Photographic documentation of spontaneous extrusion of a subconjunctival cysticercus cyst

Spontaneous extrusion of a subconjunctival cysticercus cyst is a rare occurrence. The case reported is of a 20-year-old man who presented with a subconjunctival cysticercus cyst that was suspected to be undergoing spontaneous extrusion. The eye was photographed as the parasite extruded through the conjunctival opening with undulating movements over 3-4 min.     

Altered immune response to liposomal allergens of Aspergillus fumigatus in mice

Aspergillus fumigatus has been implicated as the major pathogenic fungus causing Aspergillus-mediated disorders. It secretes complex glycoprotein antigens and allergens, which induce type I and type III mediated hypersensitivity reactions. The immune response to these allergens/antigens in allergic disorders is characterized by elevated levels of specific IgE, Th2 cytokines and eosinophilia. In the current study, the ability of negatively charged liposomes entrapped with glycoprotein antigens and allergens of A. fumigatus to modulate the immune response was studied. Immune response in mice was evaluated with both free and liposomal formulations. Liposome entrapped glycoprotein antigens/allergens of A. fumigatus elicited a Th1 type response with increased levels of TNF-alpha (5.5-folds), IFN-gamma (four-folds), specific IgG (three-folds) and IgG2a (2.4-folds), low titers of specific IgG1 (2.2-folds decrease) and IgE (three-folds decrease), and decreased peripheral eosinophilia by four-folds in comparison to mice receiving free glycoprotein allergens/antigens of A. fumigatus. Histopathological examination of lung tissue sections clearly indicated reduced eosinophil infiltration in mice immunized with liposomal formulations. These results suggest potential of liposomal formulations for A. fumigatus allergens/antigens for exploration in immunotherapy.     

Corneal ulceration in pediatric patients: a brief overview of progress in topical treatment

Pediatric microbial keratitis is a rare but potentially devastating condition. The condition is similar to adult microbial keratitis, but is often characterized by a more severe inflammatory response. The micro-organisms that cause microbial keratitis in children are similar to the causative agents in adults, with herpes simplex and bacteria being the predominant causative agents, and fungi being less frequent. Of the bacterial pathogens, Pseudomonas aeruginosa, Staphylococcus aureus and alpha-hemolytic streptococci are common. The risk factors for pediatric keratitis include colonization of the eyes during birth and trauma to the cornea. Certain microbial factors involved in microbial keratitis are common to all micro-organisms, including adhesion to the cornea, penetration into the cornea, destruction of the corneal stroma (usually by microbial and/or host proteases), and recruitment of white blood cells to help defend the eye. Specific inflammatory responses that occur during pediatric microbial keratitis are not known in detail, but it is likely that cytokines and polymorphonuclear leucocytes are major factors, as they are in adult microbial keratitis. Treatment for pediatric microbial keratitis is usually the same as treatment for adult microbial keratitis; topical application of antimicrobial agents initially, followed by application of anti-inflammatory agents. With pediatric microbial keratitis, extra care must be taken to ensure nontoxicity due to blood adsorption. New microbial keratitis treatments are being developed and these mainly focus on new antimicrobials, antivirulence agents (such as vaccination against microbial toxins) or specific anti-inflammatory agents. There remains a clear need for increased research into the specific responses during microbial keratitis in children which will help progress new therapies as well as the development of new antimicrobials, especially new antifungal therapies.     

Mifepristone-misoprostol abortion: a trial in rural and urban Maharashtra,India

As several important policy questions remain regarding the use of medical abortion in developing countries, we investigated the safety, efficacy, and acceptability of mifepristone-misoprostol abortion in the outpatient family planning departments of two urban hospitals and one rural hospital in India. Nine-hundred women (with gestations of < or =63 days in the urban sites and < or =56 days in the rural site) received 600 mg mifepristone followed 48 h later by 400 microg oral misoprostol in the clinic. Four point four percent or fewer urban women and 1.0% rural women were lost to follow-up. Perfect and typical-use failure rates were low at all sites. While rural women reported fewer side effects at all sites, the vast majority of women were satisfied with their medical abortions. Medical abortion can be offered safely, effectively, and acceptably in the outpatient family planning departments of urban and rural hospitals in India.     

Hedgehog: an attribute to tumor regrowth after chemoradiotherapy and a target to improve radiation response.

PURPOSE: Despite aggressive chemotherapy, radiotherapy, surgery, or combination approaches, the survival rate of patients with esophageal cancer remains poor. Recent studies have suggested that constitutive activation of the Hedgehog (Hh) pathway in cancers of the digestive tract may contribute to the growth and maintenance of cancer. However, the relationship between Hh signaling and therapeutic response is unknown. EXPERIMENTAL DESIGN: The expression and temporal kinetics of Hh signaling and proliferation biomarkers after chemoradiotherapy were examined in esophageal tumor xenografts. Additionally, immunohistochemical analysis of Sonic Hh (Shh) and Gli-1 expression were done on residual tumors from patients who received neoadjuvant chemoradiotherapy followed by surgery. The ability of Shh signaling to induce proliferation in esophageal cell lines was determined. Expression of cell cycle checkpoint proteins was analyzed in cells in which Hh signaling was activated or inhibited. We further determined the effect of inhibiting Hh signaling in sensitizing esophageal tumors to radiation. RESULTS: We showed that the Shh signaling pathway was extensively activated in esophageal cancer xenografts and residual tumors after chemoradiotherapy and the temporal kinetics of Hh signaling preceded increases in proliferation biomarker expression and tumor size during tumor regrowth. We further showed that Hh pathway activity influences proliferation rates of esophageal cancer cell lines through up-regulation of the G1-cyclin-Rb axis. Additionally, we found that blocking Hh signaling enhanced radiation cytotoxicity of esophageal cancer cells. CONCLUSIONS: These results suggest that activation of the Hh pathway may promote tumor repopulation after chemoradiotherapy and contribute to chemoradiation resistance in esophageal cancers.     

Isolated Splenic Metastasis from Colorectal Mucinous Carcinoma

Metastatic tumors of the spleen are rare and occur in the presence of disseminated visceral metastasis. Isolated splenic metastases from colorectal carcinoma are rare and only 19 cases have been reported in English literature. We report a case of isolated splenic metastasis in a 52-year-old man, occurring 9 years after the primary colorectal mucinous carcinoma was treated by anterior resection. The patient underwent splenectomy along with adjuvant chemotherapy and is alive and asymptomatic at 22 months follow-up.     

Spectrum and the susceptibilities of microbial isolates in cases of congenital nasolacrimal duct obstruction.

PURPOSE: To determine the microbial profile of congenital nasolacrimal duct obstruction (CNLDO) and the appropriate antimicrobial agents based on the sensitivity pattern of the isolated microorganisms. METHODS: Two hundred thirty-eight eyes of 187 young children in the age group of 0-5 years with CNLDO were included in the study. A group of 40 children (80 eyes) who had attended the hospital for other ocular disorders was considered a control. Material obtained from the lacrimal sac was cultured, and infectious agents were isolated. Susceptibility testing was done by Kirby-Bauer disk diffusion method for 7 different antibiotics. Fisher's exact test was used to look for statistical associations between the age group, the type of discharge, and the type of microorganisms isolated. RESULTS: Of the 238 samples with a clinical diagnosis of CNLDO, 197 (83%) yielded a positive culture. There was no growth in 41 samples (17%). Altogether, there were 217 isolates. One hundred twenty-four (57%) isolates were Gram-positive bacteria, the most frequent isolate being Streptococcus pneumoniae. Gram-negative bacteria accounted for 93 (43%) of the isolates, the most frequent isolate being Haemophilus influenza. There was one fungal isolate (0.5%) of Candida tropicalis. Gram-positive bacteria were sensitive to chloramphenicol, vancomycin, and ofloxacin and Gram-negative bacteria to ofloxacin and ciprofloxacin. CONCLUSIONS: Chronic dacryocystitis caused by CNLDO is associated with an almost-equal proportion of Gram-positive and Gram-negative bacteria. Ofloxacin topical drops can be used in the treatment of cases with CNLDO.     

Pharmacokinetics, toxicity, and efficacy of ends-modified raf antisense oligodeoxyribonucleotide encapsulated in a novel cationic liposome.

Raf-1 protein serine threonine kinase plays an important role in cell survival and proliferation. Antisense inhibition of Raf-1 expression has been shown to enhance the cytotoxic effects of radiation and anticancer drugs. Here we have evaluated the toxicity, pharmacokinetics, and antitumor efficacy of a novel formulation of liposome-entrapped raf antisense oligodeoxyribonucleotide (LErafAON). The LErafAON preparation showed high liposome entrapment efficiency of rafAON (>85%) and stability at room temperature. In CD2F1 mice, administration of LErafAON produced no morbidity/mortality (5-35 mg/kg/dose, i.v., x12). Dose-related elevations in liver enzymes (alanine aminotransferase and aspartate aminotransferase) and histopathological changes in liver were noted in LErafAON and blank liposome groups. No morbidity/mortality and changes in clinical chemistry or histopathology were observed in New Zealand white rabbits (3.75 mg/kg/dose, i.v., x8; 6.5 mg/kg/dose, i.v., x6) or in cynomolgous monkeys (3.75 or 6.25 mg/kg/dose, i.v., x9). Transient decrease in total hemolytic complement activity (approximately 62-74%) and increases in C3a (approximately 3-fold) and Bb levels (approximately 5-12-fold) were observed in LErafAON and blank liposome groups of monkeys. A 30 mg/kg i.v. dose of LErafAON in human prostate tumor (PC-3)-bearing BALB/c athymic mice gave a terminal plasma half-life of 27 h, and intact rafAON could be detected in plasma and in normal and tumor tissues for up to at least 48 h. In monkeys, the terminal plasma half-life of 30.36 +/- 23.87 h was observed at an i.v. dose of 6.25 mg/kg. LErafAON (25 mg/kg/dose, i.v., x10) or ionizing radiation (3.8 Gy/day, x5) treatment of PC-3 tumor-bearing athymic mice led to tumor growth arrest, whereas a combination of LErafAON and ionizing radiation treatments resulted in tumor regression. LErafAON treatment caused inhibition of Raf-1 protein expression in normal and tumor tissues in these mice (>50%, versus controls). These data have formed a basis of the clinical Phase I studies of LErafAON for cancer treatment.