Transcutaneous bilirubin measurement in preterm infants]

Transcutaneous bilirubinometry is an effective screening tool for neonatal jaundice in full-term babies. But its accuracy is not shown yet in preterm infants. METHODOLOGY: We carried out a prospective study in a neonatal intensive care unit. The study included 47 preterm infants. From birth, a transcutaneous bilirubin measurement (BTc) using the BiliCheck was made on the forehead of each newborn every 8 h. Blood sampling for determination of total serum bilirubin (BS) was combined with BTc: 1) if value of BTc was higher than limits values for phototherapy; 2) on the second day of life and 3) 4 hours after cessation of phototherapy. RESULTS: Mean gestational age was 30 week and mean birth weight was 1419 g. We studied 151 pairs of BTc and BS. Mean values obtained by BTc and BS were respectively 160.6+/-50 mumol/L and 190.6+/-61.4 mumol/L. A significant correlation between BTc and BS was found. But the limits of agreement were very wide. The negative predictive value (NPV) of BTc was above 90% in each group of gestational age. DISCUSSION: The need for phototherapy cannot be determined by BTc in preterm infants. But the BTc is reliable when its value is under the limits for phototherapy. CONCLUSION: With a very high incidence of neonatal jaundice (87%) in our cohort, a value of BTc under the limits for phototherapy has a good NPV in preterm infants.     

Pharmacokinetics and Biodistribution of Oligonucleotide Adsorbed onto Poly(isobutylcyanoacrylate) Nanoparticles After Intravenous Administration in Mice

Purpose. The goal of this study was to evaluate the ability of nanoparticles to be used as a targeted delivery system for oligonucleotides. Methods. Pharmacokinetic and tissue distribution were carried out in mice by measuring the radioactivity associated to the model oligothymidylate ³³P-pdT₁₆ loaded to poly(isobutylcyanoacryrate) (PIBCA) nanoparticles. In addition, we have used a TLC linear analyzer to measure quantitatively on a polyacrylamide gel electrophoresis, the amount of non degraded pdT₁₆ Results. Organ distribution study has shown that nanoparticles deliver ³³P-pdT₁₆ specifically to the liver reducing its distribution in the kidney and in the bone marrow. Nanoparticles could partially protect pdT₁₆ against degradation in the plasma and in the liver 5 min after administration, whereas free oligonucleotide was totally degraded at the same time. Conclusions. Nanoparticles protect oligonucleotides in vivo against degradation and deliver them to the liver.     

The Cdx2 homeobox gene has a tumour suppressor function in the distal colon in addition to a homeotic role during gut development

BACKGROUND: During development, the homeobox gene Cdx2 exerts a homeotic function, providing the positional information necessary for correct specification of the midgut endoderm. This is illustrated by the non-neoplastic gastric-type heteroplasias present at birth in the pericaecal region of Cdx2(+/-) mice. Furthermore, intestinal expression of Cdx2 continues throughout life but diminishes in colorectal cancers compared with adjacent normal tissue, suggesting a role in tumorigenesis. Aim: To investigate the consequence of altered Cdx2 expression on colon tumour initiation and/or progression. METHODS: Heterozygous Cdx2(+/-) mice were analysed for spontaneous malignant tumours and for tumour development after treatment with a DNA mutagen, azoxymethane. RESULTS: Cdx2(+/-) mice did not spontaneously develop malignant tumours. After azoxymethane treatment, the gastric-like heteroplasias in the pericaecal region did not evolve into cancer indicating that they are not precancerous lesions. However, azoxymethane treated Cdx2(+/-) mice developed tumours specifically in the distal colon 12 weeks after azoxymethane treatment whereas no tumours were found in wild-type littermates at this stage. Histopathological and molecular analyses indicated that these tumours were invasive adenocarcinomas that recapitulated the malignant sequence observed in the majority of sporadic colorectal cancers in human. In addition, we found that the colonic epithelium was less sensitive to radiation induced apoptosis in Cdx2(+/-) than in wild-type mice. CONCLUSION: This study provides the first experimental evidence that Cdx2 is a tumour suppressor gene involved in cancer progression in the distal colon. This action in adults is functionally and geographically distinct from its homeotic role during gut development.     

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia

Through two consecutive trials, a policy that considered allogeneic stem cell transplantation (SCT) from a sibling donor in second rather than first complete remission (CR) in selected younger patients with acute myeloid leukemia (AML) with t(8;21)/inv(16) (core binding factor (CBF) group) or a normal karyotype (NN group) was followed by Acute Leukemia French Association (ALFA) centers. The outcome of 92 of these patients in first relapse (32 CBF, 60 NN) was reviewed with the aim of validating this strategy. The presence of an FLT3 internal tandem duplication (ITD) was retrospectively assessed in 50 patients. A total of 61 patients (66%) reached a second CR. Donor availability was an independent prognostic factor for survival in the whole patient population as well as in the CBF subset, but not in NN patients, further supporting this strategy for CBF-AMLs. In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD patients with a donor.     

An unusual case of hip septic arthritis due toBacteroides fragilis in an alcoholic patient

Summary We describe a 53-year-old alcoholic man who presented with hip septic arthritis due toBacteroides fragilis. This arthritis involved a severe destruction of the femoral head, which was completely devitalized. Recovery was achieved after 4 months of antimicrobial therapy with imipenem/cilastatin plus metronidazole, surgical debridement of the necrotic tissues and four sessions of hyperbaric oxygen.

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Ein ungewöhnlicher Fall von septischer Hüftarthritis durchBacteroides fragilis bei einem Alkoholiker

Zusammenfassung Wir berichten über einen Fall von septischer Hüftarthritis durchBacteroides fragilis bei einem 53 Jahre alten Alkoholiker. Die Arthritis führte zu einer schweren Femurkopfzerstörung mit völliger Devitalisierung. Nach chirurgischem Debridement des nekrotischen Gewebes, 4 Monaten Behandlung mit Imipenem/Cilastatin und Metronidazol und vier Behandlungen mit hyperbarem Sauerstoff trat Heilung ein.

     

AT2 Receptor and Tissue Injury: Therapeutic Implications

The converging clinical effectiveness of mineralocorticoid receptor antagonists (MRAs) Spironolactone and Eplerenone has made their safety profiles/cost-effectiveness key determinants of “agents of choice” across a broad range of clinical indications. The clinical biology of the aldosterone molecule and its range of effects in varied organ systems have been well elucidated from recent mechanistic and systematic studies. Clinical experience with Spironolactone is well established, as is its adverse effects profile. The range of adverse effects experienced with Spironolactone subsequently led to its modification and synthesis of Eplerenone. Recent published reports have confirmed lower prevalence rates of sex-related adverse effects attributable to Eplerenone compared to Spironolactone. There is, however, not much to choose between these agents in regards to other adverse effects including hyperkalemia and kidney failure. As was the experience with Spironolactone, as more robust observational data on Eplerenone accrues, it is possible that the real-life experience of its adverse profile may be discordant with that reported by randomized controlled clinical trials (RCTs). In addition, its metabolism by the vulnerable and highly polymorphic cytochrome dependent pathway also makes it susceptible to various drug interactions. The potential implication of the latter (including morbidity and mortality) may take years to evolve.     

Hypothyroidism: from the desire for pregnancy to delivery

The link between hypothyroidism and infertility is still a matter of debate. Hypothyroidism can result in cycle disturbances, such as oligomennorhea and functional bleeding. Additionally, several studies have shown that thyroid autoimmunity (detection of anti peroxydase antibodies) may account for the occurrence of repetitive miscarriages. In infertility work-up, screening thyroid function should be specifically recommended for women with clinical hypothyroidism, with a personal, familial history of thyroid or other auto immune diseases (such as type I diabetes) as well as for women with unexplained anovulation or functional bleeding. Moreover, detection of thyroid antibody seems to be worthwhile for the assessment of recurrent miscarriages, due to the potential benefit of thyroid supplementation. In pregnant women, assessment of thyroid function seems specifically crucial to ensure adequate foetal development. Indeed, it has been well established that untreated maternal hypothyroidism may be associated with disturbances of brain development and low intellectual quotient. Additionally, other foetal (growth deficiency, premature birth, low birth weight) as well as maternal (gestational hypertension, pre-eclampsia...) complications have been also reported in pregnant women with untreated hypothyroidism. Consequently, screening of thyroid function should be performed in every woman at risk of thyroid disease. Recent studies even advocate that thyroid screening should be extended to the overall pregnant population. The objective is to adjust L-thyroxin supplementation to maintain serum TSH concentrations below the threshold of 2.5 mUI/l. Finally, iodine deficiency, currently observed in pregnant women, should be prevented by iodine supply prior to conception, during pregnancy and during breast feeding as well.     

Prospective evaluation of elective single-embryo transfer versus double-embryo transfer following in vitro fertilization: a two-year French hospital experience

OBJECTIVE: Multiple embryo transfer is responsible for a high rate of multiple pregnancies (ICSI), with subsequent risks of premature birth and perinatal death. This prospective non randomized study aimed to assess the ability of an elective single-embryo transfer (eSET) policy to reduce the twin pregnancy rate, compared to a double embryo transfer (DET) approach. PATIENTS AND METHODS: Between March 2005 and May 2006, 180 eligible women were proposed to benefit from an eSET transfer rather than a DET. Inclusion criteria were (i) age less than 37 years old; (ii) at least two good quality embryos available (three to five cells at day 2 or six to nine cells at day 3; less than 20% fragmentation and the absence of multinucleates blastomeres), after IVF or ICSI and (iii) no more than one previous failed treatment cycle. Outcome analysis included cycles with frozen-thawed embryo transfer (FET). RESULTS: According to patients' decision, 107 and 73 women had an eSET (59.4%) and a DET (40.6%) respectively. No differences were found between eSET and DET groups regarding demographics and biologicals parameters. The clinical pregnancy rate (PR) per transfer was 43.9% in eSET group and 57.5% in DET group (p=0.07). The twin pregnancy rates were 0 and 14.3%, in eSET and DET groups, respectively (p=0.007). The cumulative PR per patient, including the outcome of performed FET cycles, was 63.6% in eSET group and 61.6% in DET group. In this case, the cumulative twin pregnancy rates were 2.9 and 15.6% in eSET and DET groups, respectively (p=0.02). DISCUSSION AND CONCLUSION: Our data show that in a selected population of women, transferring one fresh embryo and then, if required, one or two frozen-thawed embryos significantly reduces the twin pregnancy rate without decreasing the overall pregnancy rate. This study supports the policy of eSET in this subgroup of patients.