Single Nucleotide Polymorphism-Based Noninvasive Prenatal Testing: Experience in India

Introduction

Noninvasive prenatal testing (NIPT) has revolutionized prenatal screening for chromosomal aneuploidies in some countries. Its implementation has been sporadic in developing countries. Given the genetic variation of the people in different countries, we evaluated the performance of the SNP-based NIPT in India .

Materials and Methods

The Panorama? NIPT was performed in 516 pregnancies, which had tested intermediate-to-high risk on conventional first and second trimester screening. Results were confirmed either by invasive diagnostic testing or by clinical evaluation after birth.

Results

Of 511 samples analyzed, results were obtained in 499 (97.7%). Of these, 480 (98.2%) were low risk and 19 were high risk. A sensitivity of 100% was obtained for detection of trisomies 21, 18, 13 and sex chromosomal abnormalities. The specificity ranged from 99.3 to 100% for abnormalities tested. Taken together, the positive predictive value for trisomies 21, 18, 13 and monosomy X was 85.7%. The average fetal fraction was 8.2%, which is lower than the average observed elsewhere.

Conclusion

This is the first report of detailed experience with NIPT in India and demonstrates comparable performance in all aspects of testing to the results elsewhere.

     

Isolated late testicular relapse of B‐cell acute lymphoblastic leukemia treated with intensive systemic chemotherapy and response‐based testicular radiation: A Children's Oncology Group study

1 Background

The incidence of isolated testicular relapse (ITR) of acute lymphoblastic leukemia (ALL) has decreased with contemporary treatment strategies, but outcomes are suboptimal with a 58% 5‐year overall survival (OS). This study aimed to improve outcome in patients with ITR of B‐cell ALL (B‐ALL) occurring after 18 months of first clinical remission using intensive systemic chemotherapy and to decrease long‐term sequelae by limiting use of testicular radiation.

2 Procedure

Forty patients in first ITR of B‐ALL were enrolled. Induction (dexamethasone, vincristine, daunorubicin, and intrathecal triple therapy) was preceded by one dose of high‐dose methotrexate (MTX, 5 g/m²). Following induction, 25 of 26 patients who had persistent testicular enlargement underwent testicular biopsy. Eleven had biopsy‐proven disease and received bilateral testicular radiation (24 Gy), whereas twenty‐nine did not.

3 Results

Overall 5‐year event‐free survival (EFS)/OS was 65.0 ± 8.8%/73.1 ± 8.3%, with 5‐year EFS 62.1 ± 11.0% vs. 72.7 ± 14.4% for patients who did not receive radiation therapy (XRT) (n = 29) compared with those who did (n = 11), respectively (P = 0.64). There were six second bone marrow relapses and six second ITRs. The proportion of second relapses was similar in the patients that received testicular radiation and those who did not. However, the 5‐year OS was similar for patients who did not receive XRT (72.6 ± 10.2%) compared with those who did (72.7 ± 14.4%) (P = 0.85).

4 Conclusions

A 5‐year OS rate of 73.1 ± 8.3% was obtained in children with first ITR of B‐ALL occurring after 18 months of CR1 (length of first clinical remission) using intensive chemotherapy and limiting testicular radiation.     

Papillon-Lefevre syndrome: a report of two cases

Papillon-Lefevre Syndrome (PLS) is an inherited autosomal recessive disorder presenting with Palmar plantar Keratoderma and Juvenile Periodontitis leading to early loss of both the dentitions. Two cases of PLS in a family with a history of consanguineous descent are presented.     

Age effect on prognosis for functional recovery in acute, traumatic central cord syndrome

The purpose of this study was to determine if age is significant in functional recovery in acute, traumatic central cord syndrome (CCS). Recovery of ambulation, ADL status, and bowel and bladder function were evaluated. A retrospective study tested the hypothesis that functional recovery in 51 consecutive CCS patients was better in younger patients than in older patients. Four patients, all more than 50 years, died. Ability to ambulate independently at discharge was compared in 30 patients younger than 50 years with 21 patients 50 years or older. Results showed that 29 of 30 (97%) of the younger patients were ambulatory compared to seven of 17 (41%) of the older patients (p less than .002). The younger patients were also able to achieve independence in self-care and bowel and bladder function in a significantly greater proportion. The prognosis for functional recovery in acute traumatic CCS should consider the patient's age. The prognosis is less optimistic in older patients, but it is considerably more favorable in younger patients than previously reported.     

Role of tumor necrosis factor receptor expression in anterior chamber-associated immune deviation (ACAID) and corneal allograft survival

PURPOSE: To determine the role of tumor necrosis factor receptors (TNFRs) in corneal allograft rejection. METHODS: Corneal epithelial and endothelial cells were examined by flow cytometry for the expression of TNFRI and TNFRII and their susceptibility to TNF-alpha-induced apoptosis. Corneal allografts from normal and TNFRI and TNFRII knockout (KO) C57BL/6 mice were transplanted to BALB/c hosts, and the fate of the allografts was monitored. C57BL/6 spleen cells were injected into the anterior chamber (AC) of BALB/c mice to induce anterior chamber-associated immune deviation (ACAID) and promote corneal allograft survival. The presence of ACAID suppressor cells in corneal allograft recipients was tested using a local adoptive transfer (LAT) assay. RESULTS: Murine corneal epithelial and endothelial cells expressed TNFRI and TNFRII and were susceptible to TNF-alpha-induced apoptosis, yet corneal allografts from either TNFRI or TNFRII donors did not enjoy a lower incidence of rejection or a prolongation in survival time compared to corneal allografts from normal C57BL/6 donors. Moreover, all 31 of the TNFRII KO corneal grafts were rejected by na?ve BALB/c hosts. Rejection of TNFRII KO corneal grafts occurred even though suppressor cells developed in the hosts and inhibited the expression of delayed-type hypersensitivity to donor alloantigens. CONCLUSIONS: Expression of TNFRII on corneal cells conveys a degree of protection against immune rejection of corneal allografts by a mechanism that is independent of ACAID. Moreover, induction of ACAID before the application of TNFRII KO corneal allografts fails to improve survival and does not replace the TNFRII-dependent protective mechanism.     

Role of free radicals in the toxicity of airborne fine particulate matter

Exposure to airborne fine particles (PM2.5) is implicated in excess of 50 000 yearly deaths in the USA as well as a number of chronic respiratory illnesses. Despite intense interest in the toxicity of PM2.5, the mechanisms by which it causes illnesses are poorly understood. Since the principal source of airborne fine particles is combustion and combustion sources generate free radicals, we suspected that PM2.5 may contain radicals. Using electron paramagnetic resonance (EPR), we examined samples of PM2.5 and found large quantities of radicals with characteristics similar to semiquinone radicals. Semiquinone radicals are known to undergo redox cycling and ultimately produce biologically damaging hydroxyl radicals. Aqueous extracts of PM2.5 samples induced damage to DNA in human cells and supercoiled phage DNA. PM2.5-mediated DNA damage was abolished by superoxide dismutase, catalase, and deferoxamine, implicating superoxide radical, hydrogen peroxide, and the hydroxyl radical in the reactions inducing DNA damage.     

Epidemiological characteristics and laboratory diagnosis of fungal keratitis. A three-year study

PURPOSE: To study the epidemiological characteristics and laboratory diagnosis of fungal keratitis seen at a tertiary eye care referral centre in South India. METHODS: A retrospective review of all culture-proven fungal keratitis seen over a 3-year period, September 1999 through August 2002. RESULTS: Fungal aetiology were confirmed in 1095 (34.4%) of 3183 corneal ulcers. The predominant fungal species isolated was Fusarium spp (471; 42.82%) followed by Aspergillus spp (286; 26%). Males (712; 65.08%) were more often affected (P<0.0001). A large proportion of the patients (732; 66.85%) were in the younger age group (21 to 50 years). A majority (879; 80.27%) came from rural areas (P<0.0001), and most patients (709; 64.75%) were farmers (P<0.0001). Ocular trauma (1009; 92.15%) was a highly significant risk factor (P<0.0001) and vegetative injuries (671; 61.28%) were identified as a significant cause for fungal keratitis (P<0.0001). 172 (15.71%) patients had concurrent diabetes mellitus. The sensitivity of 10% potassium hydroxide (KOH) wet mount preparation was higher (99.23%) than Gram-stained smear (88.73%) (P<0.0001). Incidence of fungal keratitis was higher between June and September. CONCLUSION: Agricultural activity and related ocular trauma were principal causes of mycotic keratitis. A potassium hydroxide (KOH) wet mount preparation is a simple, and sensitive, method for diagnosis     

Air embolism during anaesthesia for shoulder arthroscopy

We report a case of venous air embolism during an elective shoulderarthroscopy in which air was used as a joint distending agent.Venous air embolism was diagnosed by the sudden decrease inthe end-tidal carbon dioxide concentration. The patient sufferedno serious complications of venous air embolism and made a fullrecovery. We present this case to make surgeons and anaesthetistsaware of the possibility of gas/air embolism during electivearthroscopy, when gas/air is used to distend the joint. Thiscase also illustrates that the end-tidal carbon dioxide monitor,which is part of the standard anaesthetic monitoring system,is very sensitive in detecting venous air embolism. Br J Anaesth 2000; 85: 925–7     

Antrochoanal polyps and allergy—A comparative study

Antrochoanal polyps, are solitary polyps arising from the maxillary autrum. Their aetiology largely remains unknown; allergy has been implicated. The study attempts to define the relation between antrochoanal polyps and allergy and the need for such an investigation by studying 24 cases with antrochoanal polyps and comparing them with 20 cases of sinonasal polyps. Nasal smear cytology, serum total IgE and polyp fluid IgE was evaluated. 52.38% of cases turned out to be allergic. In their presentation, antrochoanal polyps do not significantly differ from other polyps.