Mutations in FGFR3 gene associated with maxillary retrognathism

Context: Understanding the role of fibroblast growth factor receptor (FGFR) in the regulation of bone development and disease will ultimately lead to better prevention and treatment of related bone deformities and disorders. Aims: To evaluate the role of gene FGFR3 in individuals with retrognathic maxilla by polymerase chain reaction (PCR) technique at molecular level and evaluate the significance of the same. Settings and Design: Hospital based fundamental research involving individuals having maxillary retrognathism. Methodology: A total of 62 individuals (30M and32F) who were willing to take part in the study were selected from cephalometric measurements of N I A and the length PNS to ANS. The institution based basic genetic research study involved collection of fresh blood samples, DNA extraction, PCR analysis, and amplification using the specifically designed forward and reverse primers for targeting the commonly occurring mutations in FGFR3 gene. Further the products were sequenced to evaluate the presence of any novel mutations. Results: The targeted single-nucleotide polymorphisms, at position 1138 in exon 10 of the FGFR3 gene were not identified in the analyzed blood samples. The detailed sequencing of full gene revealed the presence of 2 novel mutations, Exon 3: A213G and Exon 3: A223A/G in one individual. Conclusions: The present study indicated 2 novel mutations in gene FGFR3 in individual with maxillary retrognathism. The genetic–environmental interactions might have played a significant role in the expression of retrognathic maxilla.

Molecular and Functional Basis of Cystic Fibrosis in Indian Patients: Genetic, Diagnostic and Therapeutic Implications

Cystic fibrosis (CF, MIM#219700) is a common autosomal recessive disorder among Caucasians, which was considered as rare disease for Indian population. CF is caused due to presence of mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In this study, we established a spectrum of mutations from both classical CF as well as from infertile male patients with congenital absence of vas deferens (CAVD). In Indian classical CF patients, we reported 14 previously known and eight novel mutations, viz. 3986-3987 delC, 876-6 del4, 1792 InsA, L69H, S158N, Q493L, 1530L and E1329Q. The frequency of delta 508 was found to be 27%. Absolute linkage between delta 508 and KM19-GATT TUB9-M470V-T854T haplotype predicts a relatively recent appearance of delta 508 mutations in Indian population. The CFTR gene analysis in CAVD infertile males documented 13 different CFTRgene mutations and 1 intronic variant that led to aberrant splicing. P.Phe 508 del (n= 16) and p.Arg 117 His (n=4) were among the common severe forms of CFTR mutations identified. The IVS-8-T5 allele (mild form of mutations) was formed with an allele frequency of 28.3%. Eight novel mutations were also found in the CFTR gene from our patient cohort. We also investigated whether genetic modifiers, viz. transforming growth factor (TGF-β) and endothelial receptor type A(EDNRA) of CF lung disease also predispose to CAVD in association with CFTR mutations, which were associated with the CAVD phenotype. Functional characterization of identified 11 novel CFTR gene mutations disclosed that a significant reduction in channel activity for L69H and S549N mutants in CFTR expressing cells was observed whereas impaired CFTR protein maturation was noticed only in L69H substitute CFTR. CFTR correctors (VX809) rescued the defect due to L69H mutation, which is evidenced from detection of C band in L69H mutant expressing cells pre-treated with VX809. The chloride channel activity in S549N and L69Hmutant CFTR was also restored in presence of CFTRpotentiators VX770. Above findings confirms heterogeneity of CFTR mutations in Indian classical and non-classical CF patients. They may help in developing a strategy to develop counseling and therapeutic approach for CF patients in India.

The advantage of PCR for MTB in comparison to ADA in diagnosing tubercular pleural effusion

Background: Tuberculosis continues to be an important health problem globally. The bacteriological confirmation of diagnosis in extrapulmonary tuberculosis patients is more difficult because most of the cases of extrapulmonary tuberculosis are paucibacillary in nature. In this study we have compared the pleural fluid ADA levels with PCR for MTB in pleural fluid to confirm the diagnosis of tuberculosis in the pleural fluid.Methods: The study was done over two years and a total of 106 patients with a clinico-radiological diagnosis of pleural effusion were enrolled for the study. The pleural fluid was aspirated and examined for total cell count, differential cell count, protein, sugar, ADA and PCR for MTB.A CT Thorax was done in all the 106 patients of pleural effusion and underlying consolidation along with pleural effusion was found in 60 patients.Results: The pleural fluid was exudative in nature in all the patients. 90 patients (84.9%) had lymphocyte predominant pleural effusion while 16 patients (15.1%) had neutrophil predominant pleural effusion. The overall sensitivity of ADA in all the cases of pleural effusion was 85.2% while the overall sensitivity of PCR for MTB in all the cases of pleural effusion was 51.1%. However, in the 60 patients of pleural effusion with underlying lung consolidation, the overall sensitivity of ADA was 69.1% while the overall sensitivity of PCR for MTB was 92.8% for diagnosing tubercular pleural effusion.Conclusions: PCR for MTB is a useful test along with ADA for diagnosing tubercular pleural effusion. PCR for MTB is especially useful in the diagnosis of tubercular pleural effusion in patients with underlying lung consolidation.

Comparative study of glyceryl trinitrate ointment versus surgical management of chronic anal fissure

Background: Fissures are common, but are often confused with other anal conditions, such as haemorrhoids. Fissures are usually caused by trauma to the inner lining of the anus from a bowel movement or other stretching of the anal canal. Aim: This study evaluated the efficacy of 0.2% glyceryl trinitrate versus lateral internal sphincterectomy in treatment of chronic anal fissure. Materials and Methods: This was a study which included 80 patients between November 2014 to September 2017. In this study, based on computer generated randomization, the patients were divided into two groups. Group A consisted of 40 patients with chronic anal fissure who were treated with 0.2% glyceryl trinitrate ointment, which was applied twice daily for 5 weeks. Group B included 40 patients who were treated by lateral internal sphincterotomy. Results: The mean duration of symptoms was 15.35±10.87 weeks in group A, it was 15.02±11.7 weeks in group B. Mean pain score during defecation was 7.89±1.58 in group A, it was 7.52±2.41 in group B. Bleeding during defecation was observed in 82% of patients in group A, 75% of patients in group B. Constipation was present in 27 patients i.e. 67% in group A and it was present in 31 patients i.e. 77% in group B. In Group A, 36 (90%) patients had posterior midline fissure, 4 (10%) had anterior midline fissure, In group B, 40 (100%) had posterior midline fissure. In group A, 24 (60%) had anal tag, in group B, 22 (56%) had anal tag. The VAS score in both the groups decreased gradually but the decrease was more in group B compared to group A at the end of 7th week which was statistically significant (p<0.05). Hence, the number of patients who had pain relief after surgical treatment was statistically significant as compared to patients who were treated with 0.2% glyceryl trinitrate ointment Awais Ghori, Bhooma Reddy M, Rajendra Prasad. Comparative study of glyceryl trinitrate ointment versus surgical management of chronic anal fissure. IAIM, 2017; 4(12): 188-194. Page 189 application. At the end of the 1st week, none of the patients were healed completely. But at the end of the 4th , in group A, only 14 patients were completely healed, 38 patients were completely healed in group B. At the end of the 7th week, all patients in group B were healed i.e. 100% were healed and in group A, 32 patients were healed completely. Conclusion: Chemical treatment by applying glyceryl trinitrate is also advantageous in that it doesn’t cause any complications. Surgical treatment by lateral sphincterotomy is most effective when patients fail to respond to chemical treatment.

Tuberculosis Of The Azygous Lobe Of Lung: Case Report And Review Of Literature

The Azygous lobe is usually an incidental finding in chest x ray PA view. Although pulmonary tuberculosis is common in India, involvement of the azygous lobe by this disease has never been reported in literature to the best of our knowledge. We describe the case of a patient with tuberculosis of the azygous lobe of the lung. The patient presented with a normal chest x-ray PA view. Further investigations revealed pulmonary tuberculosis of the azygous lobe and the patient improved with anti-tuberculosis therapy.

An Unusual Cause of a Pulmonary Mass: Actinomycosis.

We present the case of a 62-year-old male with chronic obstructive pulmonary disease and poorly controlled diabetes mellitus who presented with haemoptysis. A radiograph of the chest showed a right lower parahilar opacity which on the contrast enhanced computed tomography was seen to be an irregular, spiculated mass localised to the middle lobe. Considering malignancy as the most probable diagnosis, a bronchoscopic endobronchial biopsy was performed which surprisingly established pulmonary actinomycosis as the diagnosis. The patient was successfully managed with amoxicillin and clavulanic acid and glycaemic control.

Co-existence of Bronchiectasis and Chronic Obstructive Pulmonary Disease.

We present the case of a 56-year-old male who presented with cough and breathlessness. Chest radiograph (postero-anterior view) showed bulla and signs of hyperinflation in the right upper zone with cystic shadows in the left lower zone. Spirometry showed severe irreversible airflow obstruction with restriction and decreased diffusion capacity for carbon monoxide. On high resolution computed tomography (HRCT), right upper lobe bulla with emphysematous changes and left lower lobe cystic bronchiectasis were seen. Considering its rarity of occurrence and paucity of data in literature regarding co-existence of bronchiectasis with emphysema, this case is being reported.

Consensus & Evidence-based INOSA Guidelines 2014 (First edition).

Obstructive sleep apnoea (OSA) and obstructive sleep apnoea syndrome (OSAS) are subsets of sleep-disordered breathing. Awareness about OSA and its consequences amongst the general public as well as the majority of primary care physcians across India is poor. This necessiated the development of the INdian initiative on Obstructive Sleep Apnoea (INOSA) guidelines under the auspices of Department of Health Research, Ministry of Health & Family Welfare, Government of India. OSA is the occurrence of an average five or more episodes of obstructive respiratory events per hour of sleep with either sleep related symptoms or comorbidities or >15 such episodes without any sleep related symptoms or comorbidities. OSAS is defined as OSA associated with daytime symptoms, most often excessive sleepiness. Patients undergoing routine health check-up with snoring, daytime sleepiness, obesity, hypertension, motor vehicular accidents and high risk cases should undergo a comprehensive sleep evaluation. Medical examiners evaluating drivers, air pilots, railway drivers and heavy machinery workers should be educated about OSA and should comprehensively evaluate applicants for OSA. Those suspected to have OSA on comprehensive sleep evaluation should be referred for a sleep study. Supervised overnight polysomnography (PSG) is the “gold standard” for evaluation of OSA. Positive airway pressure (PAP) therapy is the mainstay of treatment of OSA. Oral appliances are indicated for use in patients with mild to moderate OSA who prefer oral appliances to PAP, or who do not respond to PAP or who fail treatment attempts with PAP or behavioural measures. Surgical treatment is recommended in patients who have failed or are intolerant to PAP therapy.

An Adult with Haemoptysis: A Rare Case of Congenital Anomaly.

A non-smoker adult male presented with haemoptysis of short duration. Chest radiograph (postero-anterior view) suggested an opaque left hemithorax. Further evaluation of lung lesion pointed towards a left lung hypoplasia with absent left pulmonary artery and a right-sided aortic arch (RAA). Both kidneys were enlarged with multiple cysts and thinning of parenchyma. This case describes a unique coexistence RAA and probable autosomal dominant polycystic kidney disease.

Multidrug Resistant Tuberculosis: Trends and Control.

Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to the control of tuberculosis (TB). The exact magnitude of problem of resistance to anti-tuberculosis drugs worldwide was not known till the 1994-97 global project on anti-tuberculosis drug resistance surveillance initiated by the World Health Organization (WHO) and International Union Against Tuberculosis and Lung Diseases (IUATLD). The Global Tuberculosis Report 2014 estimated that an 3.5% of newly diagnosed and 20.5% of previously treated TB cases had MDR-TB. It has been estimated that 480,000 cases emerged and 210,000 deaths occurred due to MDR-TB globally in 2013. In India, estimates showed that the prevalence of MDR-TB among new and previously treated patients was 2.2% and 15%, respectively. It is estimated that 99,000 cases of MDR-TB emerge every year of which 62,000 were among notified cases of TB in 2013. The MDR-TB is a human-made problem and results largely from poorly managed cases of TB. Adequate, timely diagnosis and optimal treatment of MDR-TB will help curb the epidemic. Efforts must be focused on the effective use of anti-tuberculosis drugs in every new patient, so as to prevent the emergence of MDR-TB.

Medical Thoracoscopy: A Useful Diagnostic Tool for Undiagnosed Pleural effusion.

Objective. We aimed to assess the role of medical thoracoscopy in patients with undiagnosed pleural effusion. Methods. Patiens presenting with pleural effusion underwent three pleural aspirations. Patients in whom pleural fluid analysis was inconclusive underwent closed pleural biopsy for diagnostic confirmation. Patients in whom closed pleural biopsy was incolcusive underwent medical thoracoscopy using a rigid thoracoscope with a viewing angle of zero degrees was done under local anaesthesia and sedation with the patient lying in lateral decubitus position with the affected side up. Biopsy specimens from parietal pleura were obtained under direct vision and were sent for histopathological examination. Results. Of the 128 patients with pleural effusion who were studied, pleural fluid examination established the diagnosis in 81 (malignancy 33, tuberculosis 33, pyogenic 14 and fungal 1); 47 patients underwent closed pleural biopsy and a diagnosis was made in 28 patients (malignancy 24, tuberculosis 4). The remaining 19 patients underwent medical thoracoscopy and pleural biopsy and the aetiological diagnosis could be confirmed in 13 of the 19 patients (69%) (adenocarcinoma 10, poorly differentiated carcinoma 2 and mesothelioma 1). Conclusion. Medical thoracoscopy is a useful tool for the diagnosis of pleural diseases. The procedure is safe with minimal complications.

Smoking cessation: An update.

Intervention for smoking cessation has become on urgent need because of increasing tobacco use and health hazards, especially in developing countries. Smoking cessation will be at different states of readiness. The states may be: (i) not ready (pre-contemplation), (ii) unsure (contemplation), (iii) ready (preparation), (iv) action, and (v) maintenance. Counselling and behavioural management is important. The ‘5 A’s-based intervention in the form of Ask, Advise, Assess, Assist and Arrange is implemented. Pharmacologic management is based on first-line treatment in the form of nicotine replacement therapy, bupropion and varinicline and second-line treatment as clonidine and nortriptalin. Every health professional has obligation to help their patients to quit and the intervention should be diagnostic and therapeutic. The best results are obtained by behavioural and social support combined with pharmacotherapy whenever needed. The paper highlights the important component of intervention in smoking cessation.