The limbus spiralis and its relationship to the developing tectorial membrane in the cochlear duct of the guinea pig fetus

Summary The development of the interdental cells of the limbus spiralis and of the inner spiral sulcus cells as well as the formation of the mesenchymal teeth of Huschke are described during fetal life up to the day of birth in the guinea pig. Additionally, the changes of the developing tectorial membrane are studied. The ultrastructural observations allow the conclusion that during fetal development at least a considerable part of the material of the tectorial membrane is secreted by the interdental cells of the limbus spiralis.Supported by Deutsche Forschungsgemeinschaft     

Inhalation of concentrated particulate matter produces pulmonary inflammation and systemic biological effects in compromised rats

Although significant progress has been made over the past few years, there is still debate on the causal fractions that are responsible for particulate matter (PM)-associated adverse health effects. A series of 1-d inhalation exposures to concentrated ambient particles (CAPs) were performed in compromised rats, focusing on pulmonary inflammation and changes in blood factors as biological outcomes. Studies were carried out in The Netherlands at an urban background location in Bilthoven, an industrialized location in the city of Utrecht, as well as at a location that is heavily dominated by freeway emissions. It was hypothesized that exposure to CAPs resulted in oxidative stress in the lung, producing a release of inflammatory mediators, which in turn can result in cardiovascular effects. Both spontaneously hypertensive rats and rats preexposed to ozone were studied. The effects were studied at 2d postexposure, focusing on pathology and cell proliferation, bronchoalveolar lavage fluid (BALF) analysis (including cytokines, biochemistry, cell differentials, cell viability and proliferation, and Clara-cell 16 protein), and blood analyses (fibrinogen, Clara-cell 16 protein, Von Willebrand factor, and cell differentials). Using CAPs exposures as a binary term, mild inflammation (increased numbers of neutrophils) and increased lung permeability (protein and albumin leakage in BALF) were evident. In addition, CAPs also produced increased fibrinogen concentrations in blood of spontaneously hypertensive rats. In conclusion, inhalation up to 3700 microg/m3 CAPs in the size range of 0.15-2.5 microm did induce statistically significant effects in the lung and blood, but the effects observed may not potentially be very biologically relevant. PM mass concentrations and lung permeability were weakly associated. This suggests that other PM metrics might be more appropriate.     

Results and complications after ileal pouch anal anastomosis: a meta-analysis of 43 observational studies comprising 9,317 patients

OBJECTIVE: To analyze the literature of ileal pouch anal anastomosis (IPAA) regarding complications and functional outcome, to provide audit data for individual surgeons and units to assess their own performance against and also to serve as reference standard for the assessment of novel alternatives. BACKGROUND: IPAA is the standard restorative procedure for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). This operation is, however, associated with distinct rates of failure, complications and fecal incontinence. METHODS: A meta-analysis on pooled incidences of complications of IPAA was conducted. Medline search and cross-reference search identified studies on IPAA (n > or = 50). Two authors independently performed the data extraction on study characteristics, diagnosis, type of operation, pouch-related complications, pouch failure and functional results. In case of disagreement consensus was reached by joint review of the study. Estimates of pouch-related complications, pouch failure and functional results are described as pooled percentages with 95% confidence interval. RESULTS: The initial search based on 1,206 abstracts yielded 43 studies eligible for further analysis. Indications for IPAA were UC in 87.5%, FAP in 8.9% and other diagnoses in 3.6%. The median follow-up was 36.7 months. Pouch failure was 6.8%, increasing to 8.5% in case of follow-up of more than 60 months. Pelvic sepsis occurred in 9.5%. Severe, mild and urge fecal incontinence were reported in 3.7, 17, and 7.3%, respectively. No effect of experience, duration of follow-up and type of surgical technique on the incidence of pouch failure and pelvic sepsis was demonstrable. CONCLUSIONS: Current techniques for restorative surgery after proctocolectomy are associated with non-negligible complication rates and leave room for improvement and continuation of development of alternative procedures.     

The musculocutaneous nerve: ultrasound appearance for peripheral nerve block

BACKGROUND AND OBJECTIVES: To gain complete anesthesia of the forearm, block of the musculocutaneous nerve is necessary. Variations in its course and position make localization of the musculocutaneous nerve problematic. The aim of the study is to describe the ultrasound appearance of the musculocutaneous nerve in the axilla and to suggest potential areas to target neural block. METHODS: We scanned the axillary regions of 19 volunteers and assessed the size and shape of 34 musculocutaneous nerves at entry into, exit from, and in the center of the coracobrachialis muscle. Furthermore, we measured the depth of the musculocutaneous nerve under the skin surface and its distance from the axillary artery at those 3 measurement points. RESULTS: As it travels through the coracobrachialis muscle, the musculocutaneous nerve changes in shape from oval to flat-oval to triangular. During this course, the musculocutaneous nerve also separates from the axillary artery and becomes more lateral while changing its depth from the surface. The musculocutaneous nerve increases its transverse area along this nerve path. In 2 subjects, the musculocutaneous nerve could not be visualized unilaterally within the course of the coracobrachialis muscle. CONCLUSIONS: Knowledge of its ultrasound appearance facilitates localization and successful block of the musculocutaneous nerve. Because the distance between the musculocutaneous nerve and brachial plexus varies, different locations of musculocutaneous nerve puncture during ultrasound-guided regional anesthesia can be chosen.     

BRAF and NRAS mutations are frequent in nodular melanoma but are not associated with tumor cell proliferation or patient survival

Previous studies have shown frequent mutations in the BRAF (V-raf murine sarcoma viral oncogene homolog B1) or NRAS (neuroblastoma RAS viral [V-ras] oncogene homolog) genes in cutaneous melanoma, but the relationship between these alterations and tumor cell proliferation has not been examined in human melanoma. In our study of 51 primary nodular melanomas and 18 paired metastases, we found mutations in BRAF (codon 600, previously denoted 599) in 15 primary tumors (29%) and eight metastases (44%). The figures for NRAS mutations were 27% and 22%, respectively. Mutations in BRAF and NRAS genes were mutually exclusive in all but one case, and were maintained from primary tumors through their metastases. Mutations, however, were not associated with tumor cell proliferation by Ki-67 expression, tumor thickness, microvessel density, or vascular invasion, and there were no differences in patient survival. Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma.     

Postnatally acquired cytomegalovirus infection via breast milk: effects on hearing and development in preterm infants

BACKGROUND: In preterm infants there is a high risk of transmission of cytomegalovirus (CMV) via breast milk from seropositive mothers with reactivation of the virus during lactation. There is little information about the long term sequel of early postnatally acquired CMV infection in pre-term infants. This study aimed to investigate whether there was an increased frequency of impaired neurodevelopmental outcome and sensorineural hearing loss in preterm infants with postnatally acquired CMV infection through transmission by CMV-positive breast milk. METHODS: Twenty-two preterm infants [median birth weight, 1020 g (range, 600 to 1870 g); median gestational age, 27.6 weeks (range, 23.6 to 32 weeks] with early postnatally acquired CMV infection by breast-feeding (onset of viruria between Days 23 and 190 postnatally) were compared with 22 CMV-negative preterm infants individually matched for gestational age, birth weight, gender, intracranial hemorrhage and duration of ventilation. At 2 to 4.5 years of age, follow-up assessments were conducted consisting of neurologic examination, neurodevelopmental assessment and detailed audiologic tests. RESULTS: None of the children had sensorineural hearing loss. There was no difference between the groups with regard to neurologic, speech and language or motor development. CONCLUSION: The results of this study suggest that early postnatally acquired CMV infection via CMV-positive breast milk does not have a negative effect on neurodevelopment and hearing in this group of patients. Because we studied a small number of infants, further follow-up studies are warranted in preterm infants with early postnatally acquired CMV infection.     

In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins

The well known gender-related differences in drug action may partly be explained by changes in activity and expression of drug metabolising enzymes, but also by modulation of active drug transport systems (e.g. P-glycoprotein, Pgp) by sexual steroids, which is yet not well investigated. Because many women are using hormones (e.g. as oral contraceptives) we investigated the influence of different synthetic progestins on Pgp activity. Pgp inhibition of progesterone, medroxyprogesterone, chlormadinone, cyproterone, levonorgestrel, norethisterone, desogestrel, and norgestimate was measured in vitro in two Pgp over-expressing cell lines (L-MDR1, P388/dx cells) and the corresponding parental cell lines by means of calcein assay, and ex vivo in human peripheral blood mononuclear cells (PBMCs) by rhodamine123 efflux. For most progestins tested, concentrations needed to double baseline fluorescence (f2) in L-MDR1 cells were similar to that of the potent Pgp inhibitor quinidine, whereas levonorgestrel and norethisterone did not reach f2. The results in P388/dx cells essentially confirmed our findings in L-MDR1 cells. Additionally, Pgp inhibitory activity of all progestins tested was also shown ex vivo in PBMCs. The potent Pgp inhibition by several synthetic progestins in vitro and ex vivo suggests that such an interaction might be clinically relevant despite generally low plasma concentrations of progestins. The results may be of particular importance for Pgp substrates, such as protease inhibitors and chemotherapeutic agents, for which intracellular concentrations are critical.