Interferon-alpha and ribavirin treatment of hepatitis C in children with malignancy in remission.

Twenty-eight cases of hepatitis C virus (HCV) infection were identified in children in a pediatric oncology ward during 2 nosocomial outbreaks. HCV infection spontaneously cleared in 6 patients (21%). Eleven patients with persistent HCV viremia who had malignant diseases in remission after treatment were given a 48-week course of combined therapy with interferon-alpha (5x106 U 3 times weekly) and oral ribavirin (15 mg/kg/d). Seven (64%) of the 11 patients had sustained virological responses 6 and 12 months after cessation of therapy. Side effects were common but generally were mild or moderate.     

Noneosinophilic CD4 lymphocytic airway inflammation in menopausal women with chronic dry cough

BACKGROUND: Chronic dry cough without dyspnea and wheezing is a well-known condition that is considered to be clinically overrepresented in women. The etiology and morphology remain unknown in many cases despite thorough investigations. DESIGN: To examine inflammatory cells and the lymphocyte profile in the lower airways and blood in women with chronic cough of unknown etiology. SETTING: University hospital department of respiratory medicine. PARTICIPANTS: Twenty-five otherwise healthy women with idiopathic cough and 11 age-matched healthy control women, all nonatopic nonsmokers. MEASUREMENTS: In order to characterize the cough, a careful standardized interview of the patients was made. Lung functions were tested. Cells were collected by BAL and analyzed for differential cell counts separate in the bronchial (first) wash and in the pooled peripheral washes (BAL fluid). The lymphocyte profile in BAL fluid and blood was characterized by dual-color flow cytometry. RESULTS: Eleven female patients formed a specific group with a history of a dry, nonproductive cough that always started in connection with an airway infection coinciding with menopause. Neither exercise, climate, nor seasonal change influenced the cough. BAL fluid contained an increased number of T (CD3+) lymphocytes: median. Seventy-three percent of T lymphocytes were T-helper lymphocytes (CD4+). A median of 57% of the BAL fluid T cells expressed HLA-DR activation marker compared with a median of 20% in the control subjects and in the other 14 included patients with chronic cough but with minor expectoration periodically (p < 0.001 and p < 0.0001, respectively). No differences between the groups were found in the blood. CONCLUSIONS: HLA-DR-activated CD4+ lymphocytic airway inflammation with a low number of eosinophils was identified in a group of nonsmoking, nonatopic otherwise healthy women patients with dry cough of life-long character. The disease appeared exclusively in connection to menopause.     

Serum cystatin C advantageous compared with serum creatinine in the detection of mild but not severe diabetic nephropathy

OBJECTIVE: To determine whether serum cystatin C is more accurate than serum creatinine in the detection of diabetic nephropathy, also after adjustment for age. METHODS: Forty-one patients with type 1 and 82 patients with type 2 diabetes were evaluated with serum creatinine, serum cystatin C, and (51)Cr-EDTA clearance (reference method). Cystatin C was measured by a particle-enhanced turbidimetric method and creatinine by an enzymatic method. Statistical estimations were performed both without and with age adjustment created by z-scores for (51)Cr-EDTA clearance, creatinine, and cystatin C. The cut-off levels for glomerular filtration rate (GFR) ((51)Cr-EDTA clearance) were 60 and 80 mL min(-1) 1.73 m(-2), respectively, in absolute values and 80, 90 and 95% CIs, respectively, in age-adjusted values (z-scores). RESULTS: Estimations without age adjustment showed significantly (P = 0.0132) closer correlation for cystatin C (r = 0.817) versus (51)Cr-EDTA clearance as compared with creatinine (r = 0.678). However, when using age-adjusted values, the correlation for cystatin C and creatinine, respectively, versus (51)Cr-EDTA clearance did not differ. When comparing the diagnostic utilities for serum cystatin C versus serum creatinine in manifest renal impairment (GFR < 60 mL min(-1) 1.73 m(-2) or z-scores <-1.28 SD), there were no significant differences between the two markers whether age adjusted or not. However, for diagnosing mild nephropathy (GFR < 80 mL min(-1) 1.73 m(-2) or z-score -0.84 SD), serum cystatin C is significantly more useful. CONCLUSIONS: Serum cystatin C performed better compared with serum creatinine even when measured enzymatically, to detect mild diabetic nephropathy. However, serum creatinine was as efficient as serum cystatin C to detect advanced diabetic nephropathy.     

Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases

Treatment with granulocyte colony-stimulating factor plus erythropoietin may improve haemoglobin levels in patients with ringsideroblastic anaemia (RARS) and reduce bone marrow apoptosis. We studied bone marrow from 10 RARS patients, two of whom were also investigated after successful treatment. Mononuclear, erythroid and CD34+ cells were analysed with regard to proliferation, apoptosis, clonogenic capacity and oncoprotein expression, in the presence or absence of Fas-agonist, Fas-blocking antibody 2 and caspase-3 inhibitor. During culture, RARS bone marrow cells showed higher spontaneous apoptosis (P < 0.05) and caspase activity (P < 0.05)) than bone marrow cells from healthy donors. Eight out of nine patients had reduced growth of erythroid colony-forming units (CFU-E) (< 10% of control) and granulocyte-macrophage CFU (CFU-GM) (< 50% of control) from CD34+ cells. Fas ligation increased apoptosis and decreased colony growth equally in RARS and controls, but caused significantly more caspase activation in RARS (P < 0.01). Fas-blocking antibody showed no significant inhibitory effect on spontaneous apoptosis or ineffective haematopoiesis, as measured using phosphatidylserine exposure, the terminal deoxynucleotide transferase-mediated dUTP-biotin nick-end labelling technique, caspase activity or clonogenic growth. Caspase inhibition reduced apoptosis, increased proliferation and enhanced erythroid colony growth from CD34+ cells in RARS, but showed no effect on normal cells. CFU-E improved > 1000% after successful treatment. Thus, erythroid apoptosis in RARS is initiated at the CD34+ level and growth factor treatment may improve stem cell function. Enhanced caspase activation at the stem cell level, albeit not mediated through endogenous activation of the Fas receptor, contributes to the erythroid apoptosis in RARS.     

Midwives' experience of organisational and professional change

OBJECTIVE: to describe midwives' experiences of changes in their caring role and professional function in postpartum wards in the northern part of Sweden. In this part of the country, three out of eight maternity departments have been closed over the last 5 years. During the same period, hospital stays have reduced in length, and an early discharge model has been introduced. DESIGN: focus-group discussions. SETTING: four focus groups at two hospitals in northern Sweden. PARTICIPANTS: 21 midwives experienced in midwifery practice in maternity wards. FINDINGS: the analysis revealed four categories of comments: 'to have limited time when caring for the mother and the baby'; 'no longer being valued as the expert'; 'a wish to have responsibility for childbirth in its entirety'; 'to see future possibilities in the development of the profession'. The theme identified is 'being ahead in ideas about caring but still partly caught up in the past'. KEY CONCLUSIONS AND IMPLICATIONS: the identified theme of being ahead in ideas about caring but still partly caught up in the past can be understood as representing a transition. The midwives experienced loss and grief over their former midwifery practice, but had ideas and visions for developing and expanding their future professional role. A healthy transition requires support, participation and skilled management.     

CGH of microdissected Kaposi's sarcoma lesions reveals recurrent loss of chromosome Y in early and additional chromosomal changes in late tumour stages

BACKGROUND: It is still unclear if Kaposi's sarcoma (KS) is a monoclonal cell proliferation or a polyclonal, hyperplastic, reactive process. Reports on KS cytogenetics are few and restricted to late stage disease and cell lines. METHOD: We analysed 27 KS, early and late, AIDS related (AKS) and endemic (EKS) by laser microdissection, global DNA amplification and comparative genomic hybridization (CGH). RESULT: Loss of Y chromosome was detected in 20/23 male KS, which was the only recurrent chromosomal aberration in all nine male early (patch) KS. Only one patch EKS showed in addition to the Y loss a loss of Xq. Late (nodular) AKS and EKS showed recurrent copy number changes in chromosomes 16, 17, 21, X and Y, as well as other random changes. The loss of chromosome 16, 17 and Y was confirmed by interphase fluorescence in situ hybridization (FISH) on paraffin sections. EKS showed a higher number of chromosomal abnormalities than AKS, indicating that rapid growth of AKS is less dependent on genetic changes than is EKS, possibly because of the immunosuppressed host environment in AKS. CONCLUSION: Clonal loss of chromosome Y was detected in all early male KS, while additional chromosomal aberrations appeared during development to late KS. This increase in chromosomal abnormalities during tumour growth indicates genetic instability and the selection of survival cell clones establishing late, aggressive sarcoma growth. Our data support the view that KS (in males) develops into a clonal tumour yet initially is a hyperplastic reactive cell proliferation.     

Low antibody levels against cell wall-attached proteins of Streptococcus pyogenes predispose for severe invasive disease

Acute-phase serum samples from 70 patients with group A streptococcal (GAS) invasive disease were analyzed for IgG antibodies against 6 recently characterized GAS virulence factors (SclA, SclB, GRAB, MtsA, EndoS, and IdeS) and SpeB. Antibody levels against the cell wall-attached GAS antigens SclA, SclB, and GRAB were significantly lower in patients with severe invasive disease (streptococcal toxic shock syndrome [STSS] and/or necrotizing fasciitis [NF]; n=35), compared with levels in patients with nonsevere GAS bacteremia (n=35). Among patients with severe invasive disease, significantly lower antibody levels against GRAB were found in patients with STSS (n=10) than in patients with NF (n=17). Antibody levels against SpeB in patients with severe bacteremia were similar to those in patients with nonsevere bacteremia, and levels in patients with STSS were similar to those in patients with NF. The data indicate that immunity to cell wall-attached proteins may play a role in the protection against severe invasive disease and that antibodies against GRAB may be of importance in the pathogenesis of STSS.     

The effect of amperozide on uptake and release of [3H]-dopamine in vitro from perfused rat striatal and limbic brain areas

Amperozide, a putatively antipsychotic drug, was studied for its effects on uptake and release of [³H]-dopamine in rat brain in vitro. Amperozide inhibited uptake of [³H]-dopamine in striatal chopped tissue in vitro with an IC₅₀ of 18 μM. It also increased basal release of [³H]-dopamine from perfused rat striatal and limbic tissue in vitro at concentrations above 5 μM. Release of [³H]-dopamine from perfused rat striatal and limbic tissue stimulated with 5 μM amphetamine, was inhibited by 1 μM amperozide to 46%. No significant difference was found for the effect of amperozide on in vitro release of [³H]-dopamine from corpus striatum compared to tissue from limbic brain regions; neither on basal release nor on amphetamine-stimulated release of dopamine.     

Shigella infection induces cellular activation of T and B cells and distinct species-related changes in peripheral blood lymphocyte subsets during the course of the disease.

Immunophenotypic changes in peripheral blood lymphocytes (T, B, and NK cells) in patients during shigellosis was characterized by using triple-color flow cytometry. Eleven Shigella dysenteriae 1-infected adult patients (SDIP), 11 Shigella flexneri-infected adult patients (SFIP), 15 age- and sex-matched healthy controls from Bangladesh (C-B), and 15 healthy volunteers from Sweden (V-S) were studied. In SDIP and SFIP, a significant increase in the CD45RO+ cells in both CD4+ and CD8+ T cells were seen. We found evidence for sequential T-cell activation, as shown by increased proportions of CD25 and CD4+ cells; HLA-DR and CD38 on CD8+ cells, and CD54 on CD4+ and CD8+ cells. We found differences in the lymphocyte activation and subset patterns related to the infecting Shigella species. Thus, a decrease in CD45 expression was seen in SFIP; this decrease progressed further during the disease. The proportions of NK cells (CD56+ cells) and CD3- CD8+ cells out of the total CD8+ cells were increased in SFIP but not in SDIP. The CD3+ CD8+ CD57+ T-cell subset was significantly lower in SDIP than in C-B. The proportion of B-lymphocyte-expressing activation markers CD80 and CD23 was higher in patients than in C-B. There was a significant increase in the proportion of CD4+ T cells and a significant decrease in the percentages of total B cells, the CD3+ CD8+ CD57+ T-cell subset, and the CD56+ CD16+ NK-cell subset for V-S compared with C-B. Our results indicate that distinct subset changes and activation patterns are elicited in SDIP compared with SFIP and also that the degree of activation is related to disease severity. In addition, a common sequence of cell activation was seen during the disease course. The difference in the subset patterns seen in C-B and V-S may be related to differences in the levels or spectra of infectious agents in the environment.