Pitfalls of ketogenic diet in a neonate.
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Biomedical subjects
Publications and source records attributed to M Robert.
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The aim of this study was to analyze the effect of robotic milking (RM) on fertility and somatic cell counts (SCC) among dairy herds participating in the national Dutch milk recording system. It was hypothesized that RM, and a higher milking frequency in general, would have negative effects on fertility, due to expected and supposed deeper negative energy balance (NEB). Herds increasing milking frequency from two to three times daily consistently had increased production. Milk production during RM was intermediate between the amounts obtained by milking twice versus three times a day. Milking three times a day and the associated higher production had no significant effect on reproductive measures such as nonreturn rate at 56 d post insemination (NR56) or days to first service. Although RM did not affect NR56, use of the robot was associated with an increase in days to first service. An increase in milking frequency from two to three times daily did not affect SCC, but SCC were significantly increased after milking with the robot. Robotic milking has a significant positive effect on production and no negative effect on fertility as measured by NR56. The effect of RM in increasing days to first service appears due to reasons other than increased production and a more NEB. Increased SCC during RM is potentially of concern. From the data available, the relationship of RM to clinical mastitis could not be determined but this aspect needs further attention.
BACKGROUND: The aims of the study were to characterize the relatives at high risk of progression to diabetes and to determine whether rate of progression to diabetes varied according to age, specific combination of antibodies and genetic markers of susceptibility. METHODS: Family members of type 1 diabetic patients were examined through a large medical network for the presence of specific antibodies to beta cell constituents and high risk DQB1 alleles. Antibodies to insulin, GAD and IA-2 as well as ICA were examined in 4,044 family members recruited in a large prospective family study in the Rhone-Alpes region (the GRADI study). Among them, 3,951 non diabetic first degree relatives have been tested on a median of 2.2 occasions and were followed for up to 16 years. RESULTS: Presence of antibodies to GAD (3.6%), IA-2 (4.9%), insulin (2.2%) and ICA at titers equal or above 20JDF units (1.1%) were noticed at the first determination and prevalence increased among ICA positive relatives versus ICA negative relatives. All combinations of markers resulted in specificities above 90%. The positive predictive value of antibodies was dependent on the number of positive antibodies. Combination of antibodies to GAD and IA-2 or GAD and IAA had higher predictive values and sensitivities than ICA titers above 20 JDF units. Additional positivity of IAA increased the predictive value but reduced the sensitivity of the screening procedure. Using a combi GAD/IA-2 assay increased the sensitivity of the screening up to 87.8% but reduced the predictive value to 13.8%. CONCLUSIONS: These data confirm in a large French cohort of first degree relatives of type 1 diabetic patients that combinations of antibodies to beta cell constituents can replace ICA in the first screening procedure. We report that combi GAD/IA-2 assay is well suited for screening purposes. However, time to diabetes in antibody positive relatives appears to be more heterogeneous to what has been described. The importance of genetic markers needs further evaluation.
The idea that significant ion/radical interactions should vary with solvent if they do exist in the liquid phase was pursued by an investigation of the dissociative electron-transfer reactivity of carbon tetrachloride and 4-cyanobenzyl chloride in four different solvents, 1,2-dichloroethane, N,N-dimethylformamide, ethanol, and formamide, by means of their cyclic voltammetric responses. Modification of the conventional dissociative electron transfer theory to take account of an interaction between fragments in the ion/radical pair resulting from the dissociative electron reaction allows a satisfactory fitting of the experimental data leading to the determination of the interaction energy. There is an approximate correlation between the interaction energies in the ion/radical pair and the solvation free energies of the leaving anion, Cl(-). The interaction is maximal in 1,2-dichloroethane, which is both the least polar and the least able to solvate Cl(-). The interaction is smaller in the polar solvents, albeit distinctly measurable. The two protic solvents, ethanol and formamide, which are the most able to solvate Cl(-), give rise to similar interaction energies. The interaction is definitely stronger in N,N-dimethylformamide, which has a lesser ability to solvate Cl(-) than the two other polar solvents. The existence of significant ion/radical interactions in polar media is thus confirmed and a route to their determination opened.
The osmotic compressibility and correlation length of a colloid-polymer system, consisting of grafted silica particles in cyclohexane in the presence of the soluble polymer polydimethylsiloxane, are determined by turbidity measurements in the entire one-phase liquid region, with emphasis on the critical region. The renormalized critical exponents of the osmotic compressibility and the correlation length are found to be respectively gamma(*)=1.39+/-0.01 and nu(*)=0.71+/-0.01, while the amplitude of the correlation length is 16.0+/-0.3 nm. Comparison is made with theoretical predictions.
BACKGROUND: To address the feasibility and outcome of moderate dose intensification with granulocyte-colony stimulating factor (G-CSF) for patients with aggressive non-Hodgkin lymphoma (NHL), the Cancer and Leukemia Group B (CALGB) conducted two studies evaluating dose-escalated cyclophosphamide and etoposide in the cyclophosphamide, doxorubicin, vincristine, prednisone, etoposide (CHOPE) regimen. METHODS: Eligibility criteria included histologically documented, diffuse small cleaved, diffuse mixed, diffuse large cell, or immunoblastic lymphoma, Stage III--IV or bulky Stage II disease, and an ECOG performance status of 0--1. CALGB 8852, a group-wide study, accrued 227 patients: 120 patients in the pilot study to determine the maximum tolerated dose (MTD) without G-CSF and 107 in the pilot study of dose-escalated CHOPE with G-CSF. CALGB 8854, a limited-institution, Phase I study, enrolled 38 patients and determined the MTD of CHOPE with G-CSF to be used in CALGB 8852. The MTD in both studies was defined as the dose at which 50% of patients had 1) Grade 4 neutropenia or thrombocytopenia lasting 7 days or more, or 2) Grade 3--4 hemorrhage or nonhematologic toxicity (excluding alopecia, nausea, and emesis), or 3) were prevented from receiving 100% of drug on Day 22. RESULTS: The MTD of CHOPE without G-CSF was cyclophosphamide 1000 mg/m(2) on Day 1 and etoposide 100 mg/m(2) on Days 1--3 with doxorubicin 50 mg/m(2) on Day 1, vincristine 1.4 mg/m(2) (maximum, 2 mg) on Day 1, and prednisone 100 mg on Days 1--5. With the addition of G-CSF at 200 microg/m(2) on Days 5--19, the MTD was cyclophosphamide 1500 mg/m(2) and etoposide 160 mg/m(2) on Days 1-3 with standard doses of doxorubicin, vincristine, and prednisone. Increasing the dose of G-CSF from 200 microg/m(2) to 400 microg/m(2) did not allow for further dose escalation. The primary toxicity in all cohorts was neutropenia. Four toxic deaths occurred on CALGB 8852. The 5-year failure free survival (FFS) and overall survival (OS) rates for eligible patients on CALGB 8852 were 31% (95% confidence interval [95%CI], 23--39) and 48% (95%CI, 40--57), respectively. The 5-year FFS and OS rates for eligible patients on CALGB 8854 were 34% (95%CI, 17--52) and 51% (95%CI, 33--70), respectively. CONCLUSIONS: Moderate dose escalation with G-CSF is feasible. However, response and survival rates of patients who receive dose-escalated CHOPE, even with the addition of G-CSF, appear similar to the rates reported with standard-dose CHOP.
The electrochemical (cyclic voltammetry) and photoinduced (fluorescence quenching, quantum yields) reductive cleavages of four compounds, 4-cyano-alpha-trifluorotoluene (1), dimethylphenyl sulfonium (2), 4-cyanobenzylmethylphenyl sulfonium (3), and 4-cyanobenzyl chloride (4), are investigated and compared in terms of concerted vs stepwise mechanisms. Bearing in mind that an increase of the thermodynamic driving force shifts the mechanism from concerted to stepwise and that the driving force is larger under photochemical than under electrochemical conditions, 1 and 2 are typical examples where a stepwise mechanism is followed with compatible kinetic characteristics under both regimes. 4 undergoes a concerted electrochemical reductive cleavage, and the same mechanism is followed in the photoinduced reaction with consistent kinetic characteristics. The case of 3 is of particular interest, since a trend of passing from a concerted to a stepwise mechanism when going from the electrochemical to the photochemical conditions indeed appears upon analysis of the experimental results. The change of mechanism is, however, not complete since, in the photoinduced reaction, there is a balanced competition between the two pathways. In the same families of compounds, the unsubstituted benzylmethylphenyl sulfonium cations shows such a borderline behavior during the electrochemical reaction. In the photoinduced reaction, it is the 4-cyano derivative which behaves in a borderline manner, in line with the fact that it gives rise more readily to a concerted mechanism than the unsubstituted compound.
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The intensive use for over 100 years of copper sulfate (Bordeaux mixture) to fight against mildew in vineyard soils has led to an important, widespread accumulation of Cu (100 to 1500 mg Cu kg-1 soil). In Champagne vineyards, organic amendments are used currently to increase soil fertility and to limit soil erosion. Organic amendments may have a direct effect on the retention of Cu in the soil. To assess the influence of the organic management on the fate of Cu in calcareous Champagne vineyard soils, we studied Cu distribution (1) in the soil profile and (2) among primary soil particles, in vineyard parcels with different amendments. Amendments were oak-bark, vine-shoots and urban compost. The results were compared with the amount and the distribution of Cu in an unamended calcareous soil. Physical soil fractionations were carried out to separate soil primary particles according to their size and density. Cu has a heterogeneous distribution among soil particle fractions. Two fractions were mainly responsible for Cu retention in soils: the organic debris larger than 50 microns or coarse particulate organic matter (POM) issued from the organic amendments, and the clay-sized fraction < 2 microns. The POM contained up to 2000 mg Cu kg-1 fraction and the clay fraction contained up to 500 mg Cu kg-1 fraction. The clay-sized fraction was responsible for almost 40% of the total amount of Cu in the four parcels. POM was predominantly responsible for the differences in Cu contents between the unamended and the three amended parcels. Our results attested that methods of soil particle-size fractionation can be successfully used to assess the distribution of metal elements in soils.
OBJECTIVE: To assess the effects of the interposition of pelvic bones and abdominal gas in the shockwave pathway during piezoelectric extracorporeal shock wave lithotripsy (ESWL) of distal ureteric stones. PATIENTS AND METHODS: The study included 35 patients who were evaluated with unenhanced spiral computed tomography (CT), used according to their positioning during ESWL. The shockwave pathway was simulated on the sagittal and coronal views crossing the ureteric calculi, allowing a theoretical evaluation of the effective shockwave focusing (with no bone or gas interference). Vertical and oblique approaches were statistically compared for bone and gas interposition. RESULTS: Overall, the effective shockwave focusing during in situ piezoelectric ESWL of distal ureteric stones was 71% of the theoretical area. The interposition of bone and gas was significantly lower for an oblique access than for a vertical approach in the sagittal plane (P < 0.001 and 0.03 on the sagittal and coronal views, respectively). Using stepwise logistic regression, the difference between vertical and oblique accesses in the sagittal plane was mainly affected by the bladder volume (P < 0.001). On the coronal views, the interposition of bone and gas affected 31 patients (89%). Such interference was eliminated in 73% of the patients with a contralateral inclination of the shockwave axis in the coronal plane. CONCLUSION: The interposition of pelvic bones and abdominal gas in the shockwave pathway can affect the performance of piezoelectric ESWL of distal ureteric stones. While awaiting clinical confirmation of these theoretical data, we recommend that patients are treated with the bladder full and that the shockwave generator is inclined in both the coronal and sagittal planes.
E-4767 [(-)-7-[3-(R)-amino-2-(S)-methyl-1-azetidinyl]-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid] and E-5065 [(-)-7-(3-amino-1-azetidinyl)-8-chloro-1-cyclopropyl-1,4-dihydro-6-fluoro-4-oxo-3-quinolinecarboxylic acid] are two new chlorofluoroquinolones with an azetidine moiety at position 7. Their in vitro activities were evaluated in comparison with those of ciprofloxacin, ofloxacin, fleroxacin, and tosufloxacin, while ciprofloxacin was used as a reference for in vivo studies. Against gram-positive organisms, E-4767 and E-5065 were, in general, eight- and fourfold more active than tosufloxacin, which is the most potent of the reference compounds. E-4767 and E-5065 were also more potent than the reference compounds against all species of enteric bacteria tested. The MICs of E-4767 and E-5065 at which 90% of the isolates tested were inhibited (MIC(90)s) were 0.007 to 0.5 microg/ml and 0.03 to 2 microg/ml, respectively, for gram-positive organisms and <or=0.003 to 0.06 microg/ml and 0.007 to 0.12 microg/ml, respectively, for members of the family Enterobacteriaceae except Serratia marcescens and Providencia spp. (MIC(90)s of E-4767 and E-5065 for these species were <or=0.5 microg/ml and <or=2 microg/ml, respectively). For Pseudomonas aeruginosa both compounds had a MIC(90) of 0.5 microg/ml. E-4767 and E-5065 were 356- and 32-fold more potent than ciprofloxacin against Bacteroides spp., and their MIC(90)s for Clostridium spp. were 0.25 and 0.5 microg/ml, respectively. Both products showed a remarkable reduction of activity when the pH was below 4.8 and, in general, were less active in the presence of 5 or 10 mM Mg(2+). The presence of horse serum or human urine (pH 7.2) decreased the activity of E-4767 and E-5065 only two- to fourfold more than the activity observed in broth. After an oral dose of 50 mg/kg of body weight, the maximum levels in serum (the maximum concentration of drug in serum was reached 30 min postadministration) of E-4767 and E-5065 were approximately threefold higher than that of ciprofloxacin. The area under the concentration-time curve from 0 to 4 h for ciprofloxacin was about two- and fourfold lower than that for E-4767 and E-5065, respectively. These two new chlorofluoroquinolones were as effective as or more effective than ciprofloxacin against all experimental infections evaluated, not only against gram-negative bacteria, such as Escherichia coli or P. aeruginosa, but also against gram-positive pathogens, such as Staphylococcus aureus or Streptococcus pneumoniae. E-4767 was the most effective compound, with a 50% effective dose (ED(50)) of <or=17 mg/kg for all strains tested except ciprofloxacin-resistant S. aureus strains. The ED(50) of E-4767 for these strains was <or=47.5 mg/kg. Against gram-positive experimental infections, the ED(50) values of E-4767 were 3- to 14-fold lower than those of E-5065 and up to 25 times lower than those of ciprofloxacin.
Chronic exposure to sunlight may induce skin damage such as photoaging and photocarcinogenesis. These harmful effects are mostly caused by ultraviolet-B (UVB) rays. Yet, less is known about the contribution of low UVB doses to skin damage. The aim of this study was to determine the tissue changes induced by repeated exposure to a suberythemal dose of UVB radiation. Human keratinocytes in monolayer cultures and in skin equivalent were irradiated daily with 8 mJ/cm2 of UVB. Then structural, ultrastructural, and biochemical alterations were evaluated. The results show that exposure to UVB led to a generalized destabilization of the epidermis structure. In irradiated skin equivalents, keratinocytes displayed differentiated morphology and a reduced capacity to proliferate. Ultrastructural analysis revealed, not only unusual aggregation of intermediate filaments, but also disorganized desmosomes and larger mitochondria in basal cells. UVB irradiation also induced the secretion of metalloproteinase-9, which may be responsible for degradation of type IV collagen at the basement membrane. DNA damage analysis showed that both single and repeated exposure to UVB led to formation of (6-4) photoproducts and cyclobutane pyrimidine dimers. Although the (6-4) photoproducts were repaired within 24 h after irradiation, cyclobutane pyrimidine dimers accumulated over the course of the experiment. These studies demonstrate that, even at a suberythemal dose, repeated exposure to UVB causes significant functional and molecular damage to keratinocytes, which might eventually predispose to skin cancer.
Ovarian cyst is a rare disease in infancy and childhood. Functional cysts are the most common benign ovarian tumor observed during childhood. Ultrasound examination in children with abdominal pain has improve diagnostic accuracy with an associated increase in the frequency of functional cysts (60% of the cases). Diagnosis of organic cysts is often made late. Germ cell tumors, often dermoid cysts, occur more frequently than in adults. Ultrasonography and laparoscopy are important diagnostic tools for ovarian cysts in children. Serum CEA, alpha-fetoprotein and beta HGC are routine tests for organic tumors. Laparoscopy is generally proposed for treatment except for small functional cysts with a transonic structure. Spontaneous involution is generally observed.
We have shown that several isoforms of triadin, a protein involved in calcium release process through the ryanodine receptor, are expressed in rat skeletal muscle, and we have cloned two of these isoforms. One is the rat homolog of the 95-kDa triadin identified in rabbit skeletal muscle, and the second one, shorter, is a truncated form of the previous one, but with a new unique COOH-terminal end. We propose to name the two proteins identified here Trisk 95 and Trisk 51. We have produced antibodies specific to each isoform. Using these antibodies, we have shown that the newly identified protein, Trisk 51, is actually expressed in adult rat skeletal muscle and also in rat embryo skeletal muscle. Immunofluorescent labeling of rat skeletal muscle with anti-Trisk 95, anti-Trisk 51, or anti-ryanodine receptor antibodies shows a similar localization of these proteins, in the tissue. Transfection of L6 cells with cDNA of Trisk 51 or Trisk 95 leads to the expression of proteins with the expected molecular weight, identical to those detected in rat skeletal muscle. Both proteins appear during differentiation of satellite cells in myotubes which may indicate the involvement of these two isoforms in the building of a functional calcium release machinery.
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In this double-blind study, the efficacy and tolerability of a single dose of almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized patients, 722 evaluable patients completed the study. The total number of attacks relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or 12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a consistent response was achieved across and within patients for almotriptan 6.25 or 12.5 mg compared with placebo (pain relief in at least two out of three attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third of the patients relapsed within 24 h. Almotriptan was well tolerated with no significant differences between the almotriptan and placebo treatment groups in the percentage of patients reporting adverse events. Overall, the 12.5-mg dose was associated with the most favourable efficacy/tolerability ratio and is, therefore, the recommended dose.
BACKGROUND/PURPOSE: The appendix graft (AG) is used widely for urinary tract replacement in children. Biliary tract replacement is less common. The purpose of this retrospective multicentric study was to evaluate the safety of appendix grafting for biliary reconstruction. METHODS: The files of 33 patients treated at 7 European pediatric centers were reviewed. Indications included choledochal cyst (CC) in 5 cases, biliary trauma (BT) in 1, and biliary atresia (BA) in 27. In CC and BT patients, the graft was inserted isoperistaltically between the proximal biliary duct and second duodenum. In all but one of the BA patients, the graft was placed antiperistaltically by patching its cecal end onto the porta hepatis. RESULTS: Postoperatively, all CC and BT patients initially became asymptomatic but developed laboratory evidence of anicteric cholestasis within 1 year. The most common manifestation was increased gamma-glutamyl-transpeptidase level (GGT), whereas histologic findings showed liver damage (mainly fibrosis). Reoperation has been carried out in 4 CC and 1 BT patients within a mean period of 19 months after appendix grafting. The graft procedure was converted to hepaticojejunostomy (HJ) in 4 and to choledocoduodenostomy in 1. Surgical exploration showed kinking in 1 patient and stenosis in 1. In the remaining 3 cases, there was no discernible cause of cholestasis, and appendix histology findings were normal. In all 5 reoperated patients, liver function findings returned to normal within 1 month. Reoperation is scheduled for the remaining CC patient who currently requires ursodesoxycholic medication to maintain normal liver function and presents histologic evidence of "de novo" sclerosing cholangitis. Results of appendix grafting also were poor in the 27 BA patients. Procedure-related perioperative complications occurred in 4 (15%) including 1 early death from graft necrosis. Another early death resulted from intestinal hemorrhage. Jaundice cleared in only 8 (28%). CONCLUSIONS: The findings of this study suggest that the AG is unsuitable for routine biliary repair in children. It should be used only as a salvage technique when conventional HJ repair is contraindicated. Because of the high risk of graft dysfunction, we recommend screening tests to detect biochemical or histologic cholestasis in any patient previously treated with appendix grafting.