Studies of molecular structure parameters of 20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol and its N-methyl derivative: two inhibitors of Delta24(25) sterol methyl transferase and Delta24(24') sterol methyl reductase of Trypanosoma cruzi.

Molecular structural parameters of two potential drugs against Trypanosoma cruzi epimastigotes, 20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol (1) and 20-N-methylpiperidin-2-yl-5alpha-pregnan-3beta, 20-diol (2) were studied using a combination of a stereoselective synthetic route, spectroscopic characterization and single-crystal X-ray analysis. Both compounds were synthesized with an R configuration at C20. This chirality is a consequence of the stereoselectivity observed during the formation of the intermediate 20-pyridin-2-yl-5alpha-pregnan-3beta,20R-diol (4). NMR data indicated that the six-membered aza ring of (2) is conformationally more restrained, in CDCl3 solution, than (1). X-ray studies showed that maximum deviations among structural molecular parameters of (1) and (2) correspond to torsion angles along the C20-C22 bonds, leading to a different relative orientation of the N atom; a critical structural parameter for the binding properties of aza-sterols to Delta(24(25)) sterol methyl transferase. Cremer-Pople parameters of the five-membered rings of (1) and (2) lie in the observed range for a family of tetracyclic fused ring systems retrieved from the CSD. The phi2 parameter of (1) lies just on the mean of the family, while phi2 of (2) deviates significantly towards the lower limit.

Use of clonidine as a component of the peribulbar block in patients undergoing cataract surgery.

BACKGROUND AND OBJECTIVES: This study was designed to determine whether administration of clonidine as a component of a peribulbar block enhanced analgesia increased sedation, improved akinesia, or decreased intraocular pressure. METHODS: A randomized, double-blinded study was undertaken at a University-affiliated tertiary care hospital. Forty outpatients undergoing unilateral cataract surgery by a single surgeon (J.P.) under peribulbar blockade were evaluated. Patients received either 100 microg (1 mL) clonidine or 1 mL preservative-free normal saline mixed with the local anesthetic (7 mL 1% preservative-free lidocaine). A Honan adapter was applied for 10 minutes after block placement. The outcome measures included sedation scores, intraocular pressure (IOP) before and after peribulbar block, need for supplemental block, 24-hour analgesic requirement, and patient satisfaction. RESULTS: There were no differences between groups with respect to pain, sedation, or satisfaction scores. There was no difference with respect to onset of akinesia. This study revealed no significant difference in baseline IOP and postperibulbar IOP. CONCLUSIONS: Clonidine did not alter, in any appreciable way, the perioperative course for patients undergoing cataract operations. We do not recommend clonidine as a component of a peribulbar block in patients undergoing cataract extraction operations.

Effects of exogenous lipids on blood gas measurements.

OBJECTIVE: Numerous reports have appeared describing the effects of intravenous lipid administration on the pulmonary function of the critically ill patient. Our study was undertaken to determine whether the lipid content of an arterial blood gas specimen affects the measurement of arterial pH, PaO2, PaCO2, or arterial oxygen saturation. DESIGN: Prospective, in vitro controlled study. SETTING: Medical and cardiac intensive care units. PATIENTS: Critically ill patients undergoing clinically-directed blood gas sampling via indwelling arterial catheters. INTERVENTIONS: None. MEASUREMENTS: Arterial blood gas specimens were modified in vitro by dividing the sample and adding a known amount of lipid emulsion to half of the sample, resulting in a difference between the plasma triglyceride concentrations of the two halves. Two series of experiments were run: one series was run with a predicted plasma triglyceride difference of 400 mg/dL (4.5 mmol/L) between the two samples; the other series was run with a predicted plasma triglyceride difference of 800 mg/dL (9.0 mmol/L) between the two samples. Blood gas measurements were performed on each half of a sample, and the results were compared. Because some studies have only noted changes in patients with the adult respiratory distress syndrome (ARDS), samples from these patients were also analyzed as a separate group. RESULTS: No significant changes were found in arterial pH, PaO2, PaCO2, or arterial oxygen saturation between the two halves of the sample. With 95% confidence, differences as small as 1.5 torr (0.2 kPa) for PaO2 and PaCO2, 0.5% for arterial oxygen saturation, and 0.005 for pH, would have been detected. No differences were found in the ARDS subgroup. CONCLUSIONS: The addition of clinically relevant amounts of lipid to blood samples does not affect blood gas measurements. Any observed changes in blood gas values after lipid feeding are presumably due to products of lipid metabolism or alterations in pulmonary function.

Adenocarcinoma of the ciliary body pigment epithelium in a child.

Tumors arising from the pigment epithelium of the ciliary body are rare and most commonly occur in white adults. We describe a tumor that was clinically indistinguishable from a melanoma or medulloepithelioma occurring in a 7-year-old Japanese boy. Three months after initial evaluation, the eye was enucleated because of intractable intraocular pressure elevation and pain. On pathologic examination the tumor was found to fill approximately one third of the anterior chamber. Light microscopic and ultrastructural findings were consistent with an adenocarcinoma of the ciliary body pigment epithelium. To our knowledge, this is the youngest patient described with this tumor.

Sex-linked hereditary bilateral anophthalmos. Pathologic and radiologic correlation.

A 27-year-old man had X-linked true anophthalmos. No evidence of optic globe, nerves, or chiasm was found. Rudimentary structures suggesting optic tracts were present. Lateral geniculate nuclei were present but gliotic. Calcarine cortex was thinner but had usual lamination. The normal patches of cytochrome oxidase activity in layers II and III of visual cortex were absent.

Detection of human papillomavirus DNA sequences in conjunctival papilloma.

Two histologically proven conjunctival papillomas (one from a 33-month-old boy and the other from a 28-year-old woman) were examined for the presence of papillomavirus by DNA molecular hybridization. The first case, a recurrent tumor known to be positive for papillomavirus structural antigen, demonstrated human papillomavirus DNA sequences that cross-hybridized to a human papillomavirus type 11 DNA probe. The second case, an initial tumor, which was negative for papillomavirus structural antigen, demonstrated no viral DNA sequences by hybridization.

In vitro malignant transformation of hamster retina by herpes simplex virus.

Hamster retina was infected in vitro with irradiated herpes simplex virus type 2. Cells underwent malignant transformation, and when injected subcutaneously into nude mice and hamsters, produced transferable tumors. Transformed cells were found to have HSV antigen as determined by indirect fluorescent staining. In addition, the undifferentiated transformed retinal cells possess neurosecretory granules and retinoic acid receptors and produce growth factor, features similar to those found in spontaneous human retinoblastoma. This is the first neoplasm of ocular tissues induced experimentally by herpes simplex virus (HSV).

Intraocular hemangiopericytoma.

A 40-year-old woman had an intraocular lesion consistent with a choroidal hemangioma. Xenon arc photocoagulation was applied to reduce subretinal fluid, and the lesion remained stationary until the patient's death eight years later. The lesion was composed of spindle-shaped and ovoid cells with numerous inconspicuous capillaries. The tumor cells were surrounded by reticulin-positive fibers. The diagnosis of hemangiopericytoma was confirmed by electron microscopy, which demonstrated proliferating pericytes associated with basal lamina. Although hemangiopericytomas are occasionally found in the orbit, to our knowledge this report is the first of an intraocular hemangiopericytoma. Because the pericyte is an integral component of the choroidal vasculature, the origin of this tumor in the choroid is not unexpected. The diagnosis of hemangiopericytoma should be considered when evaluating vascular choroidal lesions.

Papillomavirus in human conjunctival papillomas.

Forty-one human conjunctival papillomas were histopathologically examined for koilocytosis and papillomavirus common antigen with a peroxidase-antiperoxidase technique immunospecific for genus-specific papillomavirus antigen. Koilocytotic cells, typically found in other papillomavirus-induced tumors, were present in 24 of the 41 specimens. Two of the 41 specimens were positive for viral antigen. The positive reactions were intranuclear within the superficial layers of the epithelium.

Induction of ocular neoplasms in Fischer rats by intraocular injection of nickel subsulfide.

Nickel subsulfide, alpha Ni3S2, was administered to albino Fischer rats by a single injection into the vitreous body of the right eye (0.5 mg alpha Ni3S2/rat, suspended in 20 microliter of NaCl vehicle). Control rats received a similar injection of the vehicle. Malignant tumors developed in the injected eyes of 14/15 alpha Ni3S2-treated rats by 8 months (vs. 0/11 controls, p less than 0.001). Five of the injected eyes of alpha Ni3S2-treated rats contained multiple tumors. The 21 eye tumors that were induced by alpha Ni3S2 included 11 melanomas, four retinoblastomas, three gliomas, and three unclassified malignant neoplasms. Three of the melanomas developed extraocular extensions; one of the melanomas metastasized to lungs and brain. Although the melanomas arose from amelanotic uveal melanocytes, melanosomes were observed in electron micrographs of the tumor cells. This study provides a new experimental model for chemical induction of ocular neoplasms. As a procedure to test the carcinogenicity of nickel compounds, intraocular injection has the advantages of short latency period, high tumor incidence, and ease of tumor detection.

Uveal tuberculosis.

Ocular tuberculosis should be considered in the differential diagnosis of panophthalmitis, uveitis, and intraocular neoplasms. We have presented 6 cases illustrating some of the clinical and pathological characteristics of two types of ocular involvement, acute tuberculous panophthalmitis and ciliary body tuberculoma. The former should be entertained when panophthalmitis or uveitis occur in debilitated patients with obvious systemic tuberculosis foci. Ciliary body tuberculoma should be suspected in relatively healthy individuals with a history of tuberculosis and an intraocular mass. The diagnosis is confirmed by positive cultures or the identification of the organism by acid-fast stains. Typical histopathology in the appropriate clinical setting is sufficient to start specific antituberculous therapy, which should be used in all cases.