Complications of laser-in-situ-keratomileusis

Laser-in-situ-keratomileusis (LASIK) has become a popular technique of refractive surgery because of lower postoperative discomfort, early visual rehabilitation and decreased postoperative haze. Compared to photorefractive keratectomy (PRK), LASIK involves an additional procedure of creating a corneal flap. This may result in complications related to the flap, interface and underlying stromal bed. The common flap-related complications include thin flap, button holing, free caps, flap dislocation and flap striae. The interface complications of diffuse lamellar keratitis, epithelial ingrowth and microbial keratitis are potentially sight threatening. Compared to PRK, there is less inflammation and faster healing after LASIK, but there is a longer period of sensory denervation leading to the complication of dry eyes. The refractive complications include undercorrection, regression, irregular astigmatism, decentration and visual aberrations. Honest and unbiased reporting is important to understand the aetiology and redefine the management.     

Leptin signaling in the hypothalamus: emphasis on energy homeostasis and leptin resistance

Leptin, the long-sought satiety factor of adipocytes origin, has emerged as one of the major signals that relay the status of fat stores to the hypothalamus and plays a significant role in energy homeostasis. Understanding the mechanisms of leptin signaling in the hypothalamus during normal and pathological conditions, such as obesity, has been the subject of intensive research during the last decade. It is now established that leptin action in the hypothalamus in regulation of food intake and body weight is mediated by a neural circuitry comprising of orexigenic and anorectic signals, including NPY, MCH, galanin, orexin, GALP, alpha-MSH, NT, and CRH. In addition to the conventional JAK2-STAT3 pathway, it has become evident that PI3K-PDE3B-cAMP pathway plays a critical role in leptin signaling in the hypothalamus. It is now established that central leptin resistance contributes to the development of diet-induced obesity and ageing associated obesity. Central leptin resistance also occurs due to hyperleptinimia produced by exogenous leptin infusion. A defective nutritional regulation of leptin receptor gene expression and reduced STAT3 signaling may be involved in the development of leptin resistance in DIO. However, leptin resistance in the hypothalamic neurons may occur despite an intact JAK2-STAT3 pathway of leptin signaling. Thus, in addition to defective JAK2-STAT3 pathway, defects in other leptin signaling pathways may be involved in leptin resistance. We hypothesize that defective regulation of PI3K-PDE3B-cAMP pathway may be one of the mechanisms behind the development of central leptin resistance seen in obesity.     

Silica induced early fibrogenic reaction in lung of mice ameliorated by Nyctanthes arbortristis extract

Objective To investigate the pharmacological effect of Nyctanthes arbortristis (NAT) leaf extract in the prevention of lung injury induced by silica particles. Method Lung injury was induced in Swiss mice through inhalation exposure to silica particles (<5μ) using a Flow Past Nose Only Inhalation Chamber at the rate of -10 mg/m3 respirable mass for 5 h. Lung bronchoalveolar lavage (BAL) fluid collected between 48 and 72 h was subjected to protein profiling by electrophoresis and cytokine evaluation by solid phase sandwich ELISA. Lung histopathology was performed to evaluate lung injury. Results Inhalation of silica increased the level of tumor necrosis factor-α(TNF-α), and of the 66 and 63 kDa peptides in the BAL fluid in comparison to sham-treated control. Pre-treatment of silica exposed mice with NAT leaf extract significantly prevented the accumulation of TNF-α in the BAL fluid, but the 66 and 63 kDa peptides remained unchanged. The extract was also effective in the prevention of silica-induced early fibrogenic reactions like congestion, edema and infiltration of nucleated cells in the interstitial alveolar spaces, and thickening of alveolar septa in mouse lung. Conclusion NAT leaf extract helps in bypassing silica induced initial lung injury in mice.     

Invasive aspergillosis in cancer

Ten confirmed cases of invasive aspergillosis (IA) in cancer patients were analysed retrospectively. Eight were pulmonary, one was sinonasal and one was cutaneous. The majority of patients had haematological malignancies (7), the remaining three were cases of solid tumours. Fever was present in all 10 cases. Cough and lung signs were present in all eight cases of invasive pulmonary aspergillosis. Haemoptysis was encountered in three of nine cases of pulmonary and sinonasal aspergillosis. Mortality was low (2%). While corticosteroids, antibiotics and anticancer chemotherapy/radiotherapy were factors predisposing the patients to IA, neutropenia was perhaps responsible for their mortality. Seven of the patients had other associated pathogens isolated in culture in addition to Aspergillus spp. Aspergillus fumigatus was the predominant species, followed by A. flavus, A. glaucus, A. nidulans and A. niger. Direct microscopic examination (in six of seven cases) and culture (six of seven cases) correlated well with radiographic and clinical findings in cases with lung involvement. Serology for anti-Aspergillus antibodies performed by gel diffusion precipitin test was positive in one case of sinonasal aspergillosis, wherein only one precipitin band was observed. Correlation of clinical symptoms, consistent radiographic findings and microbiological work-up (the latter including a triad of direct microscopy, culture and serology) are required to arrive at a diagnosis of IA, especially where histology cannot form the mainstay of diagnosis.     

Translation of microarray data into clinically relevant cancer diagnostic tests using gene expression ratios in lung cancer and mesothelioma

The pathological distinction between malignant pleural mesothelioma (MPM)and adenocarcinoma (ADCA) of the lung can be cumbersome using established methods. We propose that a simple technique, based on the expression levels of a small number of genes, can be useful in the early and accurate diagnosis of MPM and lung cancer. This method is designed to accurately distinguish between genetically disparate tissues using gene expression ratios and rationally chosen thresholds. Here we have tested the fidelity of ratio-based diagnosis in differentiating between MPM and lung cancer in 181 tissue samples (31 MPM and 150 ADCA). A training set of 32 samples (16 MPM and 16 ADCA) was used to identify pairs of genes with highly significant, inversely correlated expression levels to form a total of 15 diagnostic ratios using expression profiling data. Any single ratio of the 15 examined was at least 90% accurate in predicting diagnosis for the remaining 149 samples (e.g., test set). We then examined (in the test set) the accuracy of multiple ratios combined to form a simple diagnostic tool. Using two and three expression ratios, we found that the differential diagnoses of MPM and lung ADCA were 95% and 99% accurate, respectively. We propose that using gene expression ratios is an accurate and inexpensive technique with direct clinical applicability for distinguishing between MPM and lung cancer. Furthermore, we provide evidence suggesting that this technique can be equally accurate in other clinical scenarios.     

Estimation of the effect of food on the disposition of oral 5-fluorouracil in combination with eniluracil

AIMS: To determine the effect of food on the pharmacokinetics of 5-fluoruracil (5-FU) taken orally with eniluracil and to compare the performance of different pharmacokinetic analysis methods in the detection a potential food-drug interaction. METHODS: In a randomized, open-label, two-way crossover study, 12 patients received eniluracil (50 mg, orally) on days 1 and 2 and 5-FU (20 mg/m(2), orally) on day 2 following either a 2-h fast or 20 min after a standard meal. Treatments were separated by 7 days. Timed blood samples were collected during the first two treatment periods and 5-FU concentrations determined by GC/MS. Data were analyzed and pharmacokinetic parameter estimates were obtained using a noncompartmental, two-stage and population analysis methods. RESULTS: In fasted individuals, the clearance/bioavailability of 5-FU was estimated to be 5.6 l/h. The mean absorption lag-time was 0.24 h and was followed by rapid absorption of 5-FU. Administration of 5-FU and eniluracil with food resulted in a decrease in the 5-FU absorption rate constant by 90%. As a result, the peak plasma concentration (C(max)) of 5-FU was decreased by 21% and the time to C(max) was increased 2.9-fold. Clearance of 5-FU, relative bioavailability, and area under the plasma concentration vs time curve (AUC) remained unchanged with coadministration of food. Similar results were obtained using all three data analysis methods. CONCLUSIONS: Administration of food with oral 5-FU and eniluracil slowed absorption of 5-FU and decreased 5-FU C(max), but did not effect AUC. Further investigation of the incorporation of population pharmacokinetic approaches in food effect studies is warranted.     

DNA microarrays in clinical oncology.

Aberrant gene expression is critical for tumor initiation and progression. However, we lack a comprehensive understanding of all genes that are aberrantly expressed in human cancer. Recently, DNA microarrays have been used to obtain global views of human cancer gene expression and to identify genetic markers that might be important for diagnosis and therapy. We review clinical applications of these novel tools, discuss some important recent studies, identify promising avenues of research in this emerging field of study, and discuss the likely impact that expression profiling will have on clinical oncology.     

Outbreak of neonatal septicemia with multidrug resistantKlebsiella Pneumoniae

A nosocomial outbreak of neonatal septicemia due toK. pneumoniae occurred in nursery during June–July, 1991.Klebsiella pneumoniae (Klebocin type 314) was recovered from blood of 33(70.2%) of 47 neonates with septicemia. Multiple drug resistance was observed in all the cases. The same strain ofK. pneumoniae was recovered from the neonates and environment of nursery and labour room as well. The outbreak was attributable to environmental dissemination.