Clinicopathologic features of ulcerative-atrophic sarcoidosis

BACKGROUND: Sarcoidosis is a chronic granulomatous disease of unknown etiology. Cutaneous disease is common and includes two clinicopathologic categories: granulomatous infiltration or a reactive phenomenon. In the granulomatous infiltrative group, clinical manifestations can be variable. Ulcers in sarcoidosis are uncommonly recognized and have been categorized previously under the rubric of atrophic, necrobiosis-like, or ulcerative sarcoidosis. PATIENTS AND METHODS: We evaluated retrospectively sarcoidosis patients presenting to the Johns Hopkins Department of Dermatology between June 1989 and May 2002. Multiple skin biopsies were performed for histopathologic evaluation. Investigation for extracutaneous manifestations, including routine serologic assays, chest radiography, pulmonary function tests, electrocardiogram, and angiotensin-converting enzyme level, and referral for ophthalmologic examination were performed in all patients. RESULTS: Of 147 consecutive patients presenting with cutaneous sarcoidosis, seven demonstrated ulcerative-atrophic sarcoidosis lesions. All patients were African-American (five females and two males). All patients had ulcers surrounded by atrophic necrobiosis lipoidica-like plaques on the pretibial areas. All patients had other mucocutaneous manifestations of sarcoidosis, with the majority having evidence of internal disease. Combined immunosuppressive and immunomodulatory therapy was effective in controlling the cutaneous manifestations of all patients with ulcerative sarcoidosis. CONCLUSIONS: The ulcerative variant is a poorly defined subset of cutaneous sarcoidosis. Trauma, superimposed on atrophic plaques, appears to be the principal mechanism of this rare variant of cutaneous sarcoidosis.     

A prospective study on clinical response and cell-mediated immunity of pemphigus patients treated with rituximab

Rituximab has recently been reported in retrospective studies to be effective in pemphigus at the dosing schedule used for treating rheumatoid arthritis (RA) of two 1,000 mg infusions 2 weeks apart. While the effect of rituximab on B cells has been well described, its effect on global T cell function has not been assessed. Ten patients who received RA dosage rituximab were prospectively assessed for clinical response. Immunological response including autoantibody titers, CD20+ B cell, and CD4+ T cell counts was assessed pre- and post-treatment. The CD4+ T cell function was determined by a novel assay measuring intracellular ATP levels in response to mitogenic stimulus. At 6 months, 90 % of patients achieved remission. Disease control and remission were achieved at median times of 1 and 3.7 months, respectively. There was a 67 % relapse rate during an average follow-up of 22 months. Global CD4+ T cell numbers and function were preserved 3 months after rituximab. A single cycle of RA dosage rituximab with concomitant immunosuppression is effective in pemphigus. We did not find an effect on total CD4+ T cell numbers or function 3 months after treatment.     

Cystoid macular edema: a correlation between macular volumetric parameters and visual acuity

Objective

To study in patients with cystoid macular edema (CME) the correlation between macular volumetric parameters on ocular coherence tomography (OCT) and visual acuity (VA).

Design

A retrospective consecutive cohort design was used.

Participants

The sample included 167 examinations of 92 consecutive patients (130 eyes).

Methods

Patients underwent spectral-domain OCT for CME from the years 2008 to 2010 at a tertiary medical centre. Background and VA data were recorded from the files. The custom-developed Cystometer software was used to calculate volumetric parameters from the OCT videos.

Results

In univariate analyses, VA correlated best with cystoid macular volume (CMVol; R² = 8.57) and total macular volume (TMV; R² = 7.46). By underlying disease, the strongest correlation was found with CMVol (R² = 8.47) in patients with diabetic CME (n = 91) and with TMV (R² = 22.18) in patients with branch retinal vein occlusion (n = 46). In multiple regression analyses, TMV, age, and CMVol/TMV accounted for 17.57% of the variation in VA. In the diabetic CME group, CMVol/TMV and age accounted for 15.34% of the variation; in the branch retinal vein occlusion group, TMV accounted for 22.18% of the variation.

Conclusions

Macular volumetric parameters measured by OCT and Cystometer software significantly correlate with VA in patients with CME, with variations by underlying CME causative factor.     

Can computerized cognitive tests assist in the clinical diagnosis of attention-deficit hyperactivity disorder?

A group of 34 children and adolescents suspected of having attention-deficit hyperactivity disorder were referred for a computerized evaluation that included sustained attention, working memory, planning, and set-shifting. Although only sustained attention had reasonable specificity, all tests had questionable contribution to the diagnostic evaluation.     

Energy expenditure in human milk- versus formula-fed preterm infants

OBJECTIVE: We compared energy expenditure (EE) of preterm infants fed their mother's milk versus preterm infant formula.Study design A prospective, randomized crossover study of 13 healthy, appropriate weight for gestational age, gavage-fed, preterm infants. Before the study and according to our feeding protocol, infants uniformly received alternate feeds of human milk and formula. Each infant was randomly assigned to 24 hours of formula feeding followed by 24 hours of breast milk or the reverse. Infants were studied asleep, at the end of each 24-hour period. EE was measured by indirect calorimetry 1 hour before feeding, 20 minutes during feeding, and 1 hour after feeding in a servo-controlled convective incubator. Energy content of human milk was analyzed by bomb calorimetry. RESULTS: EE was significantly lower in breast milk-fed infants during prefeeding (52+/-6 vs 57+/-10 kcal/kg per 24 hours) (P<.05), per feeding (55+/-6 vs 60+/-10 kcal/kg per 24 hours) (P<.05), and at the postfeeding measurement (60+/-7 vs 65+/-7 kcal/kg per 24 hours) (P=.059). After correction of the results for the actual measured energy intake, all statistical differences reached the <.05 level. CONCLUSIONS: Preterm infants have lower EE when they are fed breast milk than when they are fed preterm infant formula.     

Protective effect of intravenous immunoglobulin (IVIG) in an experimental model of pemphigus vulgaris

Uncontrolled studies have found intravenous immunoglobulin (IVIG) to be effective in the treatment of pemphigus vulgaris (PV). The aim of this study was to evaluate the role of IVIG in preventing IgG autoantibodies binding to desmoglein-3 and blister formation using a controlled experimental design. The ability of IVIG to affect the binding of IgG affinity purified from two patients with PV to desmoglein-3 in comparison to IgG from one donor, was conducted by enzyme-linked immunosorbent assay (ELISA). The specificity was confirmed by competition assay. We assessed the effect of IVIG on the induction of experimental-PV in CD1 newborn mice by subcutaneous subjection of IgG affinity purified from two patients with PV. The treatment was conducted by subcutaneous administration of IVIG together with IgG from the pemphigus patients or appropriate control. The skin of the newborns was examined 24-48 h later for blisters, and samples of the affected areas were analysed by immunohistochemistry. IVIG as a whole molecule and its F(ab)(2) portion inhibited the binding of anti-desmoglein-3 antibody to recombinant desmoglein-3 in a dose-dependent manner. The specificity was confirmed by competition assays. In-vivo, IVIG and its F(ab)(2) portion prevented blister formation in the newborn mice. Cutaneous lesions were noted only in the groups of newborn mice who were injected with IgG fractions from the PV patients. Immunopathological evaluation revealed that IVIG prevented the formation of acanthylosis with IgG deposition in the intercellular spaces. These results point to the efficacy of IVIG in the prevention of blister formation in an experimental PV model.     

Absolute nucleated red blood cells counts do not predict the development of bronchopulmonary dysplasia

Objective: We tested the hypothesis that infants with bronchopulmonary dysplasia (BPD) have higher absolute nucleated red blood cells (aNRBCs) counts at birth than controls as a proxy measurement of exposure to intrauterine hypoxia.

Methods: We studied 39 preterm infants with BPD and compared them to 39 pair-matched controls without BPD. Criteria for exclusion in both groups included factors that may influence the aNRBCs at birth.

Results: In logistic regression, when pre-eclampsia, birthweight, gender, antenatal steroid therapy, 1-min Apgar scores, respiratory distress syndrome (RDS) (or surfactant use), intraventricular hemorrhage of grade 3 or more, nosocomial sepsis, patent ductus arteriosus, and aNRBC counts (or lymphocyte counts) were used as independent variables, and BPD as the dependent variable, only RDS (or its proxy measurement of surfactant use) and nosocomial sepsis remained included in the final analysis.

Conclusions: aNRBC counts and lymphocyte counts do not appear to be elevated in infants that develop BPD, as compared to pair-matched controls without BPD. We speculate that chronic intrauterine hypoxia does not appear to play a major role in the pathogenesis of BPD. In contrast, postnatal events such as RDS and nosocomial sepsis appear to play a determining role in the pathogenesis of BPD.     

Prophylaxis of calcium oxalate stones by Herniaria hirsuta on experimentally induced nephrolithiasis in rats

OBJECTIVE: To evaluate the prophylactic potential of a herbal decoction from Herniaria hirsuta, a medicinal plant widely used in Morocco to treat kidney stones, by assessing the effect of oral administration in experimentally induced calcium oxalate (CaOx) nephrolithiasis in rats. MATERIAL AND METHODS: Two groups of six rats each were rendered nephrolithic by treating with ethylene glycol 0.75% and ammonium chloride 1% for 3 days, and then ethylene glycol only for 3 weeks. Maintained on ethylene glycol, one group of rats was also given 1 mL/day of the plant decoction, while the others received 1 mL of water instead for 2 weeks. Urine samples (24 h) were collected individually at 1, 3, 7, and 14 days for physicochemical analysis. On completing the treatment the kidneys were collected and analysed by light microscopy. RESULTS: The water intake and diuresis decreased in the treated rats; there was no significant difference in urinary pH between the groups. Urinary chemistry was apparently unaffected by the plant extract, except for the magnesium content, which was higher in treated rats. Crystalluria was characterized by the excretion of large CaOx monohydrate and dihydrate crystals in untreated, but smaller crystals in treated rats. The histology showed large deposits of CaOx crystals in all parts of the kidney in untreated rats but with almost no deposits in those of treated rats. CONCLUSION: H. hirsuta has an impressive prophylactic effect on CaOx stones in nephrolithic rats; the effect did not seem to be mediated by biochemical or diuretic changes.