Spectrophotometeric Determination of Cefuroxime Axetil from bulk and in its tablet dosage form

A simple rapid spectrophotometric method has been developed for estimation of cefuroxime axetil from bulk drug and tablet dosage form by using 1-nitroso-2-napthol and sodium hydroxide. The method is based on the formation of yellow-orange coloured complex of drug with 1-nitroso-2-napthol having absorbance maxima at 424 nm. The Beer’s law is obeyed in the concentration range of 10-50 μg/ml of the drug but more precisely it obeys in the range of 10- 30 μg/ml. The slope and intercept values are 0.0101 and 0.0838, respectively. Results of analysis of this method were validated statistically and by recovery studies. The method is applied to the marketed tablet formulation. Result of analysis of tablet formulation given as percentage of label claim ±standard deviation is 99.17±1.57. The precision and accuracy was examined by performing recovery studies and was found to be 99.50±1.82. Sandell’s correlation coefficient is calculated as 0.4434. The developed method is simple, sensitive and reproducible and can be used for routine analysis of cefuroxime axetil from bulk and tablet dosage form.     

Incidence of fungal infections in chronic maxillary sinusitis

Fifty patients with chronic maxillary sinusitis were included in our study. Antrat aspirate of chronically inflamed maxillary sinuses collected by antrat puncture were subjected to fungal culture. The study revealed the presence of fungi in 3 cases. Aspergillus fumigatus was isolated in 2 cases while Candida albicans was found in 1 case. The role of fungi, particularly aspergillus as pathogen is discussed in the context of antibiotics and immuno-suppressive therapy and local predisposing factors.     

A patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma]

We here reported a 54-year-old female patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma. She was found to have scattered tumor in 1990. Although the tumor had slowly grown for the last 10 years, she showed no clinical symptoms. Numbness and weakness of lower extremities began in June 1999, and she was referred to Kyoto University Hospital on Oct. 21 1999 for evaluation of progressive symptoms. She had skin pigmentation, edema of the lower extremities, lymphadenopathy, muscle weakness and sensory disturbance in a glove-and-stocking distribution. Serological examination showed monoclonal IgG-lambda gammopathy. Serum vascular endothelial growth factor (VEGF) was markedly elevated. Microscopic studies on biopsied sural nerve demonstrated mild decrease of myelinated fibers. Immunohistochemically, the pulmonary tumor was defined as an IgG (lambda type) plasmacytoma. After treatment with melphalan-prednisolone therapy, the neurological symptoms improved along with decrease of serum VEGF levels as well as the size of pulmonary plasmacytoma. This is the first report of a patient with Crow-Fukase syndrome associated with pulmonary plasmacytoma. This case suggests that growth of pulmonary plasmacytoma might have played an important role in the overproduction of VEGF and thus development of Crow-Fukase syndrome.     

Guidelines for the safe practice of total intravenous anaesthesia (TIVA)

Guidelines are presented for safe practice in the use of intravenous drug infusions for general anaesthesia. When maintenance of general anaesthesia is by intravenous infusion, this is referred to as total intravenous anaesthesia. Although total intravenous anaesthesia has advantages for some patients, the commonest technique used for maintenance of anaesthesia in the UK and Ireland remains the administration of an inhaled volatile anaesthetic. However, the use of an inhalational technique is sometimes not possible, and in some situations, inhalational anaesthesia is contraindicated. Therefore, all anaesthetists should be able to deliver total intravenous anaesthesia competently and safely. For the purposes of simplicity, these guidelines will use the term total intravenous anaesthesia but also encompass techniques involving a combination of intravenous infusion and inhalational anaesthesia. This document is intended as a guideline for safe practice when total intravenous anaesthesia is being used, and not as a review of the pros and cons of total intravenous anaesthesia vs. inhalational anaesthesia in situations where both techniques are possible.     

Suicide amongst anaesthetists – an Association of Anaesthetists survey

Following a 2–3-month period of publicity, anaesthetists were invited to participate in an online survey that was administered by a third party company on behalf of the Association of Anaesthetists and ran between 3 September and 31 October 2018. Anaesthetists working in the UK or Ireland were asked about the presence or absence of welfare/support structures or resources in their workplace in the case of mental illness, addiction and/or suicide. Anaesthetists working anywhere in the world were also asked for their experiences of a colleague's suicide, defined as a colleague's taking his or her own life – whether intentional or not – while practising as an anaesthetist in the UK or Ireland, in the same department and at the same time as the respondent. Respondents were also asked about experiences of other suicides not meeting this definition. A total of 3638 responses were received. Most respondents were unaware of the existence of policies/guidance on mental illness, addiction or suicide, or of welfare leads, within their Trust or department. A total of 1916 cases of suicide meeting the survey's definition were reported by 1397 respondents, although the actual number of discrete cases is unknown because of likely multiple reporting of the same cases. A third of respondents who reported a suicide had experience of more than one case. Most reports were of suicide in the last 10 years, and most reported cases involved anaesthetic drugs. Deficiencies were noted in the support available and in the way the deaths were handled, although examples of good support were also described. A further 1715 respondents reported suicides that did not meet the primary definition. Overall, 92% of respondents reporting suicide experienced it through work, and 41% outside of work (total > 100% as some reported both). Although unable to provide estimates of suicide rates, or numerical associations between the features of the deaths, this survey highlights the considerable emotional and mental burden of suicide on anaesthetists.     

High-Throughput Identification and Quantification of Candida Species Using High Resolution Derivative Melt Analysis of Panfungal Amplicons

Fungal infections pose unique challenges to molecular diagnostics; fungal molecular diagnostics consequently lags behind bacterial and viral counterparts. Nevertheless, fungal infections are often life-threatening, and early detection and identification of species is crucial to successful intervention. A high throughput PCR-based method is needed that is independent of culture, is sensitive to the level of one fungal cell per milliliter of blood or other tissue types, and is capable of detecting species and resistance mutations. We introduce the use of high resolution melt analysis, in combination with more sensitive, inclusive, and appropriately positioned panfungal primers, to address these needs. PCR-based amplification of the variable internal transcribed regions of the rDNA genes generates an amplicon whose sequence melts with a shape that is characteristic and therefore diagnostic of the species. Simple analysis of the differences between test and reference melt curves generates a single number that calls the species. Early indications suggest that high resolution melt analysis can distinguish all eight major species of Candida of clinical significance without interference from excess human DNA. Candida species, including mixed and novel species, can be identified directly in vaginal samples. This tool can potentially detect, count, and identify fungi in hundreds of samples per day without further manipulation, costs, or delays, offering a major step forward in fungal molecular diagnostics.Rapid and economical detection, identification, and quantification of fungal species directly from clinical samples is a long-sought goal of clinicians that has still not been fulfilled.^1,2,3,4,5,6 Culture-based diagnosis of fungal infections is inadequate in that many species do not culture efficiently or require unacceptably long incubations.⁷ Antigen-based tests for galactomannan or β-glucan are improvements over culture, but are either too specific, too insensitive, plagued by false positives, or not yet validated by widespread testing.^{8,9,10,11,12,13} Identification of C. albicans and C. glabrata by Peptide nucleic acid-fluorescence in situ hybridization (PNA-FISH) is in clinical use. However, this tool requires an initial culture step to increase fungal titer to detectable levels and is limited in the number of species it can identify.^14,15,16,17PCR-based strategies are the most likely solutions to challenges posed by fungal diagnostics. However, clinical diagnosis of fungal infections by PCR is perhaps its most challenging application, due to low cell numbers, potentially <1 cell/ml sample, to the added problems in lysing fungal walls, and to the similarity in rDNA sequences to human. It is clear that PCR is sufficiently sensitive and specific by in vitro testing, but sample processing under these extreme demands remains problematic. Reviews from 2002 to 2008 indicate that both the promise and problems are great.^6,8,18,19 Most approaches detect positives in clinical samples at their limits of detection, meaning they lack the level of robustness needed to avoid false negatives when widely applied.^1,20PCR strategies using panfungal primers that complement conserved regions of rDNA but span the variable internal transcribed spacer regions (ITS1 and ITS2) have the strong advantage that any and all fungal species will be captured in a single reaction.^{21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47} Traditionally, these amplicons are then sequenced to identify species, using standard, automated capillary sequencing, pyrosequencing, or sequencing-grade microarrays.^{27, 29, 32,33,34,35, 37, 44, 47,48,49,50} Alternatively, precise determination of the base composition of the amplicons by electrospray mass spectroscopy may identify species.⁵¹ Less precise but adequate resolution may be achieved by restriction enzyme analysis of the amplicon.^24,30 Repetitive sequence-PCR (REP-PCR), a version of randomly amplified polymorphic DNA (RAPD) in which primers target repetitive sequence elements, have been used for fungal identification.^52,53 However, this requires pure cultures as the starting material, which is useful in some applications but is not an acceptable precondition for a clinical fungal diagnostic tool. An alternative is to identify species with probes, either standard hybridization after PCR, or during amplification using Taqman, Beacon, or Scorpion probes,^{22,25,28,38,41,45} or hybridization-based fluorescence resonance energy transfer (FRET) probes.⁵⁴An alternative is the use of species-specific PCR, which is typically more sensitive and does not require sequencing of product. Species that are certain to be seen with reasonable frequencies can be detected by species-specific PCR. Approximately 80% of these are species of Candida (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, and C. lusitaniae), or Aspergillus (A. fumigatus, A. flavus, A. terreus, A. niger). The remaining ∼20% include Fusarium, Sporothrix schenckii, zygomycetes (Absidia corymbifera, Rhizomucor pusillus, Rhizopus arrhizus, Mucor, and Cunninghamella). Some of the less common species are also the most problematic in terms of resistance or virulence. There are a number of publications reporting a variety of primers for this approach, with widely varying levels of rigor in their validation.^{55,56,57,58,59,60,61,62} In general, this approach has the disadvantage that multiple assays have to be run on each sample, adding cost and labor. Multiplexing is a possible alternative, but this is widely associated with reduced sensitivity. A further limitation is that many clinical samples will have novel species that may be missed by these primers.High resolution melt analysis is likely to provide an even simpler, faster, and cheaper identification tool sufficiently specific for fungal speciation. This approach more fully exploits the shape of the melting curve of an amplicon, which is a much richer source of information than melting temperature alone. Short, regional sequences denature to form single stranded regions, which release double-stranded DNA-binding fluorescent dyes, before reaching the temperature at which the entire amplicon denatures. This influences the shape of the melt curve, to generate nuances that reflect species-specific sequence differences. Resolution can be further enhanced or normalized by several methods.^63,64 This has enabled identification of bacterial and viral species.⁶⁵Our application of this tool to species of Candida shows that the separation between species is great enough to call species without any postamplification handling.     

Immune response modulation to DPT vaccine by aqueous extract of Withania somnifera in experimental system

Immunopotentiation on oral feeding of standardized aqueous extract of Withania somnifera (Linn. Dunal, Family Solanaceae) was evaluated in laboratory animals immunized with DPT (Diphtheria, Pertussis, Tetanus) vaccine. The immunostimulation was evaluated using serological and hematological parameters. Treatment of immunized animals with test material (100 mg/kg/day) for 15 days resulted in significant increase of antibody titers to B. pertussis (P=0.000007). Immunized animals (treated and untreated) were challenged with B. pertussis 18,323 strain and the animals were observed for 14 days. Results indicate that the treated animals did show significant increase in antibody titers as compared to untreated animals after challenge (P=0.000003). Immunoprotection against intracerebral challenge of live B. pertussis cells was evaluated based on degree of sickness, paralysis and subsequent death. Reduced mortality accompanied with overall improved health status was observed in treated animals after intracerebral challenge of B. pertussis indicating development of protective immune response. Present study indicates application of the test material as potential immunopotentiating agent possible applications in immunochemical industry. The test material also offers direct therapeutic benefits resulting in reduced morbidity and mortality of experimental animals.