Outbreak of Anthrax in Livestock with Human Occupational Exposures - Minnesota, 2023.

In July 2023, the Minnesota Department of Health (MDH) was notified of possible occupational exposures to anthrax during an outbreak in animals. In consultation with the Centers for Disease Control and Prevention, MDH epidemiologists created a questionnaire that assessed exposure risks and helped determine individual illness monitoring and antibiotic post-exposure prophylaxis needs. This investigation and the resources developed for it could be useful in future scenarios where there are occupational exposures to naturally occurring anthrax.

Modelling uptake and transport of therapeutic agents through the lymphatic system.

The ability of the lymphatic network to absorb large molecules and bypass the first-pass liver metabolism makes it appealing as a delivery system for therapeutic substances. In most cases, the drug is injected into the subcutaneous tissue and must negotiate the tissue space, before being drained via the lymphatics. Tracking the transport of drug molecules through this route is challenging, and computational models of lymphatic drainage can play an important role in assessing the efficacy of a proposed delivery strategy. The three-dimensional computational model we present here of the peripheral lymphatic network and surrounding interstitium is informed by anatomical data, and quantifies the degree to which uptake and transit times are affected by drug particle size, physiological flow rates, and specifics of drug injection.

Quality of life in breast cancer survivors: An assessment of international breast cancer dragon boat racers.

Resistance exercise is deemed safe for women recovering from conventional breast cancer therapies but few clinicians are aware that dragon boat racing, as a form of resistive exercise, is available to the breast cancer community. The objectives of this study were to 1) increase clinician awareness of dragon boat racing (DBR) in breast cancer survivors as a community-based physical activity, and 2) evaluate quality of life (QOL) in breast cancer survivors with or without lymphedema who participate in DBR. This prospective, observational study surveyed 1,069 international breast cancer dragon boat racers from eight countries to compare function, activity, and participation in women with and without selfreported lymphedema using the Lymph-ICF questionnaire. Seventy-one percent of women (n=758) completed the questionnaires. Results revealed significantly higher Lymph-ICF scores in the lymphedema participants, signifying reduced QOL, when compared to the nonlymphedema participants (p<0.05), except for "go on vacation" for which no statistical difference was reported (p=0.20). International breast cancer survivors with lymphedema participating in DBR at an international competition had reduced function, limited activity, and restricted participation compared to participants without lymphedema. Clinicians should consider utilizing DBR as a community-based activity to support exercise and physical activity after a breast cancer diagnosis.

Development of an in situ procedure to evaluate the reticulo-rumen morphology of sheep selected for divergent methane emissions.

Published studies have shown that methane yield (g CH4/kg dry matter) from sheep is positively correlated with the size (volume and surface area) of the reticulo-rumen (RR) and the weight of its contents. However, the relationship between CH4 yield and RR shape has not been investigated. In this work, shape analysis has been performed on a data set of computerised tomography (CT) scans of the RR from sheep having high and low CH4 yields (n=20 and n=17, respectively). The three-dimensional geometries of the RRs were reconstructed from segmented scan data and split into three anatomical regions. An iterative fitting technique combining radial basis functions and principal component (PC) fitting was used to create a set of consistent landmarks which were then used as variables in a PC analysis to identify shape variation within the data. Significant size differences were detected for regions corresponding to the dorsal and ventral compartments between sheep with high and low CH4 yields. When the analysis was repeated after scaling the geometries to remove the effect of size, there was no significant shape variation correlating with CH4 yield. The results have demonstrated the feasibility of CT-based computational shape determination for studying the morphological characteristics of the RR and indicate that size, but not shape correlates with CH4 yield in sheep.

Carbon dioxide insufflation deflects airborne particles from an open surgical wound model.

BACKGROUND: Surgical site infections remain a significant burden on healthcare systems and may benefit from new countermeasures. AIM: To assess the merits of open surgical wound CO2 insufflation via a gas diffuser to reduce airborne contamination, and to determine the distribution of CO2 in and over a wound. METHODS: An experimental approach with engineers and clinical researchers was employed to measure the gas flow pattern and motion of airborne particles in a model of an open surgical wound in a simulated theatre setting. Laser-illuminated flow visualizations were performed and the degree of protection was quantified by collecting and characterizing particles deposited in and outside the wound cavity. FINDINGS: The average number of particles entering the wound with a diameter of <5µm was reduced 1000-fold with 10L/min CO2 insufflation. Larger and heavier particles had a greater penetration potential and were reduced by a factor of 20. The degree of protection was found to be unaffected by exaggerated movements of hands in and out of the wound cavity. The steady-state CO2 concentration within the majority of the wound cavity was >95% and diminished rapidly above the wound to an atmospheric level (∼0%) at a height of 25mm. CONCLUSION: Airborne particles were deflected from entering the wound by the CO2 in the cavity akin to a protective barrier. Insufflation of CO2 may be an effective means of reducing intraoperative infection rates in open surgeries.

An Experimental and Numerical Investigation of CO2 Distribution in the Upper Airways During Nasal High Flow Therapy.

Nasal high flow (NHF) therapy is used to treat a variety of respiratory disorders to improve patient oxygenation. A CO2 washout mechanism is believed to be responsible for the observed increase in oxygenation. In this study, experimentally validated Computational Fluid Dynamics simulations of the CO2 concentration within the upper airway during unassisted and NHF assisted breathing were undertaken with the aim of exploring the existence of this washout mechanism. An anatomically accurate nasal cavity model was generated from a CT scan and breathing was reproduced using a Fourier decomposition of a physiologically measured breath waveform. Time dependent CO2 profiles were obtained at the entrance of the trachea in the experimental model, and were used as simulation boundary conditions. Flow recirculation features were observed in the anterior portion of the nasal cavity upon application of the therapy. This causes the CO2 rich gas to vent from the nostrils reducing the CO2 concentration in the dead space and lowering the inspired CO2 volume. Increasing therapy flow rate increases the penetration depth within the nasal cavity of the low CO2 concentration gas. A 65% decrease in inspired CO2 was observed for therapy flow rates ranging from 0 to 60 L min(-1) supporting the washout mechanism theory.

A double-blind placebo-controlled study of lithium in hospitalized aggressive children and adolescents with conduct disorder.

BACKGROUND: A subgroup of children and adolescents with conduct disorder are characterized by severe and persistent aggression. Although there is no agreed on treatment for such aggression, lithium carbonate has shown promise in some studies involving children. Our study was designed to critically assess the efficacy of lithium in the treatment of aggression in children and adolescents using a measure specific for aggression. METHODS: Subjects were inpatients with conduct disorder hospitalized because of severe and chronic aggression. A parallel-groups design was used in this double-blind, placebo-controlled trial with randomization to lithium or placebo. Only those who met the aggression criterion during the 2-week placebo-baseline period were randomized to 4 weeks of treatment. Outcome measures included Clinical Global Impressions, the Global Clinical Judgements (Consensus) Scale, and the Overt Aggression Scale. RESULTS: Eighty-six inpatients enrolled in the study; 40 (33 male and 7 female; median age, 12.5 years) entered and completed the treatment phase. Lithium was statistically and clinically superior to placebo. Sixteen of 20 subjects in the lithium group were responders on the Consensus ratings vs 6 of 20 in the placebo group (P=.004). Ratings on the Overt Aggression Scale decreased significantly for the lithium group vs the placebo group (P=.04). More than half of the subjects in the lithium group experienced nausea, vomiting, and urinary frequency. CONCLUSIONS: Lithium is a safe and effective short-term treatment for aggression in inpatients with conduct disorder, although its use is associated with adverse effects.

A boundary-integral representation for biphasic mixture theory, with application to the post-capillary glycocalyx.

We describe a new boundary-integral representation for biphasic mixture theory, which allows us to efficiently solve certain elastohydrodynamic-mobility problems using boundary element methods. We apply this formulation to model the motion of a rigid particle through a microtube which has non-uniform wall shape, is filled with a viscous Newtonian fluid, and is lined with a thin poroelastic layer. This is relevant to scenarios such as the transport of small rigid cells (such as neutrophils) through microvessels that are lined with an endothelial glycocalyx layer (EGL). In this context, we examine the impact of geometry upon some recently reported phenomena, including the creation of viscous eddies, fluid flux into the EGL, as well as the role of the EGL in transmitting mechanical signals to the underlying endothelial cells.

Variables affecting birthweight and graft survival in 197 pregnancies in cyclosporine-treated female kidney transplant recipients.

Outcomes from 197 pregnancies in 141 female kidney transplant recipients were analyzed from data collected via questionnaires, hospital records, and phone interviews. All recipients were maintained on cyclosporine (CsA) before and during pregnancy. Of the livebirths, 54% were premature (< 37 wk) and 50% were low-birthweight (LBW) (< 2500 g). The incidence of recipient drug-treated hypertension (HTN) was 56%; preeclampsia, 29%; infections and complications 22%; and rejection during pregnancy and up to 3 mo. post delivery (rej.), 11%. Graft loss within 2 years of delivery occurred in 9% of recipients (GrL < 2). No recipients reported a pregnancy after a postpregnancy graft loss. Mean serum creatinine was reported before, during, and after pregnancy. Mean cyclosporine doses were similar in recipients during and after pregnancy. Data were analyzed by logistic regression using SAS. Outcomes included prematurity, LBW, rej., and GrL < 2. In a case-controlled study comparing a recipient group with graft dysfunction during pregnancy vs. a group with good graft function, there was a trend toward lower mean prepregnancy CsA doses (in mg/kg) in the graft dysfunction group. A decline in recipient graft function during pregnancy is associated with lower newborn birthweights and lower maternal graft survival in cyclosporine treated female kidney recipients. Pregnancy-related infections and complications are associated with rejection and graft loss in this population. Close monitoring of CsA dosing and serum creatinine levels during pregnancy and immediately postpartum is recommended as CsA dosage adjustment may be required.

Diffuse choroidal melanoma. Clinical features predictive of metastasis.

OBJECTIVE: To assess the clinical features that predict metastasis of diffuse choroidal melanoma. DESIGN: A review of patients who had been diagnosed clinically as having diffuse choroidal melanoma evaluated on the Oncology Service at Wills Eye Hospital, Philadelphia, Pa. MAIN OUTCOME MEASURE: Effect on metastasis of clinical features of the tumor. RESULTS: Of 3500 consecutive patients with choroidal melanoma, 111 (3%) had diffuse choroidal melanoma. Of these 111 tumors, the mean tumor base was 14.7 mm and the mean overall tumor thickness was 2.1 mm. The thickness-to-base percentage averaged 14.8%. The tumor had poorly defined margins in 39 patients (35%), orange pigment on its surface in 49 (44%), and a secondary serous retinal detachment in 76 (68%). Optic nerve invasion was clinically suspected in 2 patients (2%) and transcleral extension in 3 (3%). Initial management was enucleation in 36 patients (32%), plaque radiotherapy in 60 (54%), laser photocoagulation in 3 (3%), and observation in 12 (11%). During a mean follow-up of 5.3 years (median, 3.9 years), metastasis developed in 29 patients (26%). Using Kaplan-Meier survival estimates, the probability of metastasis developing was 16% at 3 years, 24% at 5 years, and 36% at 10 years. The clinical factors predictive of metastasis by univariate analysis included tumor basal dimension 18 mm or more (P = .002), poorly defined tumor margins (P = .03), transcleral extension (P = .003), and optic nerve invasion (P = .03). The clinical factors predictive of metastasis by multivariate analysis included basal dimension of 18 mm or more (P = .01), optic nerve invasion (P = .03), and poorly defined tumor margins (P = .05). CONCLUSIONS: Despite its relative flatness, diffuse choroidal melanoma carries a metastatic potential of 24% at 5 years. The risks for metastasis are greatest with increasing tumor base and poorly defined margins. Recognition of the clinical features of this tumor in the earliest stage and prompt treatment are encouraged.

Plaque radiotherapy for juxtapapillary choroidal melanoma. Visual acuity and survival outcome.

OBJECTIVES: To assess the effect of plaque radiotherapy on the visual acuity of patients with juxtapapillary choroidal melanoma and to determine the clinical predictive factors for radiation retinopathy, radiation papillopathy, local tumor recurrence, and distant metastasis. DESIGN: A retrospective review of the medical records of 93 patients with juxtapapillary choroidal melanoma who were treated initially with plaque radiotherapy. RESULTS: During a mean follow-up of 78 months, radiation retinopathy developed in 81 patients (87%) and radiation papillopathy developed in 48 patients (52%) after a mean interval of 21 and 27 months, respectively. The univariate variables that were significant predictors of radiation retinopathy were history of diabetes mellitus (P = .05) and use of a notched radioactive plaque (P = .04). The factors predictive of radiation papillopathy were age (> 45 years; P = .01), history of diabetes mellitus (P = .05), mushroom-shaped tumor configuration (P = .006), and nasal location of the tumor (P = .04). By using Kaplan-Meier survival curves, we found that the proportion of the 93 patients with radiation retinopathy was 87 (94%) at 5 years and with radiation papillopathy was 53 (57%) at 5 years. By using life-table analysis, we found that the proportion of the 93 patients who experienced a decrement of at least 3 lines of visual acuity was 67 (72%) by 50 to 60 months. Local tumor recurrence was documented in 14 patients (15%) after a mean interval of 41 months. The age of the patient (< 35 years; P = .02) and the superior (P = .004) and inferior (P = .05) locations of the tumor were predictive of local tumor recurrence. Distant metastasis developed in 11 patients (12%) after a mean interval of 44 months. The factors predictive of distant metastasis were a tumor with a basal diameter larger than 6.0 mm (P = .05), the superior location of the tumor (P = .01), and local tumor recurrence (P < .001). CONCLUSION: Based on these observations, plaque radiotherapy remains a potential option vs enucleation for the management of juxtapapillary choroidal melanoma.

Combination of clinical factors predictive of growth of small choroidal melanocytic tumors.

OBJECTIVE: To better define the effect of individual risk factors and combinations thereof on the growth of small choroidal melanocytic tumors. DESIGN: Retrospective analysis. SETTING: Clinical practice of ocular oncology. PATIENTS: The study included 1287 patients with small suspicious choroidal melanocytic tumors, measuring 3 mm or less in thickness, managed with observation. RESULTS: On multivariate analysis, the clinical risk factors predictive of growth of small choroidal melanocytic tumors include tumor thickness greater than 2.0 mm, posterior tumor margin touching the disc, visual symptoms, orange pigment, and subretinal fluid. Tumor growth was detected in 4% of those patients with no risk factors. Growth was detected in approximately 36% of patients with 1 risk factor, 45% of patients with 2 risk factors, 50% of patients with 3 risk factors, 51% of patients with 4 risk factors, and 56% of patients with all 5 risk factors. The combination of risk factors offering the greatest risk for growth was tumor thickness greater than 2.0 mm, tumor margin touching disc, and subretinal fluid that was associated with tumor growth in 63% of the affected patients. The relative risk for growth was 1.9 for 1 factor, 3.8 for 2 factors, 7.4 for 3 factors, 14.1 for 4 factors, and 27.1 for all 5 risk factors combined. CONCLUSIONS: Five risk factors for growth of small choroidal melanocytic tumors have been identified. The combinations of various factors increase the risk for tumor growth from 4% if no factors are present to more than 50% if 3 or more risk factors are present. These factors may be important when counseling patients with small suspicious choroidal melanocytic tumors.

Radiation retinopathy following plaque radiotherapy for posterior uveal melanoma.

OBJECTIVE: To identify the risk factors that lead to the development of radiation retinopathy following plaque radiotherapy for posterior uveal melanoma. Radiation retinopathy is a slowly progressive, occlusive vasculopathy characterized by radiation-induced endothelial damage. METHODS: Review of the medical records of patients with posterior uveal melanoma treated with plaque radiotherapy. RESULTS: Of 1300 patients with posterior uveal melanoma treated with plaque radiotherapy from July 1, 1976, through June 30, 1992, radiation retinopathy developed in 560 (43.1%). By using Kaplan-Meier survival estimates, we found that 5% of the patients had nonproliferative radiation retinopathy at 1 year (95% confidence interval [CI], 3%-6%) and 42% at 5 years (95% CI, 38%-45%). The proportion of patients with proliferative retinopathy was 1% at 1 year (95% CI, 0.2%-1.5%) and 8% at 5 years (95% CI, 5%-10%). Multivariate analyses showed that the subset of clinical variables best related to the development of nonproliferative radiation retinopathy were tumor margin of less than 4 mm from foveola (P<.001), tumor limited to the choroid (P = .002), and radiation dose rate of greater than 260 cGy/h to the tumor base (P = .02). The best subset of independent variables related to the development of radiation maculopathy were tumor of less than 4 mm to foveola (P<.001) and the use of radioisotope iridium 192 (192Ir) (P = .02) compared with iodine 125 (125I). From a multivariate model, the most important factors for the development of proliferative radiation retinopathy included diabetes mellitus (P = .01), radioisotope 192Ir (P = .01) compared with 125I, and tumor base of greater than 10 mm (P = .02). CONCLUSIONS: Radiation retinopathy is a common finding after plaque radiotherapy for choroidal melanoma, occurring in 42% of patients at 5 years. The main predictors of radiation retinopathy are posterior tumor location with margin near the foveola and high radiation dose rate to the tumor base.

Plaque radiotherapy of uveal melanoma with predominant ciliary body involvement.

BACKGROUND: There are several options for management of ciliary body melanoma, including plaque radiotherapy, charged particle irradiation, local resection, and enucleation. The choice of therapy depends on many factors, and plaque radiotherapy is often used. OBJECTIVES: To determine the outcome of plaque radiotherapy in the management of ciliary body melanoma and to identify the risk factors associated with the development of radiation complications, tumor recurrence, metastasis, and melanoma-related death after plaque radiotherapy of ciliary body melanoma. METHODS: We analyzed the clinical records of 136 patients with ciliary body melanoma who were treated with plaque radiotherapy between July 1976 and June 1992. RESULTS: The median follow-up period was 70 months. Using Kaplan-Meier survival estimates, the most frequent radiation complication at 5 years' follow-up was cataract, developing in 48% of the patients, followed by neovascular glaucoma (21%), retinopathy (20%), scleral necrosis (12%), and vitreous hemorrhage (11%). Visual acuity decrease (by > or =3 Snellen lines) was noted in 40% of the patients at 5 years. Kaplan-Meier estimates showed that 8% of the patients developed recurrence, 28% had metastasis, and 22% died of melanoma-related causes by 5 years. Univariate analysis demonstrated that the factors predictive of radiation cataract were superonasal (P = .003) and inferior tumor meridian (P = .02) compared with inferonasal meridian and apex dose rate greater than 57 cGy/h (P = .05). The development of neovascular glaucoma was significantly related to iris involvement with the ciliary body tumor (P<.001). The factors predictive of development of radiation retinopathy were base dose rate greater than 230 cGy/h (P = .03) and the presence of diabetes mellitus (P = .05). The only predictor of metastasis was tumor thickness greater than 7 mm (P = .02). The risk factors for melanoma-related death were the presence of metastasis (P<.001), tumor thickness greater than 7 mm (P = .02), and recurrence (P = .02). Multivariate analyses showed that the most significant variables predictive of the development of scleral necrosis were intraocular pressure greater than 15 mm Hg (P<.001) and tumor thickness greater than 7 mm (P = .007). The most significant predictive factors for vitreous hemorrhage were visual acuity of 20/40 to 20/200 (P = .02) and intraocular pressure greater than 15 mm Hg (P = .02). The best subset of independent predictors of vision decrease were mushroom tumor shape (P = .002), age older than 61 years (P = .006), and superonasal meridian (P = .04). The risks for melanoma-related death were presence of metastasis (P<.001) and tumor thickness greater than 7 mm (P = .01). There was no group of significant variables predictive for radiation cataract, neovascular glaucoma, retinopathy, tumor recurrence, and metastasis in multivariate analysis. CONCLUSIONS: Plaque radiotherapy offers 92% 5-year local control rate for ciliary body melanoma. Metastasis occurs in 28% of the patients treated with this method by 5 years. Patients with tumors greater than 7 mm in thickness are at greater risk than patients with thinner tumors for metastatic disease and melanoma-related death. Major radiation complications include radiation cataract, neovascular glaucoma, retinopathy, and scleral necrosis.

Conjunctival melanoma: risk factors for recurrence, exenteration, metastasis, and death in 150 consecutive patients.

OBJECTIVE: To identify the risk factors of conjunctival malignant melanoma that predict local tumor recurrence, orbital exenteration, distant metastasis, and tumor-related mortality. DESIGN: The clinical parameters of the patient, tumor, and treatment were analyzed in a nonrandomized fashion for their relation to 4 main outcome measures using Cox proportional hazards regression models. PARTICIPANTS: One hundred fifty consecutive patients. MAIN OUTCOME MEASURES: Local tumor recurrence, orbital exenteration, distant metastasis, and death from conjunctival melanoma. RESULTS: The Kaplan-Meier estimates of local tumor recurrence was 26% at 5 years, 51% at 10 years, and 65% at 15 years. The mean number of recurrences per patient was 1 (median, 0 recurrences). There was no recurrence in 98 patients (65%), 1 recurrence in 28 patients (19%), 2 recurrences in 11 patients (7%), 3 recurrences in 5 patients (3%), and 4 or more recurrences in 8 patients (5%). Using multivariate analysis, the factors correlated with local tumor recurrence were melanoma location (not touching the limbus) (P =.01) and pathological tumor margins (lateral margin involved) (P =.02). Multivariate analysis for features correlated with ultimate exenteration included initial visual acuity (20/40 OU or worse) (P<. 001), melanoma color red (P =.01), and melanoma location (not touching the limbus) (P =.02). Tumor metastasis was present in 16% of patients at 5 years, 26% of patients at 10 years, and 32% of patients at 15 years. Metastasis was first located in the regional lymph nodes in 17 cases, the brain in 4 cases, the liver in 3 cases, the lung in 2 cases, and was disseminated in 1 case. The risks for metastases using multivariate analysis included pathological tumor margins (lateral margin involved) (P =.002) and melanoma location (not touching limbus) (P =.04). Tumor-related death occurred in 7% patients at 5 years' follow-up and 13% at 8 years' follow-up. The risk factors for death using multivariate analysis included initial symptoms (lump) (P =.004) and pathologic findings (de novo melanoma without primary acquired melanosis) (P =.05). The technique of initial surgery was shown to be an important factor in preventing eventual tumor recurrence (P =.07), metastasis (P =.03), and death (P =.006) in the univariate analysis, but did not reach significance in the multivariate analysis. CONCLUSIONS: Conjunctival malignant melanoma is a potentially deadly tumor. In the present study, metastasis was detected in 26% of patients, and death occurred in 13% of patients at 10 years. Extralimbal melanoma and tumor involvement of the surgical margins were especially poor prognostic factors. Meticulous surgical planning using wide microsurgical excisional biopsy working with the "no touch" technique and supplemental alcohol corneal epitheliectomy and conjunctival cryotherapy is advised. Arch Ophthalmol. 2000;118:1497-1507

Plaque radiotherapy for uveal melanoma: long-term visual outcome in 1106 consecutive patients.

OBJECTIVE: To identify clinical predictive factors for visual outcome in a large series of patients who underwent plaque radiotherapy for uveal melanoma. DESIGN: Clinical factors, including patient data, tumor features, and radiation variables, were analyzed for their impact on visual acuity using Cox proportional hazards regression models. PARTICIPANTS: Patients with uveal melanoma and initial visual acuity of 20/100 or better in the affected eye who were treated with plaque radiotherapy between July 1976 and June 1992. MAIN OUTCOME MEASURES: Two end points were used to evaluate posttreatment visual acuity: (1) final visual acuity (good [20/20-20/100] vs poor [20/200 to no light perception]) and (2) loss of visual acuity (minimal [<5 lines Snellen visual acuity] vs moderate [> or = 5 lines Snellen visual acuity]). RESULTS: Of 1300 consecutive patients with uveal melanoma treated by plaque radiotherapy, 1106 had a visual acuity of 20/100 or better at the time of treatment. In this group, poor visual acuity was found in 34% at 5 years and 68% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted poor visual acuity were increasing tumor thickness, proximity to foveola of less than 5 mm, notched plaque shape, tumor recurrence, patient age 60 years or older, subretinal fluid, cobalt isotope, anterior tumor margin posterior to equator, and worse initial visual acuity. Moderate loss of visual acuity of 5 Snellen lines or more was found in 33% at 5 years and 69% at 10 years of follow-up. From multivariable analysis, clinical factors that best predicted moderate visual acuity loss included increasing tumor thickness, worse initial visual acuity, notched plaque shape, tumor recurrence, proximity to foveola of less than 5 mm, patient age of 60 years or older, subretinal fluid, and diabetes mellitus or hypertension. When analyzing visual outcome with regard to tumor thickness, ultimate poor visual acuity of 20/200 or worse at 5 years was found in 24% with a small melanoma (< or = 3.0 mm), 30% with a medium melanoma (3.1-8.0 mm), and 64% with a large melanoma (>8.0 mm). When analyzing visual outcome with regard to tumor proximity to visually important structures, tumors less than 5 mm from the optic disc or foveola demonstrated poor visual acuity in 35% at 5 years, whereas those 5 mm or more from the optic disc and foveola showed poor visual acuity in 25% at 5 years. CONCLUSIONS: Ultimate visual acuity after plaque radiotherapy for uveal melanoma depends on many factors, including patient age and general health, initial visual acuity, tumor location and size, subretinal fluid, radioactive isotope, and final tumor control. At 10 years' follow-up, 68% of patients demonstrate poor visual acuity. Visual acuity is most effectively preserved in eyes with small tumors outside a radius of 5 mm from the optic disc and foveola. Arch Ophthalmol. 2000;118:1219-1228

Familial uveal melanoma. Clinical observations on 56 patients.

OBJECTIVE: To study the clinical profile and kindreds of patients with familial uveal melanoma (FUM). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Medical charts of 4500 patients with uveal melanoma were reviewed for family history of uveal melanoma. The clinical profile of these patients and their kindreds were studied to determine the incidence of FUM and pattern of inheritance. The association of FUM to cutaneous melanoma, familial atypical mole and melanoma syndrome, and other nonmelanocytic cancers was analyzed using statistical methods. RESULTS: Of 4500 patients with uveal melanoma, 56 patients in 27 families (0.6%) had a family history of uveal melanoma. The uveal melanoma in all 56 familial patients was unilateral. In 17 cases (63%), the second affected relative was a first-degree relative. In the remainder, the second affected relative was a second- (22%) and third-degree (15%) relative. In 25 families (93%) only two members were affected, and in two families (7%) three members had uveal melanoma. Patients with FUM were four times as likely to have a second primary malignant neoplasm than were people in the general population. However, no evidence was seem that unaffected kindreds of patients with FUM were at higher risk of having a second primary malignant neoplasm. CONCLUSIONS: Familial involvement in uveal melanoma is rare. Familial uveal melanoma most often (63%) affects first-degree relatives, rarely affects more than two persons in a family, and may be associated with a generalized inherited predisposition to cancer. Further genetic studies are necessary to fully characterize FUM syndrome.

Thermotherapy for retinoblastoma.

OBJECTIVE: To evaluate the results of thermotherapy for retinoblastoma. DESIGN: Prospective, nonrandomized analysis of the treatment method. PARTICIPANTS: A total of 188 retinoblastomas in 80 eyes of 58 patients who were treated with thermotherapy. MAIN OUTCOME MEASURES: Tumor response and ocular adverse effects. RESULTS: Of 188 retinoblastomas treated with thermotherapy, mean tumor base was 3.0 mm and tumor thickness was 2.0 mm. Complete tumor regression was achieved in 161 tumors (85.6%), and 27 tumors (14.4%) developed recurrence. Using univariate analysis, the predictors of local tumor recurrence were male sex (P = .005), no color change ("no visible take") in tumor after treatment (P = .01), increasing number of treatment sessions (P = .002), and previous use of chemoreduction (P = .02). By multivariate analysis, the most important predictors of local tumor recurrence were male sex (P = .01) and previous use of chemoreduction (P = .03), the latter likely reflecting the fact that these tumors were initially larger with more ominous findings, and required chemoreduction therapy to reduce them to a size amenable to focal treatment with thermotherapy. When evaluating thermotherapy variables as a function of tumor size, it was apparent that larger tumors (> or =3.0-mm base) required greater energy and time than did smaller tumors (<3.0-mm base). Comparison of treatment variables for larger vs smaller tumors was as follows: number of treatment sessions, 3.3 vs 2.3; spot size, 1.7 vs 1.3 mm; power, 540 vs 370 mW; treatment duration, 49 vs 14 minutes; and coupling of thermotherapy with chemotherapy, 79% vs 48% of cases (P < or =.001 for each variable). Complications of thermotherapy in the 80 eyes included focal iris atrophy in 29 eyes (36%), peripheral focal lens opacity in 19 eyes (24%), retinal traction in 4 eyes (5%), retinal vascular obstruction in 2 eyes (2%), and transient localized serous retinal detachment in 2 eyes (2%). There were no cases of corneal scarring, central lens opacity, iris or retinal neovascularization, or rhegmatogenous retinal detachment. All eyes with focal lens opacity demonstrated adjacent focal iris atrophy. By multivariate analysis, the predictors of thermotherapy-induced focal iris atrophy were increasing number of treatment sessions (P = .001) and increasing tumor base (P = .02). CONCLUSIONS: Thermotherapy is used for relatively small retinoblastomas without associated vitreous or subretinal seeds. This treatment provides satisfactory control for selected retinoblastomas, with 86% of tumors demonstrating lasting regression. Tumors that measure 3.0 mm or larger in base at the time of thermotherapy require more intense treatment than smaller tumors and are at greatest risk for ocular complications such as focal iris atrophy and focal paraxial lens opacity.

The outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma.

OBJECTIVE: To determine the outcome of chemoreduction treatment in patients with Reese-Ellsworth group V retinoblastoma. METHODS: Prospective analysis of 27 eyes in 22 patients with group V retinoblastoma treated with either 2- or 6-cycle chemoreduction and focal treatment methods (argon laser photocoagulation, transpupillary thermotherapy, cryotherapy, and plaque radiotherapy). The need for external beam irradiation and the eventual globe salvage rate were assessed. Median follow-up was 28 months. RESULTS: There were 16 eyes in the 2-cycle chemoreduction treatment group and 11 eyes in the 6-cycle chemoreduction treatment group. No significant difference was noted between the 2 groups with respect to baseline patient and eye findings. After chemoreduction treatment, external beam irradiation was necessary in 12 (75%) of 16 eyes in the 2-cycle chemoreduction treatment group and in 4 (36%) of 11 eyes in the 6-cycle chemoreduction treatment group. There was no statistical difference between the 2- and 6-cycle chemoreduction treatment groups with respect to necessity for external beam irradiation (logistic regression analysis). All 4 eyes in the 2-cycle chemoreduction treatment group and 3 of 12 eyes in the 2-cycle chemoreduction treatment and irradiation group were eventually enucleated, the globe salvage rates being 0% and 75%, respectively. Two of 7 eyes in the 6-cycle chemoreduction treatment group and 1 of 4 eyes in the 6-cycle chemoreduction treatment and irradiation group were enucleated, the globe salvage rates being 71% and 75%, respectively. Except for the 2-cycle chemoreduction treatment group, in which the globe salvage rate was significantly lower (P = .03), there was no difference among the other 3 groups (2-cycle chemoreduction treatment and irradiation, 6-cycle chemoreduction treatment, and 6-cycle chemoreduction treatment and irradiation) with respect to globe salvage (logistic regression analysis). CONCLUSIONS: Local tumor control of group V retinoblastoma is possible with 6-cycle chemoreduction and focal therapy when external beam irradiation is not used. A larger sample size is necessary to determine how often external beam irradiation can be avoided.

Olanzapine versus haloperidol in children with autistic disorder: an open pilot study.

OBJECTIVES: Conventional neuroleptics ameliorate symptoms in children with autistic disorder; however, they are known to cause dyskinesias. Atypical neuroleptics, including olanzapine, may have less risk for dyskinesia, but their efficacy in autistic disorder is not established. This study was designed to investigate the safety and effectiveness of open-label olanzapine as a treatment for children with autistic disorder by using haloperidol as a standard comparator treatment. METHOD: In a parallel groups design, 12 children with DSM-IV autistic disorder (mean age 7.8+/-2.1 years) were randomized to 6 weeks of open treatment with olanzapine or haloperidol. Mean final dosages were 7.9+/-2.5 mg/day for olanzapine and 1.4+/-0.7 mg/day for haloperidol. Outcome measures included the Clinical Global Impressions (CGI) and the Children's Psychiatric Rating Scale (CPRS). RESULTS: Both groups had symptom reduction. Five of six in the olanzapine group and three of six in the haloperidol group were rated as responders according to the CGI Improvement item. Subjects showed improvement on the CPRS Autism Factor (F1,9 = 24.4, p = .0008). Side effects included drowsiness and weight gain. CONCLUSIONS: The findings suggest that olanzapine is a promising treatment for children with autistic disorder. Further placebo-controlled and long-term studies of olanzapine in autistic disorder are required.