Bilateral macular hemorrhage caused by azathioprine-induced aplastic anemia in a corneal graft recipient

PURPOSE: To report the occurrence of bilateral macular hemorrhage following the use of azathioprine for immunosuppression in a corneal transplant recipient. METHODS: The patient underwent therapeutic penetrating keratoplasty for progressive fungal keratitis in his left eye. Although the infection did not recur, the graft failed with vascularization of the cornea in three quadrants. He underwent repeat penetrating keratoplasty 2 years later and was treated with azathioprine (100 mg daily) to enhance graft survival. Four months after instituting azathioprine therapy, he developed aplastic anemia and macular hemorrhage in both eyes. RESULTS: Fluorescein angiography revealed a preretinal location of the macular hemorrhage. After cessation of azathioprine therapy and treatment with blood component replacement, hematological parameters improved and the macular hemorrhage cleared with good visual recovery during the next 2 months. CONCLUSION: This report highlights the serious ocular and systemic complications that can occur following the use of systemic immunosuppressants after ophthalmic surgery.     

Simultaneous bilateral fungal keratitis caused by different fungi

Fungal keratitis is an important cause of corneal disease in the tropical world. We report a rare presentation of simultaneous bilateral corneal ulceration caused by different fungi.     

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.     

Optic nerve entrance coloboma associated with situs inversus

A rare case of optic nerve entrance coloboma associated with situs inversus is reported.     

Pneumatization of the intraorbital optic nerve after severe head trauma

Radiological evidence of pneumatization of the intraorbital optic nerve sheath following severe head trauma in an adult is reported. A young man was admitted to the emergency department following a high-speed motorcycle accident with unconsciousness, forehead laceration, and multiple fractures of the skull and extremities. On admission, the pupils were dilated and fixed. Computed tomography revealed right subdural hematoma with midline shift, brain stem hemorrhage, contusion of the left temporal lobe, multiple facial bone fractures, cerebral edema with intracerebral air, and meningeal pneumatization of the optic nerve sheaths bilaterally. This case demonstrates that after severe head trauma, air may extend in the optic nerve sheath, which could be a marker of severe optic nerve injury.     

Pleiotropic relationships between cortisol levels and adiposity: The HERITAGE Family Study

OBJECTIVE: To investigate familial basis for the relationship between cortisol adiposity at baseline and their training responses. RESEARCH METHODS AND PROCEDURES: Bivariate correlation and segregation analyses were employed between cortisol and several adiposity measures [body mass index, fat mass (FM), fat-free mass, percentage of body fat (% BF), abdominal visceral fat (AVF), abdominal subcutaneous fat (ASF), and abdominal total fat (ATF)] from 99 white families and 105 black families. RESULTS: In both races, significant inverse phenotypic correlations were generally observed between cortisol and adiposity measures at baseline but not for training responses. Significant cross-trait familial correlations were found for cortisol with abdominal fat (ASF, AVF, ATF) and overall body adiposity (FM, % BF) measures at baseline, which accounted for 14% to 20% of the phenotypic variance in whites. The cross-trait correlations were not significant for baseline phenotypes in blacks, perhaps because of the small sample size. A bivariate segregation analysis showed evidence of polygenic pleiotropy for cortisol with both abdominal fat and overall adiposity measures that accounted for 14% to 17% of the phenotypic covariance, but major gene pleiotropy was not suggested in whites. However, when ASF, AVF, and ATF were additionally adjusted for FM, no familial cross-trait correlations or polygenic pleiotropy between cortisol and the abdominal fat measures remained. DISCUSSION: Evidence was found for polygenic pleiotropy but not for pleiotropic major gene effects between cortisol and overall adiposity in whites. However, the covariation of cortisol with abdominal fat phenotypes is dependent on concomitant polygenic factors for total-body fat.     

Chemical Asphyxiants and Noise

The damaging effects of noise on auditory function can be altered significantly by exposure to additional agents that may or may not by themselves be ototoxic. This chapter focuses on the ability of chemical asphyxiants present in both occupational settings and ambient environments to potentiate noise induced hearing loss in a laboratory animal model. Since the chemical agents under study do not produce permanent impairment of hearing by themselves, the finding of auditory impairment in excess of that which is produced by noise exposure alone can be defined as noise potentiation. This chapter focuses both on the exposure conditions that favour such potentiation and also on potential mechanisms for potentiation. The data show that low to moderate exposure levels of carbon monoxide (CO) and hydrogen cyanide can potentiate noise induced hearing loss (NIHL) and the relationship between such levels and those permitted in work environments is provided. Finally, evidence is presented that free oxygen radicals may be responsible for potentiation of NIHL by the chemical asphyxiants. First, the ability of a free radical spin trap agent, PBN, to prevent the adverse effects of CO is demonstrated. Then, in an additional experiment, electron paramagnetic spin resonance is used to demonstrate a high level of free radicals in the cochlea with combined exposure to CO + noise while individual exposures to CO and noise do not produce free radicals at levels detectable by this method.     

Design,synthesis, structure-activity relationships,and molecular modeling studies of 2,3-diaryl-1,3-thiazolidin-4-ones as potent anti-HIV agents

Starting from 1H,3H-thiazolo[3,4-a]benzimidazoles (TBZs), we performed the design, synthesis, and the structure-activity relationship studies of a series of 2,3-diaryl-1,3-thiazolidin-4-ones. Some derivatives proved to be highly effective in inhibiting HIV-1 replication at nanomolar concentrations with minimal cytotoxicity, thereby acting as nonnucleoside HIV-1 RT inhibitors (NNRTIs). Computational studies were used to delineate the ligand-RT interactions and to probe the binding of the ligands to HIV-1 RT.     

Intratumoral administration of paclitaxel in an in situ gelling poloxamer 407 formulation

In order to examine the efficacy of paclitaxel (Taxol, Bristol-Myers Squibb) after administration locally at the tumor site, we have developed a thermo-reversible gelling formulation in poloxamer 407 (Pluronic F-127) solution. Paclitaxel was incorporated in poloxamer 407 [20% (w/w)] at 0.5- and 1.0-mg/mL concentrations. The in vitro release studies were carried out in phosphate-buffered saline (pH 7.4) at 37 degrees C. Control and paclitaxel-poloxamer 407 formulations were administered intratumorally at a dose of 20 mg/kg in B16F1 melanoma-bearing mice. The change in tumor volume as a function of time and the survival of treated animals were used as measures of efficacy. Poloxamer 407 solution undergoes a reversible sol-gel transition when the temperature is raised to above 21 degrees C. In vitro paclitaxel release from poloxamer 407 gels was very slow (only 6.1% after 6 hr) probably due to the poor aqueous solubility of the drug. Significant enhancement in the anti-tumor efficacy was noted following intratumoral administration of paclitaxel-poloxamer 407 formulation. The initial tumor growth rate was delayed by 67% and the tumor volume doubling time was increased by 72% relative to saline control. In addition, more than 91% of the tumor-bearing animals that received paclitaxel in poloxamer 407 gel survived on day 15 post-administration as compared to 58% in the control group. The results of this study show significant benefit of paclitaxel for solid tumor when administered locally in an in situ gelling poloxamer 407 formulation.