The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Herpes zoster ophthalmicus and the orbital apex syndrome

Herpes zoster ophthalmicus (HZO) commonly causes isolated ophthalmoplegic syndromes. Visual loss caused by optic neuritis secondary to HZO can be reversible or irreversible. HZO rarely presents as an orbital apex syndrome, when an association with meningo-encephalitis has been reported. We report a case of orbital apex syndrome secondary to HZO treated with systemic steroids and acyclovir. Our patient suffered no systemic complications and displayed a rapid resolution of optic neuropathy. We discuss this case in the light of previous reports and explore the possible pathogenic mechanisms involved.     

Suppurative corneal ulceration in Bangladesh

Suppurative keratitis is an important preventable cause of blindness, particularly in the developing world. This study analyses 142 cases of suppurative keratitis referred to Chittagong Eye Infirmary, Bangladesh. Some 53.5% of cases were bacterial and 35.9% were fungal. The five most common pathogens were: Pseudomonas sp. 24%, Streptococcus pneumoniae 17%, Aspergillus sp. 13%, Fusarium sp. 7% and Curvularia sp. 6%. Gram stain and culture results were consistent in 62.6% of cases. Previous antibiotic treatment was a significant factor for failure of culture isolation and less so for Gram stain failure. On Gram stain, 55.9% of pseudomonal cases were missed, but only 2% of fungal cases were missed. Over all, Gram stain had a sensitivity of 62% and positive predictive value of 84% for bacterial cases, and 98% and 94% for fungal cases, respectively. Fungal ulcers were typically filamentous, but an antecedent history of trauma was not common. The most frequent injury was due to rice grains, but the inoculum appeared to be introduced during eye washing with contaminated water. Pseudomonal ulcers occurred most frequently in the monsoon season, and Fusarium cases were seen only in the hot, dry season.     

Desmoplastic malignant melanoma presenting with orbital involvement

Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM of the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasise readily.     

Uveal effusion syndrome

The history and clinical findings are presented of a patient who suffered from the uveal effusion syndrome over a 10-year period from 1956. The funduscopic appearance is illustrated both at the time of initial presentation and 36 years later. This condition typically affects healthy middle-aged men and causes recurrent, spontaneous, serous retinal and ciliochoroidal detachments, often resulting in significant visual impairment. Two separate hypotheses have been postulated to explain the pathogenesis of the uveal effusion syndrome, one relating to abnormally thickened sclera, the other to chronic bulbar hypotony. Both are discussed, as is the rationale behind the current management of this unusual condition.