CXCR3 expression in human central nervous system diseases.

The CXCR3 chemokine receptor, expressed on activated T lymphocytes, is seen within the central nervous system (CNS) in inflammatory conditions where a T-cell response is prominent. However, the distribution of CXCR3 in parenchymal CNS cells is unknown. Using a monoclonal antibody against CXCR3 and post-mortem tissue of patients with and without CNS pathology, we have determined its expression pattern. CXCR3 was found in subpopulations of cells morphologically consistent with astrocytes, particularly reactive astrocytes, and in cerebellar Purkinje cells. It was also detected in arterial endothelial and smooth muscle cells, particularly in areas associated with atherosclerotic plaques. CXCR3-positive astrocytes were particularly prominent in the CNS of HIV-positive patients, in patients with Multiple Sclerosis (MS), in ischaemic infarcts and in astrocytic neoplasms. Immunofluorescence studies of mixed adult primary glial cultures and fetal glial cultures also showed expression of CXCR3 in astrocytes. CXCR3 mRNA was detected in Purkinje cells by in situ hybridization with a CXCR3-specific probe. Thus, the predominant expression of CXCR3 in reactive astrocytes may indicate that it plays a role in the development of reactive gliosis in a variety of infectious, inflammatory, vascular and neoplastic processes in the CNS. The relationship between CXCR3 expression in astrocytes to its expression in Purkinje cells, endothelial cells and smooth muscle cells is yet to be determined.

Expression pattern of CXCR3, CXCR4, and CCR3 chemokine receptors in the developing human brain.

Chemokine receptors are essential components of the immune and central nervous systems, but little is known about their distribution during development. We evaluated the distribution of 3 chemokine receptors: CXCR3, CXCR4, and CCR3 in the human developing brain. Of these, CXCR3 was the only receptor expressed in fetal brain at 26 wk of gestation and its expression was restricted to glial cells, endothelial cells, and the choroid plexus. Neuronal staining was only seen at term in the Purkinje cells of the cerebellum. CCR3 appeared only at term in both neurons and glial cells. The expression pattern of these 2 receptors in the late gestation and term resembled that of adults. CXCR4 could not be detected in the fetal brain on neurons nor on glial cells. By examining pediatric cases, we determined that CXCR4 expression commences sometimes between 3.5 and 4.5 yr. Two of the chemokine receptors examined, CCR3 and CXCR4, can be used as co-receptor together with CD4 for HIV entry, but neither was expressed during the second trimester of pregnancy. Our findings suggest that it is unlikely that CCR3 or CXCR4 play a major role in HIV-1 transmission in the fetal brain before 37 wk of gestation.

Polymerase chain reaction analysis of human herpesvirus-6 sequences in the sera and cerebrospinal fluid of patients with multiple sclerosis.

Several studies have suggested a possible association of human herpesvirus-6 (HHV-6) with multiple sclerosis (MS), a demyelinating disease with a variable course and progression. To determine whether HHV-6 could be detected in the sera of CSF of patients with different subtypes of MS, we performed nested polymerase chain reaction (PCR) on samples obtained from MS patients as well as samples from normal adults or individuals with other neurological diseases. Ninety-six serum samples from 24 patients with MS, including 13 individuals with relapsing remitting MS, one individual with primary progressive MS, seven individuals with secondary progressive MS and three individuals with an unspecified type were analyzed. Multiple serum samples were examined from individuals over varying periods of time and included samples obtained during exacerbations, remissions, and at different stages of progressive disease. HHV-6 DNA was detected only in one out of 15 serum samples that were collected over a number of years from one individual with secondary progressive MS. No HHV-6 DNA was detected in CSF from six patients with MS or 14 patients with other neurologic disease. These results indicate that the presence of HHV-6 DNA in the serum or CSF of patients with MS is not a common phenomenon, at least within the limits of the sensitivity of our assay.

Squamous cell tumors and ocular prostheses.

Conjunctival squamous cell carcinoma is an infrequent tumor. It has been reported to occur in association with actinic damage and chronic irritation. To the authors' knowledge, however, this tumor has not been reported secondary to poorly fitting ocular prostheses. Two patients were studied in whom conjunctival squamous cell carcinoma had developed. In both instances, the patient had been enucleated and fitted with an ocular prosthesis more than 40 years before tumor development. Histopathologic evaluation of each tumor revealed its squamous cell origin. In one of the patients, the tumor was found to be metastatic to the ipsilateral parotid gland, an uncommon finding. The authors attempted to identify risk factors that may have contributed to the development of these tumors. Aside from the poor fit of the prostheses, neither patient had significant risk factors for the development of conjunctival squamous cell carcinoma. It is concluded that a new, sanguineous conjunctival discharge or focal eyelid swelling after years of prosthetic wear may not be due to mechanical irritation alone. The onset of these symptoms, especially years after the initial fitting of an ocular prosthesis, should prompt a thorough investigation of its cause.

Managing Year 2000 risks within health care systems.

With every kind of health care provider turning to computers for efficiency and to enable smooth transactions with other providers, it is time--and beyond time--to ensure that these networks and tools will continue to function when the year 2000 rolls around. Much media attention has focused on this Year 2000 problem; what does it mean for home care providers?

Tumors of the orbit.

Orbital tumors may present with abrupt or insidious visual loss, proptosis, and disturbance of ocular motility. The treatment of many tumors of the orbit remains elusive. Recent contributions to the literature concerning the diagnosis and management of primary and secondary tumors of the orbit, including the intraorbital optic nerve, are reviewed.

Herpes simplex blepharoconjunctivitis presenting as complete acquired ankyloblepharon.

PURPOSE: A 90-year-old woman was referred to us with a 1-month history of progressively worsening blepharoconjunctivitis. She had a complete acquired ankyloblepharon of the right lids, which resulted in the appearance of a right upper lid abscess on computed tomography. METHODS: Blepharotomy with separation and debridement of the lid margins was performed. RESULTS: Cultures were positive only for herpes simplex virus, type II. CONCLUSIONS: Herpes simplex blepharoconjunctivitis may take many clinical forms. Our patient's severe manifestations led to the clinical and radiologic appearance of preseptal cellulitis with a right upper lid abscess.

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate.

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Orbital imaging techniques.

Recent years have seen refinements in techniques of orbital imaging. CT scanning remains the standard technique of orbital imaging. Magnetic resonance imaging has become a useful adjunct; progressive refinements will further enhance its utility. Modifications of time-honored ultrasonography have resulted in color Doppler imaging, a diagnostic test presently in its evolutionary-developmental phase.

Orbital fractures in women due to sexual assault and domestic violence.

PURPOSE: Because domestic violence and sexual assault have a widespread societal and medical impact, this retrospective study was designed to determine the frequency of sexual assault and domestic violence as causes of orbital fractures in women. METHODS: The records of 54 consecutive patients with orbital fractures presenting to the Ophthalmic Plastic and Orbital Surgery service of Penn State University's Department of Ophthalmology were reviewed. The type of trauma resulting in each patient's orbital injury was identified. The frequency of orbital fractures resulting from sexual assault or domestic violence was determined. RESULTS: The study included 35 male and 19 female patients, ranging in age from 27 months to 63 years. Orbital fracture was the result of sexual assault or domestic violence in one third of the female patients, but no male patients. Motor vehicle accidents accounted for another 31.6 percent of orbital fractures in female patients. CONCLUSIONS: Based on this retrospective study, sexual assault and domestic violence are frequent causes of orbital fractures in women. Healthcare workers evaluating female patients with orbital fractures should have a high index of suspicion regarding sexual assault or domestic violence as a possible origin of the injury. A pointed but sensitive approach may be necessary to elicit this history from the patient.

The cost of treating genital warts.

BACKGROUND: Genital warts is a common sexually transmitted disease treated by a variety of medical specialists. Standard therapies offer symptomatic relief but cannot ensure lasting remission. Using the clinical literature, claims databases, and a panel of experienced practitioners, the relative efficacy, cost, and cost effectiveness of five common treatments for genital warts were assessed in this study. METHODS: We reviewed the clinical literature for the following genital wart therapies: podofilox, podophyllin, trichloroacetic acid, cryotherapy, and laser therapy, focusing on their relative efficacy. Physicians experienced in treating genital warts defined standard treatment protocols for men and women patients with moderate wart burdens. Using national claims data and protocols developed by physicians, we derived three economic models based on provider charges, third-party payments, and a resource-based relative value scale, respectively. RESULTS: The literature review demonstrated highly variable success and recurrence rates among treatment methods and failed to show that one treatment provides consistently superior efficacy. In the economic models, treating women generally proved more costly than treating men per episode of care. This was due to the need for more extensive follow-up visits in the treatment of women. Total costs were highest for cryotherapy and lowest for a patient-applied therapy that reduced the need for follow-up visits. CONCLUSIONS: Clinicians should consider both clinical and cost issues when choosing the appropriate treatment for patients with genital warts.

Management of eyelid dog bites.

Eyelid dog bites are common facial injuries that occur frequently in children and often involve the lacrimal canaliculi. Even though the incidence of infection following repair of these lacerations is low, prophylactic antibiotics should be administered to all patients. Good function and appearance of repaired eyelid dog bites is achieved with appropriate surgical management. This article presents 2 cases and a retrospective review of 7 patients with eyelid dog bite injuries evaluated and treated between August 1989 and June 1994; 6 of 9 patients were children. The lacrimal drainage system was lacerated in 6 of 9 patients. All patients underwent surgical repair of their injuries and received antibiotics directed at common canine oral bacterial flora. The patients were followed for a minimum of 3 months postoperatively. There was only 1 case of facial wound infection. Good functional results were achieved in all patients.

An animal model of visual loss from orbital hemorrhage.

Intraorbital hemorrhage may arise spontaneously or following orbital or periorbital surgery or trauma and may be associated with visual loss or impairment. This project was designed to evaluate the ophthalmic effects and underlying mechanism(s) associated with visual impairment secondary to intraorbital hemorrhage. An experimental surgical procedure was developed to simulate intraorbital hemorrhage. A reversible state of unilateral visual loss secondary to acutely increased intraorbital volume was induced and maintained under general anesthesia for either 90, 120, or 180 min duration in nine adult nonhuman primates (NHPs) (Macaca arctoides). Color funduscopic photography, i.v. fluorescein angiography, electrophysiological testing, and tonometry were obtained during baseline, experimental, and follow-up procedures. The globes and optic nerves were obtained for histopathologic evaluation. One of three animals in the 180 min experimental group exhibited clinical and histopathological changes of optic neuropathy 6 weeks after the experimental procedure. Optic neuropathy is one of several proposed etiologies for producing visual loss secondary to intraorbital hemorrhage. This study offers a reliable, safe, and reversible technique to study the effects of acutely increased intraorbital volume in nonhuman primates. The animal model described may be useful for evaluating mechanism(s) involved with visual impairment in other acquired optic neuropathies.

The evolution of patients' theories of pathogenesis.

The author views the patient's theory of pathogenesis as a compromise formation to which both patient and analyst contribute in important ways. Unlike conventional autobiography or case histories, the patient's theory of pathogenesis is an ever-evolving product of the analytic collaboration that is subject to ongoing analysis and self-inquiry. Like any explanatory theory, it both opens and constrains interpretive possibilities. The collaborative attempt to arrive at the best possible explanatory narratives entails both uncovering and joint construction. Explanatory efforts that are anchored in consensually agreed-upon present experiences of resistances and transferences are more closely related to therapeutic action and are more likely to be verifiable than explanatory theories tied to distant past events. The open-ended nature of the life historical and explanatory narratives leads to an emphasis on continued self-analytic activities after termination.

Margins of safety in dacryocystorhinostomy.

We attempted to clarify the anatomic relationships of the lacrimal sac by performing standard orbital dissections to expose the lacrimal canaliculi, lacrimal sac, the ethmoid air cells, nasal septum, frontal sinuses, and the cribriform plate in five human cadaver heads; and then measuring the distance between the internal common punctum (ICP) and five key structures. The mean vector distance from the ICP to the anterior aspect of the cribriform plate was 25.1 +/- 2.95 mm. This measurement, along with the others, helps clarify osteotomy placement for dacryocystorhinostomy, so that, for example, cerebrospinal fluid leak can be prevented. Improved understanding of the anatomy of this region is also valuable in planning surgery for orbital and naso-orbital tumors, trauma, and congenital abnormalities.