[Transbronchial lung cryobiopsy in interstitial lung diseases]. / Les cryobiopsies pulmonaires transbronchiques dans les pneumopathies infiltrantes diffuses.

In some cases of interstitial lung disease (ILD), clinical and biological findings associated with CT scan pattern during multidisciplinary discussion (MDD) fail to yield a confident diagnosis. In these cases, histology may be necessary. Transbronchial lung cryobiopsy (TBLC) is a bronchoscopic procedure that has been developed in recent years and currently contributes to diagnostic work-up in patients with ILD. TBLC provides tissue samples for histological analysis with an acceptable risk of complications, consisting mainly in pneumothorax or bleeding. In addition to higher diagnostic yield than conventional forceps biopsies, the procedure shows a better safety profile than surgical biopsies. The indication to perform TBLC is decided during a 1st MDD and during a 2nd MDD, results can provide a diagnostic yield approximating 80%. TBLC appears to be an attractive, minimally invasive technique to be proposed as a first-line procedure in selected patients in experienced centers, while surgical lung biopsy may be considered as a second-line solution.

Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aß was rescued compared to cultures exposed only to Aß. Here we investigated treatment with Aß for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aß exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aß for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aß exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aß, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aß treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aß amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted.

Adverse events associated with regional ophthalmic anaesthesia in an Australian teaching hospital.

This study prospectively audited 3339 peribulbar and 2688 sub-Tenon's eye blocks in an Australian teaching hospital with regard to the occurrence of adverse events. Complications were classified into three groups: ocular complications directly due to the eye block technique, systemic medical complications possibly associated with block technique and adverse events which were unlikely to have been associated with block technique. Five serious ocular complications were associated with peribulbar block compared to none with sub-Tenon's block (P = 0.07).

Identification of genes associated with ovarian cancer metastasis using microarray expression analysis.

Although the transition from early- to advanced-stage ovarian cancer is a critical determinant of survival, little is known about the molecular underpinnings of ovarian metastasis. We hypothesize that microarray analysis of global gene expression patterns in primary ovarian cancer and metastatic omental implants can identify genes that underlie the metastatic process in epithelial ovarian cancer. We utilized Affymetrix U95Av2 microarrays to characterize the molecular alterations that underlie omental metastasis from 47 epithelial ovarian cancer samples collected from multiple sites in 20 patients undergoing primary surgical cytoreduction for advanced-stage (IIIC/IV) serous ovarian cancer. Fifty-six genes demonstrated differential expression between ovarian and omental samples (P < 0.01), and twenty of these 56 differentially expressed genes have previously been implicated in metastasis, cell motility, or cytoskeletal function. Ten of the 56 genes are involved in p53 gene pathways. A Bayesian statistical tree analysis was used to identify a 27-gene expression pattern that could accurately predict the site of tumor (ovary versus omentum). This predictive model was evaluated using an external data set. Nine of the 27 predictive genes have previously been shown to be involved in oncogenesis and/or metastasis, and 10/27 genes have been implicated in p53 pathways. Microarray findings were validated by real-time quantitative PCR. We conclude that gene expression patterns that distinguish omental metastasis from primary epithelial ovarian cancer can be identified and that many of the genes have functions that are biologically consistent with a role in oncogenesis, metastasis, and p53 gene networks.

Sub-Tenon block: a learning curve of 100 cases.

This study measures the learning curve for accomplishing sub-Tenon blocks for ophthalmic surgery applicable to anaesthetists skilled in peribulbar techniques. We defined criteria for a good block in terms of chemosis, subconjunctival haemorrhage, globe movement and the need for additional peribulbar block. The overall success rate, by our definitions, was 72% and 56% for the two operators. The overall requirement for an additional peribulbar block was 10%. The rate of additional blocks and reduction in globe movement reached a plateau after about 60 procedures for both operators. The rates of chemosis (6% and 12% overall) and subconjunctival haemorrhage (6% and 12% overall) did not trend with increased experience. The results applied to both a cataract and a vitreo-retinal surgery casemix.

A quality assurance index for brachytherapy treatment plan verification.

A method is described which provides an independent verification of a brachytherapy treatment plan. The method is applicable to any common geometric configuration and utilises a simple equation derived from a common form of non-linear regression. The basis for the index value is the relationship between the treatment time, prescribed dose, source strength and plan geometry. This relationship may be described mathematically as: Total Treatment Time proportional to (Prescribed Dose/Source Strength) x (a geometric term) with the geometric term incorporating three geometric components, namely the distance from source positions to points of dose normalisation d, the total length of the dwell positions L, and the number of source trains or catheters N. A general equation of the form GF = k (d)(-alpha) (L)(-beta) (N)(-gamma) is used to describe the plan geometry, where GF is what we have termed the geometric factor, k is a constant of proportionality and the exponents are derived from the non-linear regression process. The resulting index is simple to calculate prior to patient treatment and sensitive enough to identify significant error whilst being robust enough to allow for a normal degree of geometric distortion.

[A rare dyspnea in internal medicine: platypnea-orthodeoxia after pneumonectomy]. / Une dyspnée exceptionnelle en médecine interne: la platypnée-orthodéoxie après pneumonectomie.

BACKGROUND: A right-to-left shunting across a patent foramen ovale is a rare cause of acute respiratory failure after pneumonectomy. CASE REPORTS: We report two cases of posture dependent dyspnea (platypnea-orthodeoxia) secondary to postoperative right-to-left shunting across a patent foramen ovale. Both cases occurred three months after pneumonectomy, the first in a 63-year-old man and other in a 52-year-old man. CONCLUSION: A platypnea-orthodeoxia (dyspnea induced by the upright position with arterial deoxygenation relieved by recumbency) should lead to the diagnosis which is confirmed by echography or cardiac catheterization. The prognosis is good after surgical closure of the patent foramen ovale. The physiopathologic mechanism is poorly understood. We report two cases of platypnea-orthodeoxia.

The effect of intraoperative ventilation strategies on perioperative atelectasis.

Several methods of ventilation have previously been shown to reduce intraoperative atelectasis and alveolar to arterial oxygen gradient (A-a DO2) in healthy patients. This study was designed to show firstly the relative intra-operative benefit and secondly if any method had an effect on atelectasis postoperatively. Using a factorial design we randomized 24 patients to each of the four ventilatory interventions (manual inflations, large tidal volumes, PEEP, and pressure control inverse ratio ventilation (IRV)). The A-a DO2 was used as the measure of atelectasis and data collected intra- and postoperatively for 24 hours. The mean pre-induction A-a DO2 was 80 mmHg. This study demonstrated that PEEP and IRV were most effective in reducing intraoperative A-a DO2 (P < 0.05 ANCOVA). Using more than one intervention did not improve the A-a DO2. No method had any effect on postoperative A-a DO2.

Radiographic evaluation of anterior cruciate ligament graft failure with special reference to tibial tunnel placement.

Graft failure in anterior cruciate ligament (ACL) reconstruction can result from anterior placement of the tibial tunnel. Conventional radiographic evaluation of this problem does not take into account potential changes in tibio-femoral relationship caused by ACL instability. A retrospective radiographic evaluation of failed as well as successful ACL reconstructions was carried out. Both published radiographs as well as those obtained of patients treated by the authors were evaluated for tibial tunnel placement, roof impingement, and tibial position relative to the femur. In the second part of the study, the radiographs were obtained under standard conditions in both failed ACL reconstructions and normal knees. The results of both parts of the study indicate that lateral radiographs of the extended knee with ACL instability are likely to show subtle anterior tibial subluxation. The subluxation can give the impression of roof impingement on the graft. However, the majority of the failed knees had similar tibial tunnel placement compared with successful reconstructions and would appear unimpinged once corrected for subluxation. The diagnosis of graft impingement by the femoral intercondylar roof has to take into account potential tibial subluxation. Impingement as a cause graft failure may be less common than previously thought.

The effects of inverse ratio ventilation on intracranial pressure: a preliminary report.

OBJECTIVE: To determine the effects of pressure control inverse ratio ventilation [PC-IRV], as compared with volume controlled normal ratio ventilation [VC], on the intracranial pressure [ICP] of patients with severe head injury. DESIGN: A prospective study with unblinded intervention. SETTING: The Intensive Therapy Unit of a base hospital. PATIENTS AND PARTICIPANTS: Nine cases of head injury requiring mechanical ventilation and intracranial pressure monitoring were studied. INTERVENTIONS: Patients were twice transferred from VC (1:E ratio 1:2) to PC-IRV (1:E ratio 2:1). Firstly, tidal volume was maintained at an equal value. Secondly, end tidal CO2 was maintained at an equal value. No other changes were made to ventilation, vasopressor therapy or ICP control. MEASUREMENTS AND RESULTS: Measurements were taken of ICP, mean arterial pressure (MAP) end tidal CO2 and respiratory parameters. In the first observation, there were significant changes in peak inspiratory pressure (PIP), mean airway pressure (Paw) and intrinsic positive end expiratory pressure (PEEP) but not for ICP, end tidal CO2, MAP and cerebral perfusion pressure (CPP). The correlation between change in ICP and change in end tidal CO2 was r = -0.74. In the second observation there were significant changes in tidal volume, PIP, Paw and intrinsic PEEP but not for ICP, MAP and CPP. The correlation between the change in ICP and the change in Paw was insignificant. CONCLUSIONS: PC-IRV has a minimal net effect on ICP. Changes in ICP correlate more strongly with changes in CO2 than changes in Paw.

Distinct desmocollin isoforms occur in the same desmosomes and show reciprocally graded distributions in bovine nasal epidermis.

The adhesive core of the desmosome is composed of cadherin-like glycoproteins of two families, desmocollins and desmogleins. Three isoforms of each are expressed in a tissue-specific and developmentally regulated pattern. In bovine nasal epidermis, the three desmocollin (Dsc) isoforms are expressed in overlapping domains; Dsc3 expression is strongest in the basal layer, while Dsc2 and Dsc1 are strongly expressed in the suprabasal layers. Herein we have investigated whether different isoforms are assembled into the same or distinct desmosomes by performing double immunogold labeling using isoform-specific antibodies directed against Dsc1 and Dsc3. The results show that individual desmosomes harbor both isoforms in regions where their expression territories overlap. Quantification showed that the ratio of the proteins in each desmosome altered gradually from basal to immediately suprabasal and upper suprabasal layers, labeling for Dsc1 increasing and Dsc3 decreasing. Thus desmosomes are constantly modified as cells move up the epidermis, with continuing turnover of the desmosomal glycoproteins. Statistical analysis of the quantitative data showed a possible relationship between the distributions of the two isoforms. This gradual change in desmosomal composition may constitute a vertical adhesive gradient within the epidermis, having important consequences for cell positioning and differentiation.

Expression of full-length desmosomol glycoproteins (desmocollins) is not sufficient to confer strong adhesion on transfected L929 cells.

Desmocollins are cadherin-like glycoproteins that are localized in desmosomes. They are thought to play a role in cell adhesion but direct evidence for this is currently unavailable. For this reason we have expressed cDNAs encoding full-length bovine desomocollin type 1a and type 1b in mouse fibroblast (L929) cells. This system has previously been used to demonstrate the adhesive properties of E-cadherin. E-cadherin-mediated cell-cell adhesion is thought to require interaction of the cytoplasmic domain with the catenins that are expressed in L-cells. Because L929 cells do not express cytoplasmic desmosomal components that may be required for desmocollin-mediated adhesion, we constructed a chimeric cDNA encoding the bovine type 1 extracellular domain linked to the mouse E-cadherin transmembrane and cytoplasmic domains. cDNAs were transfected into cells and clones that expressed heterologous protein at the cell surface were isolated. The full-length desmocollins apparently did not interact with any other molecules, but the chimeric protein did bind to endogenous mouse alpha- and beta-catenin. Surprisingly none of the desmocollin-transfected cell lines showed significant adhesive properties under conditions where cells transfected with E-cadherin exhibited strong adhesiveness. We conclude that desmcollin expression alone is not sufficient to confer adhesion on transfected cells and more than one desmosomal component may be required.

Characterisation of a desmocollin isoform (bovine DSC3) exclusively expressed in lower layers of stratified epithelia.

Desmocollins are cadherin-like glycoproteins involved in cell adhesion and plaque formation in desmosome junctions. Three distinct isoforms, the products of different genes, have been found in bovine tissues. We have reported previously that one of these, DSC3, is expressed only in basal and lower suprabasal layers of stratified epithelia. Using RT-PCR we have now obtained the complete cDNA coding sequence of mature bovine DSC3. It has alternatively spliced 'a' and 'b' forms found in other desmocollins but is unique in having a 43 instead of a 46 base pair exon. We have characterised a monoclonal antibody, 07-4G, which is specific for the Dsc3 protein, recognising an epitope in the extracellular domain. Immunofluorescent staining with 07-4G confirms that this isoform is found only in stratified epithelia, being strongly expressed in the basal cell layers of these tissues. The intensity of expression fades gradually in the suprabasal layers and disappears completely below the upper limit of desmosome expression. These results suggest that Dsc3 plays an important role in cell epithelial differentiation.

[Horton disease of pulmonary localization]. / Maladie de Horton avec localisation pulmonaire.

A case of Horton's disease with interstitial pulmonary involvement is reported. Transbronchial biopsy of the lung and biopsy of the temporal artery provided evidence of giant cell lesions. Outcome was favourable with general corticosteroid therapy with regression of the pulmonary disease.

Cloning, sequence analysis and expression pattern of mouse desmocollin 2 (DSC2), a cadherin-like adhesion molecule.

Desmocollins are cadherin-like adhesion molecules of desmosomes. We have determined the full cDNA sequence of a murine desmocollin, the homologue of human and bovine type 2 desmocollins (DSC2), and studied its tissue distribution and expression in stratified epithelia. An 8.5 day mouse embryo cDNA library was screened yielding overlapping clones which encoded the mouse DSC2. This gene has an open reading frame of 2710 base pairs (bp) encoding a polypeptide of 902 amino acids (aa). The polypeptide comprises a signal peptide, a precursor peptide, and a mature protein of 766 aa having an extracellular domain of 549 aa, a single transmembrane domain and a cytoplasmic domain of 184 aa. Like other desmocollins, murine DSC2 has two products, Dsc2a and Dsc2b, produced by alternative splicing of a 46 bp exon which encodes 11 COOH-terminal aa followed by an in-frame stop codon. Inclusion of this exon forms Dsc2b which is 54 aa shorter than Dsc2a. Mouse Dsc2a shows 75.7% amino acid identity to human and 63.3% identity to bovine Dsc2a. The mouse desmocollin is also homologous to the cadherins; 32.2% to the most closely related typical cadherin, human N-cadherin. DSC2 is ubiquitously expressed in epithelial tissues and the heart of adult mice and from the blastocyst stage of development. In situ hybridization shows that the gene is most strongly expressed suprabasally in stratified epithelia, similar to the expression of bovine DSC2.

A review of 19 sets of triplets: the positive results of vaginal delivery.

The outcome of 19 triplet pregnancies delivered at Waikato Women's Hospital is analyzed, with particular regard to the mode of delivery. During the period 1981-1992 the incidence of triplets was 1:1,945. Twelve sets of triplets were delivered by Caesarean section (63%) with 6 perinatal deaths occurring in this group, compared to none in 7 sets of triplets delivered vaginally (37%). All triplet pregnancies were correctly diagnosed antenatally by ultrasound examination at a mean gestational age of 19 weeks (range 11-28 weeks). The most common antenatal complications were preterm labour in 18 pregnancies (95%) and preeclampsia in 4 (21%). The mean gestation at delivery was 33 weeks (range 25-39 weeks). The outcome of triplet pregnancies was better in the group that delivered vaginally than those delivered by Caesarean section. Greater maturity of the infants delivered vaginally appeared to be the major factor for the lower neonatal morbidity and mortality.

[Interstitial pneumopathy in a woman treated with althiazide]. / Pneumopathie interstitielle chez une femme traitée par altizide.

The authors report the case of interstitial pneumopathy in a woman treated with althiazide, thiadizical diuretic. This observation bring the discussion on responsibility to this drug in the origin of this pulmonary disease.