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Abstract Background Obstructive sleep apnea (OSA) is a respiratory disease characterized by the collapse of the extrathoracic airway and has important social implications related to accidents and cardiovascular risk. The main objective of the present study was to investigate whether the drop in expiratory flow and the volume expired in 0.2 s during the application of negative expiratory pressure (NEP) are associated with the presence and severity of OSA in a population of professional interstate bus drivers who travel medium and long distances. Methods/Design An observational, analytic study will be carried out involving adult male subjects of an interstate bus company. Those who agree to participate will undergo a detailed patient history, physical examination involving determination of blood pressure, anthropometric data, circumference measurements (hips, waist and neck), tonsils and Mallampati index. Moreover, specific questionnaires addressing sleep apnea and excessive daytime sleepiness will be administered. Data acquisition will be completely anonymous. Following the medical examination, the participants will perform a spirometry, NEP test and standard overnight polysomnography. The NEP test is performed through the administration of negative pressure at the mouth during expiration. This is a practical test performed while awake and requires little cooperation from the subject. In the absence of expiratory flow limitation, the increase in the pressure gradient between the alveoli and open upper airway caused by NEP results in an increase in expiratory flow. Discussion Despite the abundance of scientific evidence, OSA is still underdiagnosed in the general population. In addition, diagnostic procedures are expensive, and predictive criteria are still unsatisfactory. Because increased upper airway collapsibility is one of the main determinants of OSA, the response to the application of NEP could be a predictor of this disorder. With the enrollment of this study protocol, the expectation is to encounter predictive NEP values for different degrees of OSA in order to contribute toward an early diagnosis of this condition and reduce its impact and complications among commercial interstate bus drivers. Trial registration Registro Brasileiro de Ensaios Clinicos (local acronym RBEC) [Internet]: Rio de Janeiro (RJ): Instituto de Informaçao Cientifica e Tecnologica em Saude (Brazil); 2010 - Identifier RBR-7dq5xx. Cross-sectional study on efficacy of negative expiratory pressure test proposed as screening for obstructive sleep apnea syndrome among commercial interstate bus drivers; 2011 May 31 [7 pages]. Available from http://www.ensaiosclinicos.gov.br/rg/RBR-7dq5xx/.

Abstract Background Obesity is a major public health problem in both developed and developing countries alike and leads to a series of changes in respiratory physiology. There is a strong correlation between obesity and cardiopulmonary sleep disorders. Weight loss among such patients leads to a reduction in these alterations in respiratory physiology, but clinical treatment is not effective for a long period of time. Thus, bariatric surgery is a viable option. Methods/Design The present study involves patients with morbid obesity (BMI of 40 kg/m2 or 35 kg/m2 to 39.9 kg/m2 with comorbidities), candidates for bariatric surgery, screened at the Santa Casa de Misericórdia Hospital in the city of Sao Paulo (Brazil). The inclusion criteria are grade III morbid obesity, an indication for bariatric surgery, agreement to participate in the study and a signed term of informed consent. The exclusion criteria are BMI above 55 kg/m2, clinically significant or unstable mental health concerns, an unrealistic postoperative target weight and/or unrealistic expectations of surgical treatment. Bariatric surgery candidates who meet the inclusion criteria will be referred to Santa Casa de Misericórdia Hospital and will be reviewed again 30, 90 and 360 days following surgery. Data collection will involve patient records, personal data collection, objective assessment of HR, BP, neck circumference, chest and abdomen, collection and analysis of clinical preoperative findings, polysomnography, pulmonary function test and a questionnaire on sleepiness. Discussion This paper describes a randomised controlled trial of morbidly obese patients. Polysomnography, respiratory mechanics, chemosensitive response and quality of life will be assessed in patients undergoing or not undergoing bariatric surgery. Trial Registration The protocol for this study is registered with the Brazilian Registry of Clinical Trials - ReBEC (RBR-9k9hhv).

Chitosan is considered the second most ubiquitous polysaccharide next to cellulose. It has gained prominence in various industries including biomedicine, textile, pharmaceutical, cosmetic, and notably, the food industry over the last few decades. The polymer's continual attention within the food industry can be attributed to the increasing popularity of greener means of packaging and demand for foods incorporated with natural alternatives instead of synthetic additives. Its antioxidant, antimicrobial, and film-forming abilities reinforced by the polymer's biocompatible, biodegradable, and nontoxic nature have fostered its usage in food packaging and preservation. Microbial activity and lipid oxidation significantly influence the shelf-life of meat, resulting in unfavorable changes in nutritional and sensory properties during storage. In this review, the scientific studies published in recent years regarding potential applications of chitosan in meat products; and their effects on shelf-life extension and sensory properties are discussed. The utilization of chitosan in the form of films, coatings, and additives in meat products has supported the extension of shelf-life while inducing a positive impact on their organoleptic properties. The nature of chitosan and its compatibility with various materials make it an ideal biopolymer to be used in novel arenas of food technology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Patients with invasive fungal disease (IFD) are at significant risk of morbidity and mortality. A productive partnership between patients, their carers/families, and the multidisciplinary team managing the infection and any underlying conditions, is essential. Sharing information and addressing knowledge gaps are required to ensure those at risk of IFD avoid infection, while those with suspected or confirmed infection optimise their therapy and avoid toxicities. This new addition to the Australian and New Zealand consensus guidelines for the management of IFD and antifungal use in the haematology/oncology setting outlines the key information needs of patients and their carers/families. It specifically addresses risk factor reduction, antifungal agents and adherence, and the risks and benefits of complementary and alternative therapies. Knowledge gaps are also identified to help inform the future research agenda., (© 2021 Royal Australasian College of Physicians.)

Background: The antibacterial activity of 21 nm TiO 2 nanoparticles (NPs) and particles modified with Garcinia zeylanica ( G. zeylanica ) against Methicillin resistant Staphylococcus aureus was investigated in the presence and absence of light., Results: Surface modification of TiO 2 NPs with the adsorption of G. zeylanica extract, causes to shift the absorption edge of TiO 2 NPs to higher wavelength. TiO 2 NPs, G. zeylanica pericarp extract showed significant bactericidal activity which was further enhanced in contact with the TiO 2 modified G. zeylanica extract., Conclusions: The antimicrobial activity was enhanced in the presence of TiO 2 NPs modified with G. zeylanica and with longer contact time.

Introduction: Approximately, 33% patients with diabetes are afflicted with onychomycosis. In the past, nondermatophyte molds have been regarded as opportunistic pathogens; recently, Aspergillus species are considered as emerging pathogens of toenail infections. In Sri Lanka, the prevalence of Aspergillus species in onychomycosis among diabetics is not well documented., Objective: To determine the proportion of Aspergillus onychomycosis, risk factors and knowledge among diabetics., Materials and Methods: This was descriptive cross-sectional study. Three hundred diabetic patients were included. Clinical examinations of patients' toenails were performed by a clinical microbiologist. Laboratory identification was done, and pathogens were identified to the species level by morpho-physiological methods. All inferential statistics were tested at P < 0.05., Results: Among clinically suspected patients, 85% (255/300) were mycologically confirmed to have onychomycosis. Aspergillus species were most commonly isolated n = 180 (71%) followed by dermatophytes, yeasts, and other molds n = 75 (29%). Of the patients having Aspergillus onychomycosis, 149 (83%) were in the > age group. In men, Aspergillus onycomycosis was seen in 82%. Among patients who had Aspergillus nail infection, 114 (63%) had diabetes for a period of > years. Among patients who were engaged in agricultural activities, 77% were confirmed to have infected nails due to Aspergillus species., Conclusion: Aspergillus niger was the most common pathogen isolated from toenail infection. Aspergillus species should be considered as an important pathogen in toenail onychomycosis in diabetic patients. Risk factors associated with Aspergillus onychomycosis were age, gender, duration of diabetes, length of exposure to fungi, and occupation.

Objective: Antiseptics are widely used in wound management to prevent or treat wound infections due to their proven wound healing properties regardless of their cytotoxicity. The objective of this study was to determine the bactericidal effects of three antiseptics on pathogens known to cause wound infections., Method: The study was carried out at a tertiary care hospital and a university microbiology laboratory in Sri Lanka in 2013. The three acids (acetic acid, ascorbic acid and boric acid) in increasing concentration (0.5%, 0.75% and 1%) were tested against bacterial suspensions equivalent to 0.5 McFarland standard. The Bacteria isolates used were isolated from wound and standard strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa., Results: There were 33 (68.8%) Coliforms, 10 (20.8%) Pseudomonas species, and 5 (10.4%) strains of Staphylococcus aureus. Acetic acid at concentration of 0.5% inhibited growth of 37 (77%) and 42 (87.5%) of tested isolates when exposed for 30 and 60 minutes, respectively. However 100% inhibition was achieved at four hours. At a concentration of 0.75%, 40 (83.3%) and 44 (91.7%) were inhibited when exposed for 30 and 60 minutes, respectively, with 100% inhibition at 4 hours. At concentration of 1%, 46 (95.8%) inhibition was seen at 30 minutes and 100% inhibition at 60 minutes. Ascorbic acid, at 0.5% and 0.75 % concentrations, inhibited growth of 45(93.7%) and 47(97.9%) of isolates respectively when exposed for 30 minutes. At these two concentrations, 100% inhibition was achieved when exposed for one hour. At 1% concentration, 100% inhibition was achieved at 30 minutes. Boric acid did not show bactericidal effect at concentrations of 0.5%, 0.75 % and 1%. Pseudomonas species were inhibited at 30 minutes by 0.5% acetic acid. Bactericidal effect against all the standard strains was seen with three acids at each concentration tested from 30 minutes onwards, Conclusion: Ascorbic acid was bactericidal for all organisms tested within the shortest exposure time at the lowest concentration compared to other two acids. Despite promising bactericidal effects, further studies warrant, as ongoing debates on toxicity of acids on tissue epithelialisation. Application of antiseptics for a shorter duration could overcome this problem without losing bactericidal activity., Declaration of Interest: The authors have no conflict of interest and no funding was received for this study.

A new species of rock dwelling gecko belonging to the genus Cnemaspis is described from Sri Lanka based on a suite of morphological features. The species is the largest of its genus described from Sri Lanka so far (snout-vent length 52-54 mm) and is the second largest of the Western Ghats-Sri Lanka Biodiversity Hotspot. It may be diagnosed in details of both scalation (ventrals186-207; mid-subcaudals large; absence of precloacal pores; 15 femoral pores on each side; 22-23 and 23-25 subdigital lamellae on finger IV and on toe IV, respectively; smooth scales on tail dorsum) and colouration (five prominent trilobate shaped cream markings pointing towards head and extending from neck to vent).The species is found in a unique habitat in the Rammalakanda Forest, where it is threatened by deforestation.

Background: Superficial fungal foot infection (SFFI) in diabetic patients increases the risk of developing diabetic foot syndrome. Sixteen percent of urban population is suffering from diabetes in Sri Lanka. As the diabetes patients are more prone to get fungal foot infections, early intervention is advisable owing to the progressive nature of the infection. There is no data on the prevalence of SFFIs in diabetic patients in Sri Lanka., Objective: To determine the etiological agents causing SFFI in patients with type 2 diabetes., Materials and Methods: Three hundred eighty five diabetic patients were included. Nail clippings and swabs were collected from the infected sites using the standard protocol. Laboratory identification was done and pathogens were identified to the species level by morpho physiological methods., Results: Clinically 295 patients showed SFFI, of which 255 (86%) were mycologically confirmed for infection. Out of 236 direct microscopy (KOH) positives, 227 (96%) were culture positive. Two hundred and fifty one patients (98%) with SFFI had diabetes for more than 10 years. Of the patients with SFFIs 92% had >100 mg/dl FBS and 81% had >140 mg/dl PPBS levels and 80% had both elevated FBS and PPBS. Non-dermatophyte fungal species were the commonest pathogens followed by yeast and dermatophytes., Conclusion: Aspergillus niger was the commonest pathogen followed by Candida albicans. SFFIs were seen significantly with the increasing age, gender, duration of diabetes and with less controlled glycaemic level.

Background and Study Aim: Worldwide some endoscopy units routinely continue to use manual reprocessing techniques for disinfection of side-view endoscopes. The aim of this study was to evaluate the outcome quality of manual reprocessing techniques for removal and inactivation of the bioburden from side-view endoscopes used for endoscopic retrograde cholangiopancreatography (ERCP) in a tertiary referral endotherapy unit in Sri Lanka., Methods: 102 samples obtained from two different flexible side-view endoscopes (Olympus TJF Q 180V and Olympus TJF 160 R) were tested for microbial growth. Three samples were collected each time; one swab from the tip before and another after manual reprocessing. The third sample was collected by flushing the working channel with sterile normal saline after manual reprocessing. Microorganisms were identified by culturing the samples., Result: : After reprocessing, culture-positive rates were 20 % and 9 % for the samples obtained from the tip and the working channel of the side-view endoscopes, respectively. Klebsiella spp. and Candida spp. were found to be the commonest microorganisms in the samples from the tips and from the working channels, respectively, of the reprocessed side-view endoscopes., Conclusion: There is a high culture-positive rate after reprocessing of the side-view endoscopes using the manual reprocessing procedure, despite strict adherence to the protocol for reprocessing.

Objectives: This study aimed to determine the prevalence and underlying sociodemographic correlates of smoking among Sri Lankans., Methods: A cross-sectional sample (N = 5000, age >18 years) was selected using a multistage random cluster sampling. Data were collected using an interviewer-administered questionnaire., Results: Response rate was 91% (n = 4532); males 40%; mean age 46.1 years (±15.1). Overall, urban and rural prevalence of current smoking (smoking) was 18.3%, 17.2%, and 18.5%, respectively (P = nonsignificant, urban vs rural). Smoking was much higher in males than in females (38.0% vs 0.1%, P < .0001). Ex-smokers comprised 10.0% (males 20.7%, females 0.1%, P < .0001). Among the smokers 87.0% smoked <10 cigarettes per day. The male age groups < 20 and 20 to 29 years had the lowest (15.6%) and the highest (44.6%) prevalence of smoking, respectively. In males, smoking was highest in the least educated (odds ratio = 1.96, P = .001)., Conclusions: Smoking is common among Sri Lankan males and is associated with lower education, income, and middle age.

During neonatal hippocampal development, serotonin 1A receptor-mediated signaling initially employs PKCepsilon to boost neuronal proliferation and then uses PKCalpha to promote synaptogenesis. Such stage-specific involvement of a PKC isozyme could be determined by its relative expression level. In mouse hippocampi, we detected relatively low levels of alpha, beta, gamma, and delta isozymes at postnatal days 2-6 (P2-6), which was followed by a large increase in their expression. In contrast, the PKC isozymes epsilon and theta were relatively abundant at P6, following which they underwent a further increase by P15. Comparison with purified proteins confirmed that the PKCepsilon levels at P6 and P15 were respectively 1.75 and 7.36 ng per 60 microg of protein, whereas PKCalpha levels at P6 and P15 were respectively 160 pg and 1.186 ng per 60 microg of protein. Therefore, at P6, PKCepsilon was about 11-fold more abundant than PKCalpha. Consequently, signaling cascades could use the relatively abundant PKCepsilon (and possibly PKCtheta) molecules for early events at P2-6 (e.g. neurogenesis), following which PKCalpha (and the beta, gamma, or delta isozymes) could guide maturation or apoptosis. Notably, at P6 but not P15, PKCepsilon, was localized to the nuclei of neuroblasts, probably directing mitosis. In contrast, at P15 but not P6, PKCalpha was highly expressed in the processes of the differentiated hippocampal neurons. In summary, PKC isozymes follow differential profiles of expression in neonatal hippocampus and the relative abundance of each may determine its mode and stage of involvement in hippocampal development.

Azide-terminated poly(tert-butyl acrylate) was synthesized via atom transfer radical polymerization (ATRP). Subsequent deprotection was performed to yield poly(acrylic acid) (PAA) possessing a reactive chain-end. A one-pot sequential amidation of the PAA with the amine derivatives of a near-infrared fluorescent dye (ADS832WS) and glucose produced NIRF dye-incorporated water-soluble copolymers. End-group modifications were performed to produce alkyne/biotin-terminated copolymers which were further employed to generate dye-incorporated polymer-protein hybrids via the biotin-avidin interaction with avidin or "click" bioconjugation with azide-modified BSA. We have overcome two fundamental limitations in the synthesis of bioconjugates: (a) the basic restriction in the diversity of copolymers which can be synthesized for producing bioconjugates, (b) the limitation in the number of dyes/drug molecules that can be attached per protein molecule. The copolymers possessed enhanced optical properties compared to the dye due to increased solubility in water. Potential utility of these copolymers and conjugates in multiwell plate based assays, cell surface imaging and in vivo animal imaging were explored.

Turmeric, an essential ingredient of culinary preparations of Southeast Asia, contains a major polyphenolic compound, named curcumin or diferuloylmethane, which eliminates cancer cells derived from a variety of peripheral tissues. Although in vitro experiments have addressed its anti-tumor property, no in vivo studies have explored its anti-cancer activity in the brain. Oral delivery of this food component has been less effective because of its low solubility in water.We show that a soluble formulation of curcumin crosses the blood–brain barrier but does not suppress normal brain cell viability. Furthermore, tail vein injection, or more effectively, intracerebral injection through a cannula, blocks brain tumor formation in mice that had already received an intracerebral bolus of mouse melanoma cells (B16F10).While exploring the mechanism of its action in vitro we observed that the solubilized curcumin causes activation of proapoptotic enzymes caspase 3/7 in human oligodendroglioma (HOG) and lung carcinoma (A549) cells, and mouse tumor cells N18(neuroblastoma), GL261 (glioma), and B16F10. A simultaneous decrease in cell viability is also revealed by MTT [3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide]assays. Further examination of the B16F10 cells showed that curcumin effectively suppresses Cyclin D1, P-NF-kB, BclXL, P-Akt, and VEGF, which explains its efficacy in blocking proliferation, survival, and invasion of the B16F10 cells in the brain. Taken together,solubilized curcumin effectively blocks brain tumor formation and also eliminates brain tumor cells. Therefore, judicious application of such injectable formulations of curcumin could be developed into a safe therapeutic strategy for treating brain tumors.

The presence of serotonin 1A receptor (5-HT(1A)-R) in the hippocampus, amygdala, and most regions of the frontal cortex is essential between postnatal day-5-21 (P5-21) for the expression of normal anxiety levels in adult mice. Thus, the 5-HT(1A)-R plays a crucial role in this time window of brain development. We show that the 5-HT(1A)-R-mediated stimulation of extracellular signal-regulated kinases 1 and 2 (Erk1/2) in the hippocampus undergoes a transition between P6 and P15. At P6, a protein kinase C (PKC) isozyme is required for the 5-HT(1A)-R -->Erk1/2 cascade, which causes increased cell division in the dentate gyrus. By contrast, at P15, PKC alpha participates downstream of Erk1/2 to augment synaptic transmission through the Schaffer Collateral pathway but does not cause increased cell division. Our data demonstrate that the 5-HT(1A)-R -->Erk1/2 cascade uses PKC isozymes differentially, first boosting the cell division to form new hippocampal neurons at P6 and then undergoing a plastic change in mechanism to strengthen synaptic connections in the hippocampus at P15.

Objective: To determine the prevalence of antibodies to hepatitis C virus (HCV) in patients who have had multiple transfusions in Sri Lanka., Setting: University Medical Unit at the National Hospital, Colombo, the Cancer Institute, Maharagama, and the Lady Ridgeway Children's Hospital, Colombo., Patients: One to 5 ml of blood for serology was collected from 200 multiply transfused patients (those who have received five or more blood transfusions)., Method: The sera were tested for HCV specific antibodies using a third generation anti-HCV enzyme immuno-assay (EIA) kit. All sera giving positive or intermediate EIA results were re-tested by a commercial HCV Western blot confirmatory test., Results: Of the 200 patients, 10 (5%) were repeatedly positive and confirmed by the Western blot. 33% (7/21) of haemophiliacs and 10% (3/31) of thalassaemics were positive for antibodies to HCV. Antibodies were not detected in other groups of multiply transfused patients (haemolytic disease, aplastic anemias, chronic renal failure, haematological and other malignancies). Of the 200 patients, those who have had more than 80 blood transfusions had a significantly higher prevalence of antibodies to HCV. The frequency of HCV infection was also higher among those who had received factor concentrates., Conclusion: 33% of haemophiliacs and 10% of thalassaemics who have received multiple transfusions were infected with HCV. These findings warrant a larger study among blood donors, and justify screening and decontamination of blood and blood products given to haemophiliacs and thalassaemics in Sri Lanka.

Mutations of the p53 tumor suppressor gene often occur in a variety of human malignant tumors and are frequently associated with overexpression of p53 protein. This study was designed to examine indirectly the frequency of p53 protein in primary endometrial carcinoma and to correlate the overexpression with steroid hormone receptor status including pS2 protein status. The study was performed on 79 formalin-fixed, paraffin-embedded tissues of endometrial carcinoma. P53 protein overexpression was detected by means of immunohistochemistry using monoclonal antibody NCL-p53-DO7. Estrogen and progesterone receptor status was determined by immunohistochemistry using the monoclonal antibodies NCL-ER-LH(2) and NCL-PGR, respectively, and the pS2 protein using polyclonal antibody NCL-pS2. Overexpression of p53 protein was found in 27 (34%) of the 79 endometrial carcinomas. A strong positive relationship was demonstrated between histologic grade and p53 protein overexpression. There was a significant correlation between p53 protein overexpression and negative estrogen receptor status (49%) negative progesterone receptor status (49%) as well as a negative pS2 protein (45%). The results suggest that overexpression of p53 is associated with high malignant potential. However, p53 overexpression itself does not appear to be an independent prognostic factor in endometrial carcinomas. Int J Surg Pathol 8(3):213-222, 2000

Placental site nodules or plaques (PSN-Ps) are nodular benign lesions of the intermediate trophoblast (IT) cells in the endometrium, endocervix, superficial myometrium or fallopian tube, occurring after a remote intrauterine pregnancy. We present a study of 25 cases of PSN-Ps These lesions occurred in patients aged 18 to 44 years. Most were discovered incidentally in endometrial curettage specimens. The specimens were received as part of clinical investigations for menorrhagia, per vaginal bleeding or pelvic pain. None of the PSN-Ps was visible grossly. Microscopically, they were mostly multiple, well-circumscribed, oval or plaque-like cellular nodules. The IT cells typically had abundant vacuolated or eosinophilic cytoplasm. The nuclei were irregular, large, hyperchromatic, often degenerate-looking and either mononucleated, multinucleated or multiclefted. Hyalinization surrounding individual or groups of IT cells, or located in the centre of the nodules, was a constant feature in all cases. The lesional cells were strongly immunoreactive to CAM 5.2, 34 beta E12, AE1/AE3, EMA and vimentin. Some cases showed focal positivity to HCG and HPL. PLAP staining was consistently negative. Ultrastructurally, the IT cells showed prominent nuclear variation in size and shape. The abundant, vacuolated cytoplasm contained some rough endoplasmic reticulum and loosely arranged filaments. This study describes the clinicopathological and immunophenotypic features of 25 cases of PSN-Ps including the ultrastructural findings of one case.

Fodrin, E-cadherin, and beta-catenin immunolocalization was studied in 54 cases of infiltrating ductal carcinoma of the breast and compared with an in vitro model in order to study the dynamic relationship between these components of an adhesion complex. In low-grade tumours, the staining patterns were similar for both fodrin and E-cadherin, with localization of these proteins to the cell membranes. beta-Catenin showed reduced membrane staining compared with non-neoplastic epithelium. High-grade tumours displayed strong membranous as well as cytoplasmic immunolocalization of fodrin, while E-cadherin staining was fragmented or lost from the membranes, with only occasional weak intracellular staining. beta-Catenin showed fragmented membrane staining and cytoplasmic accumulation. In addition, nuclear staining of beta-catenin was occasionally observed. In a v-src-transformed MDCK cell line, following 15min of src activation, beta-catenin began to detach from the cell membrane and localize to the cytoplasm, while fodrin and E-cadherin remained unchanged. After 30-45min of src activation, the cells lost their cuboidal shape and began to lose cell-to-cell contact. Fodrin staining remained mostly membranous while that of E-cadherin and beta-catenin was fragmented and spiky. After 60min of src activation, fodrin localized completely in the cell cytoplasm, while E-cadherin and beta-catenin were partly cytoplasmic with fragmented and spiky membranous staining. Occasionally, beta-catenin was seen in the nucleus. Both in vivo and in vitro findings clearly demonstrated a disruption of the E-cadherin/beta-catenin/fodrin/cytoskeleton linkage concomitant with the loss of cell-to-cell adhesion and change in cell shape, from epithelioid to a fibroblastoid phenotype. Membranous localization of E-cadherin showed a positive correlation with oestrogen and progesterone expression, whereas loss of membranous E-cadherin and cytoplasmic accumulation of fodrin was more often observed in high-grade carcinomas and showed a positive correlation with p53 expression., (Copyright 1999 John Wiley & Sons, Ltd.)

Three cases (2 of which presented with torsion) of massive ovarian oedema occurring in young women, clinically suspected to be a neoplasm, are presented. Microscopic examination of each showed diffuse interstitial oedema and multiple cysts, some surrounded by luteinized cells. As the patients are young, we advocate conservative management with sparing of reproductive capacity, although that is not what happened with any of our 3 patients.

Background: In normal subjects intravenous adenosine infusion has been shown to stimulate ventilation with a consequent fall in arterial partial pressure of carbon dioxide (Paco2), probably by an action on the carotid bodies. The objective of this study was to determine whether the increase in Paco2 seen when patients with ventilatory failure secondary to chronic obstructive pulmonary disease (COPD) are given a high concentration of oxygen to breathe might be ameliorated by an intravenous infusion of adenosine., Methods: Eight subjects with chronic stable ventilatory failure secondary to COPD were studied. Their mean (SE) forced expiratory volume in one second (FEV1) was 0.63 (0.12) 1 with forced vital capacity (FVC) of 1.63 (0.21) 1. They received continuous intravenous infusions of saline and adenosine in random order, double blind. The infusions were administered for two minutes at 20 micrograms/kg/min, increasing in increments of 20 micrograms/kg/min every two minutes to a maximum infusion rate of 80 micrograms/kg/min adenosine (or an equivalent saline infusion rate), or until side effects supervened. The infusions were continued at that rate for five minutes, after which the fractional inspired oxygen (FIO2) was raised to 0.50 during a further 20 minutes of the infusion at that rate. Haemoglobin oxygen saturation (SaO2) and transcutaneous PCO2 (PtcCO2) were monitored throughout the procedure. Spirometric tests were performed before and after each infusion., Results: Adenosine infusion was accompanied by a fall in PtcCO2 from a mean (SE) of 7.29 (0.42) kPa to 6.95 (0.48) kPa: mean difference -0.34 (95% confidence interval, -0.56 to -0.11) kPa. During saline infusion oxygen administration resulted in an increase in transcutaneous PtcCO2 from 7.35 (0.34) kPa to 7.88 (0.28) kPa: mean difference 0.53 (95% CI 0.20 to 0.85) kPa. PtcCO2 did not rise above baseline levels when oxygen was administered during the adenosine infusion. A small fall in FVC was seen following adenosine infusion., Conclusions: The increase in PtcCO2 seen when patients with stable ventilatory failure secondary to severe COPD are given a high concentration of oxygen to breathe is counteracted by a continuous intravenous infusion of adenosine.

External high frequency oscillation was performed on 20 healthy volunteers using a cuirass-based system, the Hayek Oscillator. Five-min periods of oscillation were carried out on each subject at frequencies of 1, 2, 3, 4 and 5 Hz. Effective ventilation was measured in terms of the fall in alveolar partial pressure of carbon dioxide immediately after oscillation. The optimum frequency for oscillation was 1-3 Hz but most of the subjects were adequately ventilated over a wide range of frequencies. Thus, the Hayek Oscillator is capable of adequately ventilating normal subjects by means of chest wall oscillation. We also compared external high frequency oscillation with intermittent positive pressure ventilation in five patients with respiratory failure. Using the same inspired oxygen fraction, the external high frequency oscillation replaced intermittent positive pressure ventilation for a 30-min period. External high frequency oscillation improved oxygenation by 16% and reduced the arterial carbon dioxide by 6%. These preliminary findings suggest that normal subjects and intensive care unit patients can be adequately ventilated by means of external high frequency oscillation.

Overexpression of p53 protein appears to be a common event in primary mammary carcinoma. This study was performed on 80 primary carcinomas of varying type and grade. Tumor p53 protein expression was detected by means of immunohistochemistry using the monoclonal antibody D07 on formalin fixed paraffin-embedded tissue sections. p53 overexpression was found in 50 (63%) of the 80 tumors. The correlation between p53 expression and high tumor grade, presence of in situ component and lymphocytic response was significant. However, no significant association was found between p53 expression and tumor size, age of the patients or tumor vascular invasion. Our study suggested that the immunohistochemical assay was a simple method of detection of mutant p53 proteins in routinely processed paraffin-embedded tissues of primary mammary carcinoma.

The Hayek Oscillator is a recent development in external high frequency ventilation and is a useful mode of ventilatory support during anaesthesia, in chronic respiratory failure and weaning in intensive care. The Hayek Oscillator is new and its application is growing, as are the number of patients who have benefited from its use. However, there are no clear guidelines on how best to adjust the oscillator to achieve optimum ventilation. A simple method of predicting changes in tidal volume and minute ventilation following adjustment would make the oscillator more useful. We present nomograms for tidal volume, minute ventilation and effective alveolar ventilation when the three variables, oscillator frequency, mean chamber pressure and peak-to-trough pressure span were adjusted. The frequency-tidal volume relationship was unaffected by a mean chamber pressure of 0, -5, -10 cmH2O, but altered with changes in peak-to-trough pressure span. We have also determined the effect of increasing negative extrathoracic pressure on functional residual capacity. The relationship between tidal volume and frequency was non-linear and related to the peak-to-trough pressure span. Mean functional residual capacity significantly increased from 2.25 l (SEM 0.10) without the cuirass at rest to 2.61 l (SEM 0.14) at -10 cmH2O (p < 0.05; n = 5) and 2.47 (SEM 0.12) at -20 cmH2O of mean chamber pressure. Vital capacity was unchanged by increasing extrathoracic pressure as was total lung capacity.

We used single inspiratory capacity breaths of 5, 6 or 8% CO2 in air to obtain ventilatory responses in normal subjects, with ensemble averaging of repeated runs to define stimulus and response (Protocol 1). We also compared the effect of an inspiratory capacity (IC) breath of 8% CO2 with that of two tidal volumes (TV) at the same concentration (Protocol 2). The ventilatory response was defined first as the ratio of peak changes in ventilation and end-tidal PCO2, and secondly by the ratio of their integrals. We obtained group mean values of 0.21 L min-1 mmHg-1 for the peak method and 0.80 L min-1 mmHg-1 for integrals (Protocol 1). There was no significant difference between IC and TV response values (Protocol 2) either by the peak method (0.17 vs 0.19 L min-1 mmHg-1) or by integrals (0.47 vs 0.53 L min-1 mmHg-1). A significant decrease in ventilation was seen in the second tidal volume 8% CO2 breath, even though the stimulus was unperceived by four out of five subjects. CO2 responses can be obtained from these techniques, but the necessary analysis is too cumbersome for general use. Taking a deep breath had no detectable separate effect, but CO2 in the airway may depress ventilation even at concentrations which the subject cannot detect.

1. We examined the effects of twenty-four to thirty inspiratory capacity (IC), expiratory capacity (EC) and vital capacity (VC) breaths on subsequent breathing pattern in five normal subjects at rest. 2. During IC breaths and following EC and VC breaths at rest, end-tidal CO2 pressure (PET,CO2) fell by 7.5, 8.5 and 9.5 mmHg, respectively. In the group analysis significant inhibition of ventilation of 1.5 l min-1 was seen after the IC breath but not after EC or VC breaths. 3. We repeated the study with five normal subjects under conditions of higher ventilatory drive, namely 50 W exercise (one subject was common to both groups). 4. During exercise, the drop in PET,CO2 was smaller (4.0, 3.5 and 4.0 mmHg, respectively, with IC, EC and VC breaths) but ventilation was inhibited to a greater extent. Ventilatory undershoot was seen after all three types of deep breaths. 5. We propose that the expiration to residual volume in EC and VC breaths abolished the hypocapnic inhibition of ventilation at rest, possibly by a deflation reflex which was not sufficiently powerful to overcome the ventilatory undershoot during exercise. Our results also support the view that the slope of the CO2 response curve is steeper near the control point during exercise.

A 37 year old patient with chronic active hepatitis progressing to cirrhosis presented with increasing breathlessness and was found to be hypoxic with finger clubbing. A progressive exercise study with measurement of oxygen saturation (SaO2) showed abnormally high ventilation and desaturation to 81% at 100 W. Serial studies over nearly two years showed, first, deterioration, then improvement with lower ventilation and higher saturation levels at all work loads. This could not be correlated with any change in treatment with azathioprine, prednisolone, or propranolol.

Immunohistochemical analysis was carried out on 144 formalin fixed paraffin embedded cutaneous melanomas to ascertain the value of 3 different immune markers. The sensitivity and staining patterns regarding intensity and distribution, as well as correlation to pigment content, cell type, surface ulceration and host response was noted. The stains used were monoclonal HMB-45 (Dako product No M634), NKI/C3 antibodies (Biogenex product No MU077) and polyclonal rabbit anti S-100A protein (Dako product No L1845). Of the lesions tested, 63 were malignant melanoma with an adjacent component of superficial spreading type, 61 were malignant melanoma with no adjacent component, 2 were malignant melanoma with adjacent lentigo maligna, 8 were in situ with 7 superficial spreading melanoma and one lentigo maligna (HMF) and 10 were metastatic melanoma. All 144 lesions stained for S-100 (100% sensitivity). One hundred and thirty-seven stained for NKI/C3 (95%); 132 stained for HMB-45 (92% sensitivity). S-100 was the most sensitive marker and stained tumor cells diffusely. With HMB-45 and NKI/C3, though marginally less sensitive, staining was stronger and patchy. In addition, NKI/C3 showed a tendency for peripheral (membrane) staining. HMB-45 staining was directly proportional to the pigment content, with stronger staining of radial growth phase melanoma and negative staining of those lesions where pigment content was minimal or absent. Also, with HMB-45 a decrease in staining intensity with depth or vertical growth phase was observed. There was no relationship to cell type with HMB-45 but with NKI/C3, 5 out of the 7 that failed to stain showed spindle cell differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Pseudomelanosis of the duodenum is rare. Only 17 cases have been documented in the world literature. A 59-year-old man presented to Bankstown Hospital, New South Wales with dysphagia. On endoscopy, he was found to have melanosis of the duodenum in addition to oesophageal ulceration. It has been previously suggested that the pigment ferrous sulphide is derived from gastro-intestinal bleeding and lodged in the macrophages. A detailed examination of the pigment, including X-ray probe micro-analysis at various levels of the intestinal epithelium as well as in macrophages is presented.

Local anaesthesia for fibreoptic bronchoscopy should be given by a safe technique that is not unpleasant to the patient and should provide acceptable conditions for the bronchoscopist. Single injection transcricoid local anaesthesia was compared with the "spray as you go" technique in patients having day case fibreoptic bronchoscopy. Patients were randomised to receive either 100 mg lignocaine by a single cricothyroid puncture or 240 mg lignocaine instilled through the bronchoscope under direct vision. Further doses were given by the operator to both groups as required. The 30 patients receiving transcricoid lignocaine coughed less (3.56 (SD 3.1) coughs/min) than the 32 patients receiving lignocaine through the bronchoscope (5.89 (4.8)/min) despite receiving a lower total dose of lignocaine (322 (25.9) v 451 (20.9) mg). Cricothyroid puncture was not associated with any complications and was not unpleasant for the patients.

Two examples of a hitherto undescribed hamartomatous condition of the small intestine are presented. They consist of fascicles of smooth muscle derived from the muscularis mucosae, bundles of unmyelinated nerve fibres with scattered ganglion cells, and haemangiomatous vessels, occurring focally within a segment of the intestine, and causing stenosis.

A 56-year-old Caucasian male, with no obvious immune deficit or systemic disease, presented with unilateral loss of vision due to A. fumigatus infection involving the right optic nerve. There was no proptosis. Despite fungal chemotherapy he developed central nervous system involvement with mycotic arteritis of the branches of the right middle cerebral artery, temporal lobe infarction and rupture of a mycotic aneurysm of the right internal carotid artery, and died. Review of the literature concerning orbital Aspergillus infection showed both this form of presentation and a rapidly fatal course to be unusual.