Differential expression of caveolin-1 during pathogenesis of combined pulmonary fibrosis and emphysema: Effect of phosphodiesterase-5 inhibitor.

INTRODUCTION: Combined pulmonary fibrosis and emphysema (CPFE) is a relatively new entity within the spectrum of cigarette smoke induced lung disorders. Currently there is no consensus about its treatment. We hypothesized that caveolin-1 critically determines the parenchymal and vascular remodeling leading to the development of CPFE. We assessed the effect of therapeutic targeting of caveolin-1 in mesenchymal and endothelial cells by the phosphodiesterase-5 inhibitor, sildenafil. METHODS: Male Wistar rats (n = 168) were exposed to; room air (control); bleomycin (7 U/kg), bleomycin+sildenafil (50 mg/kg/day P.O.), cigarette smoke (CS) (4 Gold Flake 69 mm/day), CS + sildenafil, CS + bleomycin, CS + bleomycin+sildenafil. Animals were euthanized at 8, 9, 11, 12 weeks and lung histopathological changes, collagen deposition, ROS, Xanthine oxidase, caveolin-1 determined. RESULTS: Cigarette smoke causes progressive ROS accumulation, caveolin-1 up-regulation in alveolar epithelial cells, alveolar macrophages, peribronchiolar fibroblasts, endothelial and vascular smooth muscle cells, interstitial inflammation and emphysema. Sildenafil reduces oxidative stress, parenchymal caveolin-1 and attenuates emphysema caused by CS. Bleomycin increases lung ROS and downregulates caveolin-1 leading to fibroblast proliferation and fibrosis. Combined cigarette smoke and bleomycin exposure, results in differential caveolin-1 expression and heterogeneous parenchymal remodeling with alternating areas of emphysema and fibrosis. Increased caveolin-1 induces premature senescence of lung fibroblasts and emphysema. Decreased caveolin-1 is associated with propagation of EMT and fibrosis. Sildenafil attenuates the parenchymal remodeling however it is not effective in reducing VSMC hypertrophy in combined group. CONCLUSION: CPFE is characterized by heterogenous parenchymal remodeling and differential caveolin-1 expression. Sildenafil therapy attenuates parenchymal pathologies in CPFE. Additional therapy is however needed for attenuating VSMC remodeling.

Scoliosis in paediatric onset spinal cord injuries.

STUDY DESIGN: This is a retrospective longitudinal review. OBJECTIVE: The purpose of this review was to identify predictors of developing clinical scoliosis and compare between traumatic and neurological aetiologies of SCI. SETTING: This study was conducted at the Midland Centre of SCI. METHOD: Case notes of all patients injured at an age up to 18 years and admitted between 1971 and 2013 were reviewed. RESULTS: Sixty-nine individuals were identified, of which seven were excluded: three with pre-existing scoliosis and four with spina bifida. The remaining 62 (44 males, 18 females) had a median age at injury of 17 years (inter quartile range 13-17). Of these, 51 (82%) had traumatic and 11 (18%) had neurological injury. Most (42/51; 82%) of the children who had a traumatic injury were older than 13 years. The risk of developing scoliosis was lower for older patients (RR 0.68 per year, 95% CI 0.52-0.83) or following a traumatic injury (RR 0.36, 95% CI 0.20-0.66). A multivariable analysis based on age and trauma showed that only older age decreased the risk. A robust Receiver Operator Curve analysis suggested 14.6 years as the optimal threshold to predict development of scoliosis within 10 years (Area Under the Curve; AUC 0.83 (95% CI 0.73-0.93), sensitivity 70% (95% CI 50-89%), specificity 89% (95% CI 74-100%). CONCLUSION: Our results suggest that age below 14.6 years was a predictor for scoliosis. Once adjustment is made for age, the incidence of scoliosis does not differ between traumatic and neurological aetiologies of paediatric SCI injury.

Outcome Analysis of Neonates following Laparotomy for Acute Abdomen: A Prospective Study.

Background Low and middle-income countries (LMIC) bear the majority of the global pediatric surgical burden. Despite increasing volume of pediatric surgeries being performed in LMIC, outcomes of these surgeries in low and middle-income countries remain unknown due to lack of robust data. Objective The objective of our study was to collect data on and evaluate neonatal surgical outcomes at a tertiary level center in India. Method The surgical outcomes data of all neonates undergoing laparotomy between February 15, 2015 and October 14, 2015, at Sir Ganga Ram Hospital, New Delhi, India was collected prospectively. Descriptive statistics were used to determine the rates of various postoperative outcomes. Result A total of 37 neonatal surgeries were performed during the study period. The mean age of the neonates on the day of surgery was 7 days (range: 1-30 days). Most of the neonates (72.9%, n=27) were males. About 40% (n=15) of the neonates were preterm and 15 (40.5%) of them were small for gestational age. In our study, 10 neonates (28.6%) needed ventilation for 48 hours or less after surgery and 5 neonates (13.5%) were kept Nil per Oral (NPO) postoperatively for more than 10 days. Out of 37 neonates, 4 (10.80%) developed a surgical site infection and 8 neonates (21.6%) had postoperative sepsis. The in-hospital mortality rate among neonates undergoing laparotomy during the study period was 8.1 deaths per 100 neonates. Conclusion Co-ordination of care among pediatric surgeons, neonatologists, nursing and anesthesia team is required for optimal surgical outcome.

Deletion of P2 promoter of GJB1 gene a cause of Charcot-Marie-Tooth disease.

X-linked Charcot-Marie-Tooth disease (CMT) is the second most common cause of CMT, and is usually caused by mutations in the gap junction protein beta 1 (GJB1) gene. This gene has nerve specific P2 promoter that work synergistically with SOX10 and EGR2 genes to initiate transcription. Mutation in this region is known to cause Schwann cell dysfunction. A single large family of X linked peripheral neuropathy was identified in our practice. Next generation sequencing for targeted panel assay identified an upstream exon-splicing deletion identified extending from nucleotide c.-5413 to approximately - c.-49. This matches the sequence of 32 nucleotides at positions c.*218-*249 in the 3'UTR downstream of the GJB1 gene. The deleted fragment included the entire P2 promoter region. The deletion segregated with the disease. To our knowledge a deletion of the P2 promoter alone as a cause of CMT has not been reported previously.

Combined pulmonary fibrosis and emphysema in a welder.

Combined pulmonary fibrosis and emphysema (CPFE) syndrome is an uncommon entity characterised by emphysema of the upper lobes and diffuse fibrosis of the lower lobes and carries a bad prognosis with the onset of pulmonary hypertension. Lung involvement due to exposures suffered by welders is generally considered benign though, rarely, a diffuse interstitial fibrotic disease has been reported. CPFE syndrome has however never been reported in welders. A 65-year-old man, welder by occupation and an ex-smoker, presented with progressive exertional dyspnoea associated with dry cough noticed for the last four months. On examination, there was mild tachypnea, clubbing and bilateral basal velcro crepitations on chest auscultation. Lung function test revealed mild mixed ventilatory impairment with severe diffusion defect. HRCT chest showed bilateral upper lobe emphysema and diffuse interstitial fibrosis in the lower lobes. Transbronchial lung biopsy revealed interstitial fibrosis, chronic inflammation and iron deposits. A diagnosis of combined pulmonary fibrosis with emphysema (CPFE) with interstitial pulmonary siderofibrosis (IPS) was established. A review of literature did not show any other report of a similar nature.

Acute fibrinous and organising pneumonia presenting as complete lung consolidation.

Acute fibrinous and organising pneumonia (AFOP) is an unusual histopathological pattern of acute lung injury. The clinical manifestations, course and treatment of AFOP have yet to be characterised. All reported cases so far have described bilateral diffuse lung involvement radiologically. We report a case of an adolescent girl who presented with acute hypoxaemic respiratory failure with unilateral complete lung consolidation. She was initially diagnosed with severe community-acquired pneumonia. A computed tomography-guided percutaneous transthoracic trucut biopsy of the left lung revealed the classical histopathological pattern typically observed in AFOP. The patient responded well to treatment involving steroids. The uniqueness of such a presentation in AFOP prompted us to report this case.

Pattern of occurrence of leukemia at a teaching hospital in eastern region of Nepal - a six year study.

INTRODUCTION: Pattern of leukemia is known to vary widely throughout the world. The characterization of distribution patterns of different subtypes of leukemia in Nepal needs further study. We wanted to study the leukemia pattern in our institute. METHODS: A retrospective study of 196 cases of leukemia, diagnosed at BPKIHS, between January 1997 to December 2002 was done. We analyzed the pattern of leukemia at BPKIHS by morphological subtype, gender, age at diagnosis, time period of diagnosis (seasonality), and geographic distribution. RESULTS: Morphological sub typing showed that 121 cases were of acute leukemia and 75 of chronic leukemia. Chronic myeloid leukemia constituted the single largest group comprising 35.2 % of all cases, followed by acute myeloid leukemia (28.57 %) and acute lymphoid leukemia (19.9 %). Maximum numbers of cases were from the lowlands while least number of cases were from the mountain districts. Results were compared with literature from Nepal and other countries. This is the second series of leukemia from Nepal. CONCLUSIONS: The data published in this study reflects the leukemia pattern in the eastern region of Nepal. The pattern and distribution of AML, CML, ALL was similar to that in the developed western countries while the lesser frequency of CLL was similar to that in Southeast Asian region.

Brucellosis--cause of abortion in sheep and its public health significance.

Present study was undertaken to determine the association of brucellosis with abortions occurring naturally in sheep at an organized local sheep breeding farm. A total of 15 strains of Brucella melitensis biovar I were isolated from the abortion material. Serologically the aborted ewes were positive for brucellosis by one or more tests. During acute infection (abortion), standard tube agglutination test (SAT) detected more positive reactors (70.7%) while counter immunoelectrophoresis (CIE) detected more positive reactors (33.9%) in chronic infection (in-contact and apparently healthy sheep). Personnel handling the abortion material at the farm were found positive clinically as well as serologically for brucellosis. These observations suggest the zoonotic importance of brucellosis.

Brucellosis in poultry--an experimental study.

Experimental brucellosis with Brucella abortus has been studied in chickens, though antibody response and histopathological changes in the tissues of the birds were conspicuous and noticed consistently, it was not possible to isolate Brucella organisms from lung, liver, spleen and faecal samples of the infected chickens. These observations suggested that birds are resistant to Brucella infection and organisms succumb to death in vivo.

Faecal fistulae in children.

Faecal fistula has been a challenging problem for every surgeon. It develops spontaneously, postoperatively or post-traumatically. Spontaneous faecal fistula develops following peritonitis. Tuberculous peritonitis is an important cause in developing countries. Postoperative faecal fistula develops after enteric perforation or appendicular diseases. Abdominal trauma-blunt, penetrating or perforating, isolated or part of multiple injuries--can lead to faecal fistula. Faecal fistula is more common after emergency surgery, especially in malnourished children. Faecal fistula leads to unnatural losses of fluid and electrolytes and malnutrition. Infection is generally a causative factor or the malnourished child with faecal fistula develops infection very fast. Assessment of the general condition of the child and the level of the fistula is very important in treating the child. Correction of fluid and electrolyte balance, control of infection and supplementation of nutrition is the basis of treatment. Improved parasurgical care and parenteral hyperalimentation has improved the survival rate and the spontaneous healing, reducing the need for surgical intervention.