Dietary contribution of iron from limestone and dicalcium phosphate for broiler chickens.

Iron is routinely supplemented in broiler feeds aiming to prevent dietary deficiencies. Limestone and phosphates are very rich in Fe; however, its contribution from these sources have not been thoroughly investigated with chickens. The present research was conducted to evaluate live performance and blood parameters of broilers when using limestone and dicalcium phosphate as sources of Fe. A total of 576 one-day-old male Cobb x Cobb 500 were allocated into a total of 72 battery cages, 6 treatments with 12 replication cages of 8 chicks at placement. Chicks were fed diets formulated with corn, soybean meal (SBM) with laboratory grade calcium carbonate and phosphoric acid (having traces of Fe). All chicks were fed a common prestarter without Fe supplementation (analyzed total 58.2 ± 2.4 mg/kg Fe) from placement to 7 d. Allocation of birds to dietary treatments was completely randomized on day 8. Treatments had increasing Fe derived from commercial limestone and dicalcium phosphate (analyzed Fe 7,218 and 4,783 mg/kg, respectively) progressively replacing calcium carbonate and phosphoric acid to provide graded increases in total Fe (analyzed Fe in the feeds were 57.6 ± 2.1, 92.0 ± 2.3, 124.1 ± 2.7, 159.3 ± 3.1, 187.2 ± 3.2, 223.7 ± 3.6 mg/kg, respectively). There were no effects of dietary Fe on live performance, hematocrit, and hemoglobin the end of the study on day 28 (P > 0.05). Increasing dietary Fe from commercial limestone and dicalcium phosphate led to a linear reduction in the percent ileal digestible Fe. However, linear increments in Fe retention, serum ferritin and liver Fe occurred when compared to feeds without Fe derived from limestone and phosphate dicalcium. It is concluded that Fe from limestone and dicalcium phosphate can be partially utilized by broiler chickens. It was estimated that the Fe retained from limestone and dicalcium phosphate is of 1.9%. Broilers fed corn-soy feeds (58.2 mg/kg Fe) do not require supplemental Fe.

Manganese requirements of broiler breeder hens.

The present research was conducted to assess Mn requirements of broiler breeder hens. One hundred and twenty Cobb 500 hens, 22 wk of age, were individually allocated in cages. After fed a Mn-deficient diet (22.2 ppm), hens were randomly placed in treatments having 6 increments of 30-ppm Mn. All trace minerals were from laboratory grade sources being Mn from Mn sulfate (MnSO4H2O). Treatments were fed for 4 periods of 28 d. There were no interactions between dietary Mn and period for any evaluated response (P > 0.05). Requirements of Mn for hen day egg production and settable egg production were 115.8 and 56.6 ppm and 122.1 and 63.6 ppm (P < 0.05), respectively, using quadratic polynomial (QP) and broken line quadratic (BLQ) models, whereas total eggs and total settable eggs per hen had Mn requirements estimated at 115.7 and 56.6 and 121.8 and 61.7 ppm (P < 0.05), respectively. Number of cracked, defective, and contaminated eggs decreased, whereas hatchability, hatchability of fertile eggs, eggshell percentage, and eggshell palisade layer increased when hens were fed diets having 48.5 to 168.2-ppm Mn (P < 0.05). Maximum responses for egg weight and eggshell percentage were 117.7 and 63.6 ppm as well as 131.6 and 71.0 ppm (P < 0.05), respectively, using QP and BLQ models. Breaking strength and egg specific gravity had Mn requirements estimated at 140.2 and 112.7 ppm as well as 131.3 68.5 ppm (P < 0.05), whereas eggshell palisade layer and eggshell thickness were maximized with 128.8 and 68.8 ppm and 140.2 134.2 ppm, respectively, for QP and BLQ models (P < 0.05). Maximum yolk Mn content values were obtained using 118.0- and 118.4-ppm Mn by QP and BLQ models, respectively. The average Mn requirements estimated for QP and BLQ models is 128.4 and 92.3 ppm Mn (18.7 and 13.5 mg/hen/d), respectively, which is much lower than what has been currently recommended in commercial production.

An in vivo evaluation of the effects of feed restriction regimens on wooden breast using ultrasound images as a predictive tool.

1. Gradual feed restriction was applied to broilers in order to reduce growth rate and, as a consequence, gradually impacts wooden breast myopathy occurrence. Ultrasound (US) images of breast muscle in live birds were correlated with breast fillets presenting wooden breast characteristics (WB). 2. A total of 1800 Cobb × Cobb 500 slow-feathering male chicks were fed one of the six feed restriction treatments with 12 replicates of 25 birds each, in a completely randomised design. Birds were fed ad libitum or were pair-fed to 50%, 60%, 70%, 80% or 90% of normal ad libitum intakes from 8 to 49 d to provide a gradual reduction in growth rate. Ultrasound images were obtained weekly from all birds and, in parallel, one bird per pen was weekly slaughtered and the major breast muscle was weighed and WB graded as 0 (normal), 1 (mild hardening in the upper), 2 (moderate hardening in the upper and/or lower), 3 (severe hardening) and 4 (severe hardening with haemorrhagic lesions and yellow fluid). Blood was taken for analysis of enzymes related to muscle cell breakdown. 3. Feed restriction applied at 50%, 60%, 70%, 80% and 90% of the ad libitum feed intake (FI) resulted in decreased body weight gain (BWG; P ≤ 0.05). 4. From 21 to 49 d, the increasing feed restriction led to linear increases (P ≤ 0.05) in WB scores, fibre density as well as breast depth and breast echogenicity. Creatine kinase, lactate dehydrogenase and aspartate aminotransferase concentration decreased linearly when broilers were feed restricted (P ≤ 0.05). 5. Wooden breast was positively correlated with echogenicity at 21 d (r = 0.510), 28 (r = 0.531), 35 (r = 0.470), 42 (r = 0.430) and 49 d (r = 0.548) (P ≤ 0.001). The use of breast echogenicity can be an additional tool to early detect alterations related to wooden breast.

PERSPECTIVE: Pollen Cryopreservation for Plant Breeding and Genetic Resources Conservation.

Pollen conservation is an important tool for the maintenance of plant genetic resources and can promote improved efficiency in breeding programs and germplasm conservation and exchange. This review aims to understand the importance of pollen cryopreservation and how to use it for distinct species in order to encourage the use of this methodology in germplasm banks and plant breeding programs. Pollen from many plant species have already been successfully cryopreserved in liquid nitrogen. Analogous with other plant structures, to maintain pollen viability after storage at ultra-low temperatures it is necessary to adjust the water content so that at least the freezable is removed. Optimum pollen moisture levels for cryopreservation varies among species and different methods have been applied to control moisture content. Common methods to decrease pollen moisture content include exposure to saturated solutions of various salts (which have a well-defined relative humidity), silica gel, dry air or treatment with vitrification solutions. It is our understanding that pollen cryopreservation is a safe and practical alternative for conserving genetic material that is often neglected by potential users. The technique has the potential to overcome challenges of breeding programs, such as flowering asynchrony between different parent genotypes, and the production of insufficient pollen in nature. Generally, pollen cryopreservation techniques tend to be simple enough to be used routinely in research, plant breeding and germplasm conservation programs.

Utilization of corn-based diets supplemented with an exogenous α-amylase for broilers.

A study was conducted to evaluate the effects of a supplemental α-amylase on energy and nutrient utilization of broiler chickens fed diets with variable amounts of corn. A total of 480 slow feathering Cobb × Cobb 500 male broilers were randomly distributed into 10 treatments with 8 replicates of 6 birds each. Birds were fed a common starter to 14 D post-hatch. The experimental diets were provided subsequently until 25 D, which were a conventional corn-soy basal diet (CS) and a corn-soy diet displaced with 40% of corn (CN). These were fed as-is or supplemented with 40, 80, 120, or 160 kilo-Novo α-amylase units (KNU)/kg. Dietary treatments were distributed factorially as a 2 × 5 arrangement (diet type vs. amylase). Samples of feed, excreta, and ileal digesta were analyzed for determination of ileal digestible energy (IDE), ME, total tract retention, and digestibility of dry matter, protein, and fat. No interactions between diet type and amylase were observed. The CN diet had lower (P < 0.05) energy utilization and nutrient digestibility when compared to the CS diet. AMEn and IDE increased (P < 0.05) by 110 and 207 kcal/kg, respectively, when CS and CN diets were supplemented with 80 KNU/kg. The amylase added to the CS diet led to quadratic increases (P < 0.05) on growth performance, IDE, AME, and AMEn, as well as in dry matter, protein, and fat digestibility. Energy utilization and crude protein digestibility were linearly increased (P < 0.05) when amylase was added to the CN diet or the extrapolated 100% of corn. In conclusion, energy utilization, digestibility of crude protein, fat, and dry matter increased with amylase supplementation in corn-soy-based diets. When amylase was tested in a complete diet having 53.6% corn, 100 and 105 KNU/kg maximized AMEn and IDE, respectively; however, the maximum energy response in the CN diet or 100% of corn was not achieved until 160 KNU/kg, suggesting an association between amylase dose optimization and dietary starch concentration.

Morphological, cytogenetic, and molecular characterization of Arachis kuhlmannii Krapov. & W.C. Greg. (Leguminosae).

Arachis kuhlmannii occurs in Mato Grosso and Mato Grosso do Sul States, Brazil. Its area of occurrence partially overlaps with that of other species in the Arachis section. Because of their morphological similarities, these species are often mistaken one for another. This study aimed the correct classification of available accessions as Arachis kuhlmannii, or other species, and the characterization of similarities among accessions and Arachis hypogaea by morphological, cytogenetic, and molecular marker analyses. Thirty-eight accessions were used. Principal component analysis was used for morphological characterization, root tips for mitotic metaphase analysis, and RAPD markers for molecular characterization. Cluster analysis discriminated accessions with the A genome from the B genome. Cluster analysis based on molecular markers discriminated natural populations in a manner that correlated with geographical areas of the collection. Arachis cardenasii and A. hypogaea were isolated from other A-genome accessions. Cytogenetic analyses confirmed the existence of diagnostic characteristics that distinguish species with the A genome from those with the B genome. Results suggest the need for a taxonomic review of some species in the Arachis section, as we could not discriminate as distinct species all of the accessions identified as A. kuhlmannii, A. helodes, and A. simpsonii by using morphological, molecular, and cytogenetic markers.

Warm-Season (C4) Turfgrass Genotypes Resistant to Spittlebugs (Hemiptera: Cercopidae).

Screening for resistance to insect pests is one of the early stages of grass breeding programs. Pasture spittlebugs are sap-sucking insects that potentially cause severe damage to turfgrasses, including the loss of functional quality and perenniallity. The Brazilian flora has a large number of grass species with wide morphological variability and adaptability to different soil and climate conditions that can potentially be used as lawns. However, no study has screened turfgrass genotypes for resistance to spittlebug attack. In this study, we evaluated the intra- and interspecific variability of 35 turfgrass genotypes in the genera Paspalum, Axonopus, and Zoysia for resistance to the pasture spittlebugs, Deois flavopicta (Stal) and Notozulia entreriana (Berg) (Hemiptera: Cercopidae), as measured by damage scores, densities of nymphs and adults, and level of antibiosis resistance. Genotypes were grouped into three groups using cluster analysis and principal component analysis: GroupI had genotypes associated with low damage scores and high density of adult spittlebugs; GroupII had genotypes with intermediate damage scores and low density of nymphs and adults; and GroupIII was formed by genotypes with high damage scores and high nymph density. Intra- and interspecific genotypic variability was related to antibiosis resistance and morphological variation among genotypes with some indicating nonpreference resistance and others indicating tolerance resistance. Our results indicate that besides antibiosis resistance studies, it is essential to evaluate the morphological variability of grass genotypes when screening for resistance to insects. Further studies are needed to elucidate the intraspecific variability of Paspalum notatum Flüggé genotypes for resistance to spittlebug attack.

New hybrids from peanut (Arachis hypogaea L.) and synthetic amphidiploid crosses show promise in increasing pest and disease tolerance.

The primary gene pool of the cultivated peanut (Arachis hypogaea L., allotetraploid AABB) is very narrow for some important characteristics, such as resistance to pests and diseases. However, the Arachis wild diploid species, particularly those from the section Arachis, still have these characteristics. To improve peanut crops, genes from the wild species can be introgressed by backcrossing the hybrids with A. hypogaea. When diploid species whose genomes are similar to those of the cultivated peanut are crossed, sterile hybrids result. Artificially doubling the number of chromosomes of these hybrids results in fertile synthetic polyploids. The objectives of this study were: 1) to obtain progenies by crossing amphidiploids with the cultivated peanut, and 2) to characterize these two groups of materials (amphidiploids and progenies) so that they may be efficiently conserved and used. Using morphological, molecular, and pollen viability descriptors we evaluated one cultivar of A. hypogaea (IAC 503), eight synthetic amphidiploids, and the progenies resulting from four distinct combinations of crossing between IAC 503 and four amphidiploids.

Digestibility marker and ileal amino acid digestibility in phytase-supplemented soybean or canola meals for growing pigs.

Two experiments using soybean meal (SBM) or canola meal (CM) were conducted to investigate whether the choice of digestibility marker influenced the apparent ileal digestibility (AID) or standardized ileal digestibility (SID) of N and AA in diets supplemented with phytase. In each experiment, 18 barrows fitted with T-cannulas at the ileocecal junction were assigned to 3 diets consisting of a N-free diet to determine endogenous losses of N and AA, a semipurified diet (SBM in Exp. 1 or CM in Exp. 2), and the semipurified diet supplemented with phytase at 1,000 phytase units/kg. Three digestibility markers including acid-insoluble ash (AIA), chromic oxide (Cr2O3), and titanium dioxide (TiO2) were added to each diet at 3 g/kg. Each diet was fed for 7 d, consisting of a 5-d adjustment and a 2-d collection of ileal digesta. In both studies, basal ileal endogenous losses determined with Cr2O3 as a digestibility marker were lower (P<0.01) than with those determined with AIA or TiO2 digestibility markers. Using SBM as the protein source in Exp. 1, there was no interaction between phytase and digestibility marker on AID or SID of AA. The AID of N and AA in SBM using AIA as a digestibility marker tended to be lower (P<0.1) compared with Cr2O3 or TiO2 digestibility markers. Phytase supplementation increased (P<0.001) the AID of Ca and P. The use of AIA or Cr2O3 digestibility marker tended to be associated with lower (P<0.1) SID values compared with TiO2. Phytase did not affect the SID of N or any AA in SBM except for Met, for which there was an increase (P<0.05) with phytase supplementation. Using CM as the protein source in Exp. 2, there were significant interactions between digestibility marker and phytase. Phytase supplementation had effects (P<0.01) on AID or SID when Cr2O3 or TiO2 was used as the digestibility marker. With Cr2O3 or TiO2 as the digestibility marker in the CM diets, phytase supplementation increased (P<0.05) the SID of N and all AA (except Trp). There was no SID of N or AA response to phytase supplementation of CM when AIA was used as a digestibility marker. In contrast, there were no clear improvements in AA digestibility from phytase supplementation for SBM. Phytase effects on AID or SID of AA were dependent on the digestibility marker used in diets when CM was used as the protein source but not when SBM was used as the protein source. Therefore, AA digestibility response to phytase supplementation may depend on the protein being evaluated as well as the choice of digestibility marker.

Development of bone in chick embryos from Cobb 500 breeder hens fed diets supplemented with zinc, manganese, and copper from inorganic and amino acid-complexed sources.

Sources of Zn, Mn, and Cu (IZMC) as sulfates or as amino acid complexes (OZMC) were used to supplement Cobb 500 breeder hen diets. Experimental treatments consisted of diets supplemented with 1) 100, 100, and 10 mg/kg of Zn, Mn, and Cu, respectively, from IZMC (control); 2) 60, 60, and 3 mg/kg of Zn, Mn, and Cu, respectively, from IZMC plus 40, 40, and 7 mg/kg of Zn, Mn, and Cu, respectively, from OZMC (ISO); and 3) a diet with 100, 100, and 10 mg/kg of Zn, Mn, and Cu, respectively, from IZMC as in control plus 40, 40, and 7 mg/kg of supplemental Zn, Mn, and Cu from OZMC (on top). Ten replications of 20 females and 2 males were used per treatment. Eggs from breeders at 30, 40, 50 and 60 wk of age were incubated, and 5 embryos per replicate were collected at 10 (E10), 14 (E14), and 18 (E18) d of incubation. Midshaft width and calcification were measured for left tibia and femur stained with Alcian Blue and Alizarin Red S. At hatch, the left tibia of 5 chicks per replicate was sampled for histological evaluation of the diaphysis and distal epiphysis. Feeding the ISO treatment compared with the control diet increased the Zn (P < 0.05) but not Mn and Cu content of the yolk and albumen blend. At E14, the ISO and on-top treatments had a trend to increase tibia calcification at the rates of 1.6 and 1%, respectively (P < 0.1). The E18 ISO and on-top treatments had 2% thicker tibia compared with the control, regardless of hen age (P < 0.05). Also, at E18, calcification of tibia and femur was higher from hens fed the on-top treatment (P < 0.05). The chicks from the ISO and on-top groups had increased tibia moment of inertia (P < 0.01) at day of hatch. Broiler breeder hens consuming OZMC associated with IZMC produced embryos and hatching chicks with improvements in selected bone mineralization parameters.

Double PPH technique for hemorrhoidal prolapse: a multicentric, prospective, and nonrandomized trial.

INTRODUCTION: Longo's technique (or PPH technique) is well known worldwide. Meta-analysis suggests that the failure due to persistence or recurrence is close to 7.7%. One of the reasons for the recurrence is the treatment of the advanced hemorrhoidal prolapse with a single stapling device, which is not enough to resect the appropriate amount of prolapse. MATERIALS AND METHODS: We describe the application of "Double PPH Technique" (D-PPH) to treat large hemorrhoidal prolapses. We performed a multicentric, prospective, and nonrandomized trial from July 2008 to July 2009, wherein 2 groups of patients with prolapse and hemorrhoids were treated with a single PPH or a D-PPH. Results were compared. The primary outcome was evaluation of safety and efficacy of the D-PPH procedure in selected patients with large hemorrhoidal prolapse. RESULTS: In all, 281 consecutive patients suffering from hemorrhoidal prolapse underwent surgery, of whom 74 were assigned intraoperatively to D-PPH, whereas 207 underwent single PPH. Postoperative complications were 5% in both groups (P = .32), in particular: postoperative major bleeding 3.0% in PPH versus 4.1% D-PPH (P = .59); pain 37.9 % PPH versus 27.3% D-PPH (mean visual analog scale [VAS] = 2.5 vs 2.9, respectively; P = .72); and fecal urgency 2.1% PPH versus 5.7% D-PPH (P = .8). Persistence of hemorrhoidal prolapse at 12-month follow-up was 3.7% in the PPH group versus 5.9% in the D-PPH group (P = .5). CONCLUSIONS: Our data support the hypothesis that an accurate intraoperative patient selection for single (PPH) or double (D-PPH) stapled technique will lower in a significant way the incidence of recurrence after Longo's procedure for hemorrhoidal prolapse.

Double stapled haemorrhoidopexy for haemorrhoidal prolapse: indications, feasibility and safety.

AIM: Selected patients with haemorrhoidal prolapse undergoing double stapled anopexy with the procedure for prolapse and haemorrhoids (PPH03) were studied. METHOD: Between March 2007 and March 2010, 235 patients referred with haemorrhoids were included in the study. Patients with obstructed defaecation were excluded. At surgery intraoperative evaluation for double stapled anopexy was carried out based on the criteria of prolapse occupying half or more of the anal circumference and redundant prolapsed tissue determined by the circular anal dilator. Patients fulfilling these criteria were submitted for double stapled anopexy with the PPH03 stapler. All clinical and operative data were recorded in a prospectively maintained database. RESULTS: Among the 142 patients with haemorrhoidal prolapse having surgery 91 had a single and 51 a double stapled technique. The mean operative time was 34.8 min with no major or minor intraoperative complications. Recurrence at 48 months was 1.9% and the mean satisfaction score was 8.9. CONCLUSION: The double stapled PPH03 technique in selected cases was as safe and effective as a single stapling technique with a lower incidence of recurrence over a medium-term follow-up.

Surgery in hepatic and extrahepatic colorectal metastases.

Extrahepatic disease (EHD) has been considered a contraindication to hepatectomy. Over the last few years, some series reported interesting 5-year survival rates after resection with hepatic colorectal metastases and EHD free margins. Between August 1989 and October 2005, 116 patients underwent liver resection for colorectal metastases at Surgical Department of the University of Udine, Italy. Among these, we reviewed the data of 5 patients affected by EHD. In 3 patients there were also an anastomotic recurrence of the primary tumor, in 3 patients diaphragm was infiltrated by contiguous liver metastases. We performed in all the patients minor liver resections. We have associated the radiofrequence ablation of a lesion not surgically resectable with liver resection in one case. The surgical procedure was always considered as curative. We observed no case of operative mortality. The mean survival of the entire cohort is 23.2 months (range 4-42 months). Our study, even if based upon a limited number of patients, supports the thesis that extrahepatic disease in patients affected by colorectal cancer with hepatic metastases should not be considered as an absolute contraindication to liver resection especially for the cases in with local radical cure exeresis is achievable.

Dexamethasone-netilmicin: a new ophthalmic steroid-antibiotic combination. Efficacy and safety after cataract surgery.

PURPOSE: The purpose of this study was to evaluate both efficacy and safety of a new ophthalmic steroid-antibiotic fixed combination containing dexamethasone and netilmicin in the postsurgical management of cataract surgery. METHODS: In total, 223 patients were randomly treated with dexamethasone 1 mg/ml plus netilmicin 3 mg/ml (n=148), or dexamethasone 1 mg/ml plus tobramycin 3 mg/ml (n=75, TOBRADEX) four times in a day for 7+/-1 days starting immediately after surgery. Efficacy (anterior chamber (AC) inflammation, conjunctival hyperaemia, corneal and lid oedema, ocular infection, pain, photophobia and tearing) and safety (burning, stinging, blurred vision, intraocular pressure, and visual acuity) were analysed in the operated eye after 1 and 7+/-1 days. A follow-up visit was performed at day 14+/-2. The extent of AC inflammation, measured by slit-lamp according to a standard scoring system, was used as primary efficacy parameter. RESULTS: At the primary end point (day 7) both fixed combinations were equally effective in reducing postoperative inflammation. The safety profile of the dexamethasone/netilmicin combination was excellent with no evidence of poor local tolerance or adverse reaction. CONCLUSIONS: A new fixed combination of dexamethasone and netilmicin was effective and safe in controlling ocular inflammation after cataract surgery.

Surgical therapy for patients with extraesophageal symptoms of gastroesophageal reflux disease.

AIM: The last 20 years have seen a systematic reappraisal of the physiopathology and diagnosis of gastroesophageal reflux disease (GERD) and its associated typical symptoms, while less attention has been paid to correlating GERD with certain extraesophageal symptoms and the value of surgery for their treatment. The aim of this study was to determine the clinical and physiopathological features and the outcome of surgery, in a group of patients who underwent laparoscopic fundoplication for GERD with atypical symptoms, and to compare the results with another group of patients operated for GERD with typical symptoms. METHODS: Two hundred and forty-one patients were evaluated for GERD at our Digestive Physiopathology outpatients surgery from January 2001 to January 2003. Of the 36 patients who underwent laparoscopic fundoplication, 23 had the typical symptoms of GERD and 13 had atypical symptoms. Twelve months after surgery, these patients were compared in terms of 24-h pH monitoring, esophageal manometry, regression of symptoms and degree of satisfaction. RESULTS: Postoperatively, patients with atypical symptoms had a smaller increase in effective peristalsis (P = 0.06) and a more limited improvement in symptoms (54% vs 91%, P = 0.001), and they expressed less satisfaction with the surgical treatment (5.9 vs 8.2, P = 0.003). CONCLUSIONS: The results of surgery in GERD patients with atypical symptoms are worse than in those with typical symptoms. A careful preoperative work-up, based on 24-h pH monitoring, is fundamental for patients with atypical symptoms, who also need to be informed of the high likelihood of surgery proving clinically unsuccessful.

Economic evaluation of voriconazole compared with conventional amphotericin B for the primary treatment of aspergillosis in immunocompromised patients.

OBJECTIVE: The objective of this study was to conduct an economic evaluation of voriconazole compared with conventional amphotericin B deoxycholate (CAB) using data from a recently reported randomized comparative trial in patients with various underlying immunosuppressive conditions. This trial demonstrated the superiority of voriconazole in terms of clinical response, survival and safety when used as primary therapy for invasive aspergillosis. METHODS: A decision analytic model was designed using an expert panel and populated primarily with efficacy and resource utilization data collected prospectively during the clinical trial. The analysis was carried out from the perspective of the health care system and all costs are reported in 2002 US dollars. RESULTS: Average total treatment costs per patient were 10% lower in the voriconazole arm ($30 664) than in the CAB arm ($34 144), resulting from reduced consumption of hospital resources and fewer changes in antifungal therapy. In the base case analysis, voriconazole provided an average saving of $3481 per treated patient, resulted in a lower cost per survivor ($43 310 versus $58 971) and a lower cost per successfully treated patient ($58 100 versus $108 124) compared with CAB. Sensitivity analyses demonstrated that the cost savings observed were maintained over a wide range of alternative values for both unit costs and resource utilization, including length of hospital stay, time spent in intensive care units, bed day costs and the cost of lipid formulations of amphotericin B. CONCLUSION: Incremental cost-effectiveness analysis indicated the dominance of voriconazole because of both lower costs and greater efficacy.

Teratogenic vulnerability of Wistar rats to diphenyl ditelluride.

The effect of single maternal subcutaneous (s.c.) injection of 0.12 mg/kg diphenyl ditelluride, (PhTe)2, diluted in canola oil at days 6, 10 or 17 of gestation were evaluated in Wistar rats. The reduction of body weight gain was statistically significant at GD9, for the dams that received (PhTe)2, at GD6; at GD13, for the dams that received (PhTe)2, at GD10, and at GD20, for the dams that received (PhTe)2, at GD17, when compared to respective control groups. External and internal fetal soft tissues examination was performed on day 20 of gestation. Single maternal injection at day 10 of gestation resulted in appearance of malformation in fore- and hind-limbs, absent or short tail, subcutaneous blood clots, exophthalmia, hydrocephalus and absence of the cranial bone and cutaneous tissue in fetuses on day 20 of gestation. Besides, (PhTe)2 reduced fetal body and cerebral weight, kidney length, measurements of body dimension and provoked 73% of fetal mortality. Subcutaneous administration of (PhTe)2 on day 17 of gestation was associated with 94% mortality, hydrocephalus and edema. Histological evaluations of fetal brain demonstrated displaced brain tissue with absence of the cranial bone and cutaneous tissue when diphenyl ditelluride was administered in GD10. Histological evaluation of fetal head exposed at GD17 revealed a decrease of the brain volume with consequent dilation of the lateral ventricles and the adjacent tissues were thinner than that of control group tissues. No fetal changes were observed after administration of (PhTe)2 at day 6 of gestation. Thus, (PhTe)2 can be teratogenic to rat fetuses and toxic for dams. The late fetal stages of rat prenatal development appeared uniquely sensitive to organic tellurium exposure.

A multicenter, double-blind, placebo-controlled trial comparing piperacillin-tazobactam with and without amikacin as empiric therapy for febrile neutropenia.

In a prospective, multicenter, double-blind, randomized clinical trial, we compared the efficacy of piperacillin-tazobactam (4.5 g 3 times daily intravenously) plus placebo versus piperacillin-tazobactam plus amikacin (7.5 mg/kg twice daily intravenously) for the treatment of 760 febrile, adult patients with cancer with chemotherapy-induced profound (<500 neutrophils/mm3) and prolonged (>10 days) neutropenia. A total of 733 patients were assessable for efficacy of the drug regimens, and an overall successful outcome was reported in 49% (179 of 364) of the patients who received monotherapy, compared with 53% (196 of 369) of patients who received combination therapy (P=.2). Response rates were similar with both regimens, as were incidences of bacteremia and clinically documented and possible infections. In our epidemiological setting, the initial empiric combination therapy was not associated with improved outcomes when compared with initial monotherapy.

Infections caused by filamentous fungi in patients with hematologic malignancies. A report of 391 cases by GIMEMA Infection Program.

BACKGROUND AND OBJECTIVES: To evaluate the clinical characteristics of patients with hematologic malignancies developing a filamentous fungi infection (FFI) and to define the prognostic factors for their outcome. DESIGN AND METHODS: A retrospective study, conducted on patients admitted to 14 Hematology divisions of tertiary care or university hospitals, participating in the GIMEMA Infection Program, over a ten-year period (1988-1997). The study included patients with hematological malignancies and a histologically and/or microbiologically proven or probable FFI. RESULTS: We included 391 patients (male/female: 262/129, median age 49 years) with hematologic malignancies (225 acute myeloid leukemia, 67 acute lymphocytic leukemia, 30 chronic myeloid leukemia, 22 non-Hodgkin's lymphoma, 12 myelodysplastic syndrome, 10 aplastic anemia, 7 Hodgkin's disease, 8 chronic lymphocytic leukemia, 5 multiple myeloma, and 5 hairy cell leukemia) who developed a proven FFI. Eighty percent of the patients had been neutropenic for an average of 14 days before the infection, and 71% had an absolute neutrophil count lower than 0.5 x 10(9)/L at the time of FFI diagnosis. The primary sites of infection were: lungs (85%), nose and paranasal sinus (10%), and other sites (5%). The diagnosis was made while still alive in 310 patients (79%), and at autopsy in the remaining 81 patients (21%). Chest X-ray was diagnostic in 77% of patients with pulmonary FFI, while computed tomography (CT) scan of the thorax was positive in 95% of cases. A significant diagnostic advantage for CT scan was observed in 145 patients who had both a chest X-ray and CT scan. Aspergillus was identified as the cause of FFI in 296 patients, Mucorales in 45 patients, Fusarium in 6 patients and other filamentous fungi species in 4 patients, while in a further 40 patients no agent was identifiable. The overall mortality rate three months after the diagnosis of FFI was 74%, and fungal infection had been the cause of death in 51% of patients. INTERPRETATION AND CONCLUSIONS: Our retrospective study shows that FFI still remains a life-threatening complication in neutropenic patients. Despite appropriate treatment, half of the patients die due to this complication. The use of glucocorticoids and recovery from neutropenia are the most important prognostic factors. Mucorales infections are associated with a significantly poorer prognosis than those due to Aspergillus spp.