Topical ropivacaine for analgesia of aplasia cutis congenita in newborns with hereditary epidermolysis bullosa.

Aplasia cutis congenita (ACC) in patients with hereditary epidermolysis bullosa (EB) is often associated with major pain. We report our experience with using topical ropivacaine during dressing in newborns with ACC. Eight full-term newborns with EB and ACC were hospitalized in a neonatal intensive care unit for severe pain during dressing despite the use of paracetamol, opioids (n = 8) or ketamine (n = 7). Topical xylocaine was poorly tolerated and not effective. Ropivacaine 2 mg/ml was used directly in contact with the ACC, with a maximum 1 mg/kg/day, which enabled care without the child crying. No immediate or late systemic toxicity was observed. Topical ropivacaine 0.2% appears to be an interesting topical analgesic, with good clinical tolerance and rapid action, in newborns with ACC and EB. These data need to be confirmed in a prospective study including pharmacokinetics evaluations.

Mineral profile of crossbred F 1 Holstein x Gyr dairy cows during the transition period in summer and winter / Perfil mineral de vacas F1 Holandês x Gir durante o período de transição no verão e inverno

The transition period is often a great challenge for dairy cows and mineral imbalances are frequent. With the aim to better understand the mineral profile of F1 Holstein x Gyr dairy cows and their performances under the different conditions of summer and winter, we collected blood samples to measure calcium, magnesium and phosphorus. Samplings were performed during summer and winter, on 15 and 13 pluriparous F1 Holstein x Gyr dairy cows, respectively. Blood sampling started 4 weeks prior to the expected calving date until 30 days postpartum. The mean concentrations of all three minerals had a different pattern during the transition period in each season, representing the interaction time x season. Calcium concentration was lower in winter and more animals suffered from subclinical hypocalcemia (100%) then in summer (38.46%). Magnesium concentration was also lower in winter and 46.67% of animals had hypomagnesemia, contributing for the higher hypocalcemia frequency observed in the same season. A high proportion of animals had hyperphosphatemia what can represent an environmental problem and more attention should be given to it. The high frequency of animals with subclinical hypocalcemia is alarming once that can lead to greater consequences.(AU)

O período de transição é uma fase de grandes desafios para vacas leiteiras, e desequilíbrios minerais são frequentes. O objetivo ao desenvolver este trabalho foi de entender melhor o perfil mineral de vacas leiteiras F1 Holandês x Gir e suas performances sob as diferentes condições de verão e inverno. Para isso, foram mensurados cálcio, magnésio e fósforo sanguíneo. As coletas de sangue foram realizadas durante os períodos de verão e inverno, e utilizaram-se, respectivamente, 15 e 13 vacas leiteiras pluríparas, todas F1 Holandês x Gir. As coletas de sangue começaram quatro semanas antes da data prevista do parto até 30 dias pós-parto. As concentrações médias e o padrão de variação dos três minerais foram distintos em cada estação do ano, representando a interação tempo de coleta x estação do ano. A concentração de cálcio foi menor no inverno, período em que todos os animais apresentaram hipocalcemia subclínica, enquanto no verão 38,46% apresentaram essa condição. A concentração de magnésio foi maior no verão e nenhum animal teve hipomagnesemia, enquanto no inverno 46,67% dos animais apresentaram hipomagnesemia subclínica, contribuindo para a maior frequência de hipocalcemia observada no inverno. Uma alta proporção de animais teve hiperfosfatemia, o que pode representar um problema ambiental. A alta frequência de animais com hipocalcemia subclínica é alarmante principalmente devido às consequências geradas por essa condição.(AU)

Eficácia In Vitro De Extratos De Chenopodium Ambrosioides Sobre Teleóginas De Rhipicephalus (Boophilus) Microplus / In vitro efficacy of Chenopodium ambrosioides extracts on Rhipicephalus (Boophilus) microplus engorged females

Chenopodium ambrosioides L. (Amaranthaceae) (erva-de-santa-maria) é uma planta fortemente aromática usada popularmente por suas propriedades antiparasitárias.Avaliou-se com este estudo a eficácia in vitro de extratos hidroetanólicos de C. ambrosioides sobre a postura e a eclodibilidade larval de Rhipicephalus (Boophilus) microplus (Canestrini, 1888) (Acari: Ixodidae), usando o teste de imersão de fêmeas ingurgitadas adultas.Os tratamentos foram constituídos por extratos feitos com 5%, 10% e 25% de C. ambrosioides (massa/volume), água destilada e veículo (constituído de propilenoglicol a 5%, etanol a 25% e água destilada). Dez teleóginas foram distribuídas de forma homogênea para cada grupo e imersas por 5 minutos em cada um dos extratos testados. Os extratos feitos com 5%, 10% e 25% de C. ambrosioides apresentaram eficácias médias de 13,27%, 22,56% e 31,87%, respectivamente. Estes resultados indicam que, nas concentrações usadas, os extratos de C. ambrosioides não apresentam potencial para o controle das cepas pesquisadas de R. (B.) microplus.

In vitro efficacy of Chenopodium ambrosioides extracts on Rhipicephalus (Boophilus) microplus engorged females. Chenopodium ambrosioides L. (Amaranthaceae) (wormseed) is a strongly aromatic plant employed popularly for its antiparasitic properties. This study evaluated the in vitro efficacy on laying and hatchability of eggs of Rhipicephalus (Boophilus) microplus (Canestrini, 1888) (Acari: Ixodidae) of hydroethanolic extracts from C. ambrosioides, using the adult immersion test. The treatments consisted of hydroethanolic extracts made with 5%, 10% and 25% of C. ambrosioides (weight/volume), distilled water and vehicle solution (consisting of propylene glycol at 5%, ethanol at 25% and distilled water). Ten ticks were distributed evenly for each group and immersed for 5 minutes in each of the tested extracts. The extracts containing 5%, 10% and 25% of C. ambrosioides showed average efficacies 13.27%, 22.56% and 31.87% respectively. These results indicate that extracts of C. ambrosioides, at the concentrations used, do not present potential for the control of the R. (B.) microplus strains researched.

Functional MRI during the execution of a motor task in patients with multiple sclerosis and fatigue.

PURPOSE: This study was undertaken to assess cortical activation during execution of a motor task in patients with multiple sclerosis (MS) and fatigue. MATERIALS AND METHODS: We enrolled 24 right-handed patients affected by relapsing-remitting MS and mild disability (12 with and 12 without fatigue) and 15 healthy volunteers. Magnetic resonance imaging (MRI) examination (1.5 T) was performed with conventional sequences and an echoplanar imaging (EPI) sequence for functional MRI (fMRI). The motor task consisted of sequential finger tapping performed with the right hand. Statistical maps of motor activation were obtained. Comparison between the two subgroups of patients and between patients and controls was performed with analysis of variance (ANOVA) statistical analysis (p<0.05). RESULTS: Compared with controls, patients without fatigue showed greater activation of the primary sensorimotor cortex bilaterally, of the right supplementary motor cortex, of the left premotor cortex, of the left cerebellum and of the superior parietal lobule bilaterally. Compared with patients without fatigue, patients with fatigue demonstrated greater activation of the right premotor area, of the putamen and the dorsolateral prefrontal cortex. CONCLUSIONS: Patients with fatigue have greater activation of the motor-attentional network when performing a simple motor task.

Cognitive outcome after awake surgery for tumors in language areas.

In surgery for tumors of the dominant hemisphere, the attention devoted to quality of resection and preservation of language function has not been accompanied by comparable interest in preservation of cognitive abilities which may affect quality of life. We studied 22 patients undergoing awake surgery for glioma removal in the language areas of the brain. Besides monitoring tumor variables (size, location, histology, edema), we used a multifaceted battery of tests to investigate mood, cognition, and language in an attempt to assess the burden of disease and treatment, and the relationships between these three dimensions. Baseline assessment showed that 45% of the patients were depressed and 23% anxious; some cognitive and language impairment was noted for 59 and 50%, respectively. A general decline in postoperative cognitive performance (significant for memory and attention only) and language function (significant for picture naming) was observed, whereas depression was unchanged and anxiety decreased. Tumor histology, but not demographic variables or extent of resection, correlated with postoperative cognitive changes: patients undergoing surgery for high-grade tumors were more likely to improve. No correlation was observed between scores for mood, cognition, and language function. A subset of patients with low-grade glioma was followed up for 3-6 months; although some improvement was observed they did not always regain their preoperative performance. In conclusion, we believe that cognitive assessment performed in conjunction with language testing is a necessary step in the global evaluation of brain tumor patients both before and after surgery.

[The mother-infant encounter at birth must be protected]. / Il faut protéger la rencontre de la mère et de son nouveau-né autour de la naissance.

The medical decision to separate a newborn baby from his or her mother is frequent. This medical practice must be evaluated. The scientific literature regarding humans and other mammals was reviewed in order to describe the physiology of the interactions between mother and offspring and the consequences of disrupting their interactions around birth. Mother-infant bonding is common to all mammals. Attachment is the result of three mechanisms: behavioral programing, secretion of neuroendocrine substrates, and activation of sensory cues. Breastfeeding is a fourth component that plays a crucial role. Experimental research provides evidence that early-life maternal separation can alter biological responses to stress, disturb learning behaviors, and impair social skills. Recent advances in epigenetic research may partly explain how neonatal maternal deprivation at birth can lead to biological and behavioral disorders in adulthood. Therefore, the decision to separate a newborn infant from his or her mother is not harmless and must be carefully considered. In order to better take into account these data, the organization of perinatal care in France should be revised.

hI-con1, a factor VII-IgGFc chimeric protein targeting tissue factor for immunotherapy of uterine serous papillary carcinoma.

BACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a highly aggressive variant of endometrial cancer. Human immuno-conjugate molecule (hI-con1) is an antibody-like molecule targeted against tissue factor (TF), composed of two human Factor VII (fVII) as the targeting domain, fused to human immunoglobulin (Ig) G1 Fc as an effector domain. We evaluated hI-con1 potential activity against primary chemotherapy-resistant USPC cell lines expressing different levels of TF. METHODS: A total of 16 formalin-fixed, paraffin-embedded USPC samples were evaluated by immunohistochemistry (IHC) for TF expression. Six primary USPC cell lines, half of which overexpress the epidermal growth factor type II (HER2/neu) receptor at 3+ levels, were assessed by flow cytometry and real-time PCR for TF expression. Sensitivity to hI-con1-dependent cell-mediated cytotoxicity (IDCC) was evaluated in 5-hour-chromium release assays. Finally, to investigate the effect of interleukin-2 (IL-2) on IDCC, 5-h (51)Cr assays were also conducted in the presence of low doses of IL-2 (i.e., 50-100 IU ml(-1)). RESULTS: Cytoplasmic and/or membrane TF expression was observed in all 16 (100%) USPC samples tested by IHC, but not in normal endometrium. High expression of TF was found in 50% (three out of six) of the USPC cell lines tested by real-time PCR and flow cytometry when compared with normal endometrial cells (NECs; P<0.001). Uterine serous papillary adenocarcinoma cell lines overexpressing TF, regardless of their high or low HER2/neu expression, were highly sensitive to IDCC (mean killing+/-s.d., 65.6+/-3.7%, range 57.5-77.0%, P<0.001), although negligible cytotoxicity against USPC was seen in the absence of hI-con1 or in the presence of Rituximab control antibody. The addition of low doses of IL-2 further increased the cytotoxic effect induced by hI-con1 against chemotherapy-resistant USPC. CONCLUSION: hI-con1 induces strong cytotoxicity against primary chemotherapy-resistant USPC cell lines overexpressing TF. The hI-con1 may represent a novel therapeutic agent for the treatment of patients harbouring advanced, recurrent and/or metastatic USPC refractory to standard treatment modalities.

64-Slice CT urography: 30 months of clinical experience.

PURPOSE: This study sought to assess the diagnostic accuracy of 64-slice computed tomography urography (CTU) in evaluation of the urinary tract. MATERIALS AND METHODS: A total of 322 CTU procedures were carried out in 317 consecutive patients (mean age 64.4 years). The findings were compared with previous and subsequent patient workup considering both laboratory and imaging studies, such as urine cytology, abdominal ultrasound and CT, cystoscopy, retrograde pyelography, surgery and pathology. RESULTS: Out of 322 CTU examinations, 169 showed significant urinary tract changes, whereas 153 revealed no urinary disease, in good agreement with the follow-up. In particular, in bladder evaluation, for which we have a direct comparison with cystoscopy in 125 patients, we calculated a CTU sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 85%, 94%, 92%, 89% and 90%, respectively. CONCLUSIONS: CTU was accurate for urinary tract evaluation, but it cannot replace cystoscopy in patients in whom a malignant bladder disease is suspected.

In vitro activity of pertuzumab in combination with trastuzumab in uterine serous papillary adenocarcinoma.

BACKGROUND: Uterine serous papillary adenocarcinoma (USPC) is a rare but highly aggressive variant of endometrial cancer. Pertuzumab is a new humanised monoclonal antibody (mAb) targeting the epidermal growth factor type II receptor (HER2/neu). We evaluated pertuzumab activity separately or in combination with trastuzumab against primary USPC cell lines expressing different levels of HER2/neu. METHODS: Six USPC cell lines were assessed by immunohistochemistry (IHC), flow cytometry, and real-time PCR for HER2/neu expression. c-erbB2 gene amplification was evaluated using fluorescent in situ hybridisation (FISH). Sensitivity to pertuzumab and trastuzumab-induced antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) was evaluated in 5 h chromium release assays. Pertuzumab cytostatic activity was evaluated using proliferation-based assays. RESULTS: Three USPC cell lines stained heavily for HER2/neu by IHC and showed amplification of the c-erbB2 gene by FISH. The remaining FISH-negative USPCs expressed HER2/neu at 0/1+ levels. In cytotoxicity experiments against USPC with a high HER2/neu expression, pertuzumab and trastuzumab were similarly effective in inducing strong ADCC. The addition of complement-containing plasma and interleukin-2 increased the cytotoxic effect induced by both mAbs. In low HER2/neu USPC expressors, trastuzumab was more potent than pertuzumab in inducing ADCC. Importantly, in this setting, the combination of pertuzumab with trastuzumab significantly increased the ADCC effect induced by trastuzumab alone (P=0.02). Finally, pertuzumab induced a significant inhibition in the proliferation of all USPC cell lines tested, regardless of their HER-2/neu expression. CONCLUSION: Pertuzumab and trastuzumab induce equally strong ADCC and CDC in FISH-positive USPC cell lines. Pertuzumab significantly increases tratuzumab-induced ADCC against USPC with a low HER2/neu expression and may represent a new therapeutic agent in patients harbouring advanced/recurrent and/or refractory USPC.

[High-dose intravenous immunoglobulin therapy and neonatal jaundice due to red blood cell alloimmunization]. / Immunoglobulines polyvalentes intraveineuses et ictère néonatal par allo-immunisation érythrocytaire.

Neonatal jaundice resulting from immunological hemolysis is not uncommon. While it is possible to prevent a large number of Rh-isoimmune hemolytic diseases by administration of specific anti-D immunoglobulins to the mother, the prevention of incompatibility in the ABO groups is not feasible. In spite of advances made in the use of phototherapy, and in order to avoid kernicterus, the treatment of these jaundices can require one or several exchange transfusions (ET), a therapy which is not devoid of risk. For some time now, the data concerning the efficiency of high-dose intravenous immunoglobulin therapy (HDIIT) in the treatment of these jaundices have been increasing. A review of the literature shows that, if used as soon as possible in newborn infants over 32 weeks of gestation age, afflicted with Rh or ABO hemolytic disease, the HDIIT brings about, with no undesirable side effects, a significant decrease in the ET number as well as a significant reduction in the length of phototherapy and hospitalization. The data suggesting that HDIIT could increase the risk of late transfusion is open to controversy.

Serum amyloid A (SAA): a novel biomarker for uterine serous papillary cancer.

BACKGROUND: Uterine serous papillary carcinoma (USPC) is a biologically aggressive variant of endometrial cancer. We investigated the expression of Serum Amyloid A (SAA) and evaluated its potential as a serum biomarker in USPC patients. METHODS: SAA gene and protein expression levels were evaluated in USPC and normal endometrial tissues (NEC) by real-time PCR, immunohistochemistry (IHC), flow cytometry and by a sensitive bead-based immunoassay. SAA concentration in 123 serum samples from 51 healthy women, 42 women with benign diseases, and 30 USPC patients were also studied. RESULTS: SAA gene expression levels were significantly higher in USPC when compared with NEC (mean copy number by RT-PCR=162 vs 2.21; P=0.0002). IHC revealed diffuse cytoplasmic SAA protein staining in USPC tissues. High intracellular levels of SAA were identified in primary USPC cell lines evaluated by flow cytometry and SAA was found to be actively secreted in vitro. SAA concentrations (mug ml(-1)) had a median (95% CIs) of 6.0 (4.0-8.9) in normal healthy females and 6.0 (4.2-8.1) in patients with benign disease (P=0.92). In contrast, SAA values in the serum of USPC patients had a median (95% CI) of 15.6 (9.2-56.2), significantly higher than those in the healthy group (P=0.0005) and benign group (P=0.0006). Receiver operating characteristics (ROC) analysis of serum SAA to classify advanced- and early-stage USPC yielded an area under the ROC curve of 0.837 (P=0.0024). CONCLUSION: SAA is not only a liver-secreted protein but is also a USPC cell product. SAA may represent a novel biomarker for USPC to assist in staging patients preoperatively, and to monitor early-disease recurrence and response to therapy.

Sodium valproate does not augment Prpsc in murine neuroblastoma cells.

Sodium valproate (VPA) has been reported to increase the accumulation of the pathologic isoform of prion protein (PrPsc) in scrapie-infected murine neuroblastoma cells. In this study, the effect of VPA on PrPsc accumulation was investigated in murine N2a neuroblastoma cells chronically infected with scrapie strain 22L (N2a-22L). No accumulation of PrPsc was detected after short-term (3 days) or long-term (21 days) treatment of N2a-22L cells with 4.8, 12, 18 or 24 microM VPA. Higher VPA concentrations (240 and 600 microM) also failed to augment PrPsc expression. In conclusion, in our experimental conditions, no deleterious effect was induced by VPA on prions replication.

Measurements of the generalized electric and magnetic polarizabilities of the proton at low Q2 using the virtual-compton-scattering reaction.

The mean square polarizability radii of the proton have been measured for the first time in a virtual-Compton-scattering experiment performed at the MIT-Bates out-of-plane scattering facility. Response functions and polarizabilities obtained from a dispersion analysis of the data at Q2 = 0.057 GeV2/c2 are in agreement with O(p3) heavy baryon chiral perturbation theory. The data support the dominance of mesonic effects in the polarizabilities.

Investigation of the conjectured nucleon deformation at low momentum transfer.

We report new precise H(e,e(')p)pi(0) measurements at the Delta(1232) resonance at Q(2)=0.127 (GeV/c)(2) obtained at the MIT-Bates out-of-plane scattering facility which are particularly sensitive to the transverse electric amplitude (E2) of the gamma(*)N-->Delta transition. The new data have been analyzed together with those of earlier measurements to yield precise quadrupole to dipole amplitude ratios: Re(E(3/2)(1+)/M(3/2)(1+))=(-2.3+/-0.3(stat+syst)+/-0.6(model))% and Re(S(3/2)(1+)/M(3/2)(1+))=(-6.1+/-0.2(stat+syst)+/-0.5(model))% for M(3/2)(1+)=(41.4+/-0.3(stat+syst)+/-0.4(model))(10(-3)/m(pi(+))). The derived amplitudes give credence to the conjecture of deformation in hadrons favoring, at low Q2, the dominance of mesonic effects.

Prenatal diagnosis of a craniopharyngioma: a new case with radical surgery and review.

CASE REPORT: A case of the antenatal diagnosis of a craniopharyngioma with radical surgery in the neonatal period is reported. REVIEW OF THE LITERATURE: We have reviewed the literature of such cases in an attempt to isolate specific features in this age group and to determine the appropriate management. Only six cases of the truly antenatal diagnosis of craniopharyngiomas have been reported. Diagnosis has resulted from routine ultrasound during pregnancy or from polyhydramnios. Clinically, there is often macrocephaly due to hydrocephalus or a significant-sized tumor. CONCLUSIONS: Management of these rare cases is controversial with high postoperative mortality and significant morbidity, including panhypopituitarism, visual disturbance, and neuropsychological disorders. From the available literature, no conclusions concerning the management can be drawn at present, due to the rarity of early surgical intervention. Our case, despite the lack of important follow-up, seems to confirm the possibility of attempting radical surgery in the neonatal period as a result of advances both in surgical techniques and in neonatal intensive care.

Pharmacological complications of the chronic baclofen infusion in the severe spinal spasticity. Personal experience and review of the literature.

AIM: To evaluate the pharmacological complications and side effects of the chronic intrathecal baclofen infusion in patients suffering from intractable spinal spasticity in our Department as well as in the literature. METHODS: The pharmacological complications and side effects observed at long-term follow-up in 25 patients with chronic intrathecal baclofen infusion are evaluated; the search of the literature complications was carried out in Medline and in Ingenta web sites. RESULTS: We have been able to observe in our series 3 (12%) patients with hypotonia, 2 with impairment on erection (8%) and 1 (4%) with constipation; 5 (20%) patients showed also tolerance but only 1 (4%) needed a ''drug holiday''. In the literature the side effects range from 4% to 16%. Moreover the tolerance is reported from 3% to 15%. The overdose has been reported from 0% to 14%, while the syndrome of withdrawal is reported in 16 patients with 6 fatalities. In our series these two last complications were not observed. CONCLUSIONS: Lethal pharmacological complications are rare and, if promptly diagnosed and treated, are reversible. Side effects of minor importance can impair the patient quality of live and needed to be adjusted to patient's requirements. This kind of therapy should be restricted to specialized centres.

How to measure the phase diffusion dynamics in the micromaser.

We propose a realistic scheme for measuring the micromaser linewidth by monitoring the phase diffusion dynamics of the cavity field. Our strategy consists of exciting an initial coherent state with the same photon number distribution as the micromaser steady-state field, singling out a purely diffusive process in the system dynamics. After the injection of a counterfield, measurements of the population statistics of a probe atom allow us to derive the micromaser linewidth in all ranges of the relevant parameters, establishing experimentally the distinctive features of the micromaser spectrum due to the discreteness of the electromagnetic field.