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PubMedDate not supplied

Radial keratotomy does not affect intraocular pressure.

BACKGROUND: Recent reports have suggested that a secondary effect of radial keratotomy may be a reduction in intraocular pressure (IOP) levels. METHODS: In an effort to study the relationship of radial keratotomy to IOP, we compared the mean IOP from the baseline and follow-up visits during 1 year after surgery of operated versus nonoperated eyes of patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) study. To investigate if radial keratotomy had more of an effect on eyes with higher baseline IOPs, the same analysis was performed on a subset (134 patients) who had a baseline IOP of 15 mm Hg or greater. RESULTS: The average baseline IOP for both operated eyes and nonoperated eyes was 14.6 mm Hg. There was no significant difference in mean IOP between operated and nonoperated eyes across all time points (p = .18). Although mean IOP changed over time, it did not clinically differ in operated versus nonoperated eyes at any time point. These findings were similar in the analysis of eyes with higher baseline IOP (15 mm Hg or greater). CONCLUSION: We conclude that the radial keratotomy performed in the PERK study had no effect on IOP within 1 year after surgery.

Adult↗
PubMed2005

An in vivo evaluation of docetaxel delivered intratumorally in head and neck squamous cell carcinoma.

OBJECTIVE: To identify activity and biological mechanisms of intratumoral (IT) docetaxel on head and neck squamous cell carcinoma (HNSCC). METHODS: Docetaxel IT therapy was tested in xenograft models of 2 HNSCC lines, HN30 and HN12. The overall and disease-free survival rates, tumor growth, and toxic effects were measured. The pharmacokinetic profiles of docetaxel in plasma and tumor were compared after IT and intravenous (IV) administration. Comparisons between common and supradoses of docetaxel with regard to expression of regulators in the cell cycle, apoptosis, and signal transduction pathways were determined using Western blot analysis. RESULTS: In the HN30 and HN12 xenograft models, IT docetaxel improved overall as well as disease-free survival and reversed tumor growth. The only toxic effects noted were local (alopecia and skin breakdown). Skin breakdown resolved in all cases. At equivalent dosing levels, IT docetaxel achieved a 26-fold higher peak tumor concentration and 24-fold longer tumor exposure than IV treatment. Furthermore, limited plasma exposure was noted with IT docetaxel. Supradose levels of docetaxel produced distinct protein expression patterns for regulators of the cell cycle (cyclins A and B, p21, and p27), apoptosis (cleaved caspase-3 and cleaved PARP), and signal transduction (EGFR, pEGFR, pc-Jun, and pERK) in HNSCC, which supports a distinctive mechanism of action for supradose docetaxel levels. Since levels of cleaved caspase-3 and PARP, markers of apoptosis, were only elevated with lower doses, the observed cell death at supradose levels was probably due to necrosis. CONCLUSIONS: Injections of IT docetaxel at usual and supradoses are associated with a pharmacokinetic profile and biological mechanism distinct from those observed with usual IV doses. It is calculated that IT therapy in men will increase peak concentrations of docetaxel in tumors by 1000-fold over the conventional IV dose used clinically. These preclinical results support further testing of IT docetaxel in HNSCC.

Animals↗
PubMed2004

Experience-dependent activation of extracellular signal-related kinase (ERK) in the olfactory bulb.

Protein kinase-mediated signaling cascades play a fundamental role in translating extracellular signals into cellular responses in CNS neurons. The mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) pathway participates in regulating diverse neuronal processes such as proliferation, differentiation, survival, synaptic efficacy, and long-term potentiation by inducing cAMP-response element (CRE)-mediated gene transcription. Central olfactory structures show plasticity throughout the lifespan, but the role of the MAPK/ERK pathway in odor-evoked activity has yet to be determined. Therefore, we examined the effect of odorant exposure and early postnatal deprivation on ERK activity. We found that odor stimulation induced ERK phosphorylation, that activation of the ERK pathway was decreased with early postnatal deprivation, and that ERK phosphorylation was subsequently increased by restoring stimulation. Further, locations of ERK activation in bulbar neurons after exposure to single odorants corresponded to odor-evoked activity patterns found with other measures of activity in the bulb. Finally, due to the cytoplasmic location of pERK, activated dendrites belonging to the primary excitatory output neurons of the bulb were observed following a single odor exposure. The results indicate that the MAPK/ERK pathway is activated by odorant stimulation and may play an important role in developmental sensory plasticity in the olfactory bulb.

Animals↗
PubMed2001

Measurement of MAP kinase activation by flow cytometry using phospho-specific antibodies to MEK and ERK: potential for pharmacodynamic monitoring of signal transduction inhibitors.

Cancer cells frequently show abnormal signaling via the mitogen activated protein kinase (MAP kinase) pathway due to increased activity of surface receptors for growth factors, or as a result of ras mutations. The development of potent anti-cancer agents that target this pathway prompts the need for analytical methods that allow pharmacodynamic monitoring of drug effects in patients during early phase clinical trial. We describe such a method, based on the activation of T-lymphocytes in undiluted peripheral blood using phorbol myristate acetate (PMA). Following rapid hypotonic lysis and formaldehyde fixation, activation of the MAP kinase pathway can then be demonstrated using phospho-specific antibodies that recognize the activated mediators MEK or ERK, followed by surface labeling with anti-CD3 to identify T-lymphocytes. This method was used to investigate the effects of a MEK inhibitor, U0126, and a new raf kinase inhibitor BAY 37-9751 in blood samples from normal donors. Dose-dependent inhibition of pERK activation was demonstrated for both agents. Furthermore, differential effects on pMEK activation allowed the molecular targets of the two inhibitors to be distinguished. In addition to monitoring drug effects in patients during treatment with inhibitors of the MAP kinase pathway, the general methodology described in this paper has the potential for wide application to the study of signal transduction at the single cell level using flow cytometry.

Blotting, Western↗
PubMed2003

Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events.

BACKGROUND: Recent advances in intracellular staining techniques, cytometer technology, fluorescent reagents, and antibody production have expanded the number of intracellular antigens that can be analyzed by flow cytometry. Measurement of protein phosphorylation with phospho-specific antibodies has given insight into kinase signaling cascades. However, available techniques for phospho-epitope staining can differ greatly, making it necessary to understand the differences between the outcomes when such techniques are applied and to develop robust and reproducible methods of application. METHODS: Ten different cellular fixation and permeabilization techniques were tested for their ability to provide phospho-specific staining. Combinations of formaldehyde, methanol, ethanol, acetone, Triton X-100, and saponin were used as fixation and permeabilization reagents. Phospho-specific antibodies were labeled with Alexa Fluor dyes to provide multicolor analysis of different signaling events simultaneously within individual cells. RESULTS: Fixing cells with 1.5% formaldehyde followed by permeabilization in methanol gave optimal results for pERK, pp38, pJNK, pStat1, pStat5, and pStat6 staining. Alteration of formaldehyde fixation and methanol permeabilization times affected measurements of phosphorylation induction. Phospho-specific flow cytometric analyses correlated well with Western blotting, providing cross platform validation of the technique. CONCLUSIONS: Measuring phosphorylation events by flow cytometry provides a rapid and efficient way to measure kinase cascades in individual cells. Stability of phospho-epitopes in methanol allows long-term storage of samples prior to analysis. Multiple signaling cascades can be monitored simultaneously through the use of different fluorophore labels to determine specificity of ligands or inhibitors. Application of optimized techniques to heterogeneous cell types such as peripheral blood or murine splenocytes may allow signaling to be analyzed simultaneously in immune cell subsets.

Antibodies, Monoclonal↗
PubMed2006

Comparison of strategies targeting Raf-1 mRNA in ovarian cancer.

In this study, we characterize the uptake and specificity of a first-generation Raf-1 antisense oligonucleotide (ASO) (ISIS 5132) and compare it with a second-generation ASO (ISIS 13650) and an RNA interference approach. All three approaches resulted in inhibition of both Raf-1 expression and cellular growth. Specificity of the Raf-1 ASOs was confirmed by comparison with ASOs targeted against another Raf isoform (B-Raf) as well as mismatch sequences. Cellular uptake studies with FAM-labelled ISIS 5132 revealed that whilst the majority of cells treated at a low-intermediate plating density were labelled within 3 hr, cells treated at high density demonstrated neither Raf-1 protein knockout nor significant growth inhibition, following similar treatment. This lack of response at high cell densities was associated with reduced pERK and Raf-1 inhibition. Cell cycle analysis revealed that whilst SKOV-3 cells both accumulated in the S-phase of the cell cycle and showed enhanced annexin V levels, following Raf-1 ASO treatment; these effects were also demonstrated with first-generation but not second-generation mismatch oligonucleotides. Bromodeoxyuridine incorporation analysis suggested that these effects may indeed be partly attributable to sequence nonspecific effects. Finally, the combination of ISIS 5132 with either carboplatin or taxol showed enhanced growth inhibition, supporting the view that such ASOs may have a more effective clinical role when used in combination with cytotoxic agents.

Antineoplastic Agents↗
PubMed2007

MS-KIF18A, a kinesin, is associated with estrogen receptor.

The study of MS-KIF18A kinesin protein is focused on its cellular distribution and association with a cargo protein. Indirect immunofluorescence (IF) analyzed the intracellular distribution of endogenous MS-KIF18A and the transfected enhanced green fluorescence protein (eGFP)-MS-KIF18A in osteogenic cells. In both cases, the proteins were localized at the plasma membrane, cytosol, and nucleus. Bioinformatics analysis suggested interactions between MS-KIF18A and estrogen receptor (ERalpha) which were further elucidated by immunoprecipitation (IP). We identified interaction between endogenous MS-KIF18A with 66 and 46 kDa isoforms of ERalpha in MBA-15 cells. Moreover, MS-KIF18A and 66 kDa ERalpha complex has been demonstrated between ectopically expressed proteins in COS-7 cells. We have shown that anti-MS-KIF18A antibody immunoprecipitated the ERalpha and pERK in cells challenged with 17beta-estrogen (17beta-E2). The hormone activation induced mitogen-activated protein kinases (MAPK) pathway and increased p-ERK. The activation was interfered when cells were pre-treated with either ICI-182,780 or MAPK inhibitor PD98059 prior the challenge with 17beta-E2 that resulted in a decrease in association between MS-KIF18A and p-ERK1/2. The obtained results suggest a role for the proteins in a non-genomic response of MBA-15 cells challenged with 17beta-E2. This study presents a novel interaction between MS-KIF18A and ER that may have important physiological and pharmacological implications for estrogen action in various cells.

Base Sequence↗
PubMed2001

Characterization of phosphopeptides from protein digests using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and nanoelectrospray quadrupole time-of-flight mass spectrometry.

A two-step mass spectrometric method for characterization of phosphopeptides from peptide mixtures is presented. In the first step, phosphopeptide candidates were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) based on their higher relative intensities in negative ion MALDI spectra than in positive ion MALDI spectra. The detection limit for this step was found to be 18 femtomoles or lower in the case of unfractionated in-solution digests of a model phosphoprotein, beta-casein. In the second step, nanoelectrospray tandem mass (nES-MS/MS) spectra of doubly or triply charged precursor ions of these candidate phosphopeptides were obtained using a quadrupole time-of-flight (Q-TOF) mass spectrometer. This step provided information about the phosphorylated residues, and ruled out nonphosphorylated candidates, for these peptides. After [(32)P] labeling and reverse-phase high-performance liquid chromatography (RP-HPLC) to simplify the mixtures and to monitor the efficiency of phosphopeptide identification, we used this method to identify multiple autophosphorylation sites on the PKR-like endoplasmic reticulum kinase (PERK), a recently discovered mammalian stress-response protein.

Amino Acid Sequence↗
PubMed2001

The double-stranded RNA-activated protein kinase PKR is dispensable for regulation of translation initiation in response to either calcium mobilization from the endoplasmic reticulum or essential amino acid starvation.

The alpha-subunit of eukaryotic initiation factor eIF2 is a preferred substrate for the double-stranded RNA-activated protein kinase, PKR. Phosphorylation of eIF2alpha converts the factor from a substrate into a competitive inhibitor of the guanine nucleotide exchange factor, eIF2B, leading to a decline in mRNA translation. Early studies provided evidence implicating PKR as the kinase that phosphorylates eIF2alpha under conditions of cell stress such as the accumulation of misfolded proteins in the lumen of the endoplasmic reticulum, i.e., the unfolded protein response (UPR). However, the recent identification of a trans-microsomal membrane eIF2alpha kinase, termed PEK or PERK, suggests that this kinase, and not PKR, might be the kinase that is activated by misfolded protein accumulation. Similarly, genetic studies in yeast provide compelling evidence that a kinase termed GCN2 phosphorylates eIF2alpha in response to amino acid deprivation. However, no direct evidence showing activation of the mammalian homologue of GCN2 by amino acid deprivation has been reported. In the present study, we find that in fibroblasts treated with agents that promote the UPR, protein synthesis is inhibited as a result of a decrease in eIF2B activity. Furthermore, the reduction in eIF2B activity is associated with enhanced phosphorylation of eIF2alpha. Importantly, the magnitude of the change in each parameter is identical in wildtype cells and in fibroblasts containing a chromosomal deletion in the PKR gene (PKR-KO cells). In a similar manner, we find that during amino acid deprivation the inhibition of protein synthesis and extent of increase in eIF2alpha phosphorylation are identical in wildtype and PKR-KO cells. Overall, the results show that PKR is not required for increased eIF2alpha phosphorylation or inhibition of protein synthesis under conditions promoting the UPR or in response to amino acid deprivation.

Amino Acids↗
PubMed2001

Evidence for a novel thrombopoietin signalling event: activation of protein kinase A in human megakaryoblastic CMK cells.

Thrombopoietin (TPO) plays a crucial role in megakaryocyte development. TPO signalling, which is mediated by its receptor Mpl, includes Janus kinase, (JAK) signal transducer and activator of transcription (STAT) and Shc/Ras/mitogen-activated protein kinase (MAPK) pathways. The precise nature of these signalling routes has not been clarified in detail up until now. We investigated the effect of TPO on activation of cAMP-dependent protein kinase (PKA) and its involvement in MAPK signalling in human megakaryoblastic leukaemia CMK cells. For estimation of PKA activity, phosphorylation of a PKA-specific peptide substrate was assayed in CMK cell lysates. Since activation of PKA is associated with translocation of its catalytic subunit alpha (C-PKA) into the cell nucleus, Western blot analysis of nuclear fractions with an anti-C-PKA antibody was additionally performed. The activation of TPO-induced MAPK activation and the effect of the PKA inhibitor H-89 was measured using immunoblotting with a monoclonal anti-pERK antibody. TPO enhanced cAMP and induced activation of PKA in CMK cells. In addition, H-89 partly blocked TPO-induced MAPK activation in CMK cells. Our results indicate a novel TPO-triggered signalling event, activation of the cAMP/PKA pathway in human megakaryoblastic CMK cells. This signal transduction route seems to be involved in TPO-induced MAPK signaling.

Cell Nucleus↗
PubMed2002

Extracellular matrix oxidation modulates survival, NF-kappaB translocation, and MAPK activity in mesangial cells.

Inflammatory injury to the kidney may oxidize extracellular matrix proteins. These changes appear to impair adhesion of glomerular mesangial cells and might impact signaling mechanisms in these cells. In this study we evaluated how extracellular matrix oxidation could modulate the development of apoptosis as well as the activity of the transcription factor NF-kappaB and that of the MAPK family members ERK-1,2 and JNK. Exposure of mesangial cells to oxidized matrix enhanced the percentage of apoptotic cells. Western blot analysis revealed diminished levels of the phosphorylated form of ERK-1,2 in cells on oxidized matrix, while levels of phosphorylated JNK were increased. Cells on unmodified matrix were found to have rapid translocation of the p65 subunit of NF-kappaB, which was attenuated in cells on oxidized matrix. These findings suggest that extracellular matrix oxidation may impair survival of mesangial cells in association with decreased levels of pERK-1,2, increased levels of pJNK, and diminished nuclear translocation of the transcription factor NF-kappaB.

Active Transport, Cell Nucleus↗
PubMed2002

Mechanisms underlying suppression of protein synthesis induced by transient focal cerebral ischemia in mouse brain.

Transient global cerebral ischemia triggers suppression of the initiation step of protein synthesis, a process which is controlled by endoplasmic reticulum (ER) function. ER function has been shown to be disturbed after transient cerebral ischemia, as indicated by an activation of the ER-resident eIF2alpha kinase PERK. In this study, we investigated ischemia-induced changes in protein levels and phosphorylation states of the initiation factors eIF2alpha, eIF2B epsilon, and eIF4G1 and of p70 S6 kinase, proteins playing a central role in the control of the initiation of translation. Transient focal cerebral ischemia was induced in mice by occlusion of the left middle cerebral artery. Transient ischemia caused a long-lasting suppression of global protein synthesis. eIF2alpha was transiently phosphorylated after ischemia, peaking at 1-3 h of recovery. eIF2B epsilon and p70 S6 kinase were completely dephosphorylated during ischemia and phosphorylation did not recover completely following reperfusion. In addition, eIF2B epsilon, eIF4G1, and p70 S6 kinase protein levels decreased progressively with increasing recirculation time. Thus, several different processes contributed to ischemia-induced suppression of the initiation of protein synthesis: a long-lasting dephosphorylation of eIF2B epsilon and p70 S6K starting during ischemia, a transient phosphorylation of eIF2alpha during early reperfusion, and a marked decrease of eIF2B epsilon, eIF4G1, and p70 S6K protein levels starting during vascular occlusion (eIF4G1). Study of the mechanisms underlying ischemia-induced suppression of the initiation step of translation will help to elucidate the role of protein synthesis inhibition in the development of neuronal cell injury triggered by transient cerebral ischemia.

Animals↗
PubMedDate not supplied

Lecture skills in medical education.

The lecture is the most common method of transmitting information in medical schools and continuing medical education. In recent years this educational method has received considerable criticism because of poor lecturers and poor learning. The major advantage of the lecture is the ability to teach pertinent up-to-date information in an efficient manner. The major limitation is the passivity of the method with the teacher speaking and the listener passively receiving the material with considerable opportunity to be bored. The effective techniques of lecturing are: 1) environment aids learning: 2) an introduction perks interest; 3) stating objectives helps audience to respond analytically; 4) outlining a lecture helps clear thinking; 5) non-verbal behavior increases learning; 6) use of voice shows interest and clarity; 7) content is understood if it fits objectives; 8) organized lecture fits the time available; 9) visual aids used should be clear and understandable; 10) a summary helps to retain what is learned; 11) closure should be upbeat and should restate objectives; 12) questions should be answered succinctly. The medical lecturer can improve his skills by studying them, rehearsing while being observed by colleagues and by performing a self-analysis of video-taped lectures.

Communication↗
PubMed2003

Persistent eIF2alpha(P) is colocalized with cytoplasmic cytochrome c in vulnerable hippocampal neurons after 4 hours of reperfusion following 10-minute complete brain ischemia.

Upon brain reperfusion following ischemia, there is widespread inhibition of neuronal protein synthesis that is due to phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha), which persists in selectively vulnerable neurons (SVNs) destined to die. Other investigators have shown that expression of mutant eIF2alpha (S51D) mimicking phosphorylated eIF2alpha induces apoptosis, and expression of non-phosphorylatable eIF2alpha (S51A) blocks induction of apoptosis. An early event in initiating apoptosis is the release of cytochrome c from mitochondria, and cytochrome c release corresponds to the selective vulnerability of hippocampal CA1 neurons in rats after transient global cerebral ischemia. At present the signaling pathways leading to this are not well defined. We hypothesized that persistent eIF2alpha(P) reflects injury mechanisms that are causally upstream of release of cytochrome c and induction of apoptosis. At 4 h of reperfusion following 10-min cardiac arrest, vulnerable neurons in the striatum, hippocampal hilus and CA1 showed colocalized intense immunostaining for both persistent eIF2alpha(P) and cytoplasmic cytochrome c, while resistant neurons in the dentate gyrus and elsewhere did not immunostain for either. A lower intensity of persistent eIF2alpha(P) immunostaining was present in cortical layer V pyramidal neurons without cytoplasmic cytochrome c, possibly reflecting the lesser vulnerability of this area to ischemia. We did not observe cytoplasmic cytochrome c in any neurons that did not also display persistent eIF2alpha(P) immunostaining. Because phosphorylation of eIF2alpha during early brain reperfusion is carried out by PERK, these findings suggest that there is prolonged activation of the unfolded protein response in the reperfused brain.

Animals↗
PubMed2006

Adult bone-marrow-derived mesenchymal stem cells contribute to wound healing of skin appendages.

Adult bone-marrow-derived mesenchymal stem cells (MSCs) are well-established as having the capacity to differentiate into cells with mesodermal, ectodermal, and endodermal characteristics and can leave their niche to home toward and engraft within foreign tissues. To investigate whether adult MSCs contribute to the repair of skin appendages after injury, BrdU-labeled MSCs were co-cultured with heat-shocked confluent sweat gland cells (SGCs) in vitro and later intravenously injected into full-thickness skin wounds in rats. When adult MSCs were co-cultured with heat-shocked SGCs, a subset of adult MSCs differentiated into SGCs, the percentage of differentiation being enhanced by epidermal growth factor and the injured microenviroment, but weakened by PD98059. The ERK (extracellular signal-regulated kinase) pathway, especially pERK, was involved in the phenotype conversion of human MSCs into human SGC. Labeled MSCs were noted in hair follicles, sebaceous glands, blood vessels, and dermis in full-thickness wounds, and the incorporated cells in hair follicles and sebaceous glands were also positive for pan-cytokeratin. After wound healing, some labeled MSCs returned to the bone marrow, whereas other were retained in the dermis. We conclude that adult MSCs have the capacity to dock at specific sites, to contribute to wound healing of skin appendages, and to home toward marrow, and that engraftment of bone-marrow-derived cells is a functional event.

Adolescent↗
PubMed2006

Beta-amyloid peptides induces neuronal apoptosis via a mechanism independent of unfolded protein responses.

Accumulation of beta-amyloid (Abeta) peptides in senile plaques is one of the pathological hallmarks in Alzheimer's disease (AD), which can trigger apoptosis. We have previously demonstrated that Abeta triggered calcium release from the ER. Depletion of ER Ca(2+) ions has been reported leading to unfolded protein responses (UPR). While hypothesis has been made about UPR and neurodegeneration in AD, little is known about the effects of extracellular accumulation of Abeta on UPR. We have shown previously that activation of PKR in Abeta-triggered apoptosis. Since UPR can trigger PKR, our study aims to elucidate whether extracellular accumulation of Abeta peptides induce UPR in cultured neurons. Our results showed that Abeta could not trigger UPR signalings including phosphorylation of PERK, alternative cleavage of xbp-1 mRNA and induction of transcription of xbp-1 and Gadd153. Taken together, our results suggest that extracellular accumulation of Abeta peptides induce apoptosis via a mechanism independent of UPR.

Amyloid beta-Peptides↗
PubMed1984

Stellate iron lines in the corneal epithelium after radial keratotomy.

Biomicroscopic examinations of the corneal epithelium of 54 patients who had consecutive radial keratotomy operations in the National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) study showed that abnormal stellate epithelial iron lines had appeared at the junction of the middle and inferior thirds of the cornea in 13 of 16 eyes (81%) examined six months after surgery, in 43 of 50 eyes (86%) examined 12 months after surgery, and in seven of nine eyes (78%) examined 24 months after surgery. The density and pattern of the deposits varied from a faint tan horizontal iron line studded with small branches to a dense yellow-brown deposit with eight radiating arms that extended between all of the incisions. Analysis of the configuration of the iron line and the central keratometric readings 12 months after surgery showed that the greater the reduction in the central keratometric measurement postoperatively, the more prominent the iron line. We attribute the occurrence and variation of the stellate epithelial iron line to irregularities in the surface of the cornea present in the first year after radial keratotomy.

Adult↗
PubMed1986

Electrolyte changes in mesothelioma.

Little has been reported concerning electrolyte changes among patients with mesothelioma. Two studies have suggested that hyponatraemia is particularly common among them and should lead to suspicion of inappropriate secretion of antidiuretic hormone in those patients (Perks et al. 1979; Siafakas et al. 1984). We reviewed serum electrolyte changes in three groups of patients: 48 cases of pleural mesothelioma, 89 of peritoneal mesothelioma, associated with asbestos exposure, and 149 of asbestosis. Five of 48 (10.4%) patients with pleural mesothelioma, 17 of 89 (19.1%) with peritoneal mesothelioma, and 23 of 149 (15.4%) patients with asbestosis without mesothelioma, had hyponatraemia. No statistically significant difference among the groups was found. These findings do not support the proposal that hyponatraemia is unusually common when mesothelioma is present, at least not among patients whose neoplasms are related to asbestos exposure.

Asbestosis↗