Surgical Advances in the Management of the Silent Sinus Syndrome: Our Experience and Review of the Literature.

Silent sinus syndrome is a rare disorder characterized by ipsilateral enophthalmos and hypoglobus caused by collapse of the orbital floor in the presence of asymptomatic long-term maxillary sinusitis. The basic principles in the management are to address the diseased sinus and reconstruct the orbit concurrently or separately. Failure to accurately restore the orbit volume can have significant consequences on the patient. In this article, we provide an update on current practices and highlight our experience of using computer-assisted planning and patient-specific implant in managing this syndrome.

Self-reported alcohol consumption in doctors.

BACKGROUND: The UK government has prioritized reducing the harmful effects of excessive alcohol consumption on mental and physical well-being. AIMS: To assess self-reported alcohol consumption amongst doctors at an acute London Trust. METHODS: An opportunistic, anonymous, survey was conducted by Postgraduate Education Fellows over 2 weeks in December 2018. This included all grades of doctors from Foundation Year One to Consultant. The survey consisted of nine questions, modified from the alcohol use disorders identification test (AUDIT) and CAGE questionnaire. RESULTS: Of 446 doctors within our institution, 109 completed the survey (24%). Fourteen per cent of those surveyed abstained from alcohol, 21% drank monthly or less, 31% drank between two to four times per month, 25% drank two to three times per week and 9% drank greater than four times per week. In the preceding 2 years, 9% reported being unable to do what was expected of them on at least one occasion due to alcohol. Five per cent were concerned about alcohol affecting their performance. Two per cent were annoyed by criticism of their drinking, 9% felt guilty about drinking and 4% needed an eye-opener. Eighteen per cent wanted to reduce their alcohol consumption; however, 43% of the 109 doctors surveyed were uncertain where to seek help. CONCLUSIONS: Twenty per cent of surveyed doctors reported consuming potentially hazardous levels of alcohol and 18% of respondents wanted to cut down. Forty-three per cent were unaware of sources of support. Our findings suggest a role for collaboration between Occupational Health departments and Postgraduate Education teams to support doctors misusing alcohol.

Absolute quantification (ml blood/sec ∗ mm2 tissue) of normal vs. diabetic foot skin microvascular blood perfusion: Feasibility of FM-PPG measurements under clinical conditions.

Fluorescence-mediated photoplethysmography (FM-PPG) is the first routine clinical methodology by which to quantifiably measure tissue blood perfusion in absolute terms (mL blood/sec ∗ mm2 tissue). The FM-PPG methodology has been described in detail previously in this journal (MVR 114, 2017, 92-100), along with initial proof-of-concept measurements of blood perfusion in both ocular and forearm skin tissues. The motivation for the current study was to investigate whether FM-PPG can be used readily and routinely under realistic clinical conditions. The vehicle for doing this was to measure medial foot capillary blood flow, i.e., tissue perfusion, in 7 normal subjects, mean = 6.76 ±â€¯2.29 E-005 mL/(sec ∙ mm2), and lesion-free areas of 8 type-2 diabetic patients with skin ulceration, mean = 4.67 + 3.15 E-005 mL/(sec ∙ mm2). Thus, perfusion in the diabetics was found to be moderately lower than that in the normal control subjects. Earlier skin perfusion measurements in medial forearms of 4 normal subjects, mean = 2.64 + 0.22 E-005 mL/(sec ∙ mm2), were lower than both the normal and diabetic foot perfusion measurements. Variability in the heartbeat-to-heartbeat blood perfusion pulses in the skin capillaries, defined as the ratio of the standard deviation among beat-to-beat pulses divided by the mean perfusion of those pulses, was determined for each subject. Average variability in foot skin was 21% in the diabetic population, versus 16% for normal subjects; and it was 18% in forearm skin. We conclude that absolute quantitative FM-PPG measurement of skin blood perfusion at the level of nutritive capillaries is feasible routinely under clinical conditions, allowing for quantitative measurement of skin tissue blood perfusion in absolute terms.

[Point mutations in the DNA binding domain of p53 contribute to glioma progression and poor prognosis].

TP53 mutations play a significant role in glioma tumorigenesis. When located in in the DNA binding domain, these mutations can perturb p53 protein conformation and its function, often culminating in altered downstream signaling. Here we describe prevalent pattern of TP53 point mutations in a cohort of 40 glioma patients and show their relevance to gliomagenesis. Point mutations in exon 5-9 of TP53 gene were detected by DNA sequencing. Possible influence of identified mutations at the function of p53 was studied computationally and correlated with the survival. Point mutations in TP53 were detected in 10 glioma samples (25%), out of which 70% were from high grade glioma. A total of 19 TP53 point mutations were identified, out of which 42% were found to be in the DNA binding region of p53. Computational analysis predicted 87.5% of these mutations to be "probably damaging". In three patients with tumors possessing point mutations R273H, R248Q, Y163H and R175H and poor survival times, structural analysis revealed the nature of these mutations to be disruptive and associated with high risk for cancer progression. In high grade glioma, recurrent TP53 point mutations may be the key to tumor progression, thus, emphasizing their significance in gliomagenesis.

Sustainable Development Agenda 2030 thrives on health (Editorial).

Never before has the flight of human imagination made calls for universal development that are so loud and audacious. The all-encompassing Sustainable Development Agenda 2030 (SD Agenda 2030) has evolved over 67 years since the adoption of the Universal Declaration of Human Rights by the United Nations in 1948. Although based on the same principle of universality, the scope of the Agenda is much broader. It is a melting-pot of human rights, environmental movements and the fight against poverty; hence, it is a plan of action for people, the planet and prosperity. Moreover, it also seeks peace as a necessary condition for development.

Study of the Role of Titanium and Iron Cathodic Cages on Plasma-Nitrided AISI 430 Ferritic Stainless Steel.

In contrast to austenitic and martensitic stainless steels, ferritic stainless steels have a lower hardness and wear resistance but exhibit excellent corrosion resistance. Due to this fact, their use in the aerospace, automobile, and house construction industries is restricted. Several methods have been utilized to enhance the tribological characteristics of ferritic stainless steels. In this work, titanium nitride coating has been carried out by using a cathodic cage of titanium material, and later on, the titanium cathodic cage is replaced by an AISI-304 cathodic cage in a CCPN chamber to form iron nitride coating on AISI-430 ferritic stainless steel coupons through a plasma nitriding process for 4 h at a fixed temperature of 400 °C. The microstructures and mechanical traits of all processed and control coupons were analyzed using scanning electron microscopy, X-ray diffraction, ball-on-disc wear tester, and microhardness tester techniques. The results showed that hardness increased up to 1489 HV with the titanium cage, which is much higher than the hardness of the base material (270 HV). The titanium cage-treated coupons have high layer thickness, smooth surface morphology, and a minimum crystallite size of 2.2 nm. The wear rate was reduced up to 50% over the base material after the titanium cage plasma treatment. The base coupon exhibited severe abrasive wear, whereas nitrided coupons exhibited dominant adhesive wear. In the iron nitride coatings, this effect is also important, owing to the more influential cleaning process in a glow discharge, and the better adhesion with enhanced interlayer thickness is attributed to the fact that the compliance of the interlayer minimizes shear stresses at the coating-substrate interface. The use of a graded interface improves adhesion compared with the case where no interlayer is used but a titanium interlayer of comparable thickness provides a significant increase in measured adhesion. For both titanium and iron nitride films, there is a reduction in wear volume which is a function of interlayer thickness; this will have a substantial effect on wear lifetime. Thus by careful control of the interlayer thickness and composition, it should be possible to improve coating performance in tribological applications.

Prices and availability of locally produced and imported medicines in Ethiopia and Tanzania.

BACKGROUND: To assess the effect of policies supporting local medicine production to improve access to medicines. METHODS: We adapted the WHO/HAI instruments measuring medicines availability and prices to differentiate local from imported products, then pilot tested in Ethiopia and Tanzania. In each outlet, prices were recorded for all products in stock for medicines on a country-specific list. Government procurement prices were also collected. Prices were compared to an international reference and expressed as median price ratios (MPR). RESULTS: The Ethiopian government paid more for local products (median MPR = 1.20) than for imports (median MPR = 0.84). Eight of nine medicines procured as both local and imported products were cheaper when imported. Availability was better for local products compared to imports, in the public (48% vs. 19%, respectively) and private (54% vs. 35%, respectively) sectors. Patient prices were lower for imports in the public sector (median MPR = 1.18[imported] vs. 1.44[local]) and higher in the private sector (median MPR = 5.42[imported] vs. 1.85[local]). In the public sector, patients paid 17% and 53% more than the government procurement price for local and imported products, respectively. The Tanzanian government paid less for local products (median MPR = 0.69) than imports (median MPR = 1.34). In the public sector, availability of local and imported products was 21% and 32% respectively, with patients paying slightly more for local products (median MPR = 1.35[imported] vs. 1.44[local]). In the private sector, local products were less available (21%) than imports (70%) but prices were similar (median MPR = 2.29[imported] vs. 2.27[local]). In the public sector, patients paid 135% and 65% more than the government procurement price for local and imported products, respectively. CONCLUSIONS: Our results show how local production can affect availability and prices, and how it can be influenced by preferential purchasing and mark-ups in the public sector. Governments need to evaluate the impact of local production policies, and adjust policies to protect patients from paying more for local products.

Butane encephalopathy.

Volatile solvent abuse (VSA) is defined at the "intentional inhalation of a volatile substance for the purpose of achieving a euphoric state". The lifetime prevalence of VSA in the UK remains steady at around 15%, the fourth highest rate in Europe, and VSA is the most common form of drug abuse in the 11-15 year age group in England and Wales. A 13 year old girl presented to the accident and emergency unit following inhalation of butane based deodorant, which resulted in a prolonged semiconscious state with encephalopathic symptoms.

Prescription and dispensing practices in public sector health facilities in Pakistan: survey report.

OBJECTIVES: To gather information on existing prescription practices, dispensing practices and patient satisfaction in government health services of the NWFP, Baluchistan and Punjab province. METHODS: A cross sectional study design was used for this purpose. Ten health care facilities were selected from each province keeping appropriate representation from first level health facilities, district health facilities and tertiary care hospital. Analysis of selected indicators was carried out on the basis of provinces, health facilities, gender and different age groups. RESULTS: Documentation of 914 responses was completed from three provinces. Almost equal distribution of encounters was maintained representing different health facilities. Forty seven percent of encounters involved children under 15 years of age. Female patients comprised of 56% and the mean age of the entire sample was 26 years. The mean dispensing time was only 38 seconds, the mean consultation time was 1.79 minutes and the average number of drugs per prescription turned out to be 2.7 out of which only 1.6 drugs were being dispensed from the facility. More than half of the prescriptions contained antibiotics and 15% of patients were prescribed with injectables. Only half of the patients expressed satisfaction with their visit to health facility. CONCLUSIONS: Like many other developing countries, prescription and dispensing practices are not satisfactory in public sector health facilities of Pakistan. Appropriate and workable solutions need to be developed and implemented in the country to improve systems. Regular audits and qualitative studies should become part of the effort.

Management of suspected scaphoid fractures in accident and emergency departments--time for new guidelines.

INTRODUCTION: The objectives of this work were to assess the clinical knowledge of clinicians in the accident and emergency (A&E) departments in England & Wales and evaluate the current trend for the acute management of radiologically normal, but clinically suspected, fractures of the scaphoid. SUBJECTS AND METHODS: We conducted a telephone survey on 146 A&E senior house officers (SHOs) in 50 different hospitals. This survey assessed the clinicians' experience, their clinical and radiological diagnostic methods, and their initial treatment of suspected scaphoid fractures. RESULTS: The majority (55.8%) of SHOs performed only one clinical test to diagnose suspected scaphoid fractures. Overall, 41% were unable to cite the number of the radiographic views taken and only 10% of departments have direct access to further radiological investigation. There is wide variation in the early treatment of this injury, with the scaphoid cast used most commonly (46%). The majority of SHOs (89%) were unable to describe the features of immobilisation. The mean follow-up period was 10 days, and 53% of cases were followed-up by the senior staff in A&E. Of SHOs, 54% were not aware of any local guidelines for the management of suspected scaphoid fractures in their departments, and 92% were not aware of the existence of the 1992 British Association for Accident and Emergency Medicine (BAEM) guidelines. CONCLUSIONS: The clinical knowledge and the management of suspected scaphoid fractures in A&E are unsatisfactory. We, therefore, suggest that the dissemination of up-to-date guidelines could help to educate clinicians to provide better care to the patients.

Spontaneous carotid artery dissection presenting as migraine--a diagnosis not to be missed.

Two cases are reported in which the diagnosis of a serious condition was delayed as the symptoms had been attributed to migraine. Spontaneous carotid artery dissection is a serious but treatable cause of headache that may be misdiagnosed as recent onset migraine. The importance of correctly identifying this condition is emphasised.

Regulation of Ca(2+)-dependent nitric oxide synthase in bovine aortic endothelial cells.

Vascular endothelium responds to Ca(2+)-mobilizing agonists by producing nitric oxide (NO), a potent vasodilator and inhibitor of platelet aggregation. Regulation of constitutively expressed endothelial NO synthase (eNOS) in intact cells is not well understood. We investigated the kinetics of NO formation in response to Ca(2+)-mobilizing agonists, the requirement for extracellular L-arginine, and the role of NO in regulating eNOS activity. When endothelial cells were stimulated with bradykinin and ATP in the presence of 100 microM L-arginine, we observed a rapid and transient rise in intracellular Ca2+ concentration ([Ca2+]i) from 50 +/- 8 nM to 698 +/- 74 and 637 +/- 53 nM, respectively, and a rapid and transient rise in NO production from a basal level of 37 pmol.min-1.mg protein-1 to 256 and 275 pmol.min-1.mg protein-1, respectively. When cells were stimulated with A-23187 or thapsigargin in the presence of 100 microM L-arginine, we observed a sustained increase in [Ca2+]i and a sustained increase in NO production. The rate of NO synthesis was linear over 30 min, rising above control levels of 7 pmol/min to 53 pmol/min for A-23187 and 62 pmol/min for thapsigargin. Thapsigargin stimulated NO production and [Ca2+]i with 50% effective concentration values of 0.01 and 0.05 microM, respectively. Ca(2+)-stimulated NO production was attenuated by the NO synthase inhibitor NG-monomethyl-L-arginine, the removal of extracellular L-arginine, and the Ca(2+)-chelator ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. When we exposed cells to NO gas (3.1 mM for 15 min) and S-nitrosoglutathione (10 mM for 1 h) thapsigargin-stimulated NO production was decreased by 50%.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of oxidant lung injury by using liposome-entrapped superoxide dismutase and catalase.

Increased cellular generation of partially reduced species of oxygen mediates the toxicity of hyperoxia to cultured endothelial cells and rats exposed to 95-100% oxygen. Liposomal entrapment and intracellular delivery of superoxide dismutase (SOD) to cultured porcine aortic endothelial cells increased the specific activity of cellular SOD up to 15-fold. The liposome-mediated augmentation of SOD activity persisted in cell monolayers and rendered these cells resistant to oxygen-induced injury in a cell SOD activity-dependent manner. Addition of free SOD to culture medium had no effect on cell SOD activity or resistance to oxygen toxicity. SOD and catalase-containing liposomes injected i.v. into rats increased lung-associated enzyme specific activities two- to fourfold. Liposome entrapment of both SOD and catalase significantly increased the circulating half-lives of these enzymes and was critical for prevention of in vivo oxygen toxicity. Free SOD and catalase injected i.v. in the absence or presence of control liposomes did not increase corresponding lung enzyme activities or survival time in 100% oxygen. These studies show that O2- and H2O2 are important mediators of oxygen toxicity and that intracellular delivery of oxygen protective enzymes can reduce tissue injury owing to overproduction of partially reduced oxygen species.

Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool.

We have investigated the role of the intracellular Ca2+ pool in regulating Ca2+ entry into vascular endothelial cells. The intracellular Ca2+ pool was mobilized using either thapsigargin (TG) or 2',5'-di(tert-butyl)-1,4-benzohydroquinone (BHQ), inhibitors of the endoplasmic reticulum Ca(2+)-adenosinetriphosphatase (ATPase). Mobilization of intracellular Ca2+ stores with either inhibitor depleted intracellular Ca2+ and greatly reduced subsequent mobilization of the inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ pool by bradykinin. However, bradykinin-induced mobilization of the IP3-sensitive intracellular Ca2+ pool only partially reduced the subsequent response of cells to TG and BHQ. Mobilization of the intracellular Ca2+ pool by either TG or BHQ led to a concentration-dependent elevation of cytosolic Ca2+ concentrations ([Ca2+]i) without initiating inositol polyphosphate formation. In contrast to the rapidly developing, transient rise in Ca2+ concentration initiated by bradykinin, maximal concentrations of TG and BHQ stimulated a slowly developing, prolonged elevation of [Ca2+]i that required extracellular Ca2+ and could be blocked by extracellular Ni2+. Extracellular Ca2+ entered the cell through an activated cation entry pathway, since bradykinin, TG, and BHQ stimulated Mn2+ and 45Ca2+ entry. Bradykinin-stimulated 45Ca2+ uptake reached a peak within 2 min, whereas 45Ca2+ influx initiated by TG or BHQ continued for at least 8 min. Importantly, the [Ca2+]i response after low concentrations of BHQ was more transient than that seen after TG. The return of [Ca2+]i to basal values after low concentrations of BHQ was associated with reversal of Ca(2+)-ATPase inhibition and refilling of the IP3-sensitive Ca2+ pool. The continued elevation of [Ca2+]i and prolonged Ca2+ entry seen with TG was associated with continued Ca(2+)-ATPase inhibition and an empty IP3-sensitive Ca2+ pool. We conclude that mobilization of intracellular Ca2+ stores induces Ca2+ entry in endothelial cells which continues until the intracellular Ca2+ pool is refilled.

Inhaled procaterol inhibits histamine-induced airflow obstruction and microvascular leakage in guinea-pig airways with allergic inflammation.

BACKGROUND: Beta2-adrenoceptor agonists (beta2-agonists) are shown to inhibit airway microvascular leakage in experimental animals. This effect may change in animals with chronic airway inflammation. OBJECTIVE: We examined whether inhaled beta2-agonists inhibit microvascular leakage in guinea-pig airways with chronic allergic inflammation. METHODS: Three weeks after the sensitization with ovalbumin (OA; 6 mg/mL), each guinea pig was challenged with inhaled OA once a day for 1 or 3 weeks. Control animals without sensitization with OA also inhaled vehicle for OA (saline) for 3 weeks. One day after the last challenge, different doses of inhaled procaterol (1, 3 or 10 microg/mL) or vehicle was given to animals for 10 min after an anaesthesia. Fifteen minutes after the end of inhalation, the animals were given i.v. Evans blue dye (EB dye; 20 mg/kg), a marker of microvascular leakage, and then i.v. histamine (3 or 30 microg/kg) or vehicle. Lung resistance, a parameter of airflow obstruction, was measured for 6 min and the lungs were removed to calculate the amount of extravasated EB dye into the airways. RESULTS: A significant increase in eosinophil infiltration into the airways was seen in sensitized and challenged animals compared with control animals without sensitization. Among animals receiving antigenic exposure for either 0 (control), 1 or 3 weeks, 10 microg/mL procaterol significantly inhibited 30 microg/kg histamine-induced increase in EB dye extravasation to a similar degree (ranged from 28.7 to 69.8% inhibition) as well as that in lung resistance (more than 90% inhibition in all groups). The minimal dose of procaterol to inhibit 3 microg/kg histamine-induced microvascular leakage was not different between nonsensitized control animals and those sensitized and challenged for 3 weeks at all airway levels. CONCLUSION: Inhaled beta2-adrenoceptor agonists may be also potent in attenuating microvascular leakage even in the airways with chronic allergic inflammation.