Plasma Metabolic and Lipidomic Fingerprinting of Individuals with Increased Intestinal Permeability.

The dual-sugar intestinal permeability test is a commonly used test to assess changes in gut barrier function. However, it does not identify functional changes and the exact mechanism of damage caused by the increased intestinal permeability. This study aims to explore the application of untargeted metabolomics and lipidomics to identify markers of increased intestinal permeability. Fifty fasting male participants (18-50 years) attended a single visit to conduct the following procedures: assessment of anthropometric measures, assessment of gastrointestinal symptoms, intestinal permeability test, and assessment of blood samples 90 min post-administration of the intestinal permeability test. Rhamnose and lactulose were analysed using gas chromatography-mass spectrometry (GC-MS). Untargeted polar metabolites and lipidomics were assessed by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QToF MS). There was an elevated lactulose/rhamnose ratio in 27 subjects, indicating increased permeability compared to the remaining 23 control subjects. There were no significant differences between groups in characteristics such as age, body mass index (BMI), weight, height, and waist conference. Fourteen metabolites from the targeted metabolomics data were identified as statistically significant in the plasma samples from intestinal permeability subjects. The untargeted metabolomics and lipidomics analyses yielded fifteen and fifty-one statistically significant features, respectively. Individuals with slightly elevated intestinal permeability had altered energy, nucleotide, and amino acid metabolism, in addition to increased glutamine levels. Whether these biomarkers may be used to predict the early onset of leaky gut warrants further investigation.

Oculocardiac reflex in a medial orbital wall fracture without clinically evident entrapment.

In this report, we describe a patient with a medial wall orbital fracture, who presented with vasovagal-like symptoms secondary to an oculocardiac reflex. This case is unusual because the patient had no other clinical evidence of muscle entrapment. A 15-year-old male presented with daily 5-10 min episodes of dizziness, light headedness, and nausea consistent with a vasovagal reaction. On examination, the patient had full extra ocular motility and was orthotropic in all fields of gaze. On computed tomography a comminuted medial orbital wall fracture was identified. The adjacent medial rectus muscle was in normal position, but was "rounded" relative to the contralateral side. The patient underwent fracture repair with immediate resolution of all symptoms. Symptoms related to a vasovagal response may occur with orbital fractures despite normal extra ocular motility. Presumably this relates to tension or pulling on an extra ocular muscle, which is not to a degree that alteration in function is appreciable clinically.

Surgical management of an optic nerve glioma with perineural arachnoidal gliomatosis growth pattern.

We describe a vision sparing surgical approach for optic nerve glioma. A 7-year-old girl experienced declining academic performance and social withdrawal attributed to progressive disfiguring proptosis. Three years earlier, she had undergone a limited biopsy, a course of chemotherapy, and orbital radiation therapy for a right optic nerve glioma with perineural arachnoidal gliomatosis (PAG). Because of marked proptosis, another surgery was performed via a lateral orbitotomy. After cutting a window in the thickened dura of the optic nerve, rouge colored spongy tissue was suctioned from the subarachnoid space. Small, more solidified areas were excised with unipolar cautery. Care was taken to avoid identifiable blood vessels and the optic nerve, and approximately 60%-70% of the tumor was removed. The dural window was approximated with interrupted sutures. Postoperatively, there was 9 mm reduction in right proptosis and visual acuity improved to from 20/70 to 20/60. This case illustrates the possibility of debulking optic nerve gliomas without sacrificing vision. It should be stressed that this technique is only applicable to gliomas with PAG and the durability of the surgical benefit is unknown.

Long-term management of orbital and systemic reactive lymphoid hyperplasia with rituximab.

Rituximab, a monoclonal antibody to the B cell marker CD20, is becoming increasingly popular in the treatment of various orbital disorders. In this university-based interventional case series, we describe two patients with bilateral orbital and extra-orbital reactive lymphoid hyperplasia (RLH) treated with rituximab. Initially both had favorable responses; but roughly a year later recurrent disease necessitated maintenance therapy in both cases. Both again responded to additional courses of rituximab. Although recalcitrant disease may persist after treatment, rituxmab may play a role in the management of RLH with widespread involvement.

Evisceration in the modern age.

Evisceration is an ophthalmic surgery that removes the internal contents of the eye followed usually by placement of an orbital implant to replace the lost ocular volume. Unlike enucleation, which involves removal of the entire eye, evisceration potentially causes exposure of uveal antigens; therefore, historically there has been a concern about sympathetic ophthalmic (SO) associated with evisceration. However, critical review of the literature shows that SO occurs very rarely, if ever, as a consequence of evisceration. Its clinical applications overlap with those of enucleation in cases of penetrating ocular trauma and blind painful eyes, but it is absolutely contraindicated in the setting of suspected intraocular malignancy and may be preferred for treatment of end-stage endophthalmitis. From a technical standpoint, traditional evisceration has a limitation in the orbital implant size. Innovations with scleral modification have overcome this limitation, and accordingly, due to its simplicity, efficiency, and good cosmetic results, evisceration has once again been gaining popularity.

Orbital trapdoor fractures.

Orbital trapdoor fractures are commonly encountered in children. Awareness of trapdoor fractures is of particular importance. This is because early recognition and treatment are necessary to prevent permanent motility abnormities. In this article, we will provide a brief overview of orbital fractures. The clinical and radiographic features of trapdoor fractures will then be reviewed, followed by a discussion on their proper management.

Physical and biological aspects of renal vitrification.

Cryopreservation would potentially very much facilitate the inventory control and distribution of laboratory-produced organs and tissues. Although simple freezing methods are effective for many simple tissues, bioartificial organs and complex tissue constructs may be unacceptably altered by ice formation and dissolution. Vitrification, in which the liquids in a living system are converted into the glassy state at low temperatures, provides a potential alternative to freezing that can in principle avoid ice formation altogether. The present report provides a brief overview of the problem of renal vitrification. We report here the detailed case history of a rabbit kidney that survived vitrification and subsequent transplantation, a case that demonstrates both the fundamental feasibility of complex system vitrification and the obstacles that must still be overcome, of which the chief one in the case of the kidney is adequate distribution of cryoprotectant to the renal medulla. Medullary equilibration can be monitored by monitoring urine concentrations of cryoprotectant, and urine flow rate correlates with vitrification solution viscosity and the speed of equilibration. By taking these factors into account and by using higher perfusion pressures as per the case of the kidney that survived vitrification, it is becoming possible to design protocols for equilibrating kidneys that protect against both devitrification and excessive cryoprotectant toxicity.

Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life.

PURPOSE: To determine the incidence of new chorioretinal lesions in children with toxoplasmosis diagnosed after, and therefore not treated during, their first year. DESIGN: Prospective longitudinal cohort study. METHODS: Thirty-eight children were evaluated in Chicago between 1981 and 2005 for new chorioretinal lesions. Thirty-eight children and mothers had serum IgG antibody to Toxoplasma gondii. RESULTS: Twenty-eight of 38 children had one of the following: diagnosis with serum antibody to T. gondii indicative of chronic infection at age 24 months, central nervous system calcifications, hydrocephalus, illness compatible with congenital toxoplasmosis perinatally but not diagnosed at that time. Twenty-five returned for follow-up during 1981 to 2005. Their mean (range) age at last exam was 10.9 +/- 5.7 (range, 3.5 to 27.2) years and mean follow-up was 5.7 +/- 2.9 years. Eighteen (72%) children developed at least one new lesion. Thirteen (52%) had new central lesions, 11 (44%) had new peripheral lesions, and six (24%) had both. Thirteen (52%) had new lesions diagnosed at age > or =10 years. New lesions were found at more than one visit in four (22%), and bilateral new lesions developed in seven (39%) of 18 children who developed new lesions. Of 10 additional children with eye findings and serologic tests indicative of chronic infection, six returned for follow-up, four (67%) developing new lesions at > or =10 years of age. CONCLUSIONS: More than 70% developed new chorioretinal lesions. New lesions were commonly diagnosed after the first decade of life.

Longitudinal study of new eye lesions in treated congenital toxoplasmosis.

OBJECTIVE: To determine the incidence of new chorioretinal lesions in patients with congenital toxoplasmosis who were treated throughout their first year of life. DESIGN: Prospective longitudinal observation of a cohort. PARTICIPANTS: One hundred thirty-two children were studied as part of the longitudinal observation. METHODS: One hundred thirty-two children were treated during their first year of life with pyrimethamine, sulfadiazine, and leucovorin. They had eye examinations at prespecified intervals. MAIN OUTCOME MEASURES: New chorioretinal lesions on fundus examination and fundus photographs. RESULTS: The mean age (+/- standard deviation) is 10.8+/-5.1 years (range, 0.2-23). One hundred eight children have been evaluated for new chorioretinal lesions. Thirty-four (31%; 95% confidence interval, 23%-41%) of 108 children developed at least one chorioretinal lesion that was previously undetected. These occurred at varying times during their follow-up course. Fifteen children (14%) developed new central lesions, and 27 (25%) had newly detected lesions peripherally. Ten (9%) had more than one occurrence of new lesions developing, and 13 (12%) had new lesions in both eyes. Of those who developed new lesions, 14 children (41%) did so at age 10 or later. CONCLUSION: New central chorioretinal lesions are uncommon in children with congenital toxoplasmosis who are treated during their first year of life. This finding contrasts markedly with earlier reports in the literature for untreated children or those treated for only 1 month near birth, in whom new lesions were much more prevalent (>/=82%). Our observation that 14 (41%) of the 34 children with new chorioretinal lesions had occurrences when they were 10 years or older indicates that long-term follow-up into the second decade of life is important in assessing the efficacy of treating toxoplasmosis during infancy.

Primary acquired melanosis of the conjunctiva: risks for progression to melanoma in 311 eyes. The 2006 Lorenz E. Zimmerman lecture.

PURPOSE: To evaluate the clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. DESIGN: Noncomparative case series. PARTICIPANTS: Three hundred eleven eyes with conjunctival PAM without melanoma at initial examination from a single-center tertiary referral center. METHODS: Retrospective chart review with evaluation of the clinical features of PAM at initial presentation and follow-up. Times to PAM enlargement, recurrence, and transformation into melanoma were assessed using Kaplan-Meier estimates. Risk factors for these outcomes were analyzed using Cox proportional hazards regressions. MAIN OUTCOME MEASURES: Primary acquired melanosis enlargement, recurrence, and transformation into melanoma. RESULTS: Mean patient age at diagnosis of PAM was 56 years (range, 15-90), 62% were female, and 96% were Caucasian. The conjunctival quadrant(s) affected by PAM were temporal (57%), inferior (45%), nasal (42%), and superior (37%). The anatomic location(s) of PAM included bulbar conjunctiva (91%), limbal conjunctiva (55%), cornea (23%), forniceal conjunctiva (13%), palpebral conjunctiva (12%), and caruncle (11%). Primary acquired melanosis extended for a mean of 3 clock hours (range, 1-12). Initial management included observation (n = 194 eyes [62%]), biopsy combined with cryotherapy (n = 107 eyes [34%]), and topical chemotherapy and/or cryotherapy without biopsy (n = 10 [4%]). Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of cases of PAM without atypia, 0% of cases of PAM with mild atypia, and 13% of cases of PAM with severe atypia. Of the 9 patients with PAM who developed melanoma, none have developed systemic metastasis. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. CONCLUSION: Primary acquired melanosis without atypia or with mild atypia shows 0% progression to melanoma, whereas PAM with severe atypia shows progression to melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation to melanoma.

Primary acquired melanosis of the conjunctiva: experience with 311 eyes.

PURPOSE: To evaluate clinical features and risks for transformation of conjunctival primary acquired melanosis (PAM) into melanoma. METHODS: Retrospective chart review and Kaplan-Meier estimates of times to PAM enlargement, recurrence, and transformation into melanoma. MAIN OUTCOME MEASURES: PAM enlargement, recurrence, and transformation into melanoma. RESULTS: The mean patient age at diagnosis of PAM was 56 years; 62% were female and 96% Caucasian. The conjunctival quadrant(s) affected by PAM and its extent in clock hours were recorded. Initial management included observation in 62%, biopsy combined with cryotherapy in 34%, and other methods in 4%. Of PAM that was observed, Kaplan-Meier estimates at 10 years revealed PAM enlargement in 35% and transformation into melanoma in 12%. Of those that underwent incisional or excisional biopsy, 10-year estimates of PAM recurrence and transformation into melanoma were 58% and 11%, respectively. Progression to melanoma occurred in 0% of PAM without atypia, 0% of PAM with mild atypia, and 13% of PAM with severe atypia. Multivariable analysis revealed that the most significant factor for both PAM recurrence and progression to melanoma was extent of PAM in clock hours. CONCLUSION: PAM without atypia or with mild atypia shows 0% progression into melanoma, whereas PAM with severe atypia shows progression into melanoma in 13%. The greater the extent of PAM in clock hours, the greater the risk for transformation into melanoma.

Delays in suspicion and isolation among hospitalized persons with pulmonary tuberculosis at public and private US hospitals during 1996 to 1999.

BACKGROUND: While prior studies have shown that public and private hospitals differ in their rates of suspicion and isolation of patients who are at risk for tuberculosis (TB), no study has investigated whether this variation is due to differences in the impact of patient case-mix on hospitals or to variations attributable to specific hospital practice patterns. OBJECTIVE: To investigate patient-level and hospital-level factors associated with delays in TB suspicion and isolation among inpatients with pulmonary TB disease. DESIGN: Retrospective cohort study of patients hospitalized with culture-positive pulmonary TB during 1996 to 1999. SETTING: Patients with culture-proven pulmonary TB treated at three public hospitals (765 patients) and seven not-for-profit private hospitals (172 patients) in Chicago, Los Angeles, and southern Florida that provided care for five or more patients with TB per year during the study period. MEASUREMENTS: Two-day rates (within 48 h from admission) of acid-fast bacilli (AFB) smear orders and 1-day rates (within 24 h from admission) of TB isolation. RESULTS: Two-day rates of ordering AFB smears were > 80% at three public and two private hospitals vs 65 to 75% at five private hospitals. One-day rates of TB isolation at the three public hospitals were 64%, 79%, and 86%, respectively, vs 39 to 58% at the seven private hospitals. Delays of > 2 days in ordering AFB smears were associated with patient-level factors: absence of cough (adjusted odds ratio [AOR], 6.02; 95% confidence interval [CI], 3.82 to 9.52), cavitary lung lesion (AOR, 5.17; 95% CI, 1.98 to 13.50), night sweats (AOR, 3.38; 95% CI, 1.90 to 5.99), chills (AOR, 1.70; 95% CI, 1.01 to 2.88), and female gender (AOR, 1.66; 95% CI, 1.06 to 2.60). Delays of > 1 day in ordering pulmonary isolation were associated with patient-level factors: absence of cough (AOR, 3.40; 95% CI, 2.31 to 5.03), cavitary lung lesion (AOR, 2.66; 95% CI, 1.57 to 4.50), night sweats (AOR, 1.98; 95% CI, 1.35 to 2.92), and history of noninjecting drug use (AOR, 1.86; 95% CI, 1.16 to 2.99) and one hospital-level factor: receiving care at a nonpublic hospital. Even after adjustment for patient-level factors, TB patients at private hospitals were half as likely as those at public hospitals to be placed in pulmonary isolation (AOR, 0.47; 95% CI, 0.30 to 0.72), while odds of suspecting TB in these same patients were similar at both hospitals. CONCLUSION: Private hospitals should order TB isolation for all patients for whom AFB smears are ordered, a policy that has been instituted previously at public hospitals in our study.

HIV-related pneumonia care in older patients hospitalized in the early HAART era.

Age-related variations in care have been identified for HIV-associated Pneumocystis carinii pneumonia (PCP) in both the 1980s and 1990s. We evaluated if age-related variations affected all aspects of HIV-specific and non-HIV-specific care for HIV-infected individuals with PCP or community-acquired pneumonia (CAP), or whether age-related variations were primarily limited to HIV-specific aspects of care. Subjects were HIV-infected persons with PCP (n = 1855) or CAP (n = 1415) hospitalized in 8 cities from 1995 to 1997. Nine percent of our study patients had received protease inhibitors and 39% had received any type of antiretroviral therapy prior to hospitalization. Data were abstracted from medical records and included severity of illness, HIV-specific aspects of care (initiation of PCP medications), general measures of care [initiation of CAP medications, intubation, and intensive care units (ICU)], and inpatient mortality. Compared to younger patients, pneumonia patients 50 years of age or older were significantly more likely to: be severely ill (PCP, 20.4% vs. 10.4%; CAP, 27.5% vs. 14.9%; each p = 0.001), receive ICU care (PCP, 22.0% vs. 12.8%, p = 0.002; CAP: 15.1% vs. 9.4%; p = 0.02), and be intubated (PCP, 14.6% vs. 8.4%, p = 0.01; CAP, 9.9% vs. 5.6%, p = 0.03). Compared to younger patients, older patients (>/=50 years) had similar rates of timely medications for CAP (48.5% vs. 50.8%) but had lower rates of receiving anti-PCP medications (85.8% vs. 92.9%, p = 0.002). Differences by age in timely initiation of PCP medications, ICU use, and intubation were limited to the nonseverely ill patients. Older hospitalized patients were more likely to die (PCP, 18.3% vs. 10.4%; CAP, 13.4% vs. 8.5%; each p < 0.05). After adjustment for disease severity and timeliness of antibiotic use, mortality rates were similar for both age groups. Physicians should develop strategies that increase awareness of the possibility of HIV infection in older individuals.

US hospital care for patients with HIV infection and pneumonia: the role of public, private, and Veterans Affairs hospitals in the early highly active antiretroviral therapy era.

STUDY OBJECTIVES: We evaluated differences in processes and outcomes of HIV-related pneumonia care among patients in Veterans Affairs (VA), public, and for-profit and not-for-profit private hospitals in the United States. We compared the results of our current study (1995 to 1997) with those of our previous study that included a sample of patients receiving care during the years 1987 to 1990 to determine how HIV-related pneumonia care had evolved over the last decade. SETTING/PATIENTS: The sample consisted of 1,231 patients with HIV infection who received care for Pneumocystis carinii pneumonia (PCP) and 750 patients with HIV infection who received care for community-acquired pneumonia (CAP) during the years 1995 to 1997. MEASUREMENT: We conducted a retrospective medical record review and evaluated patient and hospital characteristics, HIV-related processes of care (timely use of anti-PCP medications, adjunctive corticosteroids), non-HIV-related processes of care (timely use of CAP treatment medications, diagnostic testing, ICU utilization, rates of endotracheal ventilation, placement on respiratory isolation), length of inpatient hospital stay, and inpatient mortality. RESULTS: Rates of timely use of antibiotics and adjunctive corticosteroids for treating PCP were high and improved dramatically from the prior decade. However, compliance with consensus guidelines that recommend < 8 h as the optimal time window for initiation of antibiotics to treat CAP was lower. For both PCP and CAP, variations in processes of care and lengths of in-hospital stays, but not mortality rates, were noted at VA, public, private not-for-profit hospitals, and for-profit hospitals. CONCLUSIONS: This study provides the first overview of HIV-related pneumonia care in the early highly active antiretroviral therapy era, and contrasts current findings with those of a similarly conducted study from a decade earlier. Quality of care for patients with PCP improved, but further efforts are needed to facilitate the appropriate management of CAP. In the third decade of the epidemic, it will be important to monitor whether variations in processes of care for various HIV-related clinical diagnoses among different types of hospitals persist.

Relationship between health insurance and medical care for patients hospitalized with human immunodeficiency virus-related Pneumocystis carinii pneumonia, 1995-1997: Medicaid, bronchoscopy, and survival.

In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients.

A rapid staging system for predicting mortality from HIV-associated community-acquired pneumonia.

STUDY OBJECTIVE: Community-acquired pneumonia (CAP) accounts for an increasing proportion of the pulmonary infections in individuals with HIV infection. During the mid-1990s, hospital mortality rates for HIV-associated CAP ranged from 0 to 28%. While hospital differences in case mix may account for mortality rate variation, few methods to evaluate illness severity for HIV-associated CAP have been reported previously. The study objective was to develop a staging system for categorizing mortality risk of patients with HIV-associated CAP using information available prior to hospital admission. DESIGN/SETTING/PATIENTS: Retrospective medical records review of 1,415 patients hospitalized with HIV-associated CAP from 1995 to 1997 at 86 hospitals in seven metropolitan areas. MEASUREMENTS: In-patient mortality rate. RESULTS: Hierarchically optimal classification tree analysis was used to develop a preadmission staging system for predicting inpatient mortality. The overall inpatient mortality rate was 9.1%. The significant predictors of mortality included the presence of neurologic symptoms, respiratory rate > or = 25 breaths/min, and creatinine > 1.2 mg/dL. The model identified a five-category staging system, with the mortality rate increasing by stage: 2.3% for stage 1, 5.8% for stage 2, 12.9% for stage 3, 22.0% for stage 4, and 40.5% for stage 5. The classification accuracy of the model was 85.2%. CONCLUSIONS: Our staging system categorizes inpatient mortality risk for patients with HIV-associated CAP using three routinely available variables. The staging system may be useful for guiding clinical decisions about the intensity of patient care and for case-mix adjustment in future studies addressing variation in hospital mortality rates.