence of HCV infection by detection in sera of antibody to HCV and/or HCV RNA by reverse transcriptase polymerase chain reaction. RESULTS: Twenty-three (11%) of 210 persons who received the IGIV Gammagard (Baxter Healthcare Corporation, Deerfield, Ill) became infected compared with none of 52 persons who received exclusively other IGIV products (P=.01). In a multivariate analysis, HCV infection was associated only with Gammagard produced from plasma screened by second-generation (multiantigen) anti-HCV tests (P=.03). Hepatitis C virus RNA was detected in Gammagard, and the risk of transmission to recipients increased with increasing quantity of HCV RNA infused, from 0 for those who received no HCV RNA-positive lots to 29% for the quartile of patients receiving the greatest amount (P<.001). At least 9 different lots of Gammagard were required to account for all cases. CONCLUSION: Gammagard was the only IGIV product implicated in the transmission of HCV. Infection was associated with higher quantities of HCV RNA in Gammagard produced from second-generation anti-HCV-screened plasma. Further studies are needed to determine reasons for the infectivity of Gammagard, and viral inactivation and removal steps are needed to ensure the safety of IGIV products.
A patient with gonadal dysgenesis was found to have a mucinous epithelial ovarian tumour on the left side and a streak gonad on the right. The preponderance of mucinous tumours (5 of 8) over other epithelial tumours in these patients is noted but the significance is not fully understood. Two models of pathogenesis (incessant ovulation and hypergonadotrophic hypogonadism) were proposed but neither satisfactorily explains the development of the tumours. Further ultrastructural, chromosomal and molecular biological study of these tumours may help to elucidate the underlying cause and pathogenesis.
To characterize the differential aging response in gonadotropin secretion that occurs before menopause, we assessed pulsatile LH and serial FSH, estradiol (E2), and progesterone (P) concentrations in aging women across the menstrual cycle. We conducted 96 daytime studies during the follicular, midluteal, and late luteal phases of the same menstrual cycle in 32 volunteers, aged 40-50 yr (n = 16) and 19-39 yr (n = 16). Mean cycle length was shorter in the older women (26 +/- 0.4 vs. 27.6 +/- 0.6 days; P = 0.02), but mean plasma E2 and P values were similar in the two age groups. Mean plasma FSH was higher in the older group on all 3 study days. For LH, an age difference was observed during the late luteal phase, when mean plasma LH and pulse amplitude were higher in women over 40 yr of age (mean LH, 6.4 +/- 0.7 vs. 3.0 +/- 0.5 IU/L (P = 0.002); mean amplitude, 4.0 +/- 0.5 vs. 2.8 +/- 0.2 IU/L (P = 0.03)]. Pulse frequency was higher in the older group, but not different from that in younger women on all study days. When the subjects aged 35-39 yr were analyzed as a third age group (n = 8), age effects for mean LH persisted, and pulse frequency was higher in the group over 40 yr of age vs. women under age 35 yr (n = 8) in both the follicular phase (7.1 +/- 0.4 us. 5.6 +/- 0.8; P = 0.03) and late luteal phase (5.8 +/- 0.7 vs. 4.4 +/- 0.3; P = 0.03). Although highly variable, individual patterns of gonadotropin secretion in the women over age 40 yr included a sustained elevation in the FSH/LH ratio as well as a failure to demonstrate slow frequency, high amplitude LH pulses in the midluteal phase. In conclusion, 1) the age-related increase in FSH concentrations in ovulatory women, although more pronounced, is associated with phase-dependent enhancement of pulsatile LH secretion; 2) the higher LH concentrations are brought about by changes in both pulse frequency and amplitude; and 3) these age effects preempt overt reductions in cyclic E2 or P concentrations.
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BACKGROUND: Hepatitis C virus (HCV) RNA was measured in immune globulins and its chemical and physical properties were characterized. STUDY DESIGN AND METHODS: The study examined 69 immune globulin lots from 7 manufacturers, including 44 intravenous and 25 intramuscular immune globulin preparations. In addition, 8 experimental intravenous immune globulin preparations were investigated. Detection and quantitation of HCV RNA were achieved by reverse transcription and nested polymerase chain reaction at limiting dilution. A multi-antigen anti-HCV enzyme immunoassay was also used to test these immune globulins. RESULTS: The highest level of HCV RNA was found in an experimental immune globulin lot derived from a plasma pool made up of 186 anti-c100-3-reactive units. HCV RNA was detected only in 1 of 7 manufacturers' experimental intravenous immune globulin preparations derived from a pool made up of 2887 anti-c100-3-negative units. It was also detected in commercial intravenous immune globulin lots prepared by the same manufacturer from source plasma, but not from recovered plasma. More than half of the commercial intramuscular immune globulin lots, including specific immune globulin products, were HCV RNA positive. All immune globulin products examined were reactive for anti-HCV. Certain similarities were found for HCV RNA present in an immune globulin product and plasma. Ethanol at 20 or 25 percent had no effect upon the buoyant density of HCV RNA. CONCLUSION: Many immune globulin preparations contained HCV RNA, with levels depending upon both the type of starting plasma and the manufacturing process. Exposure to ethanol did not appear to affect the physical characteristics of HCV RNA.
BACKGROUND: Inactivated hepatitis A vaccine is now becoming available in many countries. METHODS: To evaluate the immunogenicity and safety of inactivated hepatitis A vaccine in healthy children, 99 susceptible schoolchildren from 4 to 15 years of age received 360 enzyme-linked immunosorbent assay units of the inactivated hepatitis A vaccine at months 0, 1, and 6. RESULTS: Antibody to hepatitis A virus seroconversion (> or = 20 mIU/mL) was 97% (96/99) in vaccinees after the first dose and 100% after the second (99/99) and booster (96/96) doses. The geometric mean titers of antibody to hepatitis A virus were 167, 465, and 4133 mIU/mL after each dose of vaccine, respectively. There were no significant side effects during the vaccination. Levels of antibody to hepatitis A virus were also tested in 9 susceptible children at day 7 and months 1 and 4 after the intramuscular injection of 2 mL of immune serum globulin. All children had measurable titers of antibody to hepatitis A virus 1 week after receiving immune serum globulin by sensitive enzyme immunoassay, but measurable titers had disappeared 1-4 months later. CONCLUSIONS: The inactivated hepatitis A vaccine is safe and immunogenic in healthy children.
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