Atypical Down syndrome phenotype with severe developmental delay, hypertonia, and seizures in a child with translocation trisomy 21

An infant is reported who presented with a de novo 21;21 translocation trisomy 21 and an atypical phenotype for Down syndrome (DS). Findings included microcephaly, small stature, downslanting palpebral fissures, absent Brushfield spots, moderate micrognathia, left ptosis, left torticollis, severe developmental delay, seizures, and hypertonia. Further clinical evaluation using both the diagnostic criteria for DS and the Jackson checklist of 25 signs was inconsistent with the diagnosis for DS. Blood karyotype revealed: 46,XX,+21,dic(21;21) (p11.2;p11.2). Fluorescence in situ hybridization (FISH) analysis confirmed the trisomy 21 translocation. Both parents had normal karyotypes. Chromosome and FISH analyses were performed on skin fibroblasts. These studies revealed mosaicism for a translocation trisomy 21 cell line as wel as a second cell line consisting of one normal chromosome 21 and a ring chromosome 21 derived from translocation 21q21q which appeared to have a deletion of the critical region for DS involving the distal portion of the thelong arm of chromosome 21. The chromosome findings illustrate an atypical phenotype in the spectrum of mosaic DS and suggest possible mechanisms for the variability of the phenotype. It also emphasizes the importance of evaluating other tissues for mosaicism when presented with atypical clinical findings.     

An Analysis of Presentation,Pattern and Outcome of Chest Trauma Patients at an Urban Level 1 Trauma Center

Chest trauma is an important public health problem accounting for a substantial proportion of all trauma admissions and deaths. It directly account for 20–25 % of deaths due to trauma. Therefore, this study was conducted to analyze the presentation, patterns, and outcome of chest trauma in a level-1 urban trauma center. It was a prospective observational study of all patients presented with chest trauma to an urban level 1-trauma center over a period of 3 years. Demographic profile, mechanism of injury, injury severity scores (ISS), associated injuries, hospital stay, etc. were recorded. Morbidity and mortality rates were analyzed and compared with the published literature. Chest injuries comprised 30.9 % of all trauma admissions and the mechanism was blunt in majority (83.5 %) of the cases. Vehicular crashes (59.7 %) followed by assault were the most common modes of injury. Rib fracture was the most common chest injury seen in 724 of the 1258 patients while abdominal visceral injuries were the commonest associated injuries in polytrauma cases. Majority of the patients were managed non-operatively. Inter costal tube drainage (ICD) was the main stay of treatment in 75 % of the cases, whereas, thoracotomy was required only in 5.56 % of the patients. Overall mortality was 11 % and it was found to be significantly higher following blunt chest trauma. We observed that associated extra thoracic injuries resulted in higher mortality as compared to isolated chest injuries. Thoracic injuries can be readily diagnosed in the emergency department by meticulous and repeated clinical evaluation and majority require simple surgical procedures to prevent immediate mortality and long-term morbidity.     

Prenatal detection of mosaic trisomy 1q due to an unbalanced translocation in one fetus of a twin pregnancy following in vitro fertilization: a postzygotic error

Complete or mosaic trisomy for all of chromosome 1q has been seen rarely in a recognized pregnancy. A patient presented with twins following in vitro fertilization (IVF). Ultrasound showed twin A to have a diaphragmatic hernia, thick nuchal fold, and subtle intracranial abnormalities. Twin B appeared normal and a thick dividing membrane was seen. Amniocentesis of twin A showed a male karyotype with mosaic trisomy 1q in 57% of cells resulting from a translocation between chromosomes Yq12 and 1q12. Parental karyotypes were normal. The twins were delivered at 33 weeks. Twin A died at 1 hr of life. Autopsy confirmed the left diaphragmatic hernia and hypoplastic lungs. Autopsy also revealed a partial cleft palate, syndactyly of the second and third toes bilaterally, external deviation of the left 5th toe, and contractures of the index fingers bilaterally. A recent report documented formation of a chimera resulting from embryo amalgamation after IVF. Given the rarity of the cytogenetic findings in our case, we sought to determine if the mosaicism was a result of chimera formation related to the IVF. Thirteen polymorphic loci throughout the genome, in addition to four on 1q and four on 1p, were amplified by PCR. Only two alleles were observed at each of these loci in twin A, one paternal and the other maternal. We present further clinical findings of this case with a rare cytogenetic abnormality that appears to have originated from a postzygotic mitotic error and not embryo amalgamation.     

Activation of the mitogen-activated protein kinase pathway through p75NTR: a common mechanism for the neurotrophin family

Neurotrophins interact with two distinct classes of cell-surface receptors, the Trk receptor tyrosine kinase family and the common neurotrophin receptor p75(NTR). For many years, the biological role of p75(NTR) remained obscure, being relegated to modulating Trk binding of neurotrophins. Recently, the importance of p75(NTR) as a signaling receptor in itself has become increasingly clear. The signals initiated by p75(NTR) are likely to be as complex as those for the Trk family and probably depend on the cell system in which such signaling is being studied. In this study, all members of the neurotrophin family were demonstrated to be capable of stimulating p75(NTR)-mediated activation of the mitogen-activated protein kinase (MAPK) family (ERK1,2). This activation is rapid and transient, peaking at 5-15 min, depending on the cell system. The classical MAPK cascade consists of the reaction series Ras-Raf-MEK-MAPK. The p75(NTR)-induced MAPK activation is MEK dependent but Raf independent. This result implies that neurotrophin activation of p75(NTR) results in some cascade (as yet unknown) that bypasses Raf and converges on MEK to result in activation of MAPK. This activated MAPK is then able to translocate to the nucleus. The effect of this MAPK activation on cell survival is dependent on cell type. These results support the concept that signaling from the p75(NTR) receptor is more diverse and extensive than previously believed.     

Retrospective, propensity score-matched cohort study examining timing of fracture fixation for traumatic thoracolumbar fractures

Abstract The timing of surgery in patients with traumatic thoracic/thoracolumbar fractures, with or without spinal cord injury, remains controversial. The objective of this study was to determine the importance of the timing of surgery for complications and resource utilization following fixation of traumatic thoracic/thoracolumbar fractures. In this retrospective cohort study, the 2003-2008 California Inpatient Databases were searched for patients receiving traumatic thoracic/thoracolumbar fracture fixation. Patients were classified as having early (<72?h) or late (>72?h) surgery. Propensity score modeling produced a matched cohort balanced on age, comorbidity, trauma severity, and other factors. Complications, mortality, length of stay, and hospital charges were assessed. Multivariate logistic regression was used to determine the impact of delayed surgery on in-hospital complications after balancing and controlling for other important factors. Early surgery (<72?h) for traumatic thoracic/thoracolumbar fractures was associated with a significantly lower overall complication rate (including cardiac, thromboembolic, and respiratory complications), and decreased hospital stay. In-hospital charges were significantly lower ($38,120 difference) in the early surgery group. Multivariate analysis identified time to surgery as the strongest predictor of in-hospital complications, although age, medical comorbidities, and injury severity score were also independently associated with increased complications. We reinforce the beneficial impact of early spinal surgery (prior to 72?h) in traumatic thoracic/thoracolumbar fractures to reduce in-hospital complications, hospital stay, and resource utilization. These results provide further support to the emerging literature and professional consensus regarding the importance of early thoracic/thoracolumbar spine stabilization of traumatic fractures to improve patient outcomes and limit hospitalization costs.     

Optimizing the management of neuromyelitis optica and spectrum disorders in resource poor settings: Experience from the Mangalore demyelinating disease registry

Background:

In resource-poor settings, the management of neuromyelitis optica (NMO) and NMO spectrum (NMOS) disorders is limited because of delayed diagnosis and financial constraints.

Aim:

To device a cost-effective strategy for the management of NMO and related disorders in India.

Materials and Methods:

A cost-effective and disease-specific protocol was used for evaluating the course and treatment outcome of 70 consecutive patients.

Results:

Forty-five patients (65%) had a relapse from the onset and included NMO (n = 20), recurrent transverse myelitis (RTM; n = 10), and recurrent optic neuritis (ROPN; n = 15). In 38 (84.4%) patients presenting after multiple attacks, the diagnosis was made clinically. Only 7 patients with a relapsing course were seen at the onset and included ROPN (n = 5), NMO (n = 1), and RTM (n = 1). They had a second attack after a median interval of 1 ± 0.9 years, which was captured through our dedicated review process. Twenty-five patients had isolated longitudinally extensive transverse myelitis (LETM), of which 20 (80%) remained ambulant at follow-up of 3 ± 1.9 years. Twelve patients (17%) with median expanded disability status scale (EDSS) of 8.5 at entry had a fatal outcome. Serum NMO-IgG testing was done in selected patients, and it was positive in 7 of 18 patients (39%). Irrespective of the NMO-IgG status, the treatment compliant patients (44.4%) showed significant improvement in EDSS (P ≤ 0.001).

Conclusions:

Early clinical diagnosis and treatment compliance were important for good outcome. Isolated LETM was most likely a post-infectious demyelinating disorder in our set-up. NMO and NMOS disorders contributed to 14.9% (45/303) of all demyelinating disorders in our registry.Key Words: Demyelinating disease registry, immunosuppression, India, neuromyelitis optica, neuromyleitis optica spectrum disorders     

Isolation and Identification of Culturable Bacteria and Fungi from Mixed Dipterocarp and Mangrove Forests of Brunei Darussalam

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Unique forests comprise of culturable microbes with unique properties that are of potential biotechnological...     

Bipolar radiofrequency ablation of tibialchondroblastomas: A report of three cases

Chondroblastoma is a rare benign cartilaginous neoplasm of bone. The recurrence rate is high and complications are frequent following open curettage with bone grafting which is the standard treatment forchondroblastomas. We performed radiofrequency ablation in three cases of tibialchondroblastoma using the bipolar system. One patient experienced residual pain for which repeat ablation was performed. No other complications were observed during follow-up. Radiofrequency ablation may offer an effective alternative for the treatment of selected cases of chondroblastoma. The lesion characteristics which are likely to influence treatment outcome and the advantages offered by the bipolar system are discussed.