Congenital sodium diarrhea and chorioretinal coloboma with optic disc coloboma in a patient with biallelic SPINT2 mutations,including p.(Tyr163Cys)

Congenital sodium diarrhea is a rare and life‐threatening disorder characterized by a severe, secretory diarrhea containing high concentrations of sodium, leading to hyponatremia and metabolic acidosis. It may occur in isolation or in association with systemic features such as facial dysmorphism, choanal atresia, imperforate anus, and corneal erosions. Mutations in the serine protease inhibitor, Kunitz‐Type 2 (SPINT2) gene have been associated with congenital sodium diarrhea and additional syndromic features. We present a child with congenital sodium diarrhea, cleft lip and palate, corneal erosions, optic nerve coloboma, and intermittent exotropia who was found to have biallelic mutations in SPINT2. One mutation, c.488A > G, predicting p.(Tyr163Cys), has been previously associated with a syndromic form of congenital sodium diarrhea. The other mutation, c.166_167dupTA, predicting p.(Asn57Thrfs*24) has not previously been reported and is likely a novel pathogenic variant for this disorder. We found only one other report of an optic nerve coloboma associated with SPINT2 mutations and this occurred in a patient with congenital tufting enteropathy. Our patient confirms an association of ocular coloboma with presumed loss of SPINT2 function.     

Hepatitis E virus antigen detection as an early diagnostic marker: Report from India

Hepatitis E virus (HEV) is implicated in many outbreaks of viral hepatitis in the Indian subcontinent. The conventional diagnosis of such outbreaks rests on the detection of anti‐HEV IgM antibodies. However, IgM antibodies develop after 4–5 days of infection. An early‐diagnostic marker is imperative for timely diagnosis of the outbreak and also initiation of control measures. This study aimed to determine the use of hepatitis E virus antigen detection as an early diagnostic marker in an outbreak in comparison to anti‐HEV IgM and RT‐PCR analyses. Forty samples were collected during a suspected outbreak of viral hepatitis due to HEV. A total of 36 samples were positive for one or more HEV markers. The positivity for anti‐HEV IgM, HEV antigen, and RT‐PCR was 91.6%, 69.4%, and 47.2% respectively. RT‐PCR and HEV antigen detection gave the highest positive results (100%) in the first 3 days of illness. Positive HEV PCR declined to 54% by Days 4–7, whereas HEV antigen and IgM detection were 88% and 100%, respectively. Sequencing of representative HEV samples indicated that the strains responsible for this outbreak belonged to genotype I, subtype 1a. HEV antigen was found to be an early diagnostic marker of acute infection. HEV antigen was detected in three additional cases in the early phase (1–3 days), and they had no detectable anti‐HEV IgM antibodies. These three samples were also positive for HEV RNA. After Day 7, anti‐HEV IgM was the main diagnostic indicator of infection. J. Med. Virol. 85:823–827, 2013. © 2013 Wiley Periodicals, Inc.     

Clinical predictors of high risk histopathology in retinoblastoma

Background

Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma.

Procedure

We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF.

Results

Three hundred twenty‐six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis.

Conclusions

Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study. Pediatr Blood Cancer 2012; 58: 356–361. © 2011 Wiley Periodicals, Inc.     

Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis

Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population.     

Gastrointestinal histoplasmosis presenting as colonic pseudotumour

We report a case of gastrointestinal histoplasmosis in a 45-year-old HIV positive man who was misdiagnosed as a case of colonic cancer. The patient presented with low-grade fever, pain in lower abdomen, anorexia and weight loss of six months duration. On examination a lump in the left iliac fossa was detected. Colonoscopy revealed stricture and ulcerated growth in the sigmoid colon. Radiological investigations suggested malignant/inflammatory mass in the sigmoid colon with luminal compromise. Patient was operated and ulcerated tissue was sent for histopathological examination, which revealed numerous intracellular, 2-4 microm, oval, narrow-based budding yeast cells suggestive of Histoplasma capsulatum. Subsequently, the patient developed fluffy opacities on X-ray chest. Examination of sputum revealed presence of acid-fast bacilli and yeast forms of H. capsulatum. Patient was started on amphotericin B but died on the seventeenth postoperative day. The diagnosis of histoplasmosis was made retrospectively. Atypical presentation and rarity of the disease led to this diagnostic pitfall. To the best of our knowledge this is the first report of gastrointestinal histoplasmosis presenting as colonic pseudotumour from India.     

Object detectability at increased ambient lighting conditions

Under typical dark conditions encountered in diagnostic reading rooms, a reader's pupils will contract and dilate as the visual focus intermittently shifts between the high luminance display and the darker background wall, resulting in increased visual fatigue and the degradation of diagnostic performance. A controlled increase of ambient lighting may, however, reduce the severity of these pupillary adjustments by minimizing the difference between the luminance level to which the eyes adapt while viewing an image (L(adp)) and the luminance level of diffusely reflected light from the area surrounding the display (L(s)). Although ambient lighting in reading rooms has conventionally been kept at a minimum to maintain the perceived contrast of film images, proper Digital Imaging and Communications in Medicine (DICOM) calibration of modern medical-grade liquid crystal displays can compensate for minor lighting increases with very little loss of image contrast. This paper describes two psychophysical studies developed to evaluate and refine optimum reading room ambient lighting conditions through the use of observational tasks intended to simulate real clinical practices. The first study utilized the biologic contrast response of the human visual system to determine a range of representative L(adp) values for typical medical images. Readers identified low contrast horizontal objects in circular foregrounds of uniform luminance (5, 12, 20, and 30 cd/m2) embedded within digitized mammograms. The second study examined the effect of increased ambient lighting on the detection of subtle objects embedded in circular foregrounds of uniform luminance (5, 12, and 35 cd/m2) centered within a constant background of 12 cd/m2 luminance. The images were displayed under a dark room condition (1 lux) and an increased ambient lighting level (50 lux) such that the luminance level of the diffusely reflected light from the background wall was approximately equal to the image L(adp) value of 12 cd/m2. Results from the first study demonstrated that observer true positive and false positive detection rates and true positive detection times were considerably better while viewing foregrounds at 12 and 20 cd/m2 than at the other foreground luminance levels. Results from the second study revealed that under increased room illuminance, the average true positive detection rate improved a statistically significant amount from 39.3% to 55.6% at 5 cd/m2 foreground luminance. Additionally, the true positive rate increased from 46.4% to 56.6% at 35 cd/m2 foreground luminance, and decreased slightly from 90.2% to 87.5% at 12 cd/m2 foreground luminance. False positive rates at all foreground luminance levels remained approximately constant with increased ambient lighting. Furthermore, under increased room illuminance, true positive detection times declined at every foreground luminance level, with the most considerable decrease (approximately 500 ms) at the 5 cd/m2 foreground luminance. The first study suggests that L(adp) of typical mammograms lies between 12 and 20 cd/m2, leading to an optimum reading room illuminance of approximately 50-80 lux. Findings from the second study provide psychophysical evidence that ambient lighting may be increased to a level within this range, potentially improving radiologist comfort, without deleterious effects on diagnostic performance.     

Posttraumatic stress symptoms in parents of children with acute burns

OBJECTIVE: To develop a model of risk factors for posttraumatic stress disorder (PTSD) symptoms in parents of children with burns. METHODS: Immediately following the burn and 3 months later, parents reported on their children's and their own psychological functioning and traumatic stress responses. RESULTS: Approximately 47% of the parents reported experiencing significant posttraumatic stress symptoms 3 months after the burn. Our model indicates three independent pathways to PTSD symptoms (i.e., parent-child conflict, parents' dissociation, and children's PTSD symptoms). Additionally, parents' anxiety predicted increased parent-child conflict, conflict with extended family and size of the burn predicted parents' dissociation, and size of the burn and children's dissociation predicted children's PTSD symptoms. CONCLUSIONS: This study suggests that many parents of children with burns suffer from posttraumatic stress symptoms. Interventions that target factors such as family conflict, children's symptoms, and parents' acute anxiety and dissociation may diminish the risk for PTSD.     

Labor Induction with 50?μg Vaginal Misoprostol: Can We Reduce Induction-Delivery Intervals Safely?

Objective

To compare the efficacy and safety profile of two methods of labor induction i.e., intracervical dinoprostone gel (0.5 mg 8 h) and misoprostol (50 μg 4 h) for induction of labor in women with a poor Bishop’s score.

Design

Observational study.

Study Period

January 1st, 2009 to December 31st, 2010.

Population

A total of 329 women with unfavorable cervices induced at or near term.

Methods

Two cervical ripening agent study arms were used: dinoprostone gel (193 women) and misoprostol (137 women).

Main Outcome Measures

Induction to delivery interval, cesarean section, incidence of meconium stained liquor, FHR pattern, incidence of uterine hyperstimulation, and neonatal outcomes.

Results

The induction to delivery interval was significantly shorter in the misoprostol group as compared to the dinoprostone group (p < 0.001). There was no difference in cesarean section rates between the two groups (dinoprostone gel 43 %; misoprostol 33 %; p = 0.144). The incidence of non-reassuring fetal heart rate pattern, meconium stained liquor, and uterine hyperstimulation were equivalent in both the groups (p = 0.529; 0.733; and 0.321, respectively). The neonatal outcomes in both the groups were comparable in terms of Apgar scores at birth (p = 0.160) and NICU admissions (p = 0.951).

Conclusions

Labor induction in women with unfavorable cervices results in high caesarean section rates. However, the use of misoprostol significantly reduces the induction to delivery interval, without adversely affecting the caesarean section rates and neonatal outcomes. Hence it may become a cost-effective alternative to dinoprostone gel in resource-poor settings like India.     

Significance of false-positive serologic tests for histoplasmosis and blastomycosis in an endemic area

False-positive serologic tests for histoplasmosis (H) and blastomycosis (B) are common in populations from endemic areas. In order to determine the significance of false-positive test results, we reviewed the final diagnoses of all patients whose sera were submitted to our laboratory for radioimmunoassay (RIA) and immunodiffusion (ID) during a 3-yr period. Of the 263 patients whose sera were examined, 29 (11%) had H or B; 41 (17.5%) of the remaining 234 patients had false-positive test results. Of these 41 patients, 31 were positive for H alone, and 10 had antibodies to both H and B. All three patients with false-positive ID tests for histoplasmosis also had positive titers (greater than or equal to 1:16) on RIA. No patient had a false-positive ID result for blastomycosis. The percentage of patients in each of five major diagnostic categories with and without false-positive serologic tests was similar (p greater than 0.05). The majority of patients had pulmonary infections, almost half of which were granulomatous infections other than H or B; this reflects the clinical indications for requesting fungal serologic tests. A positive fungal serology is not useful in suggesting the presence of a pulmonary disease other than H or B in patients from an endemic area suspected of having a pulmonary mycosis.