Human herpes virus reactivations and dynamic cytokine profiles in patients with cutaneous adverse drug reactions --a prospective comparative study.

BACKGROUND: Sequential human herpes virus (HHV) reactivation is well known in drug reaction with eosinophilia and systemic symptom (DRESS), but such a phenomenon has seldom studied in other types of cutaneous adverse drug reactions (cADRs). Moreover, the association between viral reactivations and cytokine or chemokine changes is largely unknown. We aimed to evaluate the viral reactivation rates of HHV-6, HHV-7, Epstein-Barr virus (EBV), and cytomegalovirus (CMV) in different cADRs and their impacts on clinical prognosis. Cytokine and chemokine changes with viral reactivations were also examined. METHODS: A prospective study was conducted to monitor the viral statuses of patients with different cADRs by polymerase chain reaction and serum-specific antibody titers. Changes in plasma cytokine and chemokine levels were also evaluated by sequential blood samples. RESULTS: Among the various cADRs, HHV-6 reactivation was only observed in DRESS, but EBV and CMV could be detected in other cADRs. Many proinflammatory cytokines and chemokines, including interleukin (IL)-1ß, IL-2, IL-6, interferon-γ, tumor necrosis factor-α, were significantly lower in DRESS patients with HHV-6 reactivation when compared to those without HHV-6 reactivation. In addition, these mediators were significantly lower before and during HHV-6 reactivation, compared to cytokine levels after HHV-6 reactivation in the same patient. CONCLUSION: HHV-6 reactivation was only observed in DRESS patients, not in any other cADR. In DRESS patients, some proinflammatory cytokines were significantly lower before or during HHV-6 reactivation.

Effects of herpes simplex virus type 1 infection on immune functions of human neutrophils.

BACKGROUND AND OBJECTIVE: Herpesviruses may play roles in the development of periodontal diseases. This study analyzed the effects of herpes simplex virus type 1 (HSV-1) infection on neutrophil function. The effects of lipopolysaccharide (LPS) from the periodontal pathogen, Porphyromonas gingivalis, during HSV-1 infection were also determined. MATERIAL AND METHODS: Purified HSV-1 was pretreated with buffer containing no serum, with HSV-1 immunoglobulin G (IgG)-positive serum (HSV-1 antiserum) or with control serum. Neutrophils were mock-infected or infected with the pretreated HSV-1. Viral binding and phagosome formation were detected using immunostaining. Intracellular reactive oxygen species (ROS) were determined using 2',7'-dichlorofluorescin diacetate and fluorometry. Leukotriene B(4) (LTB(4)) and interleukin-8 (IL-8) were detected using enzyme immunoassays. Release of matrix metalloproteinase-9 (MMP-9) was examined using gelatin zymography. Phosphorylation of Akt/glycogen synthase kinase-3 (GSK-3) was determined using western blotting. RESULTS: HSV-1 bound directly to neutrophils and enhanced the release of MMP-9. HSV-1 immune complexes, formed in the HSV-1 antiserum, bound neutrophils and induced the formation of early phagosome more effectively than did HSV-1 alone. The relative levels of ROS and phosphorylation of Akt/GSK-3 were increased significantly in neutrophils after infection with HSV-1 immune complexes. Infection with HSV-1 and HSV-1 immune complexes also stimulated the production of inflammatory mediators, LTB(4) and IL-8. Moreover, LPS enhanced the HSV-1-stimulatory production of IL-8. CONCLUSION: This study demonstrated differences in neutrophils infected with HSV-1 alone or with HSV-1 immune complexes, suggesting that opsonization of HSV-1 might enhance its effects on neutrophils. The in vitro findings suggest that HSV-1 infection may induce the inflammatory response and affect periodontal health.

Informed choice of pregnant women in prenatal screening tests for Down's syndrome.

BACKGROUND: Although maternal serum screening (MSS) for Down's syndrome has become routinely available in most obstetric clinics in many countries, few studies have addressed the reasons why women agree to undergo the MSS test. OBJECTIVES: The aims of this study were to describe the circumstances in which MSS was offered to pregnant women and their reasons for undertaking it. METHODS: Participant observation and in depth interviews were used in this study; specifically, the experiences of women who had a positive result for MSS and who then followed this up with amniocentesis were examined. The interviewees were twenty six mothers aged between 22 and 35 years. The interviews were audio taped and transcribed for analysis. The results were analysed by the constant comparative method. RESULTS: This study identified the reasons on which pregnant women appeared to base their decisions when undergoing MSS. The reasons were first, the recognition that the procedure was a prenatal routine procedure; second, the need to avoid the risk of giving birth to a baby with Down's syndrome, and third, a trust in modern technology and in the professional authorities. CONCLUSIONS: This study offers insights into the informed choice made by women with a positive MSS result. The reasons for undergoing MSS might help health professionals and policy makers to reflect on their practice and this may, in turn, improve the quality of prenatal care during MSS.

To have or to be: ways of caregiving identified during recovery from the earthquake disaster in Taiwan.

The aim of this article is to report the results of therapy sessions conducted with survivors of an earthquake that struck Luku Township in Nantou County, central Taiwan, in September 1999. The sessions explored survivors' feelings, interactions, and interpretations of the crisis, as well as their roles in post-earthquake relief efforts. The participants were teachers and administrators from four primary schools. The results indicated three distinct forms of caring, namely: encumbered caring, connected caring, and reflected caring. The findings were used to construct a framework for caregiver self-monitoring. They also suggest that therapy groups provide an inner space that self-regulates the frustrations arising from this type of experience, for both caregivers and survivors. The intrasubjective and intersubjective dialogues within the groups are essentially reflective practices for improving services and generating new knowledge about medical ethics.

Light-induced fluorescence spectroscopy to differentiate benign and malignant uterine cervical lesions.

In Taiwan, cervical cancer is the leading malignancy among women. For the early detection of cervical neoplasia, light-induced fluorescence spectroscopy was conducted ex vivo to assess the ability of this technique to differentiate cervical neoplastic tissue (20 samples) from normal or inflammatory cervical tissue (37 samples) at an excitation wavelength of 280 nm. The principal fluorescent peaks occurred within +/- 5 nm of 330 nm and 470 nm emission. At 330 nm emission, the spectrum of the normal or inflammatory tissue was significantly stronger than that of the neoplastic tissue after are normalization. However, at 470 nm emission, the spectrum of the normal or inflammatory tissue was significantly weaker than that of the neoplastic tissue. A diagnostic algorithm based on the ratio of relative intensities of 330 nm to 470 nm emission within the 5 +/- nm peak area of each sample was calculated and paired. The ratios showed that histologically neoplastic lesions could be distinguished from inflammatory samples using a 280-nm-excitation wavelength with a sensitivity, specificity and positive predictive value of 94%, 82% and 73%, respectively. The average ratio of malignant or dysplastic cervical samples was significantly greater than that of the inflammatory samples (p < 0.001). Our ex vivo study indicated that light-induced fluorescence spectroscopy may be useful in differentiating malignant or premalignant from normal or inflammatory cervical tissue.

Light-induced fluorescence spectroscopy: a potential diagnostic tool for oral neoplasia.

For the early detection of oral neoplasia, light-induced fluorescence spectroscopy was used to measure the fluorescence emission of malignant (squamous cell carcinoma & verrucous carcinoma) and premalignant (epithelial dysplasia, hyperkeratosis & lichen planus) oral tissues as well as normal oral mucosa ex vivo to assess the ability of this technique to distinguish neoplastic from normal oral tissues. The emission spectra of histologically normal and neoplastic oral tissues were obtained under excitation wavelengths varied from 270 nm to 400 nm at 10-nm intervals. At 300-nm excitation, the most intensely fluorescent peak occurred at 330-nm and 470 nm emission. At 330-nm emission, the spectrum of the malignant oral tissue was significantly stronger than that of the normal oral mucosal tissue after area normalization. However, at 470-nm emission, the spectrum of the malignant oral tissue was significantly weaker than that of the normal oral mucosal tissue. A diagnostic algorithm based on the ratio of relative intensities of 330 nm to 470 nm emission within the +/-5 nm peak area of each sample was calculated and paired. The histogram of ratios showed that histologically neoplastic oral tissues could be distinguished from normal oral mucosal tissues using the 300 nm excitation wavelength. The average ratio of malignant or premalignant oral samples was significantly greater than that of the normal oral mucosal samples (p < 0.001). This ex vivo study indicated that fluorescence spectroscopy may be useful in differentiating malignant or premalignant oral tissue from normal oral mucosa.

Cancer patients' knowledge of their diagnoses.

The most frequently discussed ethical issue on the subject of cancer is whether patients should be told their diagnosis. Cancer patients' knowledge of their diagnosis and the relationship between patient characteristics and that knowledge were evaluated in a cross-sectional study. From July 1992 to December 1993 at Tri-Service General Hospital, Taipei, a total of 964 patients with cytologically- or pathologically-proven cancer were studied. Of those studied, 359 patients (37.2%) knew their diagnosis. The proportion of patients who believed that they had a benign tumor was 25.1%; 12.6% believed they had nonneoplastic disease (inflammation or other chronic disease); 7.5% believed they had precancerous changes; and 17.6% knew nothing about their diagnosis. Multivariate analyses showed that patients with the following characteristics were inclined to know their diagnosis: younger age (20-59 yr), higher levels of education (> 9 yr) with relatives of a high socioeconomic status, cancer of a genital organ, cancer requiring disfiguring treatment (osteosarcoma, leukemia), cancer in obvious sites (head and neck), cancer of more than one type (multiple primary lesions), cancer of good prognosis (excluding lung, liver, gall bladder or pancreatic cancers), aggressive anticancer treatment and longer duration of pathologic proof (> 14 d). The results showed that concealing the diagnosis from cancer patients is still very common in Taiwan. Patient's sociodemographic background and disease-related factors were the most important patient characteristics related to their knowledge of the diagnosis.

Isolation of the Arabidopsis GA4 locus.

Progeny from a transgenic Arabidopsis plant generated by the Agrobacterium root transformation procedure were found to segregate for a gibberellin (GA)-responsive semidwarf phenotype. Complementation analysis with genetically characterized GA-responsive mutants revealed that the transgenic plant has an insertional mutation (ga4-2) that is an allele of the ga4 locus. The semidwarf phenotype of ga4-2 is inherited as a recessive mutation that cosegregates with both the T-DNA insert and the kanamycin resistance trait. DNA gel blot analysis indicated that the insertion site contains a complex T-DNA unit. A genomic library was constructed with DNA from the tagged ga4 mutant; a DNA clone was isolated from the library that flanks the T-DNA insert. The plant sequence isolated from this clone was used to isolate the corresponding full-length genomic and cDNA clones from wild-type libraries. DNA sequence comparison of the clones to the existing data bases suggests that they encode a hydroxylase. This conclusion is in agreement with a biochemical study that indicated that the ga4 mutant is deficient in 3 beta-hydroxylase in the GA biosynthetic pathway of Arabidopsis. RNA gel blot analysis showed that the message is ubiquitously expressed in different tissues of Arabidopsis but most abundantly in the silique. Unexpectedly, a higher level of transcription was detected in the ethyl methanesulfonate-induced ga4 mutant, and this overexpression was repressed by treatment with exogenous GA.