Transmission of Balamuthia mandrillaris by Organ Transplantation.

BACKGROUND: During 2009 and 2010, 2 clusters of organ transplant-transmitted Balamuthia mandrillaris, a free-living ameba, were detected by recognition of severe unexpected illness in multiple recipients from the same donor. METHODS: We investigated all recipients and the 2 donors through interview, medical record review, and testing of available specimens retrospectively. Surviving recipients were tested and treated prospectively. RESULTS: In the 2009 cluster of illness, 2 kidney recipients were infected and 1 died. The donor had Balamuthia encephalitis confirmed on autopsy. In the 2010 cluster, the liver and kidney-pancreas recipients developed Balamuthia encephalitis and died. The donor had a clinical syndrome consistent with Balamuthia infection and serologic evidence of infection. In both clusters, the 2 asymptomatic recipients were treated expectantly and survived; 1 asymptomatic recipient in each cluster had serologic evidence of exposure that decreased over time. Both donors had been presumptively diagnosed with other neurologic diseases prior to organ procurement. CONCLUSIONS: Balamuthia can be transmitted through organ transplantation with an observed incubation time of 17-24 days. Clinicians should be aware of Balamuthia as a cause of encephalitis with high rate of fatality, and should notify public health departments and evaluate transplant recipients from donors with signs of possible encephalitis to facilitate early diagnosis and targeted treatment. Organ procurement organizations and transplant centers should be aware of the potential for Balamuthia infection in donors with possible encephalitis and also assess donors carefully for signs of neurologic infection that may have been misdiagnosed as stroke or as noninfectious forms of encephalitis.

A mutation in the start codon of γ-crystallin D leads to nuclear cataracts in the Dahl SS/Jr-Ctr strain.

Cataracts are a major cause of blindness. The most common forms of cataracts are age- and UV-related and develop mostly in the elderly, while congenital cataracts appear at birth or in early childhood. The Dahl salt-sensitive (SS/Jr) rat is an extensively used model of salt-sensitive hypertension that exhibits concomitant renal disease. In the mid-1980s, cataracts appeared in a few animals in the Dahl S colony, presumably the result of a spontaneous mutation. The mutation was fixed and bred to establish the SS/Jr-Ctr substrain. The SS/Jr-Ctr substrain has been used exclusively by a single investigator to study the role of steroids and hypertension. Using a classical positional cloning approach, we localized the cataract gene with high resolution to a less than 1-Mbp region on chromosome 9 using an F1(SS/Jr-Ctr × SHR) × SHR backcross population. The 1-Mbp region contained only 13 genes, including 4 genes from the γ-crystallins (Cryg) gene family, which are known to play a role in cataract formation. All of the γ-crystallins were sequenced and a novel point mutation in the start codon (ATG → GTG) of the Crygd gene was identified. This led to the complete absence of the CRYGD protein in the eyes of the SS/Jr-Ctr strain. In summary, the identification of the genetic cause in this novel cataract model may provide an opportunity to better understand the development of cataracts, particularly in the context of hypertension.

Angiographic evaluation of the rat carotid balloon injury model.

RATIONALE: The rat carotid balloon-injury (BI) model is a widely used model of intimal hyperplasia (IH) and vascular remodeling. A variable degree of IH after BI has been previously reported, and we have encountered technical challenges and suboptimal results with the original method. OBJECTIVE: To evaluate the original rat carotid artery BI method with the use of micro-angiography. We tested the hypothesis that in order to obtain an optimal arterial response, BI should be limited to the common carotid artery with preservation of blood flow. METHODS AND RESULTS: The left common carotid artery (CCA) was injured by one of three different methods. Carotid angiograms and pathology were examined 14 days after BI. A 2F Fogarty balloon catheter inflated to 2 atm inside the aortic arch would not slide back into the common carotid artery until deflation to 0.5 to 0.7 atm. Four out of five (80%) vessels injured with this method developed excessive inflammation without discernible IH. Six out of nine (66%) arteries that underwent BI limited to the CCA at 2 atm developed the largest angiographic stenosis (p=0.003) and IH (0.20±0.03 mm(2), p=0.028). Ten out of eleven (91%) arteries injured with a variable pressure of 1.5 to 2.2 atm, based on the operator's feedback, developed considerable IH (0.12±0.02 mm(2)). All injured carotid arteries with preserved blood flow on angiography developed IH with intact histological boundaries. CONCLUSIONS: Optimal IH with preservation of histological boundaries is achieved by graded BI limited to the CCA that preserves carotid blood flow.

Compound heterozygous mutation with a novel splice donor region DNA sequence variant in the succinate dehydrogenase subunit B gene in malignant paraganglioma.

Pheochromocytoma and paraganglioma (PGL) are rare neuroendocrine tumors in children. Apparently sporadic cases of PGL may harbor germline mutations in the succinate dehydrogenase (SDHx) gene. SDHB mutations are associated with malignant disease. We report a 13-year-old African American boy with diffusely metastatic PGL and compound heterozygous mutation leading to a novel splice donor region DNA sequence variant in the SDHB gene. Family history was positive for non-classical congenital adrenal hyperplasia and pituitary adenoma. After surgical resection of the primary PGL and chemotherapy, he was treated with metaiodobenzy lguanidine (MIBG) combined with arsenic trioxide. At 3-year follow-up, he had stable disease.

An uncommon illness with a rare presentation: neurosurgical management of ADEM with tumefactive demyelination in children.

PURPOSE: This study determined the statewide incidence and prevalence of acute disseminated encephalomyelitis (ADEM) and examined the course of three pediatric patients treated for tumefactive demyelination (TD) at the Blair E. Batson Children's Hospital. METHODS: Analyses of ICD-9-CM code hospital records and clinical database were conducted. RESULTS: From 2001 through 2007 the incidence in pediatric patients under 20 years was 0.4/100,000/year, with a prevalence of 8.6/100,000 during 2008. Three patients presented with TD. Case 1 had a 3-week history of ataxia and diplopia; case 2 presented with a sudden onset of coma, while the third child had a 4-month history of increasing lethargy and clumsiness in all extremities. Cerebrospinal fluid examinations were nondiagnostic. MRI examinations revealed asymmetric T2/fluid-attenuated inversion recovery hyperintensity within the pons (case 1), a large heterogenously enhancing temporal lobe mass, with extensive edema (case 2), and multiple small brain lesions with occasional ring enhancement (case 3). In case 1, intralesional MR spectroscopy demonstrated changes consistent with ADEM. Case 2 required intracranial monitoring, and medical treatment to control elevated ICP. Cases 2 and 3 underwent cortical biopsies that revealed ADEM. All three patients improved with corticosteroid therapy. At a minimum of 15 months follow-up, cases 1 and 2 showed resolution of deficits and MRI lesions, while the third patient demonstrated additional MRI lesions and increasing paraparesis. CONCLUSIONS: These cases demonstrate that appropriate neuroradiological evaluation, treatment of acutely elevated ICP, and brain biopsy can play critical roles in the management of children with undiagnosed ADEM and TD.

Development of a Streptococcus pneumoniae keratitis model in mice.

BACKGROUND: Streptococcus pneumoniae is a common cause of bacterial keratitis, and models to examine the ocular pathogenesis of this bacterium would aid in efforts to treat pneumococcal keratitis. The aim of this study was to establish a murine model of pneumococcal keratitis. METHODS: The corneas of A/J, BALB/c or C57BL/6 mice were scratched and topically infected with a clinical strain of S. pneumoniae. Slitlamp examination (SLE), enumeration of bacteria in the corneas and histology were performed. RESULTS: Bacteria were recovered from the eyes of A/J mice on postinfection (PI) days 1 [1.96 +/- 0.61 log(10) colony-forming units (CFU)] and 3 (1.41 +/- 0.71 log(10) CFU). SLE scores were significantly higher in the infected A/J mice as compared to the BALB/c or C57BL/6 mice on PI day 3 (p < 0.0001) and steadily increased over time, reaching a maximal value of 3.00 +/- 0.35 on PI day 10. Histopathology revealed stromal edema and the influx of polymorphonuclear leukocytes on PI days 7 and 10, and corneal disruption on PI day 7. CONCLUSIONS: S. pneumoniae keratitis was established in A/J mice, but not BALB/c or C57BL/6 mice.

Age-related differences in rabbits during experimental Staphylococcus aureus keratitis.

PURPOSE: To analyze age-related changes in susceptibility to experimental Staphylococcus aureus keratitis and purified alpha-toxin in rabbits. METHODS: Intrastromal injection of S. aureus (100 colony-forming units [CFUs]) induced keratitis in young (6-8 weeks) and aged (approximately 30 months) New Zealand White rabbits. Bacteria and polymorphonuclear leukocytes (PMNs) per cornea were quantified. Purified alpha-toxin at 1, 10, 25, or 50 hemolytic units (HU) or heat-inactivated alpha-toxin was intrastromally injected into corneas, and pathologic changes were determined by slit lamp examination (SLE) and histopathologic analysis. alpha-Toxin hemolysis assays were performed using erythrocytes from young and aged rabbits. RESULTS: S. aureus keratitis produced significantly higher SLE scores in young rabbits than in aged rabbits at 15, 20, and 25 hours postinfection (PI; P < or = 0.001); aged rabbits essentially recovered from S. aureus keratitis by 7 days PI. At 25 hours PI, numbers of CFUs and PMNs in corneas of young and aged rabbits were equivalent (P > or = 0.6); the bacterial burden in aged rabbits declined by 5 logs per cornea from day 1 to day 7 PI. Intrastromal injection of > or =10 HU alpha-toxin also produced significantly more disease in young than in aged rabbit corneas (P < or = 0.05), whereas 1 HU or heat-inactivated toxin yielded negligible pathologic changes in either group. Hemolysis assays of erythrocytes from young rabbits demonstrated greater susceptibility to alpha-toxin compared with those from aged rabbits. CONCLUSIONS: Corneas and erythrocytes of young rabbits, relative to aged rabbits, are significantly more susceptible to S. aureus keratitis and to alpha-toxin.

Newly Identified Characteristics and Suggestions for Diagnosis and Treatment of Diffuse Leptomeningeal Glioneuronal/Neuroepithelial Tumors: A Case Report and Review of the Literature.

Diffuse leptomeningeal glioneuronal tumor is unique for communicating hydrocephalus, diffuse leptomeningeal enhancement, cystic changes, absence of tumor cells in cerebral spinal fluid, and a cell population of both glial and neuronal copositivity. It has likely been misdiagnosed as mixed glioneuronal tumors, oligodendrogliomas, and neuroepithelial tumors. Children with signs of this tumor are often worked up for infection, rheumatologic disease, or disseminated primary malignancy, resulting in unnecessary testing and treatment. We describe a 14-year-old female with recurrent headaches, hydrocephalus, and diffuse leptomeningeal enhancement discovered to be neoplastic 1 year after initial presentation, owing to extensive and unrevealing infectious and immunologic workups. Biopsies revealed atypical cells with markers of both glial and neuronal cells, positivity for OLIG-2, and focal p53 positivity. Great response was seen with temozolomide and craniospinal irradiation. Additionally, we postulate additional diagnostic indicators that may aid in earlier diagnosis and treatment decisions.

Neuropathologic lesions and CSF morphine concentrations during chronic continuous intraspinal morphine infusion. A clinical and post-mortem study.

Seven patients with chronic intractable pain due to cancer were given chronic intraspinal narcotic administration (CINA) and subsequently underwent post-mortem examination. All deaths were unrelated to CINA. Two of these patients were found to have clinically unsuspected posterior column degeneration. Both patients had had epidural catheters placed, and one had received prior radiotherapy to ports which included parts of the spinal cord. In retrospect, it is impossible to ascertain whether the degeneration occurred before or after infusion of morphine began. Review of the potential causes for posterior column degeneration suggests that neuropathy associated with malignant disease is more likely the cause of the degeneration rather than intraspinal infusion of morphine. However, continued vigilance at autopsy is recommended. In addition, utilizing a new method for measuring cerebrospinal fluid (CSF) concentrations of morphine via high-pressure liquid chromatography, CSF morphine levels at steady state were measured in 5 patients. These levels were much lower than peak levels previously reported following bolus intraspinal administration. The ability of these measurements to contribute to knowledge of efficacy, toxicity, lumbar-cisternal concentration gradients, and differentiation of tolerance from drug delivery problems is discussed.

Inhibiting caspase-8 after injury reduces hypoxic-ischemic brain injury in the newborn rat.

A broad spectrum caspase inhibitor reduces brain injury. Will a caspase-8 inhibitor provide protection? Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-8 activity in the right cortex was measured enzymatically. Caspase-8 activity was increased at 12 and 24 h after injury and IETD-CHO, (Ac-Ala-Ala-Val-Ala-Leu-Leu-Pro-Ala-Val-Leu-Leu-Ala-Pro-Ile-Glu-Thr-Asp-CHO, CHO is aldehyde) a cell permeable caspase-8 inhibitor, given by i.c.v. injection after the hypoxic period eliminated this increase with significant effect at 15 and 50 microg/pup (1.7 micromol/kg). Thirty pups were randomly assigned to receive 50 microg/pup of IETD-CHO or vehicle i.c.v. immediately after the hypoxic period. The loss of brain weight in the right hemisphere 22 days after injury was 29+/-5% in the vehicle-treated animals and 12+/-5% in the IETD-CHO-treated animals (P<0.05). Inhibiting caspase-8 activity after hypoxic-ischemic brain injury reduces brain injury.

Inhibiting caspase-9 after injury reduces hypoxic ischemic neuronal injury in the cortex in the newborn rat.

A broad spectrum caspase inhibitor reduces hypoxic ischemic brain injury. We hypothesized that a specific caspase-9 inhibitor would provide similar protection. Seven-day-old rat pups had the right carotid artery ligated, then were subjected to 2.5 h of 8% oxygen. Caspase-9 activity in the right cortex was measured enzymatically. Caspase-9 activity was increased at 6, 12, and 24 h after injury. LEHD-CHO is a specific cell permeable caspase-9 inhibitor. LEHD-CHO given intracerebroventricularly (i.c.v.) into the brain after the hypoxic period eliminated the increase in caspase-9 activity. The greatest effect was at a dose of 50 microg/pup (1.6 micromol/kg). Fifty-two pups were randomly assigned to receive 50 microg/pup of i.c.v. LEHD-CHO or vehicle immediately after the hypoxic period. The loss of cortical neurons in the right hemisphere 22 days after injury was 52.0+/-8% in the vehicle treated animals, and 25+/-9% in the LEHD-CHO treated animals (P<0.05). Inhibiting caspase-9 activity reduces loss of neurons after brain injury.

Aortic response to balloon injury in obese Zucker rats.

The small diameter of the carotid artery is not compatible with the evaluation of clinically available endovascular devices in the carotid balloon-injury (BI) model. We developed an endovascular BI model in the rat descending aorta, whose size is compatible with available endovascular instruments. We also tested the hypothesis that neointima formation is enhanced in the aorta of obese Zucker rats (OZR) compared with lean Zucker rats (LZR). Left external carotid arteriotomies and BI of the thoracic and abdominal aorta were performed by using a balloon catheter. Aortograms and aortic pathology were examined at 2, 4, and 10 wk after BI. At 10 wk after BI, the abdominal aorta in OZR had narrowed 8.3% ± 1.1% relative to baseline compared with an expansion of 2.4% ± 2.2% in LZR. Simultaneously, the thoracic aorta had expanded 9.5% ± 4.3% in LZR compared with stenosis of 2.8% ± 1.6% in OZR. Calculation of the intimal:medial thickness ratio revealed significantly increased neointimal formation in the OZR descending aorta compared with that in LNR. In conclusion, this minimally invasive BI model involving the rat descending aorta is compatible with available endovascular instruments. The descending aorta of OZR demonstrates enhanced neointimal formation and constrictive vascular remodeling after BI.

What causes a prolactinoma to be aggressive or to become a pituitary carcinoma?

INTRODUCTION: Malignant prolactinoma is an exceedingly rare endocrine tumor and cannot be diagnosed on histological grounds alone. Similarly to other neuroendocrine tumors such as pheochromocytoma, the mitoses index, Ki-67, p53, and others are utilized in helping understand whether a tumor is benign or malignant or to better predict tumor behavior. We here present the unusual case of an unfortunate young man with an aggressive prolactinoma, the complications of which led to his premature death. CASE REPORT: A 25-year-old white man developed severe headaches, low energy, and decreased libido. A brain magnetic resonance imaging (MRI) showed a 4 x 3 x 2 cm pituitary tumor invading the left cavernous sinus. Laboratory findings revealed elevated prolactin (470 ng/mL) and adrenocorticotropic hormone (ACTH, 82 pg/ml) and decreased total testosterone (176 ng/dl). Visual fields showed superior quadrantanopia in the left eye. Transsphenoidal pituitary resection was undertaken. Pathology revealed a prolactinoma with atypical cells, diffuse p53 nuclear labeling, and a Ki-67 index of 23% (high). Postoperatively, prolactin remained elevated (725-891 ng/ml) and cabergoline was increased to 1 mg three times weekly, with serum prolactin further increasing to 3507 ng/ml five months postoperatively. Repeat MRI revealed extension of the tumor with optic chiasm compression and left orbit invasion. Because of acute left vision loss with ophthalmoplegia, an urgent left frontotemporal craniotomy and tumor resection were conducted. The Ki-67 index of the tumor was 24.8%, the mitotic figure immunostain phosphohistone-H3 positive. Sixty percent (60%) of tumor cells were positive for p53. Cabergoline was increased to 1 mg daily but prolactin remained elevated (770 ng/ml). The patient then underwent proton beam radiation to the area of concern involving the sella. Prolactin thereafter improved to 44 ng/ml. He then developed acute vision loss of the right eye with an MRI showing tumor in the right cavernous sinus. A 15 mm dural-based right temporal mass believed to be a metastasis was also noted. Following this scan, he was considered too high risk for debulking surgery and instead underwent gamma knife irradiation to the sella area. This shrank the right cavernous sinus tumor mass, while the right temporal mass increased in size. The patient developed blindness and left-sided weakness and required enteral feeding and tracheostomy after prolonged intubation. A trial of chemotherapy with temozolomide (350 mg daily for 5 days) near the end of his life was unsuccessful. He died on home hospice 31 months after his first surgery. CONCLUSION: Headaches, vision changes, and symptoms of androgen deficiency syndrome can be manifestations of an aggressive prolactinoma that might require surgery and additional medical therapy including cabergoline and temozolomide with an unpredictable time of survival.

An enzymatic technique to facilitate air separation of the stroma-Descemet's membrane junction.

PURPOSE: To describe an enzymatic technique that facilitates air separation of Descemet's membrane from the corneal stroma. METHODS: Fresh human corneoscleral tissue was mounted on an artificial anterior chamber. In a control group, air was injected into the stroma. A second group received a stromal injection of 2.5 mg/mL collagenase type 2 in balanced salt solution that was left in the stroma for 1 hour and 15 minutes. A third group received an injection of 2.5 mg/mL collagenase type 2 in balanced salt solution followed 1 hour and 15 minutes later by an injection of air into the stroma. All injections were performed with a 27-gauge needle into the deep stroma without penetrating Descemet's membrane. Anterior segment optical coherence tomography (AS-OCT), histologic examination, and electron microscopy of the junction between the stroma and Descemet's membrane were performed. The trypan blue exclusion and TUNEL assays were used to study endothelial cell viability after collagenase incubation. RESULTS: Injection of air or collagenase into the deep corneal stroma did not result in a reproducible separation of the stroma-Descemet's junction. In contrast, the stroma was easily and reproducibly separated from Descemet's membrane with a combination of intrastromal collagenase and air injection. The separation was confirmed by using light and electron microscopy. The cleavage plane seemed to be located between the junction of the posterior stroma and the anterior banded layer of Descemet's membrane. Trypan blue staining demonstrated the viability of endothelial cells after collagenase incubation. TUNEL assay confirmed excellent viability after collagenase+air separation. CONCLUSIONS: This technique facilitates the separation of Descemet's membrane from the stroma without affecting endothelial cell viability.

Neurosurgical intervention in the diagnosis and treatment of Balamuthia mandrillaris encephalitis.

The authors describe the unique presentation of Balamuthia mandrillaris encephalitis in a kidney donor and two recipients. All three patients suffered acute clinical deterioration, with radiological or clinical evidence of intracranial hypertension. Brain autopsy in the donor and an urgent brain biopsy in a recipient established the diagnosis. First-tier therapy, with mannitol and CSF drainage, successfully treated the intracranial hypertension in both recipients, while administration of a combination of antiamebic drugs was associated with survival in the second recipient. For both recipients, neurosurgical management played a critical role in the rapid diagnosis and treatment of Balamuthia mandrillaris encephalitis.

Asymptomatic aneurysm of the cavernous and supraclinoid internal carotid artery in a patient with Balamuthia mandrillaris encephalitis.

This is the first report to our knowledge of the successful treatment of an asymptomatic mycotic aneurysm associated with Balamuthia mandrillaris encephalitis. A 27-year-old male with end-stage renal disease presented with generalized seizures following renal transplantation. MRI demonstrated multiple brain masses and an aneurysm of the cavernous and supraclinoid carotid artery. Autopsy of the donor's brain revealed Balamuthia encephalitis. The patient was placed on an anti-amebic regimen, his condition improved, and 126 days after the kidney transplant, MRI brain showed resolution of the aneurysm and improvement of the enhancing lesions. Balamuthia mandrillaris has been shown to cause a granulomatous encephalitis, with prominent vasculitis. This is the first report to demonstrate the risk of aneurysm formation associated with this infection. Prolonged anti-amebic treatment resulted in resolution of the aneurysm without clinical evidence of subarachnoid hemorrhage.

The Streptococcus pneumoniae capsule is required for full virulence in pneumococcal endophthalmitis.

PURPOSE: To determine whether Streptococcus pneumoniae capsule was necessary for pathogenesis of pneumococcal endophthalmitis. METHODS: An isogenic capsule-deficient strain was created using homologous recombination. New Zealand White rabbits were injected intravitreously with 10(2) colony-forming units (CFU) of the parent strain or the capsule mutant. Slit lamp examination (SLE), electroretinography, and myeloperoxidase activity were performed 24 and 48 hours postinfection (PI). Serial dilutions of vitreous were plated to quantitate CFU, eyes were extracted for histology, and host cytokine mRNA expression was determined. RESULTS: Eyes infected with the parent strain had significantly higher SLE scores than eyes infected with the capsule-deficient strain 24 and 48 hours PI (P < 0.001). CFU recovered from eyes infected with the capsule mutant were significantly fewer than CFU recovered from eyes infected with the parent strain 24 and 48 hours PI (P < 0.001). The parent strain caused a significantly greater decrease in retinal function and more retinal destruction than the mutant strain 48 hours PI (P = 0.026). Vitreal IL-1ß, IL-6, and TNF-α were upregulated by both the parent and mutant strain 12 hours PI. By 48 hours PI, there was significantly more neutrophil infiltration in the vitreous infected with the parent strain. CONCLUSIONS: Endophthalmitis caused by the encapsulated strain is more damaging to retinal function and structural integrity. These findings indicate that capsule is an important virulence factor of S. pneumoniae endophthalmitis, in contrast to keratitis, suggesting that the anatomic host site in pneumococcal ocular infections is important.

Immunization with pneumolysin protects against both retinal and global damage caused by Streptococcus pneumoniae endophthalmitis.

PURPOSE: To determine whether immunization with pneumolysin (PLY) protects against pneumococcal endophthalmitis. METHODS: New Zealand white rabbits were immunized with a mutant form of PLY that retains only 1% of its cytolytic activity until serum IgG titers were ≥51,200. For a negative control, rabbits were immunized with phosphate-buffered saline (mock). Each vitreous was injected with 10(2) colony-forming units of a clinical endophthalmitis isolate of Streptococcus pneumoniae. Severity of endophthalmitis was graded by slit lamp examination at 24 and 48 h postinfection (PI). Serial dilutions of vitreous were plated for bacterial colony-forming units quantitation, eyes were extracted for histology, and a whole blood survival assay was performed. RESULTS: Immunized rabbits had a significantly lower mean slit lamp examination score at 24 and 48 h PI when compared to mock immunized rabbits (P ≤ 0.002). There was not a significant difference in bacterial load in the vitreous at 24 or 48 h PI. Histological sections showed that retinas of mock immunized rabbits appeared to be destroyed, whereas those of PLY immunized rabbits remained largely intact. Damage spread to the aqueous humor, stroma, and conjunctiva of mock immunized rabbits by 48 h PI. Minimal damage was observed in the vitreous of PLY immunized rabbits and did not spread to other parts of the eye. Whole blood from immunized rabbits inhibited the growth of bacteria better than whole blood from mock immunized rabbits. CONCLUSION: Immunization with PLY helps protect the eye from damage caused by pneumococcal endophthalmitis.