Facile Synthetic Protocols for the Preparation of New Impurities in Pemetrexed Disodium Heptahydrate as an Anti-cancer Drug.

A facile synthetic protocol was employed to prepare process-related impurities associated with the synthesis of pemetrexed disodium heptahydrate, Alimta. The research work is described for the development of the novel synthetic methods and their structure elucidation of Pemetrexed glutamide, N-methyl pemetrexed, and N-methyl pemetrexed glutamide impurities. The listed impurities were deduced through spectral analysis, such as 1H-NMR, 13CNMR, and HRMS. The target compounds can be used as the reference substances for quality control.

Functional π-Conjugated Two-Dimensional Covalent Organic Frameworks.

Fingerprints of π-conjugated compounds are ubiquitous in nature and play a crucial part in human existence. For instance, cis-retinal, an endogenous π-conjugated molecule present in the eye, performs a vital role in the function of visual perception. π-Conjugated molecules have also received a great deal of attention owing to their intriguing optical properties and created a surge in optoelectronics. Varieties of π-conjugated molecules/oligomers have been developed and explored for a number of applications such as organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs), organic photovoltaics (OPVs), and sensors, among others. While the extended π-delocalization in one-dimensional (1D) polymers versus oligomers produce superior optical and electronic properties, further extension of π-delocalization to the second dimension (2D) is expected to give rise even more intriguing properties as revealed by theoretical studies. As a matter of fact, graphene is the best example of 2D-conjugated polymers, but its zero-band-gap behavior is a major impediment for semiconducting applications. In contrast, it was challenging to prepare 2D crystalline polymers until the discovery of boroxine/boronate ester linked covalent organic frameworks (COFs) by Yaghi and co-workers. COFs are a new class of porous crystalline polymers in which organic building blocks are held together by covalent bonds. These polymers exhibit potential applications in gas storage, energy storage, photocatalyst, heterogeneous catalysis, sensors, etc. However, the first π-conjugated COF was realized in 2009 via the introduction of imine linker (-C═N-) between the building blocks. Since then, wide varieties of COFs with various π-delocalization promoting spacers have been developed and explored their electronic and optical properties and pertinent applications. In this review, we will highlight the importance of 2D π-conjugated COFs and their achievements in developing novel functionalities.

Bis(phosphinoselenoic amides) as versatile chelating ligands for alkaline earth metal (Mg, Ca, Sr and Ba) complexes: syntheses, structure and ε-caprolactone polymerisation.

We report here a series of heavier alkaline earth metal complexes with N,N'-(ethane-1,2-diyl)bis(P,P-diphenylphosphinoselenoic amide) using two synthetic routes. In the first route, the heavier alkaline earth metal bis(trimethylsilyl)amides [M{N(SiMe3)2}2(THF)n] (M = Ca, Sr, Ba), when treated with phosphinoselenoic amine [Ph2P(Se)NHCH2CH2NHPPh2(Se)] (1), afforded the corresponding alkaline earth metal complexes of the composition [(THF)3M{Ph2P(Se)NCH2CH2NPPh2(Se)}] [M = Ca (2), Sr (3), Ba (4)]. The metal complexes 2-4 were also obtained from a one-pot reaction, where potassium phosphinoselenoic amide was generated in situ by the reaction of compound 1 and [KN(SiMe3)2], followed by the addition of the respective metal diiodides in THF at room temperature. The magnesium complex [(THF)3Mg{Ph2P(Se)NCH2CH2NPPh2(Se)}] (5) was also prepared. The solid-state structures of alkaline earth metal complexes 2-5 were established by single crystal X-ray diffraction analysis. In the solid state, all the metal complexes are monomeric but in complexes 2-4, ligand 1 is chelated in a tetra-dentate fashion to each metal ion but in complex 5, ligand 1 behaves as a bidentate ligand. Complexes 2-4 were tested as catalysts for the ring-opening polymerisation of ε-caprolactone and a high level of activity for the barium complex 4 was observed, with narrow polydispersity. We also report the synthesis and structure of the bis(amidophosphino borane) ligand [Ph2P(BH3)NHCH2CH2NHPPh2(BH3)] (6) and the corresponding barium complex [(THF)2Ba{Ph2P(BH3)NCH2CH2NPPh2(BH3)}]2 (7).

The performance of routine computed tomography for the detection of colorectal cancer.

INTRODUCTION: Although colonoscopy and computed tomography (CT) colonography in expert hands are the most sensitive investigations for colorectal cancer, some patients may not tolerate the necessary bowel preparation and insufflation of gas into the colon. We assessed the performance of unprepared contrast CT for the detection of colorectal cancer. METHODS: A retrospective review was undertaken of all patients who had contrast CT of the abdomen and pelvis and then went on to have colonoscopy at our institutions between 2007 and 2010. RESULTS: Overall, 96 patients were identified as having had CT prior to colonoscopy. The sensitivity of CT in detecting colorectal cancer was 100% (95% confidence interval [CI]: 19.8-100%) and the specificity was 95.7% (95% CI: 88.8-98.6%). The positive predictive value was 33.3% (95% CI: 6.0-75.9%) and the negative predictive value was 100% (95% CI: 94.8-100%). CONCLUSIONS: Non-targeted CT that is negative for colorectal malignancy is usually reassuring but the decision for further investigations should be made on a case-by-case basis, taking into account of the likelihood of underlying colorectal malignancy and the underlying co-morbidities of the patient. However, video colonoscopy is usually necessary to assess positive CT findings.

[Improvement of power and illumination source of the indirect binocular ophthalmoscope designed by Foerster]. / Optimierung von Strom- und Beleuchtungsquelle des indirekten binokularen Brillenophthalmoskops nach Foerster.

BACKGROUND: Since 1982, the indirect binocular ophthalmoscope designed by Foerster has been in use in ophthalmology. The option to implement a new illumination technique using a light-emitting diode (LED) and a new power source should be evaluated in terms of technical feasibility and patient safety. METHODS: The cooling element was redesigned to accommodate the new LED electronics and their components, including an option for a variable brightness control. A more compact rechargeable battery was utilized with variable fixation at the headband or elsewhere. Photometric measurements of light intensity and the operating time were planned. Furthermore, a review of the new lighting technology in terms of EN ISO 15004-2 and EN ISO 10943 was necessary. RESULTS: Technical adjustments to accommodate the LED inside the cooling element could be realised. The power source was a modern rechargeable lithium-ion battery with variable fixation. The luminous intensity of the LED is superior to that of the halogen lamp and the operating time was increased to 520 minutes. The required limits according to DIN EN ISO 15004-2 for ophthalmic devices were met by our measurements. CONCLUSION: The optimisation of the indirect binocular ophthalmoscope brings improvements in illumination intensity and operating time. A conversion for models already in use is possible. A certified appraisal for compliance with the appropriate standards is the next step.

Primary care and population factors associated with NHS Health Check coverage: a national cross-sectional study.

INTRODUCTION: High and equitable coverage of systematic cardiovascular disease (CVD) prevention programmes, such as the NHS Health Check programme in England, is essential if they are to effectively reduce the population CVD burden. METHODS: We conducted a cross-sectional study using data from 151 English primary care trusts (PCTs) on NHS Health Check coverage during 2011-12. We examined the associations between programme coverage and primary care and population factors, including patient demographics, primary care workforce and cardiovascular health need. RESULTS: Median coverage of NHS Health Checks was 8.2%, with wide PCT-level variation (range = 0-29.8%). Coverage was significantly higher in PCTs in the most deprived areas compared with the least deprived (P = 0.035), adjusting for covariates. Significant negative associations between coverage and a higher proportion of PCT population aged 40-74 years-the eligible Health Check age group, a larger total population size and higher practice staffing levels were found in the unadjusted analyses. CONCLUSIONS: NHS Health Check coverage during 2011-12 was lower than the government projection of 18% coverage. Coverage must be increased through concerted multi-disciplinary strategies, for the programme to improve cardiovascular health in England. Considerable variation in participation between PCTs warrants attention, with enhanced support for poor performers.

Factors influencing lingual nerve paraesthesia following third molar surgery: a prospective clinical study.

BACKGROUND AND OBJECTIVES: The purpose of this prospective study was to evaluate the incidence and various risk factors influencing the sensory deficit in case of lingual nerve injury (LNI) in individuals whose impacted mandibular third molars are surgically removed under local anesthesia. MATERIALS AND METHODS: The study was based on the data collected prospectively from a random group of 100 patients who underwent surgical removal of bony impacted lower third molar in a dental hospital. Details of the patient, reason for extraction, type of impaction, method of surgery and signs and symptoms of nerve injury are recorded. Neurosensory testing was done to evaluate the LNI at 1 week, 1 months, 3 months and 6 months interval. Comparison was carried out using Chi square test. For all tests a P < 0.05 was considered significant. RESULTS: The incidence of LNI was 4 % and of temporary in nature which recovered well within 6 months postoperatively. The age of the patient above 26 years, lingual flap retraction, depth of impaction (red line ≥10 mm) and duration of surgery above 30 min were the significant factors for causing LNI. CONCLUSIONS: The age of the patient, depth of impaction, lingual flap retraction and longer duration of surgery are significant risk factors for LNI during mandibular third molar surgery. Greater care should be taken to avoid the morbidity and patients should be informed well ahead about the probable complications.

Nicorandil associated anal ulcers: an estimate of incidence.

INTRODUCTION: Nicorandil is a commonly prescribed antianginal medication that has been found to be associated with painful anal ulceration. The incidence of this complication is unknown. We have used the best data available to us to make an estimate of this figure in a health district with a remarkably stable population of approximately 200,000 people. METHODS: using an electronic search of all letters generated from colorectal and gastroenterology clinics as well as endoscopy reports from January 2004 to November 2010, patients with anal ulceration who were taking nicorandil were identified. Other causes of ulceration were excluded by biopsy in the majority of cases. The central hospital and community pharmacy database was interrogated to estimate the number of patients who were prescribed nicorandil over a six-year period (2004-2010). RESULTS: A total of 30 patients (24 men, 6 women) with a median age of 79.5 years were identified who fulfilled the criteria of: taking nicorandil; having no other identified cause for anal ulceration; and achieving eventual healing after withdrawal of nicorandil. In the six-year period an estimated mean of 1,379 patients were prescribed nicorandil each year. The mean annual incidence of anal ulcers among nicorandil users is therefore calculated to be in the region of 0.37%. CONCLUSIONS: Anal ulceration appears to occur in approximately four in every thousand patients prescribed nicorandil each year. Prescribing physicians should explain the risk of this unpleasant complication to their patients.

Primary cutaneous adenoid cystic carcinoma of the chest wall: a rare entity.

Primary Cutaneous Adenoid Cystic Carcinoma (PCACC) is a rare form of cutaneous carcinoma. It closely resembles adenoid cystic carcinoma of salivary glands. The lesion tends to infiltrate and recur locally but rarely metastasizes to distant organs and lymph nodes. We present here a case of a31-year-old male with complaints of swellings in the chest wall and scalp, progressively increasing in size over a period of 10 years. Clinical diagnosis of sebaceous cysts of scalp and chest wall was made. Histopathology revealed PCACC of the chest wall and dermoid cyst of the scalp.

A radiolucent lesion crossing the midline in maxilla: a rare presentation of odontogenic keratocyst in young patient.

Odontogenic Keratocyst (OKC) is a developmental non-inflammatory odontogenic cyst which is proposed to be arising from cell rests of dental lamina. Among the jaw cysts OKCs account for third most common following radicular and dentigerous cyst. Most of the studies have stated that posterior part of the mandible is the most common site, but there are inconsistencies regarding the prominent location of OKCs in the maxilla. Very few studies and cases are reported with OKCs crossing maxillary midline. If do occur they are in older individuals. According to WHO reclassification, this cyst is considered as Keratocystic Odontogenic Tumour (KCOT) because of its neoplastic nature. This article describes a rare site of occurrence of this lesion especially in young patient.

Oral focal mucinosis: report of two cases / Mucinose oral focal: relato de dois casos

Purpose: Oral focal mucinosis (OFM), an oral counterpart of cutaneous focal mucinosis, is a rare disease of unknown etiology. Its pathogenesis may be due to overproduction of hyaluronic acid by fibroblast at the expense of collagen production, resulting in focal myxoid degeneration of connective tissue primarily affecting the mucosa overlying bone. It has no distinctive clinical features, since the diagnosis is solely based on histopathological features. This paper reports two cases and discusses clinicopathological, immunohistochemical features and differential diagnosis of myxomatous lesions of the oral cavity. Case description: The two cases of OFM lesions were present in a 50 year-old patient on the hard palate and in a 26 year-old female patient in the mandible, which seem to be the first report in the Indian population. Conclusion: The histopathological and immunohistochemical analysis of Vimentin and S-100 protein may play a vital role in the correct diagnosis of OFM.

Objetivo: Mucinose oral focal (MOF), uma lesão equivalente à mucinose cutânea focal, é uma doença rara de etiologia desconhecida. Sua patogênese pode ser devido a superprodução de ácido hialurônico pelo fibroblasto às expensas de produção de colágeno, resultando em degeneração mixoide focal de tecido conjuntivo primariamente afetando a mucosa sobre o osso. Não tem características clínicas distintas e o diagnóstico é baseado somente em características histopatológicas. Este artigo relata dois casos e discute as características clinico-patológicas e imuno-histoquímicas, bem como o diagnóstico diferencial de lesões mixomatosas da cavidade bucal. Descrição dos casos: Os dois casos de lesões de MOF estavam presentes no palato duro de um paciente do sexo masculino, de 50 anos de idade, e na mandíbula de uma paciente do sexo feminino, de 26 anos. Estes parecem ser os primeiros casos relatados na população da India. Conclusão: A análise histopatológica e imuno-histoquímica de Vimentin e proteína S-100 podem ter um papel importante no correto diagnóstico de MOF.

Single layer closure of palatal fistula using anteriorly based dorsal tongue flap.

Palatal fistulas are the common complications seen after cleft palate repair. Small fistula may be asymptomatic, the large ones produce various symptoms including regurgitation of fluids into nasal cavity and interference with normal speech. Although small fistulas can be successfully treated with local flaps such as palatal or buccal mucosal flaps, large fistulas pose difficulty. Because of rich blood supply, tongue is a suitable and convenient source of large flap. The anterior based dorsal tongue flap is a safe and effective method for closure of relatively large recurrent palatal fistula with out any functional impairment of donor site. This article describes one such case treated by single layer closure using anteriorly based tongue flap with excellent outcome.

Peroxisome proliferator-activated receptor-gamma co-activator-1alpha (PGC-1alpha) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians.

AIMS: The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G, of the peroxisome proliferator activated receptor-gamma co-activator-1 alpha (PGC-1alpha) gene with Type 2 diabetes in Asian Indians. METHODS: The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Haplotype frequencies were estimated using an expectation-maximization (EM) algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. RESULTS: The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of the Type 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P = 0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002). Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals: 1.264-2.241, P = 0.0004). Age adjusted glycated haemoglobin (P = 0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL) cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001) were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. CONCLUSIONS: The A allele of Thr394Thr (G --> A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population.