Predicting feed efficiency of Angus steers using the gastrointestinal microbiome.

Microbial composition of the gastrointestinal tracts is an important factor affecting the variation in feed efficiency in ruminants. Several studies have investigated the composition of the ruminal and fecal microbiotas, as well as their impacts on feed efficiency and digestion. In addition, next-generation DNA sequencing techniques have allowed us to gain a better understanding of such microbiomes. In this study, the beef cattle microbiome data were analyzed using both a multivariate and a univariate approach and the results were compared. Moreover, a statistical procedure to classify calves in two groups with extreme Residual Feed Intake (RFI) values, using their microbiota profile, was developed. Both fecal and ruminal samples were collected from 63 Angus steers at two different time points for evaluation of their microbiomes: at the beginning and at the end of the feedlot. An additional fecal sample was collected at weaning. A total of 149 and 119 bacterial families (BFs) were retrieved from the ruminal and fecal samples, respectively. A Canonical Discriminant Analysis (CDA) was used to investigate whether BFs were able to distinguish between rumen and fecal samples. A sub-sample of 28 steers was divided in two groups based on their feed efficiency status: positive or negative for RFI. Fecal samples collected at weaning were used to assign the positive and negative RFI animals to their corresponding groups using both Stepwise Discriminant Analysis and CDA. Results revealed that CDA was able to distinguish between rumen and fecal samples. Peptostreptococcaceae was the family most associated with the fecal samples, whereas Prevotellaceae the most associated with the ruminal samples. The CDA using 19 BFs selected from the stepwise was able to correctly assign all animals to the proper RFI groups (negative or positive). Rhizobiaceae was the family most associated with negative RFI, whereas Comamonadacea was the family most linked with positive RFI. The results from this study showed that the multivariate approach can be used to improve microbiome data analysis, as well as to predict feed efficiency in beef cattle using information derived from the fecal microbiome.

The relationships between IFNL4 genotype, intrahepatic interferon-stimulated gene expression and interferon treatment response differs in HCV-1 compared with HCV-3.

BACKGROUND: The biological mechanism underlying the association between IFNL4/IFNL3 polymorphism and peginterferon/ribavirin (PR) response in HCV-1 is thought to involve differential intrahepatic interferon-stimulated gene expression. HCV-3 is more sensitive to PR, but there are no studies of the association between IFNL4 polymorphism, PR treatment response and liver interferon-stimulated gene expression in HCV-3. AIM: We evaluated the association between IFNL4/IFNL3 genotypes, PR treatment outcomes and intrahepatic interferon-stimulated gene expression, according to HCV genotype. METHODS: HCV-1 and HCV-3 patients who received PR therapy were identified. IFNL3 (rs12979860) and IFNL4 genotype (rs368234815) were determined. A second cohort with stored liver specimens was identified. Expression of ISGs was measured by rt-PCR. RESULTS: Two hundred and fifty-nine patients were identified: 55% HCV-1, 45% HCV-3. IFNL4 genotype frequency was TT/TT 44%, TT/ΔG 42% andΔG/ΔG 14%. Linkage disequilibrium with IFNL3 genotype was high (r(2) = 0.98). The association between IFNL4 genotype and PR response was attenuated in HCV-3 vs. HCV-1 (HCV-3: SVR 89% vs. 76% vs. 72% for TT/TT vs. TT/ΔG vs. ΔG/ΔG, P = 0.09; HCV-1: SVR: 82% vs. 29% vs. 24%, P < 0.001). Intrahepatic ISG expression was evaluated in 92 patients; 61% HCV-1. The association between IFNL4 genotype and liver ISG expression was significantly different for HCV-3 vs. HCV-1 (P-value for interaction = 0.046), with levels of interferon-stimulated gene expression being highest in HCV-1 patients who carried a poor-response IFNL4 genotype. CONCLUSIONS: The relationship between IFNL4 genotype and PR treatment response as well as intrahepatic interferon-stimulated gene expression differs between HCV-1 and HCV-3. These data suggest fundamental differences in host-virus interactions according to HCV genotype.

Expression of genes involved in lipogenesis is not increased in patients with HCV genotype 3 in human liver.

Hepatitis C virus (HCV) infection is frequently associated with hepatic steatosis, particularly in patients with HCV genotype-3 (HCVGT3). It has variously been hypothesized, largely from in-vitro studies, to be the result of increased synthesis, decreased metabolism and export of triglycerides. We measured by real-time PCR the expression of genes involved in lipid metabolism [acetyl-Coenzyme A carboxylase alpha, apolipoprotein B (APOB), diacylglycerol O-acyltransferase 2, fatty acid-binding protein 1, fatty acid synthase, microsomal triglyceride transfer protein (MTTP), peroxisome proliferator-activated receptor alpha (PPARA), peroxisome proliferator-activated receptor gamma (PPARG), protein kinase AMP-activated alpha 1 catalytic subunit (PRKAA1) and sterol regulatory element-binding transcription factor 1 (SREBF1)] in liver biopsies from patients infected with HCV genotype-1 (HCVGT1), HCVGT3 and Hepatitis B (HBV) using ß-glucuronidase (GUSB) and splicing factor arginine/serine-rich 4 (SFRS4) as housekeeping genes. Patients infected with HCVGT3 were younger than those infected with HCVGT1 (36.3 ± 2.5 vs 45.6 ± 1.5, P < 0.05, Mann-Whitney) and were more likely to have steatosis (69.2%vs 11.8%). No significant difference was found in the expression of genes involved in lipogenesis or transport in patients infected with HBV or HCV of either genotype. Contrary to expectation, given the greater degree of steatosis in HCVGT3-infected liver, expression of enzymes involved in lipogenesis was not elevated in HCVGT3 compared with HCVGT1 or HBV-infected liver. Significantly less mRNA for SREBF1 was found in HCVGT3-infected liver tissue compared with HCVGT1-infected liver (1.00 ± 0.06 vs 0.70 ± 0.15 P < 0.05). These results suggest that steatosis in patients infected with HCVGT3 is not the result of a sustained SREBF1 driven increase in expression of genes involved in lipogenesis. In addition, a significant genotype-independent correlation was found between the expression of APOB, MTTP, PRKAA1 and PPARA, indicating that these networks are functional in HCV-infected liver.

The usefulness of holding in the management of congenital heart disease.

BACKGROUND: In our Pediatric Cardiology Unit we have implemented a number of specific interventions in order to support parents and their children who have congenital heart disease. We paid particular attention about how communicating the diagnosis and how supporting psychologically the parents. METHODS: In order to check the validity of these interventions we used the State-Trait Anxiety Inventory to analyze and compare the anxiety levels of 380 parents of already established patients here in the hospital to the anxiety levels of 240 parents of children seen in our unit for the first time (for screening or evaluating anomalous symptoms). RESULTS: Our analysis shows that during daily life the seriousness of the disease affects parents adversely (the "anxiety trait" in parents of children with cyanotic congenital heart disease has a higher rate than other parents, p < .05). While waiting for medical assessment, the parents of children with a previous diagnosis of congenital heart disease or those with symptomatic children live an increment of the level of anxiety (the "anxiety state" has a higher score than the "anxiety trait", p < .001), but the "anxiety state" of parents of children with congenital heart disease has a lower rate in respect to parents of symptomatic children (p < .001). CONCLUSIONS: Thus adequate interventions, specifically an effective communication in a comfortable environment, can reduce anxiety of parents while waiting for medical assessment. It is very important as the child's psychological wellbeing is very directly related to the emotional state of the parents.

Integration of composite and ceramic restorations in tetracycline-bleached teeth: a case report.

UNLABELLED: The success of an esthetic rehabilitation depends on the understanding of the patient's need and expectation. The management of patients with moderate to severe tetracycline-stained teeth is very challenging. Tooth whitening may be a valid alternative to more aggressive treatments; however, patients should be aware of the limitations of tooth whitening therapy. Clinicians may select differing treatment plans; tooth whitening can improve intrinsic discoloration in a way so that no further treatment is required. Once tooth whitening is completed, direct or indirect restorative procedures may be afforded to match the existing restoration with the bleached tooth structure. This article describes a conservative clinical approach to rehabilitate the smile of a patient with moderate to severe tetracycline-stained teeth using a combination of tooth whitening and direct composite and indirect porcelain restorations in the maxillary anterior segment. CLINICAL SIGNIFICANCE: The combination of tooth whitening and adhesive restorations allows clinicians a significantly more conservative approach to intrinsically stained teeth; tooth preparation for porcelain veneers and porcelain-fused-to-metal and full-ceramic crowns can be restricted to conditions in which persistent tooth discoloration or significant loss of both dentin and enamel exists.

In vitro evaluation of giomers microleakage after exposure to 33% hydrogen peroxide: self-etch vs total-etch adhesives.

This study evaluated the microleakage of a giomer resin bonded with total-etch and self-etch adhesive systems after exposure to hydrogen peroxide. Thirty freshly extracted, caries-free human premolars and molars were used. The teeth were randomly divided into two groups: Group I was exposed to 33% hydrogen peroxide (Niveous-Shofu) for 30 minutes daily for five consecutive days; Group II received no treatment (control). A week later, Class V standardized preparations were performed on the facial and lingual surfaces, with the gingival margin placed 1 mm below the CEJ. Each group was then divided into two subgroups: in Groups IA and IIA, a self-etching adhesive system (FL Bond-Shofu) was applied, and in Groups IB and IIB, a total-etch adhesive system (Prime Bond NT-Dentsply/Caulk) was applied according to manufacturers' instructions. The teeth were restored using 2-mm increments of Beautifil A2 resin-based giomer material (Shofu). Each layer was cured using a Spectrum 800 curing light (Dentsply/Caulk) for 20 seconds at 600mW/cm2. The teeth were thermocycled 500x between 5 degrees C and 55 degrees C with a dwell of 30 seconds; they were then placed in a 0.5% methylene blue dye solution for 24 hours at 37 degrees C. Samples were sectioned longitudinally and evaluated for microleakage at the occlusal and gingival margin under a stereomicroscope at 20x magnification. Dye penetration was scored using the following scoring system 0 = no penetration; 1 = partial dye penetration along the occlusal or gingival wall; 2 = partial dye penetration along the occlusal or gingival wall but did not include the axial wall; 3 = dye penetration to and along the axial wall. A Mann-Whitney test revealed a statistically significant difference between subgroups at the occlusal level (p < 0.0001). Group IA yielded the most microleakage. No statistically significant difference was reported at the gingival level. Microleakage was affected by hydrogen peroxide exposure only at the enamel cavosurface margin when a self-etching primer adhesive system was used.

Layering and curing techniques for class III restorations: a two-year case report.

The direct resin buildup of a Class III restoration based on contemporary layering and curing techniques allows clinicians to provide conservative treatment and a virtually imperceptible blend with adjacent tooth structures. This presentation describes a new approach to the Class III buildup. The importance of restoring enamel and dentin as two different substrates is also stressed. In this context, the selection of a microhybrid composite resin system able to reproduce the optical and mechanical properties of the natural dentition can help to achieve these goals.

Secondary bone grafting of alveolar cleft.

AIM: The study evaluates the repair of residual alveolar cleft through secondary bone graft, consisting in the transplantation of autologous bone to restore the continuity of the maxillary arch and achieve normal functioning and esthetics. METHODS: During 2001-2002, 15 patients (age range 9-26 years; 7 males, 8 females) were submitted to secondary bone graft at the Maxillo-facial Surgery Operative Unit, University Hospital, Sassari. Eleven patients had complete unilateral cleft, 4 had complete bilateral cleft. All patients were operated upon by the same surgeon; they received a graft of autologous bone from the iliac crest. For preoperative and postoperative evaluation at 1 year, the following were utilised: plaster casts of the tooth arches, OPT, photographs and complete clinical documentation. RESULTS: Postoperative results were: 100% formation of a bone bridge between the maxillary segments; 70% closure of oro-nasal fistula; 100% maxillary stability; 80% spontaneous eruption of the canine within the graft; 70% height of alveolar ridge level I, 25% level II, 5% level III; 70% orthodontic closure; 80% optimal periodontal condition and 20% presence of gingival recession. In 1 subject the graft site became infected, in 4 cases an oro-nasal fistula remained. CONCLUSION: This method was found to be the most valid one at present. The best period to intervene is during late childhood (9 years). Results and functional and esthetic recovery were satisfactory and encouraging to continue utilising this technique.

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group

The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5 percent) achieved complete remission and 4 (4.3 percent) partial remission. Three patients (3.2 percent) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9 percent, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

A third generation regimen VACOP-B with or without adjuvant radiotherapy for aggressive localized non-Hodgkin's lymphoma: report from the Italian Non-Hodgkin's Lymphoma Co-operative Study Group.

The objective of this multicenter prospective study was to determine the clinical efficacy and toxicity of a polychemotherapeutic third generation regimen, VACOP-B, with or without radiotherapy as front-line therapy in aggressive localized non-Hodgkin's lymphoma. Ninety-three adult patients (47 males and 46 females, median age 45 years) with aggressive localized non-Hodgkin's lymphoma, 43 in stage I and 50 in stage II (non-bulky), were included in the study. Stage I patients received VACOP-B for 6 weeks plus involved field radiotherapy and stage II patients received 12 weeks VACOP-B plus involved field radiotherapy on residual masses. Eighty-six (92.5%) achieved complete remission and 4 (4.3%) partial remission. Three patients (3.2%) were primarily resistant. Ten-year probability of survival, progression-free survival and disease-free survival were 87.3, 79.9 and 83.9%, respectively. Eighty-four patients are surviving at a median observation time of 57 months (range: 6-126). Statistical analysis showed no difference between stages I and II in terms of response, ten-year probability of survival, progression-free survival or disease-free survival. Side effects and toxicity were negligible and were similar in the two patient groups. The results of this prospective study suggest that 6 weeks of VACOP-B treatment plus radiotherapy may be the therapy of choice in stage I aggressive non-Hodgkin's lymphoma. Twelve weeks of VACOP-B treatment with or without radiotherapy was shown to be effective and feasible for stage II. These observations need to be confirmed by a phase III study comparing first and third generation protocols in stage I-II aggressive non-Hodgkin's lymphoma.

Reconstruction of severely damaged endodontically treated and bleached teeth using a microhybrid composite resin: two-year case report.

Clinical indications for direct composite restorations have expanded in the last decade, primarily due to improved physical, aesthetic, and handling properties. As a consequence, their increased predictability has encouraged clinicians to progressively abandon amalgam. This article presents a clinical protocol to reconstruct severely damaged endodontically treated and bleached anterior teeth with particular emphasis on placement and curing techniques. Common complications encountered during the bonding of teeth that have undergone endodontic and bleaching treatments are also analyzed.

Early cervical carcinoma: the natural history of lymph node involvement redefined on the basis of thorough parametrectomy and giant section study.

BACKGROUND: Although parametrectomy is the most difficult step in the surgical treatment of cervical carcinoma and is the main cause of postoperative complications, little attention has been given to the patterns of parametrial spread. METHODS: Sixty-nine patients with previously untreated cervical carcinoma (Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] Stage IB1, 49 patients [71%]; Stage IB2, 8 patients [12%]; and Stage IIA, 12 patients [17%]; squamous, 59 patients [86%]; and adenocarcinoma, 10 patients [14%]) underwent radical hysterectomy and pelvic +/- aortic lymphadenectomy. Hysterectomy specimens were processed with the giant section technique. To obtain a thorough three-dimensional assessment of the paracervical tissue, both the superficial and deep layers of the cervicovesical ligament (anterior parametrium) and the uterosacral ligament (posterior parametrium) were separated from the uterus and submitted for pathologic evaluation. After resection of the lateral parametrium with hemoclips, the lympho-fatty tissue remaining around the pudendal vessels was removed carefully and referred to as "the distal part of the lateral parametrium." RESULTS: When analyzing all the parametria, lymph nodes were present in 64 patients (93%). Clinically undetected parametrial involvement was found by pathologic examination in 15 Stage IB1 patients (31%), 5 Stage IB2 patients (63%), and 7 Stage IIA patients (58%). Metastases were found in the cardinal, cervicovesical, and sacrouterine ligaments and principally were comprised of lymph node and vascular space invasion. Twenty-five patients (36%) had pelvic lymph node metastases whereas concomitant parametrial involvement was observed in all patients. The overall 5-year survival was 91%, being higher for parametria and lymph node negative patients (100%) than for those with lymph node and/or parametrial metastases (78%). CONCLUSIONS: A three-dimensional pathologic assessment showed that subclinical parametrial spreading of the so-called "early" tumors (Stage IB-IIA) occurred in approximately 30-60% of these patients, and metastasis to the pelvic lymph nodes always was associated with parametrial disease. A better understanding of the patterns of parametrial diffusion will improve knowledge of the natural history of cervical carcinoma and in the future may influence the treatment of these patients. Furthermore, pathologic assessment of cervical carcinoma should be modified to evaluate correctly the parametrial status of each patient. The current routine pathologic evaluation of the parametria makes it very difficult to detect lymph node metastases and tumor emboli.

Laparoscopic abdominal staging in locally advanced cervical cancer.

In order to determine patterns of peritoneal spread in locally advanced cervical cancer, 59 patients with previously untreated stages IB and IIA tumor size > 4 cm, IIB, III and IVA cervical cancer were considered for laparoscopic abdominal staging. Fifty-six patients (95%) were considered suitable and underwent laparoscopy. Peritoneal spread was found in 15 (27%) patients. The location was pelvic in nine (17%), extra-pelvic in one (2%), both pelvic and extra-pelvic in four (8%). Peritoneal washing was positive in five (9%) patients, being the unique site of peritoneal spread in one. Overall, 16 (29%) patients had evidence of abdominal disease. The median number of positive sites was one (range 1-4); uterine serosa was positive in nine (17%) patients, pre-vesical peritoneum in seven (13%), Douglas peritoneum in five (10%), paracolic gutter in three (6%), adnexa and omentum in two (4%), and sigmoid serosa in one (2%) patient. One operative complication occurred and all patients were discharged the day after the procedure. To date, with a median follow-up of 27 months (range 7-38), no metastasis has been detected at the trocar insertion sites. To summarize, laparoscopic staging in locally advanced cervical cancer is a safe, feasible and simple technique which is able to accurately detect abdominal disease.

First line Fludarabine treatment of symptomatic chronic lymphoproliferative diseases: clinical results and molecular analysis of minimal residual disease.

Fludarabine (25 mg/m2 for 5 d, every 4 wk, for 6 courses) was administered as first line therapy in 32 symptomatic chronic lymphoproliferative diseases. All CLL patients achieved at least partial response (5 CR, 2 nPR, 9 PR) but 44% of patients relapsed. In LG-NHLs response and relapse rate were similar. Haematological toxicity was low. VDJ rearrangement PCR analysis was performed on marrow samples at diagnosis and at the time of response evaluation. In the 3 patients who underwent high dose therapy with peripheral blood progenitor cell rescue analysis was also performed on apheresis samples and on marrow samples at the end of the procedure. Clonal VDJ rearrangement was always evident after Fludarabine therapy even in those patients who achieved histological and immunophenotypic complete remission, whereas it disappeared in 2 of 3 patients who underwent HDT. Our data confirm that Fludarabine monotherapy can reduce the neoplastic mass to a subclinical level and suggest the possibility that high dose therapy might produce true complete remission.

Pattern of bacterial meningitis in Italy, 1994.

During 1994, 603 cases of bacterial meningitis were reported in Italy. Seventy-five percent of cases with determined etiology was due to three agents: Neisseria meningitidis (33.4%), Streptococcus pneumoniae (23.4%) and Haemophilus influenzae (18.6%). The majority of cases due to N. meningitidis and H. influenzae occurred in subjects below five years of age (35.7% and 84.8%, respectively) while S. pneumoniae accounted for 52.8% of meningitis cases in subjects older than 44 year of age. The estimated incidence of N. meningitidis on the national population in 1994 was 0.27 per 100,000. Serogroup B accounted for 62.5% of the serotyped isolates, group C for 23.1%, group A for 7.2%, group W135 for 3.6%, group Y for 1.8%. All tested meningococcal strains were susceptible to penicillin as well as to rifampin. Incidence of meningococcal meningitis in 1994 has been low suggesting that its relative importance compared to other bacteria causing meningitis is likely to change in the future. Therefore, extended surveillance on bacterial meningitis by other etiological agents has to be maintained and implemented in order to undertake the appropriate control measures and evaluate their effect.

Bacitracin significantly reduces degradation of peptides in plant cell cultures.

Production of useful peptides using recombinant plant cells is often limited by the stability of the newly translated peptides in the plant expression system. As an initial step toward producing peptides in transformed plant cell cultures, we examined the stability of exogenously added arginine vasopressin (AVP) peptide in a suspension culture of Nicotiana plumbaginifolia cells. The peptide was lost rapidly from the plant cell culture, but the rate of loss was slowed significantly by the addition of the peptide, bacitracin, at a concentration of 150 mug/mL. At higher concentrations, bacitracin substantially inhibited the growth of the plant cells in culture. (c) 1997 John Wiley & Sons, Inc.

Ontogeny of hormonal and excretory function of the meso- and metanephros in the ovine fetus.

Using reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry we investigated the ontogeny of renin, angiotensinogen and angiotensin converting enzyme (ACE) in the mesonephros at 27 and 41 days of gestation, and the metanephros at 41 and 64 days of gestation in ovine fetuses (term is 145 to 150 days). The volume and composition of fetal urine, stored as allantoic fluid were measured in 12 fetuses at 27 days, and 13 fetuses at 41 days. Renin, angiotensinogen and ACE were identified in both meso- and metanephroi at 41 days but not in the mesonephros at 27 to 30 days. Allantoic fluid volumes were 21 +/- 3 and 45 +/- 5 ml at 27 to 30 days and 41 days, respectively. This fluid was significantly different in composition to that of amniotic fluid or maternal plasma. The results suggest that the mesonephros can substantially modify its glomerular filtrate by 27 days of gestation, and can produce local angiotensin II by 41 days.

Fluconazole versus amphotericin B as empirical antifungal therapy of unexplained fever in granulocytopenic cancer patients: a pragmatic, multicentre, prospective and randomised clinical trial.

Amphotericin B, despite its intrinsic servere toxicity, is the most commonly used empirical antifungal therapy in cancer patients with unexplained fever not responding to empirical antibacterial therapy. The aim of this study was to show whether fluconazole was as effective as, and less toxic than, amphotericin, with no effort made to compare the antifungal activity of the two drugs. A group of 112 persistently febrile (> 38 degrees C) and granulocytopenic (< 1000 cells/mm3) cancer patients, not receiving any absorbable antifungal antibiotic for prophylaxis, with a mean age of 27 years (range 1-73 years), undergoing chemotherapy for a variety of malignancies and with a diagnosis of unexplained fever after at least 96 h of empirical antibacterial therapy, were randomised to receive either fluconazole (6 mg/kg/day up to 400 mg/day) or amphotericin B (0.8 mg/kg/day) as empirical antifungal treatment. Patients were required to have normal chest X-rays at randomisation, no previous history of aspergillosis and negative surveillance cultures for Aspergillus. The intention-to-treat analysis showed defervescence and survival without treatment modification in 42 of 56 patients (75%) in the fluconazole group and in 37 of 56 (66%) in the amphotericin B group (P = 0.4). Duration of therapy was 6 days (95% CI = 4-8 days) in both groups. Death occurred in 3 patients (5%) in the fluconazole and in 2 (4%) in the amphotericin B group. No fungal death was documented in either group. Adverse events developed in 18 of 56 patients (32%) in the fluconazole group and in 46 of 56 (82%) in the amphotericin B group (P < 0.001). In the amphotericin B group, 5 patients had treatment discontinued because of toxicity, versus none in the fluconazole group, a difference which approached statistical significance (P = 0.06). This study shows that fluconazole is by far less toxic than amphotericin B and suggests that it might be as effective as amphotericin B, in pragmatical terms and for this specific indication. However, numbers are too small to allow definitive conclusions about efficacy, and the use of fluconazole for this indication remains experimental. Future studies should try to identify patients more at risk of fungal infections, with the aim of individualising antifungal approaches.

Twelve years experience with high-dose therapy and autologous stem cell transplantation for high-risk Hodgkin's disease patients in first remission after MOPP/ABVD chemotherapy.

High-dose therapy followed by autografting can cure patients with aggressive Hodgkin's disease (HD) refractory or with early relapse to first-line combination chemotherapy. On the other hand, the eradication of the disease is rarely achieved in heavily pretreated patients. It has been suggested that patients with HD with very high risk characteristics at diagnosis, often relapse despite appropriate therapy with 7-8 drugs combination. Thus it seems to us that such patients are potential candidates for early autografting during first remission. Twelve years ago, we initiated a pilot study to investigate whether patients with very high risk characteristics, would benefit from early autografting. The application of early autografting was compared with our historical group of patients in complete remission after receiving MOPP/ABVD, who had the same negative prognostic characteristics, refused autografting and who did not receive other treatment after achieving complete remission. Among the 22 consecutive patients entered into the pilot study and autografted, 18 are alive and 17 (77%) remain alive in unmaintained remission at a median of 86 months. One patient (4%) died of interstitial pneumonitis in the transplantation group. Only 8/24 (33%) patients, who did not receive an autograft, are currently alive and disease free at a median of 89 months. In conclusion, the early application of autografting appears to improve the outcome in patients with very high risk HD who achieved remission with MOPP/ABVD.