Triple Assessment of a Palpable Parotid Lump in "One-Stop" Clinics.

Introduction: The National Institute of Clinical Excellence in the UK (NICE) recommended the use of "one-stop" clinics for the assessment and management of head and neck lumps like those established for breast lumps. "One-stop" clinics should follow a triple assessment protocol involving physical examination, radiological imaging and fine-needle aspiration cytology (FNAC). Methods: A retrospective analysis of 144 patients with suspected parotid tumours from 2005 to 2011 was done. Patients were assessed for individual modalities and compared against the final histological diagnosis. Statistical analysis was used for sensitivity and specificity, as well as positive and negative predictive values. All calculations were performed using SPSS version 16 (Statistical Packages for the Social Sciences, Chicago, IL). A p value of < 0.05 was considered to indicate statistical significance. Results: A total of 105 patients underwent all the three modalities. Out of them, 93 had imaging that was considered radiologically benign and 12 were reported to have a malignant lesion. Cytologically, 75 were found to have a benign tumour, 13 were malignant, and 17 were considered to be indeterminate. The most common benign neoplasm was pleomorphic adenoma followed by Warthin's tumour. The sensitivity and specificity of triple assessment were 96% (p value 0.878-0.984) and 73% (p value 0.42-0.904), respectively. The positive predictive value was 96% (p value 0.878-0.984) and negative predictive value came out to be 93% (p value 0.42-0.904). Conclusions: The overall accuracy of triple assessment was found to be 92%. This study concludes that triple assessment is a useful assessment tool to evaluate a patient with parotid lump. Supplementary Information: The online version contains supplementary material available at 10.1007/s12663-021-01590-5.

Prevalence of pharmacotherapy in the department of paediatric dentistry.

BACKGROUND: Pharmacotherapy plays important role in the management of paediatric dental patients in the department of paediatric dentistry. Many children at their early age suffer from different kinds of dental conditions such as acute and chronic irreversible pulpitis, acute and chronic alveolar abscesses, dentoalveolar and vestibular abscesses, etc along with physiological tooth movement that requires professional help for dental treatment. Treatment of such conditions most frequently requires pharmacotherapy as an either adjunct to dental therapeutic procedure or as a monotherapy. OBJECTIVE: To assess the prescribing patterns vis-a-vis generic or trade name, generic class, dosage form, route, frequency, duration, number of drugs per patient, cost and indication of drug therapy, patterns of dental treatment and Frankl's behavioral rating. MATERIALS AND METHODS: Prescriptions of 200 paediatric dental patients undergoing dental treatment in the department of paediatric dentistry were analyzed prospectively for a period of six months in a dental teaching hospital. RESULTS: 133 (56.5%) patients were males and 87 (43.5%) females and age group 6-10 years was the most frequent group (70%, P = 0.0000000) and all the patients received pharmacotherapy. Total numbers of 357 drugs were prescribed. Out of them, 212 (59.4%, P = 0.0000008) were analgesic agents, 133 (37.3%) antimicrobial agents (AMAs) and 12 (3.3%) other drugs. Extended spectrum Penicillins were the most commonly prescribed (90.2%) AMA followed by Metronidazole (9.8%). 247 drugs (69.2%, P = 0.0000000) were prescribed by trade names. 60% (P = 0.0000002) drugs were prescribed in the form of tablet or capsule followed by syrup 37% and administered entirely through oral route. Percentage of patients receiving three drugs, two drugs and one drug was 13.5%, 56.5% (P = 0.0000000) and 30% respectively and one patient received on average 1.78 medicines. 133 patients (56.5%, P = 0.0000000) received both AMA and analgesic agent. Minimum to maximum number of days for pharmacotherapy were 2 to 15 and highest frequency was up to four times a day. Cost of medicines was in the range of 10-150 Nepalese Rupees. Chronic irreversible pulpitis was the commonest diagnosis (28%) and extraction (92.5%) was the commonest dental procedure. Frankl's behaviour rating showed that 78.5% (P = 0.0000000) patients had positive attitude towards the dental procedures. CONCLUSION: Findings of the study suggest that pharmacotherapy is the mainstay in therapy to treat the paediatric dental patients along with dental procedures either to control the dental pain or odontogenic infection. Age group 6-10 years, chronic irreversible pulpitis and dental extraction are the commonest age group, diagnosis and dental procedure respectively in the department of paediatric dentistry. Analgesic (non-steroidal anti-inflammatory drugs- Nimesulide, Ibuprofen and Paracetamol) and Amoxicillin are the most frequently prescribed drugs mostly in the solid dosage forms in trade names via oral route. Duration of pharmacotherapy ranges from 2 to 15 days with highest frequency being up to 4 times a day. Majority of the patients are manageable without any behavioural modification technique- physical or pharmacological.

Structural, functional and therapeutic biology of survivin.

Survivin is a unique member of the inhibitor of apoptosis (IAP) protein family that interferes with post-mitochondrial events including activation of caspases. Survivin regulates cell cycle also. It is expressed in most of the human tumors, but it is barely detectable in the terminally differentiated normal cells/tissues. Molecular mechanisms of regulation of survivin in cancer are not clearly understood. Nevertheless, the functional loss of wild type p53 is often associated with upregulation of survivin. Tumors that over-express survivin generally bear a poor prognosis and are associated with resistance to therapy. The differential expression of survivin in cancer versus normal tissues makes it a useful tool in cancer diagnosis and a promising therapeutic target. A growing body of literature suggests nuclear expression of survivin as a good prognostic marker. Disruption of the survivin induction pathway has resulted in an increase in apoptosis and inhibition of tumor growth. Regular therapies, such as, radiotherapy in combination with anticancer drugs in clinical practice may yield promising results.

Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase.

Agents that can suppress the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation. Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-kappaB and AP-1 modulator. We investigated the effect of oleandrin on NF-kappaB activation induced by inflammatory agents. Oleandrin blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. A proprietary hot water extract of oleander (Anvirzel) also blocked TNF-induced NF-kappaB activation; subsequent fractionation of the extract revealed that this activity was attributable to oleandrin. The effects of oleandrin were not cell type specific, because it blocked TNF-induced NF-kappaB activation in a variety of cells. NF-kappaB-dependent reporter gene transcription activated by TNF was also suppressed by oleandrin. The TNF-induced NF-kappaB activation cascade involving TNF receptor 1/TNF receptor-associated death domain/TNF receptor-associated factor 2/NF-kappaB-inducing kinase/IkappaBalpha kinase was interrupted at the TNF receptor-associated factor 2 and NF-kappaB-inducing kinase sites by oleandrin, thus suppressing NF-kappaB reporter gene expression. Oleandrin blocked NF-kappaB activation induced by phorbol ester and lipopolysaccharide. Oleandrin also blocked AP-1 activation induced by TNF and other agents and inhibited the TNF-induced activation of c-Jun NH2-terminal kinase. Overall, our results indicate that oleandrin inhibits activation of NF-kappaB and AP-1 and their associated kinases. This may provide a molecular basis for the ability of oleandrin to suppress inflammation and perhaps tumorigenesis.

Protein tyrosine kinase p56lck is required for ceramide-induced but not tumor necrosis factor-induced activation of NF-kappa B, AP-1, JNK, and apoptosis.

Ceramide has been implicated as an intermediate in the signal transduction of several cytokines including tumor necrosis factor (TNF). Both ceramide and TNF activate a wide variety of cellular responses, including NF-kappaB, AP-1, JNK, and apoptosis. Whether ceramide transduces these signals through the same mechanism as TNF is not known. In the present study we investigated the role of the T cell-specific tyrosine kinase p56(lck) in ceramide- and TNF-mediated cellular responses by comparing the responses of Jurkat T cells with JCaM1 cells, isogeneic Lck-deficient T cells. Treatment with ceramide activated NF-kappaB, degraded IkappaBalpha, and induced NF-kappaB-dependent reporter gene expression in a time-dependent manner in Jurkat cells but not in JCaM1 cells, suggesting the critical role of p56(lck) kinase. These effects were specific to ceramide, as activation of NF-kappaB by phorbol 12-myristate 13-acetate, lipopolysaccharide, H(2)O(2), and TNF was minimally affected. p56(lck) was also found to be required for ceramide-induced but not TNF-induced AP-1 activation. Similarly, ceramide activated the protein kinases JNK and mitogen-activated protein kinase kinase in Jurkat cells but not in JCaM1 cells. Ceramide also induced cytotoxicity and activated caspases and reactive oxygen intermediates in Jurkat cells but not in JCaM1 cells. Ceramide activated p56(lck) activity in Jurkat cells. Moreover, the reconstitution of JCaM1 cells with p56(lck) tyrosine kinase reversed the ceramide-induced NF-kappaB activation and cytotoxicity. Overall our results demonstrate that p56(lck) plays a critical role in the activation of NF-kappaB, AP-1, JNK, and apoptosis by ceramide but has minimal or no role in activation of these responses by TNF.

The baculovirus antiapoptotic p35 gene also functions via an oxidant-dependent pathway.

Cellular imbalance in the levels of antioxidants and reactive oxygen species resulting in apoptosis is directly associated with a number of parasitic infections, aging, and several genetic and multifactorial diseases. The baculovirus AcNPV-encoded antiapoptotic p35 gene prevents apoptosis induced by a variety of apoptotic agents in different systems. We demonstrate the ability of the p35 gene to inhibit oxidative stress-induced apoptosis. In vitro cultured Spodoptera frugiperda (Sf9) insect cells infected with wild-type AcNPV carrying the antiapoptotic p35 gene did not undergo apoptosis when subjected to oxidative stress generated by the exogenous application of oxidants or in vivo generation of reactive oxygen species or on direct exposure of cells to UV radiations. An AcNPV mutant carrying a deletion of the p35 gene failed to arrest cell death. Transfection of cells with a recombinant plasmid containing the p35 gene under the transcriptional control of a stress promoter (Drosophila hsp70) was also able to rescue cells from oxidative stress-induced cell death, demonstrating the direct involvement of P35. ESR spin-trapping studies conducted in vitro and in vivo demonstrated that P35 functions directly as an antioxidant by mopping out free radicals and consequently prevents cell death by acting at an upstream step in the reactive oxygen species-mediated cell death pathway.

Probing tenability of biochemical vis-a-vis physicochemical interpretations of modulation of radiation damage by caffeine and cysteine in barley.

Cysteine (an aminothiol) is known to protect against radiation damage, and is understood to do so by generating hydrogen peroxide which subsequently inhibits RNA synthesis. Our results showed inability of catalase to remove or reduce the magnitude of radioprotection by caffeine and/or cysteine at optimal/suboptimal temperatures in barley. This observation was adequately corroborated by data on frequency of chromosomal aberration, peroxidase activity and total protein content. On the contrary, catalase tended to enhance the radioprotective effectiveness of cysteine. Macromolecular synthetic patterns in caffeine and/or cysteine treated embryos were too inconsistent to permit a logical conclusion with regard to their positive involvement in the biochemical pathway of chemical modification of radiation damage. On the other hand, mutually annihilatory reaction hypothesis based on physico-chemical principles provides a satisfactory explanation for the observed effects.

Peroxidase changes in barley induced by ionizing and thermal radiation.

Thermal and ionizing (gamma-ray) radiations were used to induce damage to barley seeds (IB65). The activity and isozyme banding patterns of peroxidase were compared. It was found that both physical agents caused damage to barley seeds (as observed from seedling height), but their action on peroxidase activity is not similar. Gamma-Rays enhance peroxidase activity. Thermal radiation, on the other hand, tends to reduce it but fails to alter the number of peroxidase isozymes. It is conjectured that the pathways of damage by thermal and ionizing radiations are not the same.

Variation in the modulation of superoxide-induced single-strand breaks in plasmid pBR322 DNA by biological antioxidants.

Superoxide radical (O2-.), generated by the xanthine-xanthine oxidase system, induces significant amount (20%) of single-strand breaks in plasmid pBR322 DNA. This is almost completely inhibited by its specific scavenger, superoxide dismutase. The biological antioxidants, at near physiological concentrations show great variation in their modulation of DNA damage induced by O2-.. The thiols glutathione, cysteine and dithiothreitol do not protect DNA, instead they greatly enhance the strand-breaking activity of this free radical. However, the lipid soluble antioxidants tannic acid, butein, canthaxanthin, beta-carotene and lipoate offered significant protection to plasmid DNA against O2-.. Since O2-. is the most abundant reactive oxygen species generated, the above mentioned modulating abilities of biological antioxidants may have significant biological implications.

Chemical modification of postirradiation damage under varying oxygen concentrations in barley seeds.

The influence of ascorbic acid, potassium permanganate and caffeine on the postirradiation seedling injury of dry barley seeds was studied, irradiated (350 Gy 60Co gamma-rays) in vacuo and post-hydrated with varying oxygen concentrations in the soaking medium. The oxygen concentration in the post-hydration medium (OCHG) was adjusted at 0%, 10%, 30%, 50%, 80% and 100%. A linear response between the seedling injury and O2 concentration in the range of 0-80% was observed. These chemicals potentiated, protected or exerted no effect, depending upon the OCHG. Thus, ascorbic acid did not exert any effect on seeds post-hydrated at OCHG of less than or equal to 30%, but afforded radio-protection at OCHG of greater than or equal to 50%. Caffeine, on the other hand, potentiated the postirradiation injury at OCHG of less than or equal to 30%, exerted no influence at OCHG of approximately 50% and afforded radioprotection at OCHG of greater than or equal to 80%. Potassium permanganate enhanced the injury at OCHG of less than or equal to 10%, exerted no effect at OCHG of approximately 30% and afforded radioprotection at OCHG of greater than or equal to 50%. The possible radiation-chemical events in the dry irradiated seeds following their post-hydration containing different OCHG and the three test chemicals which are known free radical scavengers are discussed.

Post-irradiation modification of oxygen-dependent and independent damage by catalase in barley seeds.

If H2O2 is one of the major mediators of the 'oxygen effect' in biological systems then catalase, which enzymically decomposes H2O2 should have a significant influence on radiation damage, particularly under oxygenated conditions. The post-irradiation (300 Gy gamma rays) effect of catalase was, therefore, assessed on barley seeds of about 4 per cent moisture content under oxygenated and oxygen-free conditions at varying temperatures. Catalase affords concentration-dependent radioprotection under oxygenated condition at both 25 degrees C and 4 degrees C. The level of protection at 4 degrees C is less than at 25 degrees C. This is obviously due to a decrease in catalase activity at low temperature. Under oxygen-free conditions, catalase enhances radiation damage at 4 degrees C while at 25 degrees C it has no effect. This has been substantiated by data on the frequency of chromosomal aberrations and on peroxidase activity. Sodium azide, a catalase inhibitor, was found to eliminate the radioprotective action of catalase. The study supports the view that the 'oxygen effect' is mediated largely through peroxides in irradiated biological systems. However, the observations made particularly at 4 degrees C under oxygen-free condition seem to involve physicochemical reactions.