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Objective: To examine the relationship between the pharmacodynamic and antipsoriatic effects of alefacept, a biologic agent that targets CD4+ and CD8+ memory T cells., Design: Randomized, double-blind, placebo-controlled study of 3 parallel groups., Setting: Fifty-one study centers., Patients: Five hundred fifty-three patients with chronic plaque psoriasis., Interventions: Patients were randomized (1:1:1) to 1 of the following 3 cohorts: alefacept, 7.5 mg, in both courses (cohort 1); alefacept, 7.5 mg, in the first course and placebo in the second course (cohort 2); or placebo in the first course and alefacept, 7.5 mg, in the second course (cohort 3). In each course, alefacept or placebo was administered by intravenous bolus once weekly for 12 weeks, followed by 12 weeks of observation., Main Outcome Measures: Circulating lymphocyte levels and the Psoriasis Area Severity Index., Results: One or 2 courses of alefacept reduced CD4+ and CD8+ memory T-cell counts, while sparing the naive population. At 12 weeks after the last dose of alefacept in courses 1 and 2, 88% and 83% of patients, respectively, had CD4+ cell counts greater than the lower limit of normal. In course 1, alefacept-treated patients with the largest decreases in memory T-cell counts experienced the greatest reductions in disease activity (P<.001). The duration of clinical benefit seemed to be longer among patients who had the greatest reduction in CD4+ and CD8+ memory T-cell counts., Conclusions: One or 2 courses of intravenous alefacept reduced circulating memory T-cell counts while sparing the naïve T-cell population. The reductions in memory T-cell counts were related to all measures of disease activity evaluated and the duration of response to therapy, suggesting that prolonged remissions of psoriasis can be attained with reduction of the pathogenic T-cell count.

Alefacept is the first biologic agent approved for the treatment of chronic plaque psoriasis in the United States. Alefacept, administered intravenously (i.v.) or intramuscularly (i.m.), was found to be well tolerated, safe, and efficacious in two pivotal phase 3 studies in patients with moderate to severe psoriasis. Treatment with i.v. alefacept was associated with a median duration of off-treatment response of 216 days (approximately 7 months). In a follow-up extension study to the phase 3 i.m. study, duration of therapeutic response was also examined. Patients who achieved a > or = 75% reduction in baseline Psoriasis Area and Severity Index (PASI 75) with the first course of alefacept 15 mg i.m. in the phase 3 study maintained a PASI 50 for a median duration of 209 days. In addition, the extension study demonstrated that a second course of i.m. alefacept is safe and well tolerated in patients with psoriasis.

Objective: To determine safety and efficacy of monotherapy with etanercept., Design: Randomized, double-blind, placebo-controlled, multicenter study., Setting: Outpatient, ambulatory; private practice and university dermatology research centers., Patients: Patients aged at least 18 years, with plaque psoriasis involving 10% or more of body surface area; 148 were screened and 112 were randomly assigned to treatment groups and received study drug., Interventions: Patients received placebo or etanercept, 25 mg, subcutaneously twice a week for 24 weeks. Other psoriasis therapies were limited during the study., Main Outcome Measures: Safety measurements included tracking of adverse events and laboratory values. Efficacy was evaluated using the Psoriasis Area and Severity Index (PASI); the primary end point was a 75% improvement in PASI. Other efficacy measurements included patient and physician global assessments and quality-of-life measures., Results: After 12 weeks of treatment, 17 (30%) of the 57 etanercept-treated patients and 1 (2%) of the 55 placebo-treated patients had achieved PASI 75%, and after 24 weeks, 32 (56%) of etanercept-treated patients and 3 (5%) of placebo-treated patients had reached this level (P<.001 for both time points). By 24 weeks, psoriasis was clear or minimal by physician's global assessment in more than 50% of patients who received etanercept. Treatment failure (PASI response <50) occurred in 23% of patients at week 24. All other measures confirmed the efficacy of etanercept. Adverse events were similar among etanercept and placebo groups., Conclusion: Etanercept monotherapy provided significant benefit to patients with psoriasis and had a favorable safety profile.

Background: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis., Objective: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed., Methods: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10., Results: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%)., Conclusion: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.

Over the past three decades, laboratory and clinical research findings have shown that T cells are the primary mediators of psoriasis pathogenesis and that psoriasis can be treated by eliminating these T cells or interfering with their activation or activity. Based on these observations, many new biologic therapies to treat psoriasis are now in development. These agents, developed primarily through recombinant DNA techniques, are designed to target T cells and the immunologic cascade associated with their activation. Four basic strategic approaches that focus on the steps involved in the immunopathology of psoriasis are: 1) elimination of the pathogenic T cells; 2) inhibition of T-cell activation, proliferation, and migration; 3) immune deviation to down-regulate the type 1 (TH1) response predominant in psoriasis; and 4) blockade of cytokine production. The goal of these new therapies is to improve the treatment of psoriasis, particularly moderate to severe disease, with agents that are well tolerated and safe for long-term use.

In this review, we will discuss the immunological basis for psoriasis with special emphasis on the role of effector T cells. With the understanding of this immunologic process, we will present a model for the development of targeted immune response modifiers, termed biologic immunotherapies, and their potential role for the benefit of patients with psoriasis.

Background: Human Skin Substitute (Apligraf, Organogenesis, Inc., Canton, MA) is a bi-layered tissue-engineered living biological dressing developed from neonatal foreskin. It consists of a bovine collagen matrix containing human fibroblasts with an overlying sheet of stratified human epithelium containing living human keratinocytes. Human Skin Substitute (HSS) appears to be immunologically inert, and has shown usefulness in the treatment of chronic and acute wounds., Objective: Primary objectives were to evaluate the safety and efficacy of HSS in the treatment of full-thickness wounds in a prospective case series. Secondary objectives were to determine the rate of complete wound reepithelialization, incidence of complete wound healing, pain at wound site, overall cosmetic outcome, and patient satisfaction., Methods: Fourteen patients were enrolled in the study, of which 12 were evaluable. HSS was applied in a blinded fashion to 6 of the patients immediately following Mohs or excisional surgery for skin cancer. The remaining 6 patients were allowed to heal by secondary intention. Both groups were evaluated at weekly appointments until complete reepithelialization occurred. During each evaluation, wound quality was assessed through the Vancouver Burn Scar Assessment Scale by the investigator and an independent blinded dermatologist. The investigator, blinded observer, and patient further evaluated the cosmetic outcome of the wound through the use of a Visual Analog Scale over a 6-month period., Results: HSS patients and secondary intention patients were equivalent in comorbid factors such as pain, erythema, edema, exudate, infection, or hematoma between the groups. The incidence of complete wound healing at 6 months was 100% for both groups. Both groups also appeared to heal at similar rates, as defined by the complete reepithelialization of the wound. HSS patients ultimately resulted in more pliable and less vascular wounds as defined by the Vancouver Burn Scar Assessment Scale. Patient satisfaction with cosmetic outcome in both groups was positive at 6 months., Conclusions: HSS appears to be a safe, well-tolerated biological dressing with equivalent comorbid factors to secondary intention healing. HSS, however, seems to produce a more pliable and less vascular scar than those developed through healing by secondary intention. HSS also appears to produce more satisfactory cosmetic results when compared to secondary intention healing.

Microglial cells and astrocytes are capable of processing and presenting antigens for efficient activation of T cells. However, the antigen-presenting function and role of cerebrovascular endothelial cells (CVEs) in central nervous system inflammatory responses remain controversial. We compared the expression of necessary accessory molecules and the functional antigen-presenting capacity of cloned SJL/J CVEs and primary astrocytes in response to the pro-inflammatory cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). Astrocytes and CVEs up-regulated major histocompatibility complex (MHC) class II, and primarily B7-1 as opposed to B7-2, in response to IFN-gamma. TNF-alpha inhibited the IFN-gamma-induced up-regulation of MHC class II on CVEs correlating to a decrease in the mRNA for the class II transactivator (CIITA), whereas CIITA expression in astrocytes was unaffected. Unlike astrocytes, CVEs did not elicit significant MHC class II-restricted T-cell responses. Furthermore, we have found that CVE monolayers are altered following T-cell contact, implicating CVE/T-cell contact in the breakdown of the blood-brain barrier during neuro-inflammatory responses.

Objectives: (1) To develop a clinically useful model with which dermatologists can understand the potential uses of biologic therapy for psoriasis and understand the potential differences among these novel drugs, (2) to discuss the process by which recombinant DNA technology is used to develop rationally designed protein medications along with the potential benefits and difficulties of therapy with biologic agents, and (3) to provide a short review of the medications under development for psoriasis., Data Sources: The pertinent literature was reviewed with particular emphasis on published, randomized, and placebo-controlled trials. Phase 1 and early phase 2 trials were also included in our review when more stringent studies were not available. Studies presented as peer-reviewed abstracts at major conferences were also reviewed., Conclusions: With the development of recombinant DNA techniques, it has become possible to develop new biologic therapies that can be designed to specifically alter physiological responses. These new drugs are in use in many different medical fields and will soon be available for the treatment of dermatological diseases, primarily psoriasis. Dermatologists should be familiar with the potential benefits and risks of these therapies to make rational decisions concerning their use in the treatment of their patients with psoriasis.

Psoriasis is a chronic, debilitating skin condition that affects millions of people and is attributed to both genetic and environmental factors. Topical therapy is generally considered to be the first-line treatment of psoriasis. However, many patients do not respond to topical therapy or have disease so extensive that topical therapy is not practical. For these patients, systemic therapy is indicated. Presently, there are four available systemic treatments, psoralen with ultraviolet A (PUVA), methotrexate, oral retinoids (acitretin), and cyclosporin. Unfortunately, all of these treatments have significant potential adverse effects. PUVA may acutely cause nausea, pruritus and sunburn. More chronic and concerning is the development of PUVA lentigines, ocular complications and skin cancer. Non-melanoma skin cancer has been directly linked to PUVA; however, the association with melonoma is more elusive. Methotrexate use most notably carries the risk of hepatic fibrosis and cirrhosis, which is not always evident on liver function tests. Other more rare, but potentially life-threatening adverse effects include pancytopenia, lymphoproliferative disorders and acute pneumonitis. The addition of folic acid may help to reduce the risk of increasing liver enzymes and haematological toxicity seen in those taking methotrexate. Both methotrexate and oral retinoids are teratogenic and should never be used in pregnancy. Oral retinoids are probably the least effective available systemic medication for the treatment of plaque psoriasis. The effects are improved with the addition of other systemic therapies. Acitretin has replaced the formerly used etretinate primarily because of the significantly shorter half-life. The adverse effects are generally mild and reversible, making the drug fairly safe for long-term use. The most commonly seen adverse effects include elevated serum lipids, generalised xerosis and alopecia. Bony abnormalities, while somewhat controversial, have also been described and include diffuse idiopathic skeletal hyperostosis, skeletal calcifications and osteoporosis. Cyclosporin is the most recently approved systemic medication for plaque psoriasis. The nephrotoxicity associated with the use of cyclosporin can be minimised when used in lower doses and for a limited duration. Hypertension is usually mild and can be seen in up to about one-third of patients receiving long-term therapy. Cutaneous and internal malignancies have also been reported with cyclosporin and tend to be correlated with duration of treatment. In this review, we will examine the potential adverse effects with these US Food and Drug Administration-approved treatments in adults, with specific emphasis on the controversies that surround long-term therapy with these agents and their cumulative adverse effects.

Objective: To determine whether specific guidelines can be developed to distinguish whether retinal infiltration in leukemia patients represents infection or neoplasia., Design: Retrospective noncomparative interventional case series., Participants: Six patients recently seen at University of California San Francisco with retinal infiltrates in a setting of leukemia, for which adequate written and photographic information of disease course was available., Intervention: Observation consisted of retrospective review of clinic charts, hospital medical records, and fundus photographs., Main Outcome Measures: Determination of whether retinal infiltrates represented neoplasia or infection was made by review of medical records., Results: In this series, neoplastic retinal infiltrates were found in patients who had newly diagnosed leukemia and those who were in blast crisis. In contrast, the two patients who were in complete remission, but had undergone bone marrow transplantation, had retinal infiltrates attributable to infection., Conclusions: Every patient with retinal infiltrates in the setting of newly or previously diagnosed leukemia requires a systemic and central nervous system workup before the initiation of ophthalmologic treatment. The systemic status of the patient is highly informative in determining whether infection or neoplasia is responsible for the infiltration.

With the wide acceptance of cyclosporine in the treatment of skin disease, there has been an effort to find new immunomodulating agents with superior safety profiles for use in dermatology. Among the most promising of the classes are the new macrolide immunomodulators, including tacrolimus and pimecrolimus. Of these, only tocrolimus has had widespread use for nondermatologic indications, primarily solid organ transplantation. Both of these agents have been studied for inflammatory diseases of the skin. In this article, we review the systemic and topical toxicities of these macrolide immunomodulators.

Background: Hailey-Hailey disease is an inherited acantholytic disorder affecting the intertriginous areas of the body which is exacerbated by sweat, moisture, and friction. The disease is frequently resistant to conventional nonsurgical treatment., Objective: To evaluate whether chemodenervation of sweat glands would improve the course of the disease in a patient with Hailey-Hailey., Methods: We used low-dose treatment of the left axilla with botulinum toxin type A, the right axilla being used as a control, followed by treatment of both axillae with the optimal dose routinely used for the treatment of axillary hyperhidrosis., Results: After one treatment with a low dose of botulinum toxin type A, we observed partial improvement of the treated axilla. With subsequent treatment of both axillae with the recommended dose for axillary hyperhidrosis, we observed a sustained complete remission of the disease in the treated axillae., Conclusion: Botulinum toxin type A may be an effective and safe nonsurgical alternative for the treatment of benign familial pemphigus in intertriginous areas such as the axillae.

Interleukin-12 is proposed to have anti-neoplastic activity on the basis of both its anti-angiogenic and immunologic effects. Gene gun therapy with interleukin-12 cDNA into the peritumoral area of immunocompetent 129/J mice with life-threatening primary vascular tumors reduced tumor volume 7.5-fold and almost tripled the duration of mouse survival, in contrast with luciferase-bombarded control mice. Epidermal expression of mouse interleukin-12 elevated tumoral and serum levels of interferon-gamma and tumor necrosis factor-alpha, increased the tumoral populations of T lymphocyte and natural killer cells, and induced tumor apoptosis. Gene transfer of interleukin-12 had little effect on tumor volumes and survival of tumor-bearing athymic nude mice, emphasizing the requirement for T cell directed cellular immunity. Peritumoral gene gun introduction of interleukin-12 may be a novel, cost-effective approach to limit the growth and associated mortality of life-threatening tumors.

Many disorders of the gastrointestinal tract have cutaneous manifestations. Thus, a careful examination of the skin may uncover clues to underlying diseases of the liver, gastrointestinal tract, and pancreas. This article explores the alimentary-cutaneous relationship.

There is controversy regarding the possible role of glial cells as APCs in the pathogenesis of central nervous system (CNS) demyelinating diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Microglia have been clearly shown to present Ag in the CNS, and due to the proximity of activated astroglial cells to infiltrating T cells and macrophages in demyelinating lesions, it is also possible that astrocytes positively or negatively regulate disease initiation and/or progression. We examined the capacity of IFN-gamma-treated astrocytes from EAE-susceptible SJL/J mice to process and present myelin epitopes. IFN-gamma activation up-regulated ICAM-1, VCAM-1, MHC class II, invariant chain, H2-M, CD40, and B7-1 as determined by FACS and/or RT-PCR analyses. B7-2 expression was only marginally enhanced on SJL/J astrocytes. Consistent with the expression of these accessory molecules, IFN-gamma-treated SJL/J astrocytes induced the B7-1-dependent activation of Th1 lines and lymph node T cells specific for the immunodominant encephalitogenic proteolipid protein (PLP) epitope (PLP139-151) as assessed by proliferation and activation for the adoptive transfer of EAE. Interestingly, IFN-gamma-activated astrocytes efficiently processed and presented PLP139-151, but not the subdominant PLP178-191, PLP56-70, or PLP104-117 epitopes, from intact PLP and a recombinant variant fusion protein of PLP (MP4). The data are consistent with the hypothesis that astrocytes in the proinflammatory CNS environment have the capability of activating CNS-infiltrating encephalitogenic T cells specific for immunodominant epitopes on various myelin proteins that may be involved in either the initial or the relapsing stages of EAE.

Autoimmune diseases are initiated when patients develop aberrant T and/or B cell responses against self proteins. These responses presumably are directed to single immunogenic epitopes on these proteins. Recent data in animal models of autoimmune diseases suggest that the targets of immune responses in autoimmunity do not remain fixed, but can be extended to include other epitopes on the same protein or other proteins in the same tissue, a phenomenon termed "epitope spreading." The "epitope spreading" phenomenon also applies to situations in which tissue damage from a primary inflammatory process causes the release and exposure of a previously "sequestered" antigen, leading to a secondary autoimmune response against the newly released antigen. In experimental autoimmune animal diseases, "epitope spreading" seems to have significant physiologic importance in determining the course and duration of disease. In this paper, we review the current concepts in animal models of autoimmune diseases in order to define the "epitope spreading" phenomenon, and we then propose how this phenomenon might play a significant role in the development and the course of autoimmune skin diseases. Hopefully, an understanding of "epitope spreading" will help the dermatology community to better understand the pathogenesis of autoimmune skin diseases and to rationally fashion disease-specific immune therapy in the future.

Treatment of epidermolysis bullosa acquisita (EBA) with conventional therapy frequently does not result in improvement. Extracorporeal photochemotherapy (ECP) is a novel immunomodulating technique which might be of benefit in the treatment of autoimmune disease. We prospectively studied three patients with refractory EBA who were treated with ECP. All three patients had improvement in objective measurement of their disease severity while two of the three had significant subjective improvement in their skin fragility and the clinical activity of their disease. Both the objective and subjective manifestations of the disease continued to improve 6 months after completion of the protocol. ECP may be therapeutic option in the treatment of patients with EBA who are refractory to conventional therapy.

Astrocytes may serve as effectual APCs for T cell-mediated immune responses to myelin components during multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Although astrocytes have been reported not to constitutively express MHC class II molecules, expression is up-regulated during active EAE and by in vitro incubation with IFN-gamma. Previous studies have reported that cytokine-activated astrocytes are able to activate Ag-specific previously activated T cells, but not naive alloreactive T cells. In the current study, we show that a subset of primary murine astrocytes constitutively expresses B7-2 molecules, as determined by FACS and PCR analyses, and up-regulates surface expression and mRNA levels of both B7-2 and B7-1 upon IFN-gamma stimulation. In contrast to earlier reports, we found that both untreated and IFN-gamma-treated astrocytes were able to stimulate proliferation of previously activated OVA-specific Th1 cells. In contrast, only IFN-gamma-treated astrocytes activated naive, transgenic OVA-specific T cells. Astrocyte-induced activation of both OVA-specific naive T cells and activated Th1 cells was dependent primarily on B7-2-mediated costimulation, as proliferation was inhibited by CTLA4-Ig and by anti-B7-2 mAbs. These results suggest that astrocytes in an inflammatory environment have the capacity to express the required MHC class II and B7 costimulatory molecules necessary for efficient activation of naive T cells. Since we have shown that T cells specific for endogenous myelin epitopes released during acute EAE play the major pathologic effector role in subsequent disease relapses (epitope spreading), astrocytes could play a role in the local activation and expansion of these responses.

Specific cutaneous manifestations are found to be associated with gastrointestinal disease. A careful examination of the skin, therefore, may uncover clues to underlying diseases of the gastrointestinal tract, pancreas, and liver. This article explores the alimentary cutaneous relationship.

Background: Bowen's disease (squamous cell carcinoma in situ) is an intraepithelial neoplasm that can transform into invasive squamous cell carcinoma. The preferred method of eradication for Bowen's disease is surgical excision. However, when Bowen's disease occurs on the digit, surgical removal can lead to scar contracture and loss of use of the finger., Objective: To assess the utility of carbon dioxide (CO2) laser vaporization in eradicating Bowen's disease of the finger while maintaining the full range of motion and use of the digit., Methods: Five patients were treated with CO2 laser vaporization for Bowen's disease of the digit. Patients were followed postoperatively for recurrence, clinical appearance, especially for scar formation, and function of the involved joints over a 6-month to 3-year period., Results: Four of five patients had no recurrence. Healing resulted in only modest alterations in the cosmetic appearance in comparison with the surrounding untreated skin. Posttreatment biopsy showed slight thinning of the epidermis and mild fibroplagia limited to the papillary dermis. Patients reported only mild post-procedure discomfort and no patients had any loss of function of the digit., Conclusions: CO2 laser vaporization may be a safe and effective means by which to eradicate Bowen's disease of the finger without the risk of scar contracture and loss of function of the digit.

Purpose: To evaluate the use of spiral/helical computed tomography (CT) in the preoperative evaluation of pediatric leukocoria., Methods: A total of 34 patient charts and imaging studies were reviewed from a consecutive series of children referred with the diagnosis of presumed retinoblastoma. Of these patients, 31 had a confirmed diagnosis of retinoblastoma. Three patients had simulating lesions, including one patient with persistent hyperplastic primary vitreous and two with Coats disease., Results: In all patients, a diagnosis of intraocular retinoblastoma could be established or excluded at the same clinical level by spiral CT as by conventional CT. Spiral CT of the eye, orbit, and midline structures was performed without a requirement for patient anesthesia. This technique resulted in a reduced volume of contrast material required for evaluation of the central nervous system and a small decrease in total radiation exposure. There was an attendant reduction in the amount of monitoring equipment required and the necessity for attending anesthesia staff., Conclusions: The primary advantage of spiral CT is reduced anesthesia risk in small children. In addition, this technique provides necessary clinical information with a reduction in image acquisition time, monitoring equipment, and monitoring staff.

Background: Acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) is a common complication of patients infected with human immunodeficiency virus and can cause significant morbidity. Long term therapy with standard chemotherapeutic regimens has been limited by relatively short durations of response and potential toxicity. Once therapy is discontinued, the disease typically progresses. Liposome-encapsulated doxorubicin (DOX-SL) currently is being evaluated for treating patients with AIDS-related KS. Early reports suggest a high response rate and good patient tolerance permitting continued therapy for extended periods., Methods: Patients with AIDS-related KS are treated with a DOX-SL regimen every 2-3 weeks and are followed carefully for evidence of adverse treatment effects., Results: Two cases of hand-foot syndrome (HFS) in patients receiving DOX-SL for AIDS-related KS are reported. Tissue studies demonstrated changes consistent with a toxic effect of the drug on keratinocytes. Hand-foot syndrome was reversible once treatment stopped; however, treatment cessation resulted in primary disease recurrence., Conclusions: Hand-foot syndrome can be debilitating and may be a limiting factor in the prolonged use of DOX-SL for AIDS-related KS for some patients. It is critical for clinicians using this drug to identify this side effect to limit HFS-associated morbidity.

A clinically useful classification system is suggested that can be used in prospective trials to evaluate the effects of radiation on the visual system. We review radiation-induced pathophysiological and clinical changes of the various ocular structures as well as dose-response data and management of ocular complications. The rationale for the classification scheme chosen is also discussed.

Genomic instability appears to play an important role in the development, growth, invasiveness, and eventual metastasis of the neoplastic cell. We have used a powerful new technique, comparative genomic hybridization, to evaluate genetic alterations in 10 fresh frozen uveal melanomas. Comparative genomic hybridization utilizes dual fluorescence in situ hybridization to characterize chromosome deletions and duplications, allowing for simultaneous evaluation of the entire human genome. Several consistent chromosomal abnormalities were detected. This study confirmed previous findings obtained using standard cytogenetic techniques but demonstrated an increased incidence in abnormalities of chromosomes 3 and 8; there was loss of chromosome 3 and duplication of 8q. In addition, we identified, although less frequently, other recurrent abnormal regions including alterations on chromosomes 6p, 7q, 9p, and 13q.

No effective treatment has been established for nonarteritic anterior ischemic optic neuropathy. Although most cases occur spontaneously, acute hypotension plays a clear role in a subset of patients. We examined three patients with severe visual loss from ischemic optic neuropathy induced by hypotension. The first patient developed anterior ischemic optic neuropathy after excessively rapid correction of malignant hypertension. In the second patient, anterior ischemic optic neuropathy occurred after an episode of orthostatic hypotension from systemic hypovolemia. The third patient developed anterior ischemic optic neuropathy after becoming hypotensive during a routine hemodialysis session. Measures were undertaken immediately to reverse the hypotension in all three patients. This intervention resulted in partial recovery of vision in each patient.

Background: Ocular lymphoma is an uncommon cause of chronic vitreitis or uveitis, often refractory to steroid treatment, and frequently representing another site of multifocal primary central nervous system lymphoma (PCNSL)., Methods: The authors reviewed the medical and ophthalmologic records of 24 patients with ocular lymphoma; 23 had associated PCNSL:, Results: In half, the eyes were the initial site of disease; in the others central nervous system (CNS) lymphoma developed before, or concurrent with, ocular lymphoma. Most patients had bilateral ocular symptoms; slit-lamp examination revealed asymptomatic disease in four. Vitrectomy was not always diagnostic, particularly in patients who had received steroids. Ocular ultrasound, performed on seven patients, provided an objective measure of disease and treatment response. Patients received a variety of therapeutic combinations of steroids, radiation, and chemotherapy, including high-dose cytosine arabinoside. Despite therapy, eventual ocular or CNS relapse or both was common. Thirteen patients have died, 12 with known recurrent CNS disease., Conclusions: Ocular lymphoma frequently is associated with PCNSL: The diagnosis should be considered in patients with steroid-resistant chronic vitreitis or uveitis. Patients with PCNSL should be carefully evaluated for ocular involvement, regardless of symptoms. Treatment can contribute to prolonged remission, but eventual ocular or CNS relapse is the rule.

Clamping surgical needles between the jaws of needle holders with teeth markedly weaken the needles, making them prone to breakage. In contrast, clamping surgical needles between either smooth needle holder jaws or jaws embedded with tungsten carbide particles did not alter the ductility of surgical needles.