High-resolution Computed Tomography Findings and Serum Biomarker of Subclinical Interstitial Lung Disease in Moderate-to-severe Obstructive Sleep Apnea Patients

Background: Obstructive sleep apnea (OSA) has association with many comorbidities. Based on the postulated hypothesis from few studies, the primary objective of this study was to assess the occurrence of subclinical interstitial lung disease in moderate-to-severe OSA patients. Materials and methods: It was a prospective observational study, conducted at a tertiary care chest institute of India, 43 moderate-to-severe OSA patients diagnosed by level-I polysomnography were enrolled. All the patients underwent detailed clinical examination with high-resolution computed tomography (HRCT) chest, pulmonary function test (PFT), and serum markers MMP-1,7, SP-A, and Krebs von den Lungen-6 (KL-6). Subclinical interstitial lung disease (ILD) was identified based on the two validated measures: high-attenuation areas (HAA), defined as the percentage of imaged lung volume having computed tomography (CT) attenuation between ?600 and ?250 HU and interstitial lung abnormalities (ILA), defined as the presence of ground-glass, reticular abnormality, diffuse centrilobular nodularity, honeycombing, traction bronchiectasis, nonemphysematous cysts, or architectural distortion in at least 5% of nondependent portions of the lung in HRCT chest without respiratory symptoms with preserved lung function. Results: The mean age was 54.33 � 11.5 years with 22 (51%) males. The mean apnea?hypopnea index (AHI) was 42.38 � 27.6 with BMI >30 kg/m2 in 18 (42%) patients. The subclinical ILD was diagnosed in 12 patients. The HRCT finding of ILA was seen in 12 and high-attenuation areas (HAA) in 5 patients. The serum markers were higher in subclinical ILD compared with non-ILD OSA patients, however, only the level of MMP-7 was significantly higher in subclinical ILD patients. Conclusion: It was concluded that subclinical ILD is quite common among OSA patients with HRCT findings seen in nearly 30% of cases. This supports the hypothesis that OSA may be considered as a risk factor of subclinical ILD.

Role of a pattern-based approach in interpretation of transbronchoscopic lung biopsy and its clinical implications.

Background. Transbronchial lung biopsy (TBLB) is commonly performed for confirming the tissue diagnosis of diffuse parenchymal lung diseases (DPLDs). There is an urgent need to establish guidelines for interpretation of TBLB in order to improve its diagnostic utility. Methods. We retrospectively studied 916 consecutive patients (494 males; mean age 49 years) who underwent TBLB over a 5-year period (July 2005 to July 2010) at Vallabhbhai Patel Chest Institute. Results. In 615 (67.1%) procedures, material obtained during TBLB was adequate for histopathology interpretation. Pathological features evaluated in each case were: alveolar architecture, inflammatory infiltrate, interstitial fibrosis, atypical cells, pigment deposition, honey-comb change and fibroblast foci. The cases were categorised on the basis of histopathology into six patterns: (1) adequate biopsy without a specific diagnostic abnormality (n=137, 22.3%); (2) acute pneumonitis (n=29, 4.7%); (3) neoplasia (n=109, 17.7%); (4) chronic interstitial inflammation with or without fibrosis (n=138, 22.4%); (5) granulomatous inflammation, (n=186, 30.2%); and (6) other specific causes (n=16, 2.6%). Definitive diagnosis could be made after correlation of TBLB histopathology with clinical and radiological features in 55.3% cases. Conclusions. TBLB appears to be an important diagnostic tool for the diagnosis of DPLDs. The use of a pattern-based approach to TBLB adds to its diagnostic yield and can be helpful in cases where open lung biopsy is not available.

An in vitro evaluation of antibiotic combinations for urinary tract infections in patients with diabetes mellitus.

This prospective in-vitro study evaluates the synergistic potential of various antibiotic combinations against resistant pathogens isolated from urinary tract infections (UTIs) in patients with diabetes mellitus. Antibiotic combinations using the microtiter checkerboard method showed that overall, synergy could be seen in 41.86%-67.44% cases amongst the five different antibiotic combinations studied against the four predominant resistant pathogens namely Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella ozaenae. The checkerboard synergy studies showed that 69.23% of the S. aureus strains tested were synergistically inhibited by the combination of ofloxacin + cefotaxime [OF+CF], 83.33% of the E. coli strains and 75% of the K. ozaenae strains were synergistically inhibited by the combination of amikacin + cefotaxime [AK+CF], while 58.33% of the P. aeruginosa strains were synergistically inhibited by the combination of amikacin + piperacillin [AK+PP].

Low prevalence of Cryptosporidium parvum in hospitalized children in Kota Bharu, Malaysia.

The aim of this prospective study was to determine the prevalence of Cryptosporidium parvum in hospitalized children in Kota Bharu, Malaysia. Over a 19 month study period, 258 stool samples were examined from 159 children; 109 with diarrhea and 50 controls without diarrhea. Modified Ziehl-Neelsen staining method and a polymerase chain reaction (PCR) assay were used to detect C. parvum and the samples were also examined for the presence of other intestinal parasites. Only 1 of the 109 (0.9%) children with acute diarrhea was positive for C. parvum by microscopy and PCR. Thirty-one percent of children were infested with other intestinal parasites, the most common being Ascaris lumbricoides and Trichuris trichiura. In conclusion, we found C. parvum to be an uncommon infective agent in hospitalized children with or without diarrhea in Kota Bharu, Malaysia.

Modulation of alpha1beta1 integrin mediated adhesion of hepatocytes to collagen IV and laminin by divalent cations.

Cell matrix interactions play a critical role in hepatic development and regeneration after acute injury. These interactions are mediated by transmembrane receptors belonging mainly to the integrin family. We have tried to assess the role of divalent cations in mediating attachment of hepatocytes to matrix proteins like collagen IV (Col IV) and laminin (Ln). The three cations examined viz. Ca2+, Mg2+ and Mn2+ showed attachment promoting activity. Since alpha1beta1 integrin is a common receptor for col IV and LN in liver, the effect of cations in its binding to these matrix proteins was studied. Although cations in general enhanced the binding, different cations exhibited differential effect in promoting the binding for different ligands. Mg2+ ions were more effective in promoting the binding of alpha1beta1 integrin to col IV but Ca2+ proved to be more effective one for Ln. Kinetic analysis of binding in dot blot assays using different concentrations of cations showed that while Mg2+ was active at low concentrations Ca2+ and Mn2+ promoted the binding more at higher concentrations. Absence of competitive effect in binding studies showed that they bind at different sites on the receptor. Differential effects of cations in promoting the binding of alpha1beta1 integrin to Col IV and Ln suggest that changes in level of diffusible cations can modulate affinity of the common receptor alpha1beta1 integrin to its ligands and can influence adhesion of hepatic cells to different matrix proteins during hepatic development and regeneration.

Effects of exogenous vitamin C on ethanol toxicity in rats.

The effect of a mega dose of ascorbic acid (200 mg/100 g body wt.) on alcohol-induced toxicity in rats was evaluated. In rats administered alcohol and ascorbic acid, malondialdehyde (MDA), hydroperoxide and conjugated dienes decreased in comparison with that given alcohol alone. The reduced activities of scavenging enzymes, e.g. superoxide dismutase (SOD) and catalase, in ethanol-administered rats were also enhanced by the co-administration of ascorbic acid and ethanol. Co-administration of ethanol and ascorbic acid reduced phospholipids and MDA levels of the erythrocyte membrane in comparison with that of the ethanol fed rats. The reduction in the activities of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), gamaglutamyl transpeptidase (GGT) and the decrease in triglycerides levels also clearly showed the protective action of ascorbic acid in reducing ethanol induced toxicity.

Actin binds to the cytoplasmic tail of alpha 1 subunit of integrin in hepatocytes.

alpha 1 beta 1-Integrin is a common receptor for laminin and collagen IV on hepatocytes. The interactions of intracellular domain of integrins with cytoplasmic elements are critical in the initiation and transduction of signals. In order to understand the nature of cytoplasmic components that can interact with cytoplasmic domain of alpha 1 integrin, cytoplasmic extracts of monolayers of rat hepatocytes were subjected to chromatography over an affinity column prepared by coupling a 60-mer synthetic cytoplasmic tail of alpha 1 subunit. SDS-PAGE analysis of the eluate showed the presence of a 47 kDa protein. Dot-Blot assay using radio-iodinated 47 kDa protein showed the binding of the protein to 60-mer C tail in a concentration dependent manner. Immunoblot analysis using specific antibodies showed that the 47 kDa protein is actin.