Serum cytokine values and fatigue in chronic hepatitis C infection.

Patients with chronic hepatitis C infection often experience fatigue. In many clinical situations, an association between fatigue and altered serum cytokine levels has been found. Altered cytokine levels in patients with hepatitis C have not shown a correlation with the degree of serum transaminase elevation or pathological change on liver biopsy. The aim of our study was to examine whether there was an association between abnormal serum cytokine levels and fatigue in patients with compensated chronic hepatitis C. Patients referred to a tertiary care hepatology clinic who were hepatitis C antibody positive and who had elevated alanine aminotransferase (ALT) levels were eligible for entry into the study. A control group was also included. Subjects in both groups who had characteristics other than hepatitis C that were known to alter cytokine values and/or cause fatigue were excluded. Patients completed a validated questionnaire to determine their fatigue severity score (FSS). Bioassays were used to measure interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-alpha) levels in early morning serum samples taken from patients and controls. Altered cytokine values were defined as those more than two standard deviations above the mean control value. Data was analysed using SPSS, version 8.01. Of the 78 patients with chronic hepatitis C who participated in the study, 19 (24%), 24 (30%) and 45 (56%) had elevated levels of IL-1, IL-6 and TNF-alpha, respectively, compared with only two (6%) of the control group who had elevation of any of the three cytokines. No correlation was found between the FSS and serum cytokine levels, when analysed singly or in combination, in patients with chronic hepatitis C. Hence, alteration in early morning serum levels of IL-1, IL-6 and TNF-alpha in patients with chronic hepatitis C infection and elevated ALT levels bear no correlation with the symptom of fatigue.

Lamivudine treatment for decompensated cirrhosis resulting from chronic hepatitis B.

The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are outweighed by serious side effects and by the risk of fatal exacerbation of disease activity. Lamivudine rapidly reduces hepatitis B virus (HBV)-DNA in serum to undetectable levels. We have treated 35 patients with chronic hepatitis B and decompensated cirrhosis with lamivudine 100 mg or 150 mg orally once daily. Pretreatment, all were positive for HBV-DNA in serum. Ten had Child-Pugh class B and 25 had Child-Pugh class C liver disease. Seven patients underwent liver transplantation within 6 months of treatment initiation, 5 patients died within 6 months, and 23 patients were treated for at least 6 months (mean = 19 months). In a majority of these 23 cases, there was a slow but marked improvement in liver function, which was most apparent after 9 months of treatment, with a decrease in serum bilirubin from 67 +/- 13 to 30 +/- 4 micromol/L (P <.05, baseline vs. 9 months), an increase in serum albumin from 27 +/- 1 to 34 +/- 1g/L (P <.05), and a decrease in Child-Pugh score from 10.3 +/- 0.4 to 7.5 +/- 0.5 (P <.05). Three patients developed resistance to lamivudine because of a mutation in the YMDD motif, but liver function did not deteriorate. We conclude that inhibition of viral replication with lamivudine results in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term benefits remain uncertain.

[Cost of hormonal substitution treatment]. / Coût du traitement hormonal de substitution.

Hormone replacement therapy during menopause constitutes a long-lasting preventive treatment. The possibilities of prescriptions are varied. It is therefore important to individualise one's choice according to different criteria: simplicity, tolerance, effectiveness, comfort, cost. The latter--which currently varies between 34 BF and 681 BF for the patient per month--should no longer be an obstacle to begin or maintain hormone therapy during menopause.

Response to interferon therapy: influence of human leucocyte antigen alleles in patients with chronic hepatitis C.

The response to interferon (IFN) therapy in patients with chronic hepatitis C is characterized by normalization of the serum alanine aminotransferase (ALT) activity during treatment, but relapse within 6 months of cessation of therapy is common. Viral characteristics, such as the genotype and viral load, may influence the patient response to IFN. The aim of this study was to examine host factors, namely the genetically determined human leucocyte antigen (HLA) class II alleles, in patients with chronic hepatitis C, and their relationship to the response to IFN therapy. Seventy white patients with chronic hepatitis C, treated with IFN-alpha for 6 months, were enrolled in the study. Serum ALT was measured at the end of treatment to assess short-term response and again 6 months post-treatment to assess sustained response. Sequence-specific primers were used in the polymerase chain reaction (PCR) to amplify genomic DNA isolated from peripheral mononuclear cells. HLA class II alleles were determined by analysis of the amplicon by gel electrophoresis and hybridization of sequence-specific oligonucleotide probes. At the end of treatment, 25 of the 70 patients (36%) had a normal ALT. By 6 months post-treatment, only six patients (9%) had a sustained normalization of ALT. The frequency of the allele DRB1*0404 was significantly higher in patients with a sustained response as compared to those lacking such a response (25.0% vs 2.3%, with a Bonferonni-corrected P-value of 0.019). There was no difference in the frequency of other class II alleles at the DRB1 and DQB1 loci in responders as compared with non-responders. Therefore, we conclude that the maintenance of a response to IFN in chronic hepatitis C may be, in part, determined by genetic factors in the host.

High-dose gammaglobulin (IVIG) followed by intrauterine transfusions (IUTs): a new alternative for the treatment of severe fetal hemolytic disease.

Intrauterine fetal transfusion is currently the therapy of choice in cases of severe anti-D isoimmunisation. However, its efficacy is reduced in patients with early severe hydrops fetalis due to the technical difficulties in performing this procedure before 20 weeks' gestation. The purpose of this study was to determine whether early onset of high-dose gammaglobulin therapy followed by intrauterine transfusions (IUTs) is more effective than IUTs alone in the treatment of very severe isoimmunised fetuses. The population studied in this retrospective clinical research was assigned to one of the following two groups: 1) Gamma group: 30 patients receiving gammaglobulin therapy before 21 weeks' gestation and IUTs after 20 weeks; or 2) IUT group: 39 patients receiving IUT treatment starting at a gestational age of 20-25 weeks. Both groups were statistically similar regarding history of perinatal deaths and anti-D antibody titers. The number of hydropic fetuses at the first IUT and of fetal deaths were significantly higher in the IUT than in the Gamma group. No significant differences were observed between the groups in fetal hematocrit at first IUT and at birth. However, the percentage of severely anemic fetuses was higher in the IUT group. Fetal mortality rate was 36% less in the Gamma group. Our results suggest that high-dose gammaglobulin therapy followed by IUTs may improve fetal survival in these severe cases. Further randomised clinical trials are needed to confirm these results.

Agreement between different frequencies of measurements in ambulatory blood pressure monitoring.

The purpose of this study was to determine the degree of agreement among different frequencies of blood pressure measurements (FoM) in 24-hour ambulatory blood pressure monitoring (ABPM) in their ability to obtain useful clinical information. ABPM records were obtained with a Del Mar IV Avionics device from 49 hospitalised preeclamptic women with a FoM of 7 per hour (high-FoM). With these records, we simulated two sets of data as if measurements had been recorded at a rate of 1 measurement per hour (low-FoM) and of 2 per hour (medium-FoM). Diastolic blood pressure > 89 mmHg defined hypertension and > 109 mmHg, severe hypertension The median and 25th and 75th centiles for the differences in hypertensive rate detected (expressed as percentage points) between lowFoM vs. high-FoM was 0.00 (- 3.4-3.00) and between medium-FoM vs. high-FoM,- 1.04 (- 3.7-1.5). The agreement in the detection of severely affected patients was 85% (CI 95%: 74-96) between low-FoM and high-FoM and 87% (CI 95%: 77-98), between medium-FoM and high-FoM. Average blood pressure was similar in the three FoMs studied at day-time and night-time. We did not find any strong argument to perform ABPM at a high-FoM. Lower FoM are more comfortable for the patient and could reduce equipment deterioration, while providing equivalent information to that supplied by high-FoM.

The endoscopic assessment of esophagitis: a progress report on observer agreement.

BACKGROUND & AIMS: The study and management of reflux esophagitis require an endoscopic classification system founded on esophageal lesions that can be reproducibly identified. The aim of this study was to investigate interobserver agreement for the identification of endoscopic lesions typical of reflux esophagitis. METHODS: Paired comparisons of observers' descriptions were obtained. Seventeen endoscopists assessed 100 still images, and 42 endoscopists, including 13 endoscopists in training, assessed 23 endoscopic video recordings. In a third, ancillary study, using a simpler evaluation sheet, 219 gastroenterologists recorded their assessments of 20 still images. RESULTS: The agreement between endoscopists was similar for still images and video recordings. Agreement between experienced endoscopists was acceptable to good for recognition of minimal changes (erythema, friability, mucosal edema; kappa = 0.46 to kappa = 0.8), mucosal breaks (discretely, demarcated areas of slough or erythema; kappa = 0.84), and complications (ulceration, kappa = 0.92; stricturing, kappa = 0.80; columnar metaplasia, kappa = 0.81), although there was poor agreement when the circumferential extent and number of mucosal breaks were assessed. However, total circumferential extent of the mucosal break had a kappa value of 0.59. Agreement between inexperienced endoscopists was poor for recognition of minimal changes but was good for recognition of complications (kappa, 0.70-0.90). CONCLUSIONS: Endoscopists can identify mucosal breaks confined to a mucosal fold and lesions that extend throughout the esophageal circumference. Complications of reflux disease can be reproducibly recorded. Criteria for assessing the number of mucosal breaks and their radial extent must be defined more clearly, as must the features of minimal change esophagitis.

Toddlers' speech and cognitive effort.

Two-year-olds were videotaped while engaged in free play and problem-solving play. The periods in which they were actively manipulating objects were analyzed as to level of engagement, distinguishing between periods of intense engagement, in which the children were concentrating on the nonverbal activity, and periods of casual engagement, in which they conducted the nonverbal activity in a more leisurely fashion. A micro-analysis of the children's spontaneous speech revealed that they spoke less at moments of intense engagement than at moments of casual engagement. These and other findings are taken as support for the hypothesis that when toddlers invest cognitive effort in nonverbal behavior, there is a reduction in mental resources available for speech.

[Diagnostic score for acute appendicitis]. / Diagnosescore für akute Appendicitis.

Scoring systems seem to be ideal for supporting diagnosis of acute appendicitis because they are non invasive, require no special equipment and can be used in clinical routine. Several scores for appendicitis have been developed with good results in the original publications. Unfortunately these good results could not be reproduced on a German data base. Therefore we developed a new score using multivariate statistics and a quality controlled prospective data base. The score covers 8 variables: tenderness, rebound tenderness, micturition, type of pain, leucocytes, age, relocation of pain, rigidity. Independent evaluation of the score on a Dutch database resulted in a negative appendicectomy rate of 21% and a missing appendicitis rate of 2%. The results are encouraging, so that further testing and clinical application can be recommended.

Neonatal administration of high-dose intravenous immunoglobulin in rhesus hemolytic disease.

Our aim was to assess the effectiveness of neonatal treatment of Rh hemolytic disease with high-dose intravenous immunoglobulin (HDIVIG), in reducing neonatal hemolysis. A total of 40 neonates born to isoimmunized Rh negative women were studied. The population was randomized into 2 groups: Group 1 received IVIG 800 mg/kg/day for 3 days, plus phototherapy; and Group 2 received only phototherapy. No significant difference was observed between the groups in the severity of either the antenatal and neonatal disease, mode of delivery, mean birthweight, gestational age at delivery, proportion of preterm deliveries, 1 minute Apgar Score, days of phototherapy, and presence of neonatal cholestasis. Group 1 babies showed a significantly decreased duration of hospitalization, less hemolysis, and a less marked increase in bilirubin levels on the first day of life than Group 2 newborns. Therefore, Group 1 neonates received less treatment with transfusions (exchange-transfusions and/or simple blood treatment with transfusions) than those in Group 2. Our data suggest that the frequency of transfusional therapy can be reduced by combining conventional phototherapy with HDIVIG. Further studies are needed to determine the optimum timing and dosages of neonatal HDIVIG treatment.

[Misoprostol--a PGE1 analog for induction of labor at term: comparative and randomized study with oxytocin]. / Misoprostol--un análogo de la PGE1--para la induccíon de parto a término: estudio comparativo y randomizado con oxitocina.

The efficacy of misoprostol (a PGE1 analog) for induction of labor at term was compared with oxytocin by means of an open and randomized study in 153 pregnant women. A vaginal tablet containing 50 mcg of misoprostol was placed intravaginally in 78 women, the remaining 75 patients received i.v. oxytocin (2-32 mU/min). Bishop's score at the entry of the trial was similar in both groups. Delivery within 24 hours was achieved in 85.7% of the patients induced with misoprostol and in 64% of the patients infused with oxytocin (p < 0.05). Mean induction to delivery interval was significantly shorter in the misoprostol group (552 +/- 211 min; mean =SD) in comparison with that of the oxytocin group (745 +/- 292 min; mean +/- SD) (p < 0.05). The probability of still being pregnant at 24 hours (Life table analysis) was 14% (misoprostol group) and 26% (oxitocyn group). The difference was also statistically significant (p < 0.01). No undesirable side effects were observed in any of the patients, however, polisystoly (> 5 contractions in 10 min) was more frequently observed in the patients induced with misoprostol (24.6% vs 13.3%; p = NS). Cesarean section rate was higher in the oxytocin-induced patients (25.3%) than in the misoprostol-induced women (3.8%) (p < 0.05). The main cause of cesarean section was failure to progress in labor in both groups of patients. Neonatal outcome was good in both groups and there were no differences with respect to birthweight or to Apgar scores.(ABSTRACT TRUNCATED AT 250 WORDS)

On-orbit performance of the Hubble Space Telescope fine guidance sensors.

The observed and measured on-orbit performance of various aspects of the fine guidance sensors is presented and discussed in the light of the original requirements and predictions. The fine guidance sensors are shown to meet or exceed the original requirements concerning dynamic pointing errors, photometric repeatability, and moving-target tracking capability. Calibration accuracy has been sufficient for observations to date, and fine-lock acquisitions are approaching a 100% success rate. Improvements to the fine-guidance-sensor tolerance of telescope spherical aberration, the South Atlantic anomaly, and solar-panel vibrations have been made, and further improvements are expected.

Primary pulmonary cryptococcosis presenting as a superior sulcus tumor.

A patient underwent resection of a superior sulcus tumor after an extensive workup was nondiagnostic. Postoperatively, primary pulmonary cryptococcosis was diagnosed. Management of this patient is presented along with a review of the literature.

Cadralazine for the treatment of preeclampsia. An open, noncomparative, dose-finding pilot study.

The antihypertensive effect, tolerability, and influence on placental and fetal circulation of cadralazine, a 6-substituted derivative of 3-hydrazinopyridoxine structurally related to hydralazine, was assessed in 46 preeclamptic patients in the third trimester of pregnancy and with diastolic blood pressure of 100-120 mm Hg after 24 hours of bed rest. Patients who fulfilled the inclusion criteria at the initial report (24-48-hour run-in period after hospitalization) entered the titration period. During titration, cadralazine was administered at an initial dose of 5 mg once a day; if after 3 days diastolic blood pressure was still above 90 mm Hg, 5 mg more was added for another 3 days, and so forth, until the maximum dose (20 mg once a day) was reached. Patients who did not lower diastolic blood pressure below 90 mm Hg were considered nonresponders; those who achieved the desired diastolic level (responders) entered the maintenance period, which lasted until delivery. Eight patients delivered during the titration period (premature discontinuation group). A significant decrease in systolic and diastolic blood pressures was observed between the initial report and the titration period. During titration, there were 27 responders (71%) and 11 nonresponders. One of the responders was lost to follow-up. Cadralazine proved to be effective in lowering blood pressure levels; in the group of responders, a mean diastolic reduction of 20% was observed. This significant decrease was not affected by the diastolic blood pressure increase observed at the end of gestation. No adverse effects from the drug were observed on fetal development or immediate postnatal adaptation to stress during labor, and only mild maternal side effects were detected (headache).