Biomedical subjects

L Gallo

Publications and source records attributed to L Gallo.

At least 19 recordsLinked to original sources

PubMed2006

Role of dynamic sentinel node biopsy in penile cancer: our experience.

BACKGROUND AND OBJECTIVES: We report our initial experience with a relatively new technique, the so-called "dynamic sentinel node biopsy", in patients with penile cancer. METHODS: From January 2001 to February 2003, 17 consecutive patients with bilateral, clinically node negative penile cancer were enrolled. Dynamic sentinel node biopsy was followed by local excision of the primary lesion or penile amputation during the same session. Standard inguinal node dissection was performed 4 weeks after the first operation in all the patients. RESULTS: Pre-operative lymphoscintigraphy revealed no sentinel nodes in 1, unilateral sentinel nodes in 5, and bilateral in 11 patients. Metastases were noted in 5 out of 16 patients (31.25%), bilaterally in 3 of them. Among the five patients with sentinel node metastasis, this was the only tumor positive lymph node in one patient. In all cases with negative dynamic sentinel node biopsy, no metastatic nodes were found at the following inguinal node dissection. Therefore, the technique showed a 100% negative predictive value and an 88% sensitivity. CONCLUSIONS: We believe that dynamic sentinel node biopsy is a minimally invasive procedure that can be easily performed. The goal is to offer the possibility of less extensive surgery for selected low risk patients.

Aged↗

PubMed2005

Identification of anaerobic threshold using heart rate response during dynamic exercise.

The objective of the present study was to characterize the heart rate (HR) patterns of healthy males using the autoregressive integrated moving average (ARIMA) model over a power range assumed to correspond to the anaerobic threshold (AT) during discontinuous dynamic exercise tests (DDET). Nine young (22.3 +/- 1.57 years) and 9 middle-aged (MA) volunteers (43.2 +/- 3.53 years) performed three DDET on a cycle ergometer. Protocol I: DDET in steps with progressive power increases of 10 W; protocol II: DDET using the same power values as protocol 1, but applied randomly; protocol III: continuous dynamic exercise protocol with ventilatory and metabolic measurements (10 W/min ramp power), for the measurement of ventilatory AT. HR was recorded and stored beat-to-beat during DDET, and analyzed using the ARIMA (protocols I and II). The DDET experiments showed that the median physical exercise workloads at which AT occurred were similar for protocols I and II, i.e., AT occurred between 75 W (116 bpm) and 85 W (116 bpm) for the young group and between 60 W (96 bpm) and 75 W (107 bpm) for group MA in protocols I and II, respectively; in two MA volunteers the ventilatory AT occurred at 90 W (108 bpm) and 95 W (111 bpm). This corresponded to the same power values of the positive trend in HR responses. The change in HR response using ARIMA models at submaximal dynamic exercise powers proved to be a promising approach for detecting AT in normal volunteers.

Adult↗

PubMed2005

The interaction of plasma renin activity and plasma atrial natriuretic peptide in 21-hydroxylase deficiency patients.

Plasma renin activity (PRA) determination is the main index used to evaluate the mineralocorticoid control in 21-hydroxylase deficiency (21-OHD). PRA values within or at the upper limit of the age-appropriate range, or values <5 or 10 ng/ml/h have been regarded as adequate control. Atrial natriuretic peptide (ANP) has opposite actions to those of angiotensin II/aldosterone, and could help to understand the hydrosaline homeostasis in 21-OHD. We studied the interaction between PRA and ANP levels in 10 controls and 26 patients with 21-OHD under corticoid treatment. Patients were divided into two groups according to PRA levels, < or > or = 5 ng/ml/h, irrespective of the clinical form of 21-OHD. Blood samples for determination of PRA and ANP levels were taken after 30 min in the sitting position (basal), after 30 min in the recumbent position and after 15 min of 20 degrees head-down tilting. ANP levels (pg/ml) in the basal, supine and after head-down tilting position were 25.9 +/- 1.6, 42.7 +/- 7.4 and 54.3 +/- 5.5 in controls; 28.5 +/- 2.1, 38.3 +/- 2.1 and 48.8 +/- 4.1 in the group with PRA levels <5 ng/ml/h, and 20.9 +/- 1.9, 26.6 +/- 2.5 and 34.6 +/- 3.1 in the group with PRA levels > or = 5 ng/ml/h, respectively. Basal and after head-down tilting ANP plasma levels were similar between the controls and the group with PRA levels <5 ng/ml/h. However, the group of patients with PRA levels > or = 5 ng/ml/h showed lower basal and stimulated ANP levels compared to the control group (p<0.05). The decreased plasma ANP levels in the basal condition and after head-down tilting indicate a chronic contraction of the extracellular volume in 21-OHD patients with increased PRA levels. Therefore, mineralocorticoid deficiency is counteracted by decreased ANP secretion in order to preserve fluid and electrolyte homeostasis.

Adolescent↗

PubMed2004

Natural hybridization between a deciduous (Nothofagus antarctica, Nothofagaceae) and an evergreen (N. dombeyi) forest tree species: evidence from morphological and isoenzymatic traits.

BACKGROUND AND AIMS: Trees with a partial leaf-shedding pattern and other morphological features a priori considered intermediate between those of the deciduous Nothofagus antarctica (G. Forster) Oersted and the evergreen N. dombeyi (Mirb.) Oersted (Nothofagaceae) were found in natural stands. The hybridization between a deciduous and an evergreen species of Nothofagus has not been reported so far in natural communities. METHODS: The putative hybrids and the two presumed parental species were compared using 14 enzyme systems as well as shoot, leaf and reproductive morphology. KEY RESULTS: Six enzyme systems showed good resolution (MDH-B, IDH, SKDH, 6-PGDH, GOT and PGI) and in four of them (PGI, MDH-B, SKDH and 6-PGDH) the putative hybrids showed intermediate zymogram patterns between N. antarctica and N. dombeyi. Both principal coordinates analysis on isozyme data and principal components analysis (PCA) on quantitative morphological traits of shoots and leaves separated both parental species and located the putative hybrids closer to N. antarctica than to N. dombeyi. In the PCA, the number of basal cataphylls and the length : width ratio of leaves were the variables most discriminating among shoots of the three entities. The putative hybrids were intermediate between both species regarding leaf vernation, outline and venation, variation in leaf shape (length/width) with position on the parent shoot and in staminate inflorescence and cupule morphology. For other morphological traits, the putative hybrids resembled one of the parental species or differed from both species (e.g. valve morphology). CONCLUSIONS: Isoenzymatic and morphological data sets support the idea of the hybrid nature (probably F1 generation) of the semi-deciduous trees found. Nothofagus antarctica and N. dombeyi are probably more closely related than previously assumed. The relevance of pollen type in revealing evolutionary relationships between Nothofagus species is supported, and that of leaf-shedding pattern is rejected.

Crosses, Genetic↗

PubMed2004

Multicenter randomized phase III trial of epirubicin plus paclitaxel vs epirubicin followed by paclitaxel in metastatic breast cancer patients: focus on cardiac safety.

The aim of the study was to evaluate cardiac safety of two different schedules of Epirubicin and Paclitaxel in advanced breast cancer patients enrolled into a multicenter randomized phase III trial. Patients received Epirubicin 90 mg m(-2) plus Paclitaxel 200 mg m(-2) (3-h infusion) on day 1 every 3 weeks for eight courses (arm A), or Epirubicin 120 mg m(-2) on day 1 every 3 weeks for four courses followed by four courses of Paclitaxel 250 mg m(-2) on day 1 every 3 weeks (arm B). Left ventricular ejection fraction was evaluated by bidimesional echocardiography at baseline, after four and eight courses of chemotherapy and every 4 months during follow-up. Baseline median left ventricular ejection fraction was 60% in arm A and 65% in arm B; after four courses, figures were 57 and 60%, respectively. After eight courses, the median left ventricular ejection fraction in arm A declined to 50% while no further reduction was detected in arm B by adding four courses of high-dose Paclitaxel. Seven episodes of congestive heart failure were observed during treatment in arm A. Present monitoring demonstrated that the risk of congestive heart failure or impairment in the cardiac function correlated only with the cumulative dose of Epirubicin; no impact on cardiotoxicity can be attributed to high-dose Paclitaxel.

Adult↗

PubMed2004

Prevalence of spondylosis deformans and estimates of genetic parameters for the degree of osteophytes development in Italian Boxer dogs.

The aim of this study was to assess the prevalence of spondylosis deformans and to investigate genetic aspects of the degree of osteophytes development (DOD) in the Italian Boxer dog population. A total of 849 Boxer dogs was radiographed on the thoracic, lumbar, and sacral regions of the spine and scored for DOD. Grading of DOD was performed for all 20 intervertebral sites comprised within the first thoracic site (site T1-T2) and the site between the seventh lumbar and the first sacral vertebra (site L7-S1). Scores for DOD ranged from 0 (no osteophytes development) to 3 (presence of a bony spur formed by osteophytes on adjoining vertebrae). The first five thoracic sites exhibited no variation for DOD and were not considered in the analysis. The prevalence of spondylosis deformans was 84%, and frequency of dogs showing at least one intervertebral site that scored 3 for DOD was 50%. Scores for DOD at different sites were analyzed as different traits. Nongenetic effects influencing DOD scores were sex, age at screening, and the kennel. Posterior densities of heritability (h2) were estimated using a univariate Bayesian analysis. Eight sites exhibited a posterior probability greater than 0.8 for h2 > 10% and were considered in a multivariate restricted maximum likelihood analysis. Estimated h2 from multivariate analysis ranged from 25 to 48% (SE from 5 to 7%). Three sites exhibited h2 estimates greater than 40%. Genetic correlations for DOD scored at different sites ranged from 0.07 to 0.96. All thoracic sites had estimated correlations larger than 0.85 with other thoracic sites. Genetic correlation between the first and the second lumbar site was 0.91. Correlations between thoracic sites and the first two lumbar sites ranged from 0.5 to 0.9. Sites L6-L7 and L7-S1 also exhibited weak relationships with all remaining sites. Breeding values of dogs for DOD at the eight sites were predicted using estimated covariance matrices. A selection index for DOD was computed from predicted breeding values and a set of relative weighting factors produced by a panel of veterinarians. The index was the most important effect influencing phenotypic differences between dogs for average DOD score, number of affected sites, and number of sites with a DOD score > 1 (P < 0.001). The degree of osteophytes development is a trait showing exploitable additive genetic variance, and breeding programs for decreasing prevalence and severity of spondylosis deformans might focus on this trait.

Age Factors↗

PubMed2004

Computer image analysis for measuring lean and fatty areas in cross-sectioned dry-cured hams.

The aims of this study were 1) to apply computer image analysis to obtain measures of lean and fatty areas on the cross section of dry-cured hams, 2) to investigate variation of these measures, and 3) to evaluate reproducibility and repeatability of these techniques. Traits of concern were the cross-sectional area (SA), lean, or muscles, area (LA), and the fatty area (FA) centered on the cross section and surrounded by biceps femoris, semimembranosus, semitendinosus, and quadriceps femoris, as well as the FA-to-SA ratio (FESR). Hams were obtained from crossbred pigs (n = 279) slaughtered at 9 mo of age (mean BW of 169 +/- 17 kg). Digital images of the cross section of dry-cured hams were captured using standardized procedures. Three replicated measures of areas were collected by three operators using three image analysis techniques (automatic, automatic-assisted, and manual). Variance components were estimated using a linear model that included slaughter group, gender, and gender x slaughter group as fixed effects and operators, pig, and operator x pig as random effects. Statistical analyses considered all measures (n = 7,533) or measures collected after reinstruction of all operators for spatial calibration of the analysis system (n = 4,428). Average SA, LA, FA, and FESR were 350 cm2, 220 cm2, 8.7 cm2, and 2.5%, respectively. Variability of FA (CV = 42%) and of FESR (CV = 39%) was four times greater than that of SA and LA. Slaughter group, pig, operator, and operator x pig effects were the most (P < 0.01) important sources of variation of measures. Correlations between measures obtained with different techniques were greater (P < 0.01) than 0.90, with the exception of LA measures. Coefficients of reproducibility for SA and LA ranged from 87 to 94%, whereas those for FA and FESR ranged from 88 to 98%. Coefficients of repeatability ranged from 92 to 99%. Automatic-assisted and manual methods provided more reproducible and repeatable measures than the automatic technique. Spatial calibration of the software system was a key issue affecting reproducibility and repeatability. Reinstructing the analysts for spatial calibration enhanced both reproducibility and repeatability of all methods of analysis. Computer image analysis is a technique suitable for measuring lean and fatty areas in cross-sectioned hams, providing reproducible and repeatable measures, and it might be used in large sample-based studies to investigate causes of defective fatty areas.

Adipose Tissue↗

PubMed2003

Pulmonary function, cholinergic bronchomotor tone, and cardiac autonomic abnormalities in type 2 diabetic patients.

This prospective study analyzed the involvement of the autonomic nervous system in pulmonary and cardiac function by evaluating cardiovascular reflex and its correlation with pulmonary function abnormalities of type 2 diabetic patients. Diabetic patients (N = 17) and healthy subjects (N = 17) were evaluated by 1) pulmonary function tests including spirometry, He-dilution method, N2 washout test, and specific airway conductance (SGaw) determined by plethysmography before and after aerosol administration of atropine sulfate, and 2) autonomic cardiovascular activity by the passive tilting test and the magnitude of respiratory sinus arrhythmia (RSA). Basal heart rate was higher in the diabetic group (87.8 +/- 11.2 bpm; mean +/- SD) than in the control group (72.9 +/- 7.8 bpm, P<0.05). The increase of heart rate at 5 s of tilting was 11.8 +/- 6.5 bpm in diabetic patients and 17.6 +/- 6.2 bpm in the control group (P<0.05). Systemic arterial pressure and RSA analysis did not reveal significant differences between groups. Diabetes intragroup analysis revealed two behaviors: 10 patients with close to normal findings and 7 with significant abnormalities in terms of RSA, with the latter subgroup presenting one or more abnormalities in other tests and clear evidence of cardiovascular autonomic dysfunction. End-expiratory flows were significantly lower in diabetic patients than in the control group (P<0.05). Pulmonary function tests before and after atropine administration demonstrated comparable responses by both groups. Type 2 diabetic patients have cardiac autonomic dysfunction that is not associated with bronchomotor tone alterations, probably reflecting a less severe impairment than that of type 1 diabetes mellitus. Yet, a reduction of end-expiratory flow was detected.

Adult↗

PubMed2003

Adjuvant chemotherapy in the treatment of colon cancer: randomized multicenter trial of the Italian National Intergroup of Adjuvant Chemotherapy in Colon Cancer (INTACC).

BACKGROUND: To determine whether the addition of leucovorin to the combination 5-fluorouracil plus levamisole prolongs disease-free survival and overall survival in patients with radically resected colon cancer (Dukes' B(2-3) and C). PATIENTS AND METHODS: Patients (1703) were accrued between March 1992 and February 1995 in a large-scale clinical trial within five Italian cooperative groups. After stratification for center, patients were randomized as follows: arm A, 5-fluorouracil [450 mg/m(2) intravenous (i.v.) bolus on days 1-5] and levamisole (150 mg orally for 3 days, every 14 days for 6 months) versus arm B, 6-S-leucovorin (100 mg/m(2) i.v. bolus on days 1-5) followed by 5-fluorouracil (370 mg/m(2) i.v. bolus on days 1-5), plus levamisole (as arm A), every 4 weeks for six cycles. RESULTS: After a median follow-up of 6.4 years no significant difference was seen for either disease-free survival (58% versus 60%, not significant) or 5-year overall survival (68% versus 71%, not significant), respectively. Gastrointestinal toxicity (World Health Organization grade 3/4) was more frequent in arm B (8% versus 18%, not significant). CONCLUSIONS: In this trial the schedules used showed no statistically significant differences in terms of disease-free survival or overall survival in the treatment of colorectal cancer.

Adult↗

PubMed2002

Thymidylate synthase protein expression in colorectal cancer metastases predicts for clinical outcome to leucovorin-modulated bolus or infusional 5-fluorouracil but not methotrexate-modulated bolus 5-fluorouracil.

BACKGROUND: Different 5-fluorouracil (5-FU) schedules and/or biochemical modulators may result in different mechanisms of cytotoxicity, potentially affecting the correlation between thymidylate synthase (TS) expression and the clinical response to the fluoropyrimidine. PATIENTS AND METHODS: TS levels were measured immunohistochemically on archival specimens of colorectal cancer metastases from 124 patients homogeneously treated in a series of clinical trials at our institutions with: (A) leucovorin (LV)-modulated infusional 5-FU (n = 48); (B) LV-modulated bolus 5-FU (n = 41); (C) methotrexate (MTX)-modulated bolus 5-FU (n = 35). RESULTS: A statistically significant correlation between TS levels and the clinical response was observed with the regimens involving continuous infusion and/or LV modulation (response rate in patients with low and high TS: 66% versus 24%, P = 0.003, and 50% versus 0%, P = 0.0001, in group A and B, respectively). Conversely, TS levels failed to predict the clinical response within the group of patients treated with MTX-modulated bolus 5-FU (response rate 21% versus 13%, P = 0.50, with low and high TS, respectively). Consistently, the median time to progression/overall survival time in patients with low and high TS were 9 versus 6 months/19 versus 14 months (P = 0.009/0.035, group A), 8 versus 2 months/12 versus 6 months (P = 0.002/0.0006, group B) and 3 versus 2 months/12 versus 13 months (P = 0.14/0.74, group C). CONCLUSIONS: The correlation between intratumoral TS levels and the clinical response to 5-FU depends strongly on the schedule of administration/biochemical modulators that are used in different 5-FU regimens. These data strengthen the notion that different 5-FU schedules have different mechanisms of cytotoxicity.

Adult↗

PubMed2001

5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer.

We have reported that an alternating regimen of bolus and continuous infusion 5-fluorouracil (FU) was superior to bolus FU in terms of response rate and progression-free survival in advanced colorectal cancer. Biochemical modulation was an essential part of this regimen and it was selective for the schedule of FU administration: bolus FU was in fact modulated by methotrexate (MTX) while continuous infusion FU was potentiated by 6-s-leucovorin (LV). Considering the low cost and the favourable report on the activity of mitomycin C (mito) added to CI FU, we have incorporated this agent in the infusional part of our treatment programme. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated with the following regimen. 2 biweekly cycles of FU bolus (600 mg/m(2)), modulated by MTX (24 h earlier, 200 mg/m(2)) were alternated with a 3-week continuous infusion of FU (200 mg/m(2)daily), modulated by LV (20 mg/m(2)weekly bolus). Mito, 7 mg/m(2), was given on the first day of the infusional period. After a 1 week rest, the whole cycle (8 weeks) was repeated, if indicated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity. These results are consistent with those obtained by our group in 3 previous trials of schedule specific biochemical modulation of FU. They also indicate a highly active, little toxic, inexpensive regimen of old drugs to be used (a) as an alternative to the more expensive combinations including CPT-11 or oxaliplatin or (b) as the basis for combination programmes with these agents.

Adult↗

PubMed2001

Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group.

PURPOSE: To evaluate whether an accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of granulocyte colony-stimulating factor (G-CSF) induces a higher activity and efficacy compared with standard CEF in metastatic breast cancer patients. PATIENTS AND METHODS: Stage IV breast cancer patients were randomized to receive as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2), epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days (HD-CEF14) with the support of G-CSF. Treatment was administered for eight cycles. RESULTS: A total of 151 patients were randomized (74 patients on the CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of administered cycles was eight. The dose-intensity actually administered was 93% and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively. Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was 80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14 arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD-CEF14 arm. No difference in overall response rate (complete plus partial responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively (P =.94). A slightly non-statistically significant higher percentage of complete response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy was observed. The median time to progression was 14.3 and 12.8 months in the CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7 and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16). CONCLUSION: In metastatic breast cancer patients, an 80% increase in dose-intensity of the CEF regimen, obtained by both acceleration and dose intensification, does not improve the activity and the efficacy compared with a standard dose-intensity CEF regimen.

Adult↗

PubMed2001

The relationship between Parson's tubercle and the insertion of the anterior horn of the medial meniscus.

PURPOSE: The purpose of this investigation was to correlate the anatomic characteristics of the third intercondylar tubercle of Parsons (TITP) with the insertional variations of the anterior horn of the medial meniscus using precise measurements in an anatomic cadaver study. Our hypothesis was that the height of the TITP would correlate with the degree of inferior insertion of the medial meniscus. TYPE OF STUDY: A cadaver study using a convenience sample. METHODS: Twenty unpaired proximal tibia specimens without advanced arthritis were analyzed with a coordinate measuring machine using a 0.479-mm diameter probe. A reference plane was created using 3 reproducible points on the tibial surface. Measurements from the TITP included another reference plane through its base, which was used to calculate its absolute height. The locations of the anterior- and inferior-most insertional points of the anterior horn of the medial meniscus were also determined. Correlations between the height of the TITP and age were also made. RESULTS: The overall height of the TITP was found to correlate with the degree of inferior insertion of the anterior horn of the medial meniscus (r =.52, P =.019). No correlation was found with the anterior placement of the meniscus (r =.12, P =.629) or with the age of the specimen (r =.14, P =.592). CONCLUSIONS: This absolute height of the TITP correlates with the inferior location of the insertion of the anterior horn of the medial meniscus. This association suggests a developmental relationship between 2 anatomic structures within the knee.

Adult↗

PubMed2001

Biliary lipid composition in cholesterol microlithiasis.

BACKGROUND: Little information is available on the pathogenesis of cholesterol microlithiasis, and it is not clear if biliary lipid composition in these patients is similar to changes seen in cholesterol gall stone patients. AIMS: To measure biliary lipid composition in patients with cholesterol microlithiasis. PATIENTS: Eleven patients with cholesterol microlithiasis, 20 cholesterol gall stone patients, and 17 healthy controls. METHODS: Duodenal bile was collected in the fasting state during ceruletide infusion. Biliary cholesterol, phospholipids, and total bile acids were analysed by enzymatic assays, and conjugated bile acids by high pressure liquid chromatography. RESULTS: Patients with microlithiasis had a cholesterol saturation index significantly higher than controls (mean value 1.30 (95% confidence interval 1.05-1.54) v 0.90 (0.72-1.08)) but similar to gall stone patients (1.51 (1.40-1.63)). This was due to a significant decrease in per cent phospholipid (10.0% (7.1-12.8)) compared with controls (21.4% (18.1-24.6)) and gall stone patients (24.9% (20.5-29.3)). Per cent cholesterol was similar in patients with microlithiasis and controls (5.3% (4.5-6.1) and 5.6 % (4.3-6.8), respectively) but was significantly increased in gall stone patients (10.9% (9.3-12.4)). Bile acid composition in patients with microlithiasis was similar to controls whereas in gall stone patients deoxycholic acid was significantly increased: 27.3% (24.8-29.7) v 19.0% (15.7-22.2) in controls and 20.6% (14.9-26.2) in patients with microlithiasis. CONCLUSION: Patients with cholesterol microlithiasis have biliary cholesterol supersaturation, similarly to cholesterol gall stone patients. Whereas in the latter this is due to increased per cent cholesterol, in patients with microlithiasis this is caused by phospholipid deficiency, with normal per cent cholesterol and normal biliary bile acid composition.

Adult↗

PubMed2001

Test-day genetic analysis of condition score and heart girth in Holstein Friesian cows.

This study aimed to estimate heritability for condition score and heart girth using a test-day model, to investigate the genetic relationships between condition score, heart girth, and milk yield traits and to analyze the genetic relationships of condition score and heart girth measured at different stages of lactation. Cows from 25 dairy herds were scored for body condition and measured for heart girth at 3-mo intervals for 2 yr. Approximately 5000 test-day observations on condition score, heart girth, and milk fat and protein yield from 1344 Italian Friesian cows were analyzed using two approaches: 1) repeated observations for a trait were considered repeated measurements of the same trait; 2) observations for a trait collected in different stages of lactation (dry period, 1 to 75, 76 to 130, 131 to 210, and 211 to 300 DIM) were treated as different traits. (Co)variance components and related parameters were estimated using REML multiple-trait procedures and animal models with unequal design for different traits. Heritability estimates for fat and protein test-day yield and for test-day condition score and heart girth were 0.22, 0.18, 0.29, and 0.33, respectively. Condition score was negatively correlated with yield traits and positively correlated with heart girth, whereas genetic relationships between heart girth and milk yield traits were negligible. Heritability estimates were 0.27 for condition score recorded in the first half of lactation (1 to 75 and 76 to 130 DIM), 0.36 for condition score in the second half of lactation (131 to 210 and 211 to 300 DIM) and 0.32 for condition score recorded on dry cows. Genetic correlations between condition scores measured in different lactation stages were generally high (0.85 or more), with the exception of the relationships between the first and the last stage of lactation (0.74) and between the first half of lactation and the dry period (0.7). Heritability estimates for heart girth in different lactation stages ranged from 0.31 to 0.40, and genetic correlations between high girth measured in different lactation stages were higher than 0.80.

Animals↗

PubMed2001

In vitro measurement of platelet glycoprotein IIb/IIIa receptor blockade by abciximab: interindividual variation and increased platelet secretion.

BACKGROUND AND OBJECTIVES: Inhibition of soluble fibrinogen binding to activated platelets represents the target of pharmacologic approach with antagonists of the glycoprotein IIb/IIIa (GPIIb/IIIa) complex. In this study we assessed the effects of abciximab, a recombinant chimeric Fab fraction of the antibody against GPIIb/IIIa, on several markers of platelet activation. DESIGN AND METHODS: The platelet surface expression of GPIIb/IIIa was measured by a flow cytometry technique using a two-color assay. GPIIb/IIIa was detected by FITC-conjugated antibodies in whole blood, either unstimulated or exposed to platelet stimuli. The following antibodies were used: CD41, which recognizes the IIb/IIIa complex both in activated and non-activated conformers, and PAC-1, which is directed toward the activated conformer of GPIIb/IIIa. In addition, the same blood sample was incubated with CD62 antibody to measure P-selectin, as a marker of a-granule degranulation. The effect of abciximab was also assessed by experiments carried out on shear stress-induced platelet aggregation, a test that appears to be a predictor of platelet hemostatic function. RESULTS: Abciximab inhibited CD41 binding to glycoprotein IIb (GPIIb) in a concentration-dependent manner and also inhibited the binding of PAC-1 to active GPIIb/IIIa. In contrast, membrane-associated P-selectin was significantly increased by the drug, which suggests that blockade of GPIIb/IIIa receptors results in an increased platelet degranulation in response to agonists. Shear stress-induced platelet aggregation was inhibited by abciximab, with a more pronounced effect on blood filtration, which represents an index of platelet aggregate formation. INTERPRETATION AND CONCLUSIONS: Our results indicate that GPIIb/IIIa blockade by abciximab is accompanied by an increase of a-granule secretion, suggesting that different mechanisms regulate these aspects of platelet activation. The described flow cytometry technique, that allows the simultaneous in vitro detection of several platelet markers, is a suitable method for assessing the effects of agents which interfere with platelet function.

Abciximab↗

PubMed2000

The retinoblastoma-interacting zinc-finger protein RIZ is a downstream effector of estrogen action.

Co-immunoprecipitation experiments in cell extract from cultured cells or target tissues indicated that estrogen receptor was complexed with the retinoblastoma binding protein RIZ in a ligand-dependent manner. Mapping of interaction sites indicated that in both proteins the same regions and motifs responsible for the interaction of transcriptional co-activator and nuclear receptors were involved. In cultured cells, estradiol induced a redistribution of RIZ protein within the nucleus and in the cytoplasm. A similar effect was produced in vivo, in prepuberal rat endometrium, by administration of a physiological dose of estradiol. Therefore, RIZ protein could be a specific effector of estrogen action downstream of the hormone-receptor interaction, presumably involved in proliferation control.

Base Sequence↗

PubMed2000

Single agent epirubicin as first line chemotherapy for metastatic breast cancer patients.

In order to better explore the toxicity and the activity of high dose epirubicin (120 mg/m2, 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status < or = 2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120 mg/m2 i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to < or = 45%, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720 mg/m2 (range 120-1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.

Adult↗